Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort.

Background While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi-ethnic Study of Atherosclerosis) cohort. Methods and Results MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow-up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2-fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5-fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra-coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration https://www.clinicaltrials.gov/. Unique identifier: NCT00005487

Validation and application of the Non-Verbal Behavior Analyzer: an automated tool to assess non-verbal emotional expressions in psychotherapy

Background Emotions play a key role in psychotherapy. However, a problem with examining emotional states via self-report questionnaires is that the assessment usually takes place after the actual emotion has been experienced which might lead to biases and continuous human ratings are time and cost intensive. Using the AI-based software package Non-Verbal Behavior Analyzer (NOVA), video-based emotion recognition of arousal and valence can be applied in naturalistic psychotherapeutic settings. In this study, four emotion recognition models (ERM) each based on specific feature sets (facial: OpenFace, OpenFace-Aureg; body: OpenPose-Activation, OpenPose-Energy) were developed and compared in their ability to predict arousal and valence scores correlated to PANAS emotion scores and processes of change (interpersonal experience, coping experience, affective experience) as well as symptoms (depression and anxiety in HSCL-11). Materials and methods A total of 183 patient therapy videos were divided into a training sample (55 patients), a test sample (50 patients), and a holdout sample (78 patients). The best ERM was selected for further analyses. Then, ERM based arousal and valence scores were correlated with patient and therapist estimates of emotions and processes of change. Furthermore, using regression models arousal and valence were examined as predictors of symptom severity in depression and anxiety. Results The ERM based on OpenFace produced the best agreement to the human coder rating. Arousal and valence correlated significantly with therapists’ ratings of sadness, shame, anxiety, and relaxation, but not with the patient ratings of their own emotions. Furthermore, a significant negative correlation indicates that negative valence was associated with higher affective experience. Negative valence was found to significantly predict higher anxiety but not depression scores. Conclusion This study shows that emotion recognition with NOVA can be used to generate ERMs associated with patient emotions, affective experiences and symptoms. Nevertheless, limitations were obvious. It seems necessary to improve the ERMs using larger databases of sessions and the validity of ERMs needs to be further investigated in different samples and different applications. Furthermore, future research should take ERMs to identify emotional synchrony between patient and therapists into account

Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationship studies of a previously disclosed nonacidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although a significant fraction of these noncarboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice resulted in significantly increased insulin sensitivity and a moderate but significant reduction in bodyweight, effects that were also present in mice lacking FFA1 but absent in mice lacking FFA4

Absolute polarization angle calibration using polarized diffuse Galactic emission observed by BICEP

We present a method of cross-calibrating the polarization angle of a polarimeter using BICEP Galactic observations. \bicep\ was a ground based experiment using an array of 49 pairs of polarization sensitive bolometers observing from the geographic South Pole at 100 and 150 GHz. The BICEP polarimeter is calibrated to +/-0.01 in cross-polarization and less than +/-0.7 degrees in absolute polarization orientation. BICEP observed the temperature and polarization of the Galactic plane (R.A= 100 degrees ~ 270 degrees and Dec. = -67 degrees ~ -48 degrees). We show that the statistical error in the 100 GHz BICEP Galaxy map can constrain the polarization angle offset of WMAP Wband to 0.6 degrees +\- 1.4 degrees. The expected 1 sigma errors on the polarization angle cross-calibration for Planck or EPIC are 1.3 degrees and 0.3 degrees at 100 and 150 GHz, respectively. We also discuss the expected improvement of the BICEP Galactic field observations with forthcoming BICEP2 and Keck observations.Comment: 13 pages, 10 figures and 2 tables. To appear in Proceedings of SPIE Astronomical Telescopes and Instrumentation 201

Cost risk benefit analysis to support chemoprophylaxis policy for travellers to malaria endemic countries

BACKGROUND: In a number of malaria endemic regions, tourists and travellers face a declining risk of travel associated malaria, in part due to successful malaria control. Many millions of visitors to these regions are recommended, via national and international policy, to use chemoprophylaxis which has a well recognized morbidity profile. To evaluate whether current malaria chemo-prophylactic policy for travellers is cost effective when adjusted for endemic transmission risk and duration of exposure. a framework, based on partial cost-benefit analysis was used. METHODS: Using a three component model combining a probability component, a cost component and a malaria risk component, the study estimated health costs avoided through use of chemoprophylaxis and costs of disease prevention (including adverse events and pre-travel advice for visits to five popular high and low malaria endemic regions) and malaria transmission risk using imported malaria cases and numbers of travellers to malarious countries. By calculating the minimal threshold malaria risk below which the economic costs of chemoprophylaxis are greater than the avoided health costs we were able to identify the point at which chemoprophylaxis would be economically rational. RESULTS: The threshold incidence at which malaria chemoprophylaxis policy becomes cost effective for UK travellers is an accumulated risk of 1.13% assuming a given set of cost parameters. The period a travellers need to remain exposed to achieve this accumulated risk varied from 30 to more than 365 days, depending on the regions intensity of malaria transmission. CONCLUSIONS: The cost-benefit analysis identified that chemoprophylaxis use was not a cost-effective policy for travellers to Thailand or the Amazon region of Brazil, but was cost-effective for travel to West Africa and for those staying longer than 45 days in India and Indonesia

Nucleosynthesis Constraints on a Massive Gravitino in Neutralino Dark Matter Scenarios

The decays of massive gravitinos into neutralino dark matter particles and Standard Model secondaries during or after Big-Bang nucleosynthesis (BBN) may alter the primordial light-element abundances. We present here details of a new suite of codes for evaluating such effects, including a new treatment based on PYTHIA of the evolution of showers induced by hadronic decays of massive, unstable particles such as a gravitino. We also develop an analytical treatment of non-thermal hadron propagation in the early universe, and use this to derive analytical estimates for light-element production and in turn on decaying particle lifetimes and abundances. We then consider specifically the case of an unstable massive gravitino within the constrained minimal supersymmetric extension of the Standard Model (CMSSM). We present upper limits on its possible primordial abundance before decay for different possible gravitino masses, with CMSSM parameters along strips where the lightest neutralino provides all the astrophysical cold dark matter density. We do not find any CMSSM solution to the cosmological Li7 problem for small m_{3/2}. Discounting this, for m_{1/2} ~ 500 GeV and tan beta = 10 the other light-element abundances impose an upper limit m_{3/2} n_{3/2}/n_\gamma < 3 \times 10^{-12} GeV to < 2 \times 10^{-13} GeV for m_{3/2} = 250 GeV to 1 TeV, which is similar in both the coannihilation and focus-point strips and somewhat weaker for tan beta = 50, particularly for larger m_{1/2}. The constraints also weaken in general for larger m_{3/2}, and for m_{3/2} > 3 TeV we find a narrow range of m_{3/2} n_{3/2}/n_\gamma, at values which increase with m_{3/2}, where the Li7 abundance is marginally compatible with the other light-element abundances.Comment: 74 pages, 40 Figure

A Bitter Pill: The Primordial Lithium Problem Worsens

The lithium problem arises from the significant discrepancy between the primordial 7Li abundance as predicted by BBN theory and the WMAP baryon density, and the pre-Galactic lithium abundance inferred from observations of metal-poor (Population II) stars. This problem has loomed for the past decade, with a persistent discrepancy of a factor of 2--3 in 7Li/H. Recent developments have sharpened all aspects of the Li problem. Namely: (1) BBN theory predictions have sharpened due to new nuclear data, particularly the uncertainty on 3He(alpha,gamma)7Be, has reduced to 7.4%, and with a central value shift of ~ +0.04 keV barn. (2) The WMAP 5-year data now yields a cosmic baryon density with an uncertainty reduced to 2.7%. (3) Observations of metal-poor stars have tested for systematic effects, and have reaped new lithium isotopic data. With these, we now find that the BBN+WMAP predicts 7Li/H = (5.24+0.71-0.67) 10^{-10}. The Li problem remains and indeed is exacerbated; the discrepancy is now a factor 2.4--4.3 or 4.2sigma (from globular cluster stars) to 5.3sigma (from halo field stars). Possible resolutions to the lithium problem are briefly reviewed, and key nuclear, particle, and astronomical measurements highlighted.Comment: 21 pages, 4 figures. Comments welcom

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Characterization of the BICEP Telescope for High-precision Cosmic Microwave Background Polarimetry

The Background Imaging of Cosmic Extragalactic Polarization (BICEP) experiment was designed specifically to search for the signature of inflationary gravitational waves in the polarization of the cosmic microwave background (CMB). Using a novel small-aperture refractor and 49 pairs of polarization-sensitive bolometers, BICEP has completed three years of successful observations at the South Pole beginning in 2006 February. To constrain the amplitude of the inflationary B-mode polarization, which is expected to be at least 7 orders of magnitude fainter than the 3 K CMB intensity, precise control of systematic effects is essential. This paper describes the characterization of potential systematic errors for the BICEP experiment, supplementing a companion paper on the initial cosmological results. Using the analysis pipelines for the experiment, we have simulated the impact of systematic errors on the B-mode polarization measurement. Guided by these simulations, we have established benchmarks for the characterization of critical instrumental properties including bolometer relative gains, beam mismatch, polarization orientation, telescope pointing, sidelobes, thermal stability, and timestream noise model. A comparison of the benchmarks with the measured values shows that we have characterized the instrument adequately to ensure that systematic errors do not limit BICEP's two-year results, and identifies which future refinements are likely necessary to probe inflationary B-mode polarization down to levels below a tensor-to-scalar ratio r = 0.1.Astronom

Release of mineral-bound water prior to subduction tied to shallow seismogenic slip off Sumatra

Plate-boundary fault rupture during the 2004 Sumatra-Andaman subduction earthquake extended closer to the trench than expected, increasing earthquake and tsunami size. International Ocean Discovery Program Expedition 362 sampled incoming sediments offshore northern Sumatra, revealing recent release of fresh water within the deep sediments. Thermal modeling links this freshening to amorphous silica dehydration driven by rapid burial-induced temperature increases in the past 9 million years. Complete dehydration of silicates is expected before plate subduction, contrasting with prevailing models for subduction seismogenesis calling for fluid production during subduction. Shallow slip offshore Sumatra appears driven by diagenetic strengthening of deeply buried fault-forming sediments, contrasting with weakening proposed for the shallow Tohoku-Oki 2011 rupture, but our results are applicable to other thickly sedimented subduction zones including those with limited earthquake records