Valid and reliable biomarkers can play an important role in clinical trials as indicators of biological or pathogenic processes or as a signal of treatment response. Currently, there are no ...biomarkers for pain qualified by the U.S. Food and Drug Administration or the European Medicines Agency for use in clinical trials. This article summarizes an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials meeting in which 3 potential biomarkers were discussed for use in the development of analgesic treatments: 1) sensory testing, 2) skin punch biopsy, and 3) brain imaging. The empirical evidence supporting the use of these tests is described within the context of the 4 categories of biomarkers: 1) diagnostic, 2) prognostic, 3) predictive, and 4) pharmacodynamic. Although sensory testing, skin punch biopsy, and brain imaging are promising tools for pain in clinical trials, additional evidence is needed to further support and standardize these tests for use as biomarkers in pain clinical trials.
The applicability of sensory testing, skin biopsy, and brain imaging as diagnostic, prognostic, predictive, and pharmacodynamic biomarkers for use in analgesic treatment trials is considered. Evidence in support of their use and outlining problems is presented, as well as a call for further standardization and demonstrations of validity and reliability.
Evaluation of the causal effect of a baseline exposure on a morbidity outcome at a fixed time point is often complicated when study participants die before morbidity outcomes are measured. In this ...setting, the causal effect is only well defined for the principal stratum of subjects who would live regardless of the exposure. Motivated by gerontologic researchers interested in understanding the causal effect of vision loss on emotional distress in a population with a high mortality rate, we investigate the effect among those who would live both with and without vision loss. Since this subpopulation is not readily identifiable from the data and vision loss is not randomized, we introduce a set of scientifically driven assumptions to identify the causal effect. Since these assumptions are not empirically verifiable, we embed our methodology within a sensitivity analysis framework. We apply our method using the first three rounds of survey data from the Salisbury Eye Evaluation, a population-based cohort study of older adults. We also present a simulation study that validates our method.
•New flow and curing data for healing agents in a cementitious vascular system.•New insights into the nature of cyanoacrylate curing fronts in concrete cracks.•Characterisation of the sorption ...behaviour of cyanoacrylate in concrete.•Characterisation of cyanoacrylate flow within discrete concrete cracks.•Constitutive equations and parameters for cyanoacrylate flow and curing n concrete.
A series of characterisation studies are reported that provide new data on the behaviour of a self-healing cementitious material (SHCM) system. A ‘model’ material system is selected for study that comprises cyanoacrylate (CA) filled channels in concrete structural elements. The focus of the work is on transport and curing properties of the healing-agent, with the results of four separate studies being presented. The experimental programme encompasses the capillary flow behaviour of CA in a static natural crack, the sorption of healing-agent through a cracked surface into a concrete specimen, the development and progress of a CA curing front adjacent to a concrete substrate and the dynamic flow characteristics of CA in capillary channels. A theoretical relationship is established for each of these processes, which allows meaningful parameters to be determined that help characterise the behaviour of the material system. In all cases, the processes were shown to have a significant degree of variability but, equally, to exhibit strong behavioural trends.
We report the results of low temperature (−10°C) experiments on the stability fields and phase transition pathways of five hydrous Mg‐sulfates. A low temperature form of MgSO4·7H2O (LT‐7w) was found ...to have a wide stability field that extends to low relative humidity (∼13% RH at −10°C). Using information on the timing of phase transitions, we extracted information on the reaction rates of five important dehydration and rehydration processes. We found that the temperature dependencies of rate constants for dehydration processes differ from those of rehydration, which reflect differences in reaction mechanisms. By extrapolating these rate constants versus T correlations into the T range relevant to Mars, we can evaluate the possibility of occurrence of specific processes and the presence of common Mg‐sulfate species present on Mars in different periods and locations. We anticipate in a moderate obliquity period, starkeyite and LH‐MgSO4·H2O should be two common Mg‐sulfates at the surface, another polymorph MH‐MgSO4·H2O can exist at the locations where hydrothermal processes may have occurred. In polar regions or within the subsurface of other regions, meridianiite (coexisting with water ice, near 100% RH) and LT‐7w (over a large RH range) are the stable phases. During a high obliquity period, meridianiite and LT‐7w should exhibit widespread occurrence. The correlations of reaction rates versus temperature found in this study imply that dehydration and rehydration of hydrous Mg‐sulfates would always be slower than the sublimation and crystallization of water ice, which would be supported by mission observations from Odyssey and by Mars Exploration Rovers.
Key Points
Stability field and phase transition pathways of Mg‐sulfates at −10°C
Rate of dehydration and rehydration of Mg‐sulfates at Mars relevant temperatures
Common Mg‐sulfates on Mars in different regions and different obliquity periods
OBIS-SEAMAP Halpin, P. N.; Read, A. J.; Best, B. D. ...
Marine ecology. Progress series (Halstenbek),
07/2006, Letnik:
316
Journal Article
Recenzirano
Odprti dostop
Our ability to understand, conserve, and manage the planet’s marine biodiversity is fundamentally limited by the availability of relevant taxonomic, distribution, and abundance data. The Spatial ...Ecological Analysis of Marine Megavertebrate Animal Populations (SEAMAP) initiative is a taxon-specific geo-informatics facility of the Ocean Biogeographic Information System (OBIS) network. OBIS-SEAMAP has developed an expanding geo-database of marine mammal, seabird, and sea turtle distribution and abundance data globally. The OBIS-SEAMAP information system is intended to support research into the ecology and management of these important marine megavertebrates and augment public understanding of the ecology of marine megavertebrates by: (1) facilitating studies of impacts on threatened species, (2) testing hypotheses about biogeographic and biodiversity models, and (3) supporting modeling efforts to predict distributional changes in response to environmental change. To enhance the research and educational applications of this database, OBIS-SEAMAP provides a broad array of web-based products and services, including rich species profiles, compliant metadata, and interactive mapping services. This system takes advantage of recent technological advances in Geographic Information Systems (GIS), Internet data standards, and content management systems to stimulate a novel community-based approach to the development of a data commons for biogeographic and conservation research. To date, the global OBIS-SEAMAP database includes >1 million observation records from 163 datasets, spanning 71 yr (1935 to 2005) provided by a growing international network of data providers.
In recent years, globalization and the expansion of information technologies have reshaped managerial practices, forcing multinational firms to adjust business practices to different environments and ...domestic companies to adjust to their foreign competitors. In International Differences in the Business Practices and Productivity of Firms, a distinguished group of contributors examines the phenomenon of widespread differences in managerial practices across firms, establishments within firms, and countries. This volume brings together eight studies that combine qualitative and quantitative insider analysis of business practices such as the use of teams, incentive pay, lean manufacturing, and quality control, revealing the elements that determine which practices are adopted and why. International Differences in the Business Practices and Productivity of Firms offers a much-needed model for measuring the productivity and performance of international firms in a fast-paced global economy.
One of the primary goals of statistical precision medicine is to learn optimal individualized treatment rules (ITRs). The classification-based, or machine learning-based, approach to estimating ...optimal ITRs was first introduced in outcome-weighted learning (OWL). OWL recasts the optimal ITR learning problem into a weighted classification problem, which can be solved using machine learning methods, e.g., support vector machines. In this paper, we introduce a Bayesian formulation of OWL. Starting from the OWL objective function, we generate a pseudo-likelihood which can be expressed as a scale mixture of normal distributions. A Gibbs sampling algorithm is developed to sample the posterior distribution of the parameters. In addition to providing a strategy for learning an optimal ITR, Bayesian OWL provides a natural, probabilistic approach to estimate uncertainty in ITR treatment recommendations themselves. We demonstrate the performance of our method through several simulation studies.
Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and ...effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.
Abstract
Introduction
More than half of heavy-drinking young adults report symptoms of insomnia, which have been associated with alcohol-related problems. This study examined improvement in insomnia ...(via Cognitive Behavioral Therapy for Insomnia; CBT-I) as a mechanism for improvement in alcohol-related problems.
Methods
Fifty-six heavy-drinking young adults with insomnia (ages 18-30y) were randomized to CBT-I (n=28) or single-session sleep hygiene control (SH; n=28). Of those, 43 (77%) completed post-treatment (24 SH, 19 CBT-I) and 48 (86%) completed 1-month follow-up (25 SH, 23 CBT-I). Multiple imputation was used to estimate missing data. Treatment outcomes were assessed using multilevel models. Mediation was tested using bootstrapped confidence intervals for indirect effects in the PROCESS macro.
Results
CBT-I participants reported greater decreases in insomnia severity than those in the sleep hygiene group group X time interaction, F(2,59)=11.29, p<.001, both post-treatment and at 1-month follow-up. Both groups decreased significantly in diary-assessed sleep quality time, F(2,55)=40.30, p<.001, with a marginally significant interaction in favor of the CBT-I group F(2,55)=2.69, p=.08. There were no significant group by time interactions in the prediction of actigraphy-assessed sleep variables, although again, there was a marginally significant interaction in the prediction of actigraphy-assessed sleep efficiency F(2,66)=2.75, p=.07. Both groups reported significant decreases in drinking quantity over time time, F(2,58=13.88, p<.001. However, CBT-I participants reported greater decreases in alcohol-related consequences than those in the sleep hygiene group F(2,67)=4.13, p=.02. In the mediation model, CBT-I did not have a direct effect on change in alcohol-related consequences (B=1.49, SE=1.06, 95%CI=-0.65, 3.62); however, it influenced change in 1-month alcohol-related consequences indirectly through its influence on post-treatment insomnia symptoms (B=-1.09, SE=0.57, 95%CI=-2.30, -0.05).
Conclusion
CBT-I is effective in treating insomnia among heavy-drinking young adults and may be associated with reductions in alcohol-related problems due to its impact on insomnia symptoms.
Support
This work was supported by funding from the University of Missouri System Research Board Office (PI Miller). Mary Beth Miller’s contribution to this project was also supported by the National Institute on Alcohol Abuse and Alcoholism grant number K23AA026895.
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