Dancing with loneliness in later life: A pilot study mapping seasonal variations

Temporal variations in loneliness at the individual and population level have long been reported in longitudinal studies. Although the evidence is limited due to methodological distinctions among studies, we broadly know that loneliness as one ages is a dynamic experience with people becoming more or less lonely or staying the same over time. There is, however, less evidence to understand individual variations in loneliness over shorter periods of time. This paper reports on one element of a small mixed method pilot study to investigate seasonal variations in loneliness over the course of one year and to test the effectiveness of tools used to collect data at repeated short intervals. Our findings confirm that loneliness is dynamic even over shorter periods of time with participants reporting to be lonelier in the evenings, weekends and spring-summer period. Data measures were at times problematic due to language and/or interpretation and reinforce the relevance of reviewing the more common approaches to studying loneliness to more effectively capture the complex and individual nature of the experience.Brunel University Londo

Doxycycline alters metabolism and proliferation of human cell lines.

The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism

X-rays from Microstructured Targets Heated by Femtosecond Lasers

We have demonstrated efficient conversion of ultrashort-pulse laser energy to x rays with energies above 1 keV, using laser-produced plasmas generated on a variety of microstructured surfaces. Lithographically produced grating targets generated 0.1 mJ of kilo-electron-volt x rays, and porous gold and aluminum targets emitted 1 mJ. This represents an improvement of a factor of 100 over flat targets. The K-shell emission spectrum of porous aluminum was composed primarily of heliumlike spectral lines

Subpicosecond Thomson Scattering Measurements of Optically Ionized Helium Plasmas

We present the first subpicosecond time-resolved temperature measurements of plasmas produced by high-intensity optical ionization. Thomson scattering is used to measure electron and ion temperatures of helium plasmas created by 125 fs, 800 nm laser pulses focused to an intensity of 2 × 1017 W/cm2. We find that the electron temperature is accurately predicted by a tunneling ionization model. The measured ion temperature is consistent with direct heating by the laser pulse

Spectral Models for Early Time SN 2011fe Observations

We use observed UV through near IR spectra to examine whether SN 2011fe can be understood in the framework of Branch-normal SNe Ia and to examine its individual peculiarities. As a benchmark, we use a delayed-detonation model with a progenitor metallicity of Z_solar/20. We study the sensitivity of features to variations in progenitor metallicity, the outer density profile, and the distribution of radioactive nickel. The effect of metallicity variations in the progenitor have a relatively small effect on the synthetic spectra. We also find that the abundance stratification of SN 2011fe resembles closely that of a delayed detonation model with a transition density that has been fit to other Branch-normal Type Ia supernovae. At early times, the model photosphere is formed in material with velocities that are too high, indicating that the photosphere recedes too slowly or that SN 2011fe has a lower specific energy in the outer ~0.1 M_sun than does the model. We discuss several explanations for the discrepancies. Finally, we examine variations in both the spectral energy distribution and in the colors due to variations in the progenitor metallicity, which suggests that colors are only weak indicators for the progenitor metallicity, in the particular explosion model that we have studied. We do find that the flux in the U band is significantly higher at maximum light in the solar metallicity model than in the lower metallicity model and the lower metallicity model much better matches the observed spectrum.Comment: 9 pages, 14 figures, MNRAS, in press, fixed typ

Professional Organizations and Healthcare Industry Support: Ethical Conflict?

A good deal of attention has been recently focused on the presumed advertising excesses of the healthcare industry in its promotion techniques to healthcare professionals, whether through offering gratuities such as gifts, honoraria, or travel support2-6 or through deception. Two basic concerns have been expressed: Does the acceptance of gratuities bias the recipient, tainting his or her responsibilities as the patient's agent? Does acceptance of the gratuity by the healthcare professional contribute to the high cost of healthcare products? The California Society of Hospital Pharmacists was recently asked by its members to formulate a policy for an appropriate relationship between the Society and the healthcare industry, addressing these concerns. In formulating its policy, it became clear that the Society depended on healthcare industry support, gathered through journal advertising, fees for booths at its various educational events, and grants for speaker

Handling misclassified stratification variables in the analysis of randomised trials with continuous outcomes

Many trials use stratified randomisation, where participants are randomised within strata defined by one or more baseline covariates. While it is important to adjust for stratification variables in the analysis, the appropriate method of adjustment is unclear when stratification variables are affected by misclassification and hence some participants are randomised in the incorrect stratum. We conducted a simulation study to compare methods of adjusting for stratification variables affected by misclassification in the analysis of continuous outcomes when all or only some stratification errors are discovered, and when the treatment effect or treatment-by-covariate interaction effect is of interest. The data were analysed using linear regression with no adjustment, adjustment for the strata used to perform the randomisation (randomisation strata), adjustment for the strata if all errors are corrected (true strata), and adjustment for the strata after some errors are discovered and corrected (updated strata). The unadjusted model performed poorly in all settings. Adjusting for the true strata was optimal, while the relative performance of adjusting for the randomisation strata or the updated strata varied depending on the setting. As the true strata are unlikely to be known with certainty in practice, we recommend using the updated strata for adjustment and performing subgroup analyses, provided the discovery of errors is unlikely to depend on treatment group, as expected in blinded trials. Greater transparency is needed in the reporting of stratification errors and how they were addressed in the analysis

Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents

Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA causing an autosomal dominant retinal degeneration or a normal mRNA that is overexpressed in certain diseases. All PTGS technologies depend upon the initial critical annealing event of the PTGS ligand to the target RNA. This event requires that the PTGS agent is in a conformational state able to support hybridization and that the target have a large and accessible single-stranded platform to allow rapid annealing, although such platforms are rare. We address the biocomplexity that currently limits PTGS therapeutic development with particular emphasis on biophysical variables that influence cellular performance. We address the different strategies that can be used for development of PTGS agents intended for therapeutic translation. These issues apply generally to the development of PTGS agents for retinal, ocular, or systemic diseases. This review should assist the interested reader to rapidly appreciate critical variables in PTGS development and facilitate initial design and testing of such agents against new targets of clinical interest