Adiposity in early, middle and later adult life and cardiometabolic risk markers in later life; findings from the British regional heart study.

OBJECTIVES: This research investigates the associations between body mass index (BMI) at 21, 40-59, 60-79 years of age on cardiometabolic risk markers at 60-79 years. METHODS: A prospective study of 3464 British men with BMI measured at 40-59 and 60-79 years, when cardiometabolic risk was assessed. BMI at 21 years was ascertained from military records, or recalled from middle-age (adjusted for reporting bias); associations between BMI at different ages and later cardiometabolic risk markers were examined using linear regression. Sensitive period, accumulation and mobility life course models were devised for high BMI (defined as BMI≥75th centile) and compared with a saturated BMI trajectory model. RESULTS: At ages 21, 40-59 and 60-79 years, prevalences of overweight (BMI≥25 kg/m2) were 12%, 53%, 70%, and obesity (≥30 kg/m2) 1.6%, 6.6%, and 17.6%, respectively. BMI at 21 years was positively associated with serum insulin, blood glucose, and HbA1c at 60-79 years, with increases of 1.5% (95%CI 0.8,2.3%), 0.4% (0.1,0.6%), 0.3% (0.1,0.4%) per 1 kg/m2, respectively, but showed no associations with blood pressure or blood cholesterol. However, these associations were modest compared to those between BMI at 60-79 years and serum insulin, blood glucose and HbA1c at 60-79 years, with increases of 8.6% (8.0,9.2%), 0.7% (0.5,0.9%), and 0.5% (0.4,0.7%) per 1 kg/m2, respectively. BMI at 60-79 years was also associated with total cholesterol and blood pressure. Associations for BMI at 40-59 years were mainly consistent with those of BMI at 60-79 years. None of the life course models fitted the data as well as the saturated model for serum insulin. A sensitive period at 50 years for glucose and HbA1c and sensitive period at 70 years for blood pressure were identified. CONCLUSIONS: In this cohort of men who were thin compared to more contemporary cohorts, BMI in later life was the dominant influence on cardiovascular and diabetes risk. BMI in early adult life may have a small long-term effect on diabetes risk

Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder

Background: Manic-depression or bipolar disorder (BD) is a multi-faceted illness with an inevitably complex treatment. Methods: This article summarizes the current status of our knowledge and practice of its treatment. Results: It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. Conclusion: The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule

Web-based tools can be used reliably to detect patients with major depressive disorder and subsyndromal depressive symptoms

BACKGROUND: Although depression has been regarded as a major public health problem, many individuals with depression still remain undetected or untreated. Despite the potential for Internet-based tools to greatly improve the success rate of screening for depression, their reliability and validity has not been well studied. Therefore the aim of this study was to evaluate the test-retest reliability and criterion validity of a Web-based system, the Internet-based Self-assessment Program for Depression (ISP-D). METHODS: The ISP-D to screen for major depressive disorder (MDD), minor depressive disorder (MinD), and subsyndromal depressive symptoms (SSD) was developed in traditional Chinese. Volunteers, 18 years and older, were recruited via the Internet and then assessed twice on the online ISP-D system to investigate the test-retest reliability of the test. They were subsequently prompted to schedule face-to-face interviews. The interviews were performed by the research psychiatrists using the Mini-International Neuropsychiatric Interview and the diagnoses made according to DSM-IV diagnostic criteria were used for the statistics of criterion validity. Kappa (κ) values were calculated to assess test-retest reliability. RESULTS: A total of 579 volunteer subjects were administered the test. Most of the subjects were young (mean age: 26.2 ± 6.6 years), female (77.7%), single (81.6%), and well educated (61.9% college or higher). The distributions of MDD, MinD, SSD and no depression specified were 30.9%, 7.4%, 15.2%, and 46.5%, respectively. The mean time to complete the ISP-D was 8.89 ± 6.77 min. One hundred and eighty-four of the respondents completed the retest (response rate: 31.8%). Our analysis revealed that the 2-week test-retest reliability for ISP-D was excellent (weighted κ = 0.801). Fifty-five participants completed the face-to-face interview for the validity study. The sensitivity, specificity, positive, and negative predictive values for major depressive disorder were 81.8% and 72.7%, 66.7%, and 85.7% respectively. The overall accuracy was 76.4%. CONCLUSION: The evidence indicates the ISP-D is a reliable and valid online tool for assessing depression. Further studies should test the ISP-D in clinical settings to increase its applications in clinical environments with different populations and in a larger sample size

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times {10}^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times {10}^{-15}$ and $+7\times {10}^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1-1.4 per year during the 2018-2019 observing run and 0.3-1.7 per year at design sensitivity

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Binary Black Hole Mergers in the first Advanced LIGO Observing Run

The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers. In this paper we present full results from a search for binary black hole merger signals with total masses up to $100 M_\odot$ and detailed implications from our observations of these systems. Our search, based on general-relativistic models of gravitational wave signals from binary black hole systems, unambiguously identified two signals, GW150914 and GW151226, with a significance of greater than $5\sigma$ over the observing period. It also identified a third possible signal, LVT151012, with substantially lower significance, which has a 87% probability of being of astrophysical origin. We provide detailed estimates of the parameters of the observed systems. Both GW150914 and GW151226 provide an unprecedented opportunity to study the two-body motion of a compact-object binary in the large velocity, highly nonlinear regime. We do not observe any deviations from general relativity, and place improved empirical bounds on several high-order post-Newtonian coefficients. From our observations we infer stellar-mass binary black hole merger rates lying in the range $9-240 \mathrm{Gpc}^{-3} \mathrm{yr}^{-1}$. These observations are beginning to inform astrophysical predictions of binary black hole formation rates, and indicate that future observing runs of the Advanced detector network will yield many more gravitational wave detections