Improving the external validity of clinical trials: the case of multiple chronic conditions

The U.S. Department of Health and Human Services vision and strategic framework on multiple chronic conditions (MCCs) incorporates recommendations designed to facilitate research that will improve our knowledge about interventions and systems that will benefit individuals with MCCs (or multimorbidity). The evidence base supporting the management of patients with MCCs will be built both through intervention trials specifically designed to address multimorbidity and identification of MCCs in participants across the clinical trial range. This article specifically focuses on issues relating to external validity with specific reference to trials involving patients with MCCs. The exclusion of such patients from clinical trials has been well documented. Randomized control trials (RCTs) are considered the “gold standard” of evidence, but may have drawbacks in relation to external validity, particularly in relation to multimorbidity. It may, therefore, be necessary to consider a broader range of research methods that can provide converging evidence on intervention effects to address MCCs. Approaches can also be taken to increase the usefulness of RCTs in general for providing evidence to inform multimorbidity management. Additional improvements to RCTs would include better reporting of inclusion and exclusion criteria and participant characteristics in relation to MCCs. New trials should be considered in terms of how they will add to the existing evidence base and should inform how interventions may work in different settings and patient groups. Research on treatments and interventions for patients with MCCs is badly needed. It is important that this research includes patient-centered measures and that generalizability issues be explicitly addressed.Journal of Comorbidity 2013;3(2)30–3

On the Two-point Correlation of Potential Vorticity in Rotating and Stratified Turbulence

A framework is developed to describe the two-point statistics of potential vorticity in rotating and stratified turbulence as described by the Boussinesq equations. The Karman-Howarth equation for the dynamics of the two-point correlation function of potential vorticity reveals the possibility of inertial-range dynamics in certain regimes in the Rossby, Froude, Prandtl and Reynolds number parameters. For the case of large Rossby and Froude numbers, and for the case of quasi-geostrophic dynamics, a linear scaling law with 2/3 prefactor is derived for the third-order mixed correlation between potential vorticity and velocity, a result that is analogous to the Kolmogorov 4/5-law for the third-order velocity structure function in turbulence theory.Comment: 10 pages, to appear in Journal of Fluid Mechanics (2006

The Electrostatic Screening Length in Concentrated Electrolytes Increases with Concentration

According to classical electrolyte theories interactions in dilute (low ion density) electrolytes decay exponentially with distance, with the Debye screening length the characteristic length-scale. This decay length decreases monotonically with increasing ion concentration, due to effective screening of charges over short distances. Thus within the Debye model no long-range forces are expected in concentrated electrolytes. Here we reveal, using experimental detection of the interaction between two planar charged surfaces across a wide range of electrolytes, that beyond the dilute (Debye-Huuckel) regime the screening length increases with increasing concentration. The screening lengths for all electrolytes studied - including aqueous NaCl solutions, ionic liquids diluted with propylene carbonate, and pure ionic liquids - collapse onto a single curve when scaled by the dielectric constant. This non-monotonic variation of the screening length with concentration, and its generality across ionic liquids and aqueous salt solutions, demonstrates an important characteristic of concentrated electrolytes of substantial relevance from biology to energy storage.Comment: This document is the unedited authors' version of a Submitted Work that was subsequently accepted for publication in the Journal of Physical Chemistry Letters, copyright American Chemical Society, after peer review. To access the final edited and published work see http://pubsdc3.acs.org/articlesonrequest/AOR-EW6FuIC6wIh6D9qqEeH

Primary Care Validation of a Single-Question Alcohol Screening Test

BACKGROUND Unhealthy alcohol use is prevalent but under-diagnosed in primary care settings. OBJECTIVE To validate, in primary care, a single-item screening test for unhealthy alcohol use recommended by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). DESIGN Cross-sectional study. PARTICIPANTS Adult English-speaking patients recruited from primary care waiting rooms. MEASUREMENTS Participants were asked the single screening question, "How many times in the past year have you had X or more drinks in a day?", where X is 5 for men and 4 for women, and a response of >1 is considered positive. Unhealthy alcohol use was defined as the presence of an alcohol use disorder, as determined by a standardized diagnostic interview, or risky consumption, as determined using a validated 30-day calendar method. MAIN RESULTS Of 394 eligible primary care patients, 286 (73%) completed the interview. The single-question screen was 81.8% sensitive (95% confidence interval (CI) 72.5% to 88.5%) and 79.3% specific (95% CI 73.1% to 84.4%) for the detection of unhealthy alcohol use. It was slightly more sensitive (87.9%, 95% CI 72.7% to 95.2%) but was less specific (66.8%, 95% CI 60.8% to 72.3%) for the detection of a current alcohol use disorder. Test characteristics were similar to that of a commonly used three-item screen, and were affected very little by subject demographic characteristics. CONCLUSIONS. The single screening question recommended by the NIAAA accurately identified unhealthy alcohol use in this sample of primary care patients. These findings support the use of this brief screen in primary care.National Institute on Alcohol Abuse and Alcoholism (R01-AA010870

Scaling analysis of the screening length in concentrated electrolytes

The interaction between charged objects in an electrolyte solution is a fundamental question in soft matter physics. It is well-known that the electrostatic contribution to the interaction energy decays exponentially with object separation. Recent measurements reveal that, contrary to the conventional wisdom given by classic Poisson-Boltzmann theory, the decay length increases with ion concentration for concentrated electrolytes and can be an order of magnitude larger than the ion diameter in ionic liquids. We derive a simple scaling theory that explains this anomalous dependence of the decay length on ion concentration. Our theory successfully collapses the decay lengths of a wide class of salts onto a single curve. A novel prediction of our theory is that the decay length increases linearly with the Bjerrum length, which we experimentally verify by surface force measurements. Moreover, we quantitatively relate the measured decay length to classic measurements of the activity coefficient in concentrated electrolytes, thus showing that the measured decay length is indeed a bulk property of the concentrated electrolyte as well as contributing a mechanistic insight into empirical activity coefficients.Comment: To appear in Physical Review Letter

Enhancing research quality and reporting: why the Journal of Comorbidity is now publishing study protocols

The Journal of Comorbidity was launched in 2011 and has since become established as a high-quality journal that publishes open-access, peer-reviewed articles, with a focus on advancing the clinical management of patients with comorbidity/multimorbidity. To further enhance research quality and reporting of studies in this field, the journal is now offering authors the opportunity to publish a summary of their study protocols – a move designed to generate interest and raise awareness in ongoing clinical research and to enable researchers to detail their methodologies in order that replication by scientific peers is possible

Quantized Friction across Ionic Liquid Thin Films

Ionic liquids, salts in the liquid state under ambient conditions, are of great interest as precision lubricants. Ionic liquids form layered structures at surfaces, yet it is not clear how this nano-structure relates to their lubrication properties. We measured the friction force between atomically smooth solid surfaces across ionic liquid films of controlled thickness in terms of the number of ion layers. Multiple friction-load regimes emerge, each corresponding to a different number of ion layers in the film. In contrast to molecular liquids, the friction coefficients differ for each layer due to their varying composition

Effects of Sex and Gender on Adaptation to Space: Musculoskeletal Health

There is considerable variability among individuals in musculoskeletal response to long-duration spaceflight. The specific origin of the individual variability is unknown but is almost certainly influenced by the details of other mission conditions such as individual differences in exercise countermeasures, particularly intensity of exercise, dietary intake, medication use, stress, sleep, psychological profiles, and actual mission task demands. In addition to variations in mission conditions, genetic differences may account for some aspect of individual variability. Generally, this individual variability exceeds the variability between sexes that adds to the complexity of understanding sex differences alone. Research specifically related to sex differences of the musculoskeletal system during unloading is presented and discussed

Fungi Colonizing Redwood In Cooling Towers: Identities and Effects on Wood Properties

Heartwood from coastal redwood [Sequoia sempervirens (D. Don.) Endl.] is very durable and is often used untreated in harsh environments, such as cooling towers of power or chemical processing plants. Wood in this environment is often attacked by soft rot fungi. Some wood users attempt to bolster protection by including additives, such as chromium, in the water. Examination of sections cut from a redwood cooling tower revealed that most pieces were colonized by a variety of Fungi Imperfecti, in spite of surface chromium levels that averaged 0.26 lb/ft3. Eleven species were isolated from the material; soft rot tests of these fungi indicated that all of the isolates were capable of causing Type 2 soft rot attack (cell-wall erosion). These fungi caused little or no weight loss on redwood specimens, but did damage less durable ponderosa pine sapwood. The results suggest that the redwood cooling tower was colonized by a variety of fungi; however, the combination of redwood extractives and a shallow chromium barrier appears to protect against soft rot attack