The Clinical Significance of Subclinical Thyroid Dysfunction.

Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's ag

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Cut-off Characterisation of Energy Spectra of Bright Fermi Sources: Current instrument limits and future possibilities

In this paper some of the brightest GeV sources observed by the Fermi-LAT were analysed, focusing on their spectral cut-off region. The sources chosen for this investigation were the brightest blazar flares of 3C~454.3 and 3C~279 and the Vela pulsar with a reanalysis with the latest Fermi-LAT software. For the study of the spectral cut-off we first explored the Vela pulsar spectrum, whose statistics in the time interval of the 3FGL catalog allowed strong constraints to be obtained on the parameters. We subsequently performed a new analysis of the flaring blazar SEDs. For these sources we obtained constraints on the cut-off parameters under the assumption that their underlying spectral distribution is described by a power-law with a stretched exponential cut-off. We then highlighted the significant potential improvements on such constraints by observations with next generation ground based Cherenkov telescopes, represented in our study by the Cherenkov Telescope Array (CTA). Adopting currently available simulations for this future observatory, we demonstrate the considerable improvement in cut-off constraints achievable by observations with this new instrument when compared with that achievable by satellite observations.Comment: total number of pages 24, including 6 pages of references. Accepted by Astroparticle Physic

How do you feel about this goal? Goal-related affect, positive orientation, and personal goal realization in the family domain

Past research on individual-level differences has revealed associations between affect, positive beliefs and goal realization. Goal realization, however, varies not only between individuals (the individual level) but also within individuals according to goal (the goal level). This study analyzed family-related personal goals at both levels, examining how positive affect, negative affect and positive orientation are related to personal goal realization. The participants were 205 adults (mean age = 35.74 years); they evaluated five personal goals related to family life and completed assessments of positive orientation. Multilevel structural equation modeling demonstrated that both at the individual level and at the goal level positive orientation and positive goal-related affect were positively related to personal goal realization in family domain. Negative goal-related affect was negatively related to personal goal realization at both levels. Positive orientation, both at the individual level and as a cross-level interaction, moderated the relationship between positive goal-related affect and personal goal realization

Monochromatic Gamma Rays from Dark Matter Annihilation to Leptons

We investigate the relation between the annihilation of dark matter (DM) particles into lepton pairs and into 2-body final states including one or two photons. We parametrize the DM interactions with leptons in terms of contact interactions, and calculate the loop-level annihilation into monochromatic gamma rays, specifically computing the ratio of the DM annihilation cross sections into two gamma rays versus lepton pairs. While the loop-level processes are generically suppressed in comparison with the tree-level annihilation into leptons, we find that some choices for the mediator spin and coupling structure lead to large branching fractions into gamma-ray lines. This result has implications for a dark matter contribution to the AMS-02 positron excess. We also explore the possibility of mediators which are charged under a dark symmetry and find that, for these loop-level processes, an effective field theory description is accurate for DM masses up to about half the mediator mass.Comment: 21 pages plus appendices, 7 figures. v2: added experimental constraints from CMB and Fermi, expanded and reorganized discussion throughout. Accepted by JHE

TERT Promoter Mutations in Papillary Thyroid Microcarcinomas

Small papillary thyroid carcinomas have contributed to the worldwide increased incidence of differentiated thyroid cancer observed over the past decades. However, the mortality rate has not changed over the same period of time, raising questions about the possibility that thyroid cancer patients, especially those with small tumors, are overdiagnosed and overtreated. Molecular prognostic marker able to discriminate aggressive thyroid cancers from those with an indolent course would be of great relevance to tailor the therapeutic approach and reduce overtreatment. Mutations in the TERT promoter were recently reported to correlate strongly with aggressiveness in advanced forms of thyroid cancer, holding promise for a possible clinical application. The occurrence and potential clinical relevance of TERT mutations in papillary thyroid microcarcinomas (mPTCs) is currently unknown. This study aimed to analyze the occurrence of two TERT promoter mutations (-124C>T and -146C>T) and their potential association with unfavorable clinical features in a large cohort of mPTCs

Supramolecular assemblies involving metal organic ring interactions: Heterometallic Cu(II)-Ln(III) two dimensional coordination polymers

Three isostructural two-dimensional coordination polymers of the general formula [Ln2(CuL)3(H2O)9]$5.5H2O, where Ln is La (1), Nd (2), and Gd (3), have been synthesized and isolated from aqueous solutions and their single-crystal structures determined by X-ray diffraction. The supramolecular interaction between the non-aromatic metallorings plays an important role in stabilizing the structure of these compounds. The thermal stability, reversible solvent uptake, electronic properties and magnetic studies of these compounds are also reported