A direct image of the obscuring disk surrounding an active galactic nucleus

Active galactic nuclei (AGN) are generally accepted to be powered by the release of gravitational energy in a compact accretion disk surrounding a massive black hole. Such disks are also necessary to collimate powerful radio jets seen in some AGN. The unifying classification schemes for AGN further propose that differences in their appearance can be attributed to the opacity of the accreting material, which may obstruct our view of the central region of some systems. The popular model for the obscuring medium is a parsec-scale disk of dense molecular gas, although evidence for such disks has been mostly indirect, as their angular size is much smaller than the resolution of conventional telescopes. Here we report the first direct images of a pc-scale disk of ionised gas within the nucleus of NGC 1068, the archetype of obscured AGN. The disk is viewed nearly edge-on, and individual clouds within the ionised disk are opaque to high-energy radiation, consistent with the unifying classification scheme. In projection, the disk and AGN axes align, from which we infer that the ionised gas disk traces the outer regions of the long-sought inner accretion disk.Comment: 14 pages, LaTeX, PSfig, to appear in Nature. also available at http://hethp.mpe-garching.mpg.de/Preprint

The effects of an obesogenic diet on behavior and cognition in zebrafish (Danio rerio): Trait average, variability, repeatability, and behavioral syndromes.

The obesity epidemic, largely driven by the accessibility of ultra-processed high-energy foods, is one of the most pressing public health challenges of the 21st century. Consequently, there is increasing concern about the impacts of diet-induced obesity on behavior and cognition. While research on this matter continues, to date, no study has explicitly investigated the effect of obesogenic diet on variance and covariance (correlation) in behavioral traits. Here, we examined how an obesogenic versus control diet impacts means and (co-)variances of traits associated with body condition, behavior, and cognition in a laboratory population of ~160 adult zebrafish (Danio rerio). Overall, an obesogenic diet increased variation in several zebrafish traits. Zebrafish on an obesogenic diet were significantly heavier and displayed higher body weight variability; fasting blood glucose levels were similar between control and treatment zebrafish. During behavioral assays, zebrafish on the obesogenic diet displayed more exploratory behavior and were less reactive to video stimuli with conspecifics during a personality test, but these significant differences were sex-specific. Zebrafish on an obesogenic diet also displayed repeatable responses in aversive learning tests whereas control zebrafish did not, suggesting an obesogenic diet resulted in more consistent, yet impaired, behavioral responses. Where behavioral syndromes existed (inter-class correlations between personality traits), they did not differ between obesogenic and control zebrafish groups. By integrating a multifaceted, holistic approach that incorporates components of (co-)variances, future studies will greatly benefit by quantifying neglected dimensions of obesogenic diets on behavioral changes

Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand, and the United States: a method for systematic review of studies with different designs

<p>Abstract</p> <p>Background</p> <p>Diabetes in pregnancy, which includes gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM), is associated with poor outcomes for both mother and infant during pregnancy, at birth and in the longer term. Recent international guidelines recommend changes to the current GDM screening criteria. While some controversy remains, there appears to be consensus that women at high risk of T2DM, including indigenous women, should be offered screening for GDM early in pregnancy, rather than waiting until 24-28 weeks as is current practice. A range of criteria should be considered before changing screening practice in a population sub-group, including: prevalence, current practice, acceptability and whether adequate treatment pathways and follow-up systems are available. There are also specific issues related to screening in pregnancy and indigenous populations. The evidence that these criteria are met for indigenous populations is yet to be reported. A range of study designs can be considered to generate relevant evidence for these issues, including epidemiological, observational, qualitative, and intervention studies, which are not usually included within a single systematic review. The aim of this paper is to describe the methods we used to systematically review studies of different designs and present the evidence in a pragmatic format for policy discussion.</p> <p>Methods/Design</p> <p>The inclusion criteria will be broad to ensure inclusion of the critical perspectives of indigenous women. Abstracts of the search results will be reviewed by two persons; the full texts of all potentially eligible papers will be reviewed by one person, and 10% will be checked by a second person for validation. Data extraction will be standardised, using existing tools to identify risks for bias in intervention, measurement, qualitative studies and reviews; and adapting criteria for appraising risk for bias in descriptive studies. External validity (generalisability) will also be appraised. The main findings will be synthesised according to the criteria for population-based screening and summarised in an adapted "GRADE" tool.</p> <p>Discussion</p> <p>This will be the first systematic review of all the published literature on diabetes in pregnancy among indigenous women. The method provides a pragmatic approach for synthesizing relevant evidence from a range of study designs to inform the current policy discussion.</p

Socioeconomic questionnaire and clinical assessment in the HELENA Cross-sectional Study: methodology

Rationale: Environmental factors such as dietary habits, breastfeeding, socioeconomic conditions and educational factors are strong influences on nutritional and puberty status, physical activity, food choices and their interactions. Several diseases of adulthood seem to be linked to, or to originate from, lifestyle in childhood and adolescence. Objective: The aims of this study are to describe birth parameters and socioeconomic factors and to assess clinical status in adolescents aged 13-16 years from 10 European countries participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Cross-Sectional Study (CSS). Methodology: A self-report questionnaire on the socioeconomic status, a parental questionnaire concerning neonatal period and also a case report form (CRF), in which clinical items during clinical examination (such as medical history, treatments, anthropometry, Tanner staging, blood pressure, heart rate) were assessed. To develop these documents, first a list of items was established, a search of existing documents was performed and the advice of local and international experts was taken. All documents (questionnaires and an operations manual) were discussed in plenary HELENA meetings; a final version of these documents was fixed, and the process of translation and back translation was performed. Results: The questionnaires and CRF were tested for validation in all 10 participant cities; 208 adolescents were enrolled during the pilot study. All items that caused problems or questions in one or more participating centers or were completed by < 85% of the adolescents were reviewed before the beginning of the HELENA-CSS. Conclusion: These final questionnaires and CRF will contribute to better understanding of the inequalities in nutrition, behavior and health in the European adolescent population. The experience and process should be useful for other multicenter studies

The Receptor Tyrosine Kinase FGFR4 Negatively Regulates NF-kappaB Signaling

NFκB signaling is of paramount importance in the regulation of apoptosis, proliferation, and inflammatory responses during human development and homeostasis, as well as in many human cancers. Receptor Tyrosine Kinases (RTKs), including the Fibroblast Growth Factor Receptors (FGFRs) are also important in development and disease. However, a direct relationship between growth factor signaling pathways and NFκB activation has not been previously described, although FGFs have been known to antagonize TNFα-induced apoptosis. assays. FGF19 stimulation of endogenous FGFR4 in TNFα-treated DU145 prostate cancer cells also leads to a decrease in IKKβ activity, concomitant reduction in NFκB nuclear localization, and reduced apoptosis. Microarray analysis demonstrates that FGF19 + TNFα treatment of DU145 cells, in comparison with TNFα alone, favors proliferative genes while downregulating genes involved in apoptotic responses and NFκB signaling.These results identify a compelling link between FGFR4 signaling and the NFκB pathway, and reveal that FGFR4 activation leads to a negative effect on NFκB signaling including an inhibitory effect on proapoptotic signaling. We anticipate that this interaction between an RTK and a component of NFκB signaling will not be limited to FGFR4 alone

The Unanticipated Phenomenology of the Blazar PKS 2131-021: A Unique Supermassive Black Hole Binary Candidate

Most large galaxies host supermassive black holes in their nuclei and are subject to mergers, which can produce a supermassive black hole binary (SMBHB), and hence periodic signatures due to orbital motion. We report unique periodic radio flux density variations in the blazar PKS 2131-021, which strongly suggest an SMBHB with an orbital separation of similar to 0.001-0.01 pc. Our 45.1 yr radio light curve shows two epochs of strong sinusoidal variation with the same period and phase to within less than or similar to 2% and similar to 10%, respectively, straddling a 20 yr period when this variation was absent. Our simulated light curves accurately reproduce the "red noise" of this object, and Lomb-Scargle, weighted wavelet Z-transform and least-squares sine-wave analyses demonstrate conclusively, at the 4.6 sigma significance level, that the periodicity in this object is not due to random fluctuations in flux density. The observed period translates to 2.082 +/- 0.003 yr in the rest frame at the z = 1.285 redshift of PKS 2131-021. The periodic variation in PKS 2131-021 is remarkably sinusoidal. We present a model in which orbital motion, combined with the strong Doppler boosting of the approaching relativistic jet, produces a sine-wave modulation in the flux density that easily fits the observations. Given the rapidly developing field of gravitational-wave experiments with pulsar timing arrays, closer counterparts to PKS 2131-021 and searches using the techniques we have developed are strongly motivated. These results constitute a compelling demonstration that the phenomenology, not the theory, must provide the lead in this field

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

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

Implications of market integration for cardiovascular and metabolic health among an indigenous Amazonian Ecuadorian population

BackgroundMarket integration (MI), the suite of social and cultural changes that occur with economic development, has been associated with negative health outcomes such as cardiovascular disease; however, key questions remain about how this transition manifests at the local level.AimThe present paper investigates the effects of MI on health among Shuar, an indigenous lowland Ecuadorian population, with the goal of better understanding the mechanisms responsible for this health transition.Subjects and methodsThis study examines associations between measures of MI and several dimensions of cardiovascular and metabolic health (fasting glucose, lipids [LDL, HDL and total cholesterol; triglycerides] and blood pressure) among 348 adults.ResultsOverall, Shuar males and females have relatively favourable cardiovascular and metabolic health. Shuar who live closer to town have higher total (p &lt; 0.001) and HDL cholesterol (p &lt; 0.001), while Shuar in more remote regions have higher diastolic blood pressure (p = 0.007). HDL cholesterol is positively associated with consumption of market foods (r = 0.140; p = 0.045) and ownership of consumer products (r = 0.184; p = 0.029).ConclusionsThis study provides evidence that MI among Shuar is not a uniformly negative process but instead produces complex cardiovascular and metabolic health outcomes