Concomitant medication use and clinical outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder.

BackgroundRepetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS.MethodsMedications were tabulated for 181 MDD patients who underwent a six-week rTMS treatment course. All patients received 10 Hz rTMS administered to left dorsolateral prefrontal cortex (DLPFC), with 1 Hz administered to right DLPFC in patients with inadequate response to and/or intolerance of left-sided stimulation. Primary outcomes were change in Inventory of Depressive Symptomatology Self Report (IDS-SR30) total score after 2, 4, and 6 weeks.ResultsUse of benzodiazepines was associated with less improvement at week 2, whereas use of psychostimulants was associated with greater improvement at week 2 and across 6 weeks. These effects were significant controlling for baseline variables including age, overall symptom severity, and severity of anxiety symptoms. Response rates at week 6 were lower in benzodiazepine users versus non-users (16.4% vs. 35.5%, p = 0.008), and higher in psychostimulant users versus non-users (39.2% vs. 22.0%, p = 0.02).ConclusionsConcomitant medication use may impact rTMS treatment outcome. While the differences reported here could be considered clinically significant, results were not corrected for multiple comparisons and findings should be replicated before clinicians incorporate the evidence into clinical practice. Prospective, hypothesis-based treatment studies will aid in determining causal relationships between medication treatments and outcome

Use of methods for specifying the target difference in randomised controlled trial sample size calculations : Two surveys of trialists' practice

© The Author(s), 2014.Peer reviewedPublisher PD

Unequal Mass Binary Black Hole Plunges and Gravitational Recoil

We present results from fully nonlinear simulations of unequal mass binary black holes plunging from close separations well inside the innermost stable circular orbit with mass ratios q = M_1/M_2 = {1,0.85,0.78,0.55,0.32}, or equivalently, with reduced mass parameters $\eta=M_1M_2/(M_1+M_2)^2 = {0.25, 0.248, 0.246, 0.229, 0.183}$. For each case, the initial binary orbital parameters are chosen from the Cook-Baumgarte equal-mass ISCO configuration. We show waveforms of the dominant l=2,3 modes and compute estimates of energy and angular momentum radiated. For the plunges from the close separations considered, we measure kick velocities from gravitational radiation recoil in the range 25-82 km/s. Due to the initial close separations our kick velocity estimates should be understood as a lower bound. The close configurations considered are also likely to contain significant eccentricities influencing the recoil velocity.Comment: 12 pages, 5 figures, to appear in "New Frontiers" special issue of CQ

Dark ice in a warming world: advances and challenges in the study of Greenland Ice Sheet's biological darkening

The surface of the Greenland Ice Sheet is darkening, which accelerates its surface melt. The role of glacier ice algae in reducing surface albedo is widely recognised but not well quantified and the feedbacks between the algae and the weathering crust remain poorly understood. In this letter, we summarise recent advances in the study of the biological darkening of the Greenland Ice Sheet and highlight three key research priorities that are required to better understand and forecast algal-driven melt: (i) identifying the controls on glacier ice algal growth and mortality, (ii) quantifying the spatio-temporal variability in glacier ice algal biomass and processes involved in cell redistribution and (iii) determining the albedo feedbacks between algal biomass and weathering crust characteristics. Addressing these key research priorities will allow us to better understand the supraglacial ice-algal system and to develop an integrated model incorporating the algal and physical controls on ice surface albedo

Binary black hole evolutions of approximate puncture initial data

Approximate solutions to the Einstein field equations are a valuable tool to investigate gravitational phenomena. An important aspect of any approximation is to investigate and quantify its regime of validity. We present a study that evaluates the effects that approximate puncture initial data, based on "skeleton" solutions to the Einstein constraints as proposed by Faye et al. [PRD 69, 124029 (2004)], have on numerical evolutions. Using data analysis tools, we assess the effectiveness of these constraint-violating initial data and show that the matches of waveforms from skeleton data with the corresponding waveforms from constraint-satisfying initial data are > 0.97 when the total mass of the binary is > 40M(solar). In addition, we demonstrate that the differences between the skeleton and the constraint-satisfying initial data evolutions, and thus waveforms, are due to negative Hamiltonian constraint violations present in the skeleton initial data located in the vicinity of the punctures. During the evolution, the skeleton data develops both Hamiltonian and momentum constraint violations that decay with time, with the binary system relaxing to a constraint-satisfying solution with black holes of smaller mass and thus different dynamics

T cell repertoire to citrullinated self-peptides in healthy humans is not confined to the HLA-DR SE alleles; targeting of citrullinated self-peptides presented by HLA-DP4 for tumour therapy

Post-translational modifications are induced in stressed cells which cause them to be recognised by the immune system. One such modification is citrullination where the positive charged arginine is modified to a neutral citrulline. We demonstrate most healthy donors show an oligoclonal CD4 response in vitro to at least one citrullinated vimentin or enolase peptide. Unlike rheumatoid arthritis patients, these T cell responses were not restricted by HLA-DRB1 shared epitope (SE) alleles, suggesting they could be presented by other MHC-II alleles. As HLA-DP is less polymorphic than HLA-DR, we investigated whether the common allele, HLA-DP4 could present citrullinated epitopes. The modification of arginine to citrulline enhanced binding of the peptides to HLA-DP4 and induced high frequency CD4 responses in HLA-DP4 transgenic mouse models. Our previous studies have shown that tumours present citrullinated peptides restricted through HLA-DR4 which are good targets for anti-tumour immunity. In this study we show that citrullinated vimentin and enolase peptides also induced strong anti-tumour immunity (100% survival,