Prior stress and vasopressin promote corticotropin-releasing factor inhibition of serotonin release in the central nucleus of the amygdala

Corticotropin-releasing factor (CRF) is essential for coordinating endocrine and neural responses to stress, frequently facilitated by vasopressin (AVP). Previous work has linked CRF hypersecretion, binding site changes, and dysfunctional serotonergic transmission with anxiety and affective disorders, including clinical depression. Crucially, CRF can alter serotonergic activity. In the dorsal raphé nucleus and serotonin (5-HT) terminal regions, CRF effects can be stimulatory or inhibitory, depending on the dose, site, and receptor type activated. Prior stress alters CRF neurotransmission and CRF-mediated behaviors. Lateral, medial, and ventral subdivisions of the central nucleus of the amygdala (CeA) produce CRF and coordinate stress responsiveness. The purpose of these experiments was to determine the effect of intracerebroventricular (icv) administration of CRF and AVP on extracellular 5-HT as an index of 5-HT release in the CeA, using in vivo microdialysis in freely moving rats and high performance liquid chromatography (HPLC) analysis. We also examined the effect of prior stress (1 h restraint, 24 h prior) on CRF- and AVP-mediated release of 5-HT within the CeA. Our results show that icv CRF infusion in unstressed animals had no effect on 5-HT release in the CeA. Conversely, in rats with prior stress, CRF caused a profound dose-dependent decrease in 5-HT release within the CeA. This effect was long-lasting (240 min) and was mimicked by CRF plus AVP infusion without stress. Thus, prior stress and AVP functionally alter CRF-mediated neurotransmission and sensitize CRF-induced inhibition of 5-HT release, suggesting that this is a potential mechanism underlying stress-induced affective reactivity in humans

SPYGLASS. III. The Fornax-Horologium Association and its Traceback History within the Austral Complex

The study of young associations is essential for building a complete record of local star formation processes. The Fornax-Horologium association (FH), including the $\chi^1$ Fornacis cluster, represents one of the nearest young stellar populations to the Sun. This association has recently been linked to the Tuc-Hor, Carina, and Columba associations, building an extensive "Austral Complex" almost entirely within 150 pc. Using Gaia astrometry and photometry in addition to new spectroscopic observations, we perform the deepest survey of FH to date, identifying over 300 candidate members, nearly doubling the known population. By combining this sample with literature surveys of the other constituent populations, we produce a contiguous stellar population covering the entire Austral Complex, allowing the definitions of sub-populations to be re-assessed along with connections to external populations. This analysis recovers new definitions for FH, Tuc-Hor, Columba, and Carina, while also revealing a connection between the Austral complex and the Sco-Cen-affiliated Platais 8 cluster. This suggests that the Austral complex may be just a small component of a much larger and more diverse star formation event. Computing ages and tracing stellar populations back to formation reveals two distinct nodes of cospatial and continuous formation in the Austral Complex, one containing Tuc-Hor, and the other containing FH, Carina, and Columba. This mirrors recent work showing similar structure elsewhere, suggesting that these nodes, which only emerge through the use of traceback, may represent the clearest discrete unit of local star formation, and a key building block needed to reconstruct larger star-forming events.Comment: Accepted to ApJ; 29 pages, 10 figures, 5 tables in two-column AASTEX63 forma

Trends in blindness due to diabetic retinopathy among adults aged 18-69 years over a decade in Ireland

Aims: To describe trends in the incidence of visual impairment and blindness due to diabetic retinopathy among adults aged 18–69 years in Ireland between 2004 and 2013. Methods: Data on visual impairment due to diabetic retinopathy in adults aged 18–69 years or over who are registered with the National Council for the Blind of Ireland, (2004–2013) were analysed. Annual incidence rates were calculated for the adult population and the population with diagnosed diabetes. Poisson regression was used to test for changes in rates over time. The relative, attributable and population risk of blindness and visual impairment due to diabetic retinopathy were calculated for 2013. Results: Over the decade, the prevalence of diagnosed diabetes increased from 2.1% to 3.6%. Among people with diagnosed diabetes, the incidence of visual impairment due to diabetic retinopathy increased from 6.4 (95% CI 2.4–13.9) per 100,000 in 2004 to 11.7 (95% CI 5.9–21.0) per 100,000 in 2013. The incidence of blindness due to diabetic retinopathy varied from 31.9 per 100,000 (95% CI 21.6–45.7) in 2004 to 14.9 per 100,000 (95% CI 8.2–25.1) in 2013. Conclusions: Our findings indicate the need for increased attention to preventive measures for microvascular complications among adults with diabetes in Ireland. Retinopathy screening has been standardised in Ireland, these findings provide useful baseline statistics to monitor the impact of this population-based screening programme

Risk factors for macro- and microvascular complications among older adults with diagnosed type 2 diabetes: findings from The Irish Longitudinal Study on Ageing

Objective. To explore risk factors for macro- and microvascular complications in a nationally representative sample of adults aged 50 years and over with type 2 diabetes in Ireland. Methods. Data from the first wave of The Irish Longitudinal Study on Ageing (TILDA) (2009–2011) was used in cross-sectional analysis. The presence of doctor diagnosis of diabetes, risk factors, and macro and microvascular complications were determined by self-report. Gender-specific differences in risk factor prevalence were assessed with the chi-squared test. Binomial regression analysis was conducted to explore independent associations between established risk factors and diabetes-related complications. Results. Among 8175 respondents, 655 were classified as having type 2 diabetes. Older age, being male, a history of smoking, a lower level of physical activity, and a diagnosis of high cholesterol were independent predictors of macrovascular complications. Diabetes diagnosis of 10 or more years, a history of smoking, and a diagnosis of hypertension were associated with an increased risk of microvascular complications. Older age, third-level education, and a high level of physical activity were protective factors (\u1d45d < 0.05). Conclusions. Early intervention to target modifiable risk factors is urgently needed to reduce diabetes-related morbidity in the older population in Ireland

Quasi-stationary simulations of the contact process on quenched networks

We present high-accuracy quasi-stationary (QS) simulations of the contact process in quenched networks, built using the configuration model with both structural and natural cutoffs. The critical behavior is analyzed in the framework of the anomalous finite size scaling which was recently shown to hold for the contact process on annealed networks. It turns out that the quenched topology does not qualitatively change the critical behavior, leading only (as expected) to a shift of the transition point. The anomalous finite size scaling holds with exactly the same exponents of the annealed case, so that we can conclude that heterogeneous mean-field theory works for the contact process on quenched networks, at odds with previous claims. Interestingly, topological correlations induced by the presence of the natural cutoff do not alter the picture.Comment: To appear in Phys. Rev.

Kinematic Effects in Radiative Quarkonia Decays

Non-relativistic QCD (NRQCD) predicts colour octet contributions to be significant not only in many production processes of heavy quarkonia but also in their radiative decays. We investigate the photon energy distributions in these processes in the endpoint region. There the velocity expansion of NRQCD breaks down which requires a resummation of an infinite class of colour octet operators to so-called shape functions. We model these non-perturbative functions by the emission of a soft gluon cluster in the initial state. We found that the spectrum in the endpoint region is poorly understood if the values for the colour octet matrix elements are taken as large as indicated from NRQCD scaling rules. Therefore the endpoint region should not be taken into account for a fit of the strong coupling constant at the scale of the heavy quark mass.Comment: LaTeX, 17 pages, 5 figures. The complete paper is also available via the www at http://www-ttp.physik.uni-karlsruhe.de/Preprints

SPYGLASS. II. The Multi-Generational and Multi-Origin Star Formation History of Cepheus Far North

Young stellar populations provide a record of past star formation, and by establishing their members' dynamics and ages, it is possible to reconstruct the full history of star formation events. Gaia has greatly expanded the number of accessible stellar populations, with one of the most notable recently-discovered associations being Cepheus Far North (CFN), a population containing hundreds of members spanning over 100 pc. With its proximity (d $\lesssim$ 200 pc), apparent substructure, and relatively small population, CFN represents a manageable population to study in depth, with enough evidence of internal complexity to produce a compelling star formation story. Using Gaia astrometry and photometry combined with additional spectroscopic observations, we identify over 500 candidate CFN members spread across 7 subgroups. Combining ages from isochrones, asteroseismology, dynamics, and lithium depletion, we produce well-constrained ages for all seven subgroups, revealing a largely continuous 10 Myr star formation history in the association. By tracing back the present-day populations to the time of their formation, we identify two spatially and dynamically distinct nodes in which stars form, one associated with $\beta$ Cephei which shows mostly co-spatial formation, and one associated with EE Draconis with a more dispersed star formation history. This detailed view of star formation demonstrates the complexity of the star formation process, even in the smallest of regions.Comment: Accepted to ApJ; 34 pages, 15 figures, 6 tables in two-column AASTEX63 forma

Toward High Precision Higgs-Boson Measurements at the International Linear e+e- Collider

This report reviews the properties of Higgs bosons in the Standard Model (SM) and its various extensions. We give an extensive overview about the potential of the ILC operated at centre-of-mass energies up to 1 TeV (including the gamma gamma option) for the determination of the Higgs boson properties. This comprises the measurement of the Higgs boson mass, its couplings to SM fermions and gauge bosons, and the determination of the spin and the CP quantum numbers of the Higgs. The extensions of the SM that are analyzed in more detail are heavy SM-like Higgs bosons, heavy Higgs bosons in the framework of Supersymmetry (SUSY) and further exotic scenarios. We review recent theoretical developments in the field of Higgs boson physics. The important question what the ILC can contribute to Higgs boson physics after the LHC, the LHC/ILC interplay and synergy is discussed. The impact of Higgs boson physics on cosmology in several SUSY frameworks is analyzed. The impact of the accelerator and dector performance on the precision of measurements are discussed in detail. We propose a strategy to optimize future analyses. Open questions arising for the various topics are listed, further topics of study and corresponding roadmaps are suggested.Comment: 128 pages, lots of figures. One subsection added and other minor modification

Pevonedistat (MLN4924), a First‐in‐Class NEDD8‐activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111220/1/bjh13323.pd