High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star ...mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E^{-2.5} neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to <5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is <10^{52.5} erg. For a harder E^{-2.13} neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is <10^{52} erg. A hypothetical population of transient sources has to be more common than 10^{-5} Mpc^{-3} yr^{-1} (5×10^{-8} Mpc^{-3} yr^{-1} for the E^{-2.13} spectrum) to account for the complete astrophysical neutrino flux.
We, the undersigned, stand as a unified community of stakeholders and key opinion leaders deeply concerned about forced opioid tapering in patients receiving longterm prescription opioid therapy for ...chronic pain. This is a large-scale humanitarian issue. Our specific concerns involve: • rapid, forced opioid tapering among outpatients; • mandated opioid tapers that require aggressive opioid dose reductions over a defined period, even when that period is an extended one. Opioid tapering guidelines were created, in part, to decrease harm to patients resulting from high-dose opioid therapy for chronic pain. However, countless “legacy patients” with chronic pain who were progressively escalated to high opioid doses, often over many years, now face additional and very serious risks resulting from rapid tapering or related policies that mandate extreme dose reductions that are aggressive and unrealistic.
Abstract
We present Herschel observations of the core of the Perseus cluster of galaxies. Especially intriguing is the network of filaments that surround the brightest cluster galaxy, NGC 1275, ...previously imaged extensively in Hα and CO. In this work, we report detections of far-infrared (FIR) lines, in particular, C ii 158, O i 63, N ii 122, O ib 145 and O iii 88 μm, with Herschel. All lines are spatially extended, except O iii, with the C ii line emission extending up to 25 kpc from the core. C ii emission is found to be co-spatial with Hα and CO. Furthermore, C ii shows a similar velocity distribution to CO, which has been shown in previous studies to display a close association with the Hα kinematics. The spatial and kinematical correlation among C ii, Hα and CO gives us confidence to model the different components of the gas with a common heating model.
With the help of FIR continuum Herschel measurements, together with a suite of coeval radio, sub-millimetre and IR data from other observatories, we performed a spectral energy distribution fitting of NGC 1275 using a model that contains contributions from dust emission as well as synchrotron active galactic nucleus emission. This has allowed us to accurately estimate the dust parameters. The data indicate a low dust emissivity index, β ≈ 1, a total dust mass close to 107 M⊙, a cold dust component with temperature 38 ± 2 K and a warm dust component with temperature 116 ± 9 K. The FIR-derived star formation rate is 24 ± 1 M⊙ yr−1, which is in agreement with the far-ultraviolet-derived star formation rate in the core, determined after applying corrections for both Galactic and internal reddening. The total IR luminosity in the range 8-1000 μm is inferred to be 1.5 × 1011 L⊙, making NGC 1275 a luminous IR galaxy.
We investigated in detail the source of the Herschel FIR and Hα emissions emerging from a core region 4 kpc in radius. Based on simulations conducted using the radiative transfer code, cloudy, a heating model comprising old and young stellar populations is sufficient to explain these observations. The optical line ratios indicate that there may be a need for a second heating component. However, stellar photoionization seems to be the dominant mechanism.
We have also detected C ii in three well-studied regions of the filaments. Herschel, with its superior sensitivity to FIR emission, can detect far colder atomic gas than previous studies. We find an O i/C ii ratio about 1 dex smaller than predicted by the otherwise functional Ferland (2009) model. That study considered optically thin emission from a small cell of gas and by design did not consider the effects of reasonable column densities. The line ratio suggests that the lines are optically thick, as is typical of galactic photodissociation regions, and implies that there is a large reservoir of cold atomic gas. This was not included in previous inventories of the filament mass and may represent a significant component.
Context. Accretion is a fundamental process in star formation. Although the time evolution of accretion remains a matter of debate, observations and modelling studies suggest that episodic outbursts ...of strong accretion may dominate the formation of the central protostar. Observing young stellar objects during these elevated accretion states is crucial to understanding the origin of unsteady accretion.Aims. Z CMa is a pre-main-sequence binary system composed of an embedded Herbig Be star, undergoing photometric outbursts, and a FU Orionis star. This system therefore provides a unique opportunity to study unsteady accretion processes. The Herbig Be component recently underwent its largest optical photometric outburst detected so far. We aim to constrain the origin of this outburst by studying the emission region of the HI Br(gamma) line, a powerful tracer of accretion/ejection processes on the AU-scale in young stars.Methods. Using the AMBER/VLTI instrument at spectral resolutions of 1500 and 12 000, we performed spatially and spectrally resolved interferometric observations of the hot gas emitting across the Br(gamma) emission line, during and after the outburst. From the visibilities and differential phases, we derive characteristic sizes for the Br(gamma) emission and spectro-astrometric measurements across the line, with respect to the continuum.Results. We find that the line profile, the astrometric signal, and the visibilities are inconsistent with the signature of either a Keplerian disk or infall of matter. They are, instead, evidence of a bipolar wind, maybe partly seen through a disk hole inside the dust sublimation radius. The disappearance of the Br(gamma) emission line after the outburst suggests that the outburst is related to a period of strong mass loss rather than a change of the extinction along the line of sight.Conclusions. Apart from the photometric increase of the system, the main consequence of the outburst is to trigger a massive bipolar outflow from the Herbig Be component. Based on these conclusions, we speculate that the origin of the outburst is an event of enhanced mass accretion, similar to those occuring in EX Ors and FU Ors.
To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or ...whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial.
Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only.
Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients.
In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.
We report here an extension of the measurement of the all-particle cosmic-ray spectrum with IceTop to lower energy. The new measurement gives full coverage of the knee region of the spectrum and ...reduces the gap in energy between previous IceTop and direct measurements. With a new trigger that selects events in closely spaced detectors in the center of the array, the IceTop energy threshold is lowered by almost an order of magnitude below its previous threshold of 2 PeV. In this paper we explain how the new trigger is implemented, and we describe the new machine-learning method developed to deal with events with very few detectors hit. We compare the results with previous measurements by IceTop and others that overlap at higher energy and with HAWC and Tibet in the 100 TeV range.
Abstract
Objective
This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling and mortality in patients with systemic ...amyloidosis.
Background
Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by CT, offering a rapid and cost-effective alternative to cardiovascular magnetic resonance (CMR), especially among patients with cardiac devices or on renal dialysis.
Methods
Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent ECG-gated cardiac CT. ECVCT was analysed in the inter-ventricular septum. All patients also underwent clinical assessment, ECG, echocardiography, serum amyloid protein component (SAP) and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini Grade / AL Mayo Class) and evaluated for its association with myocardial remodelling and all-cause mortality.
Results
72 patients were studied (AL n=35, ATTR n=37; age 67 (59–76) years, 71% males). Mean septal ECVCT was 42.7±13.1% and 55.8±10.9% in AL and ATTR, respectively, and correlated with indexed left ventricular (LV) mass (r=0.426, p<0.001), LV ejection fraction LVEF, (r=0.460, p<0.001), NT-proBNP (r=0.563, p<0.001) and hsTnT (r=0.546, p=0.02). ECVCT increased with cardiac amyloid involvement in both AL and ATTR (Figure 1). Over a mean follow-up of 5.3±2.4 years, 40 deaths occurred (AL 14 35%; ATTR 26 65%). ECVCT was independently associated with all-cause mortality in ATTR (not AL) after adjustment for age and IV septal wall thickness (HR: 1.046, 95% CI: 1.003–1.090, p=0.037).
Conclusion
Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodelling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely-accessible imaging modality (Figure 2).
Funding Acknowledgement
Type of funding sources: None.
The purpose of the present article is to present a review of the Ross River virus (RRV) and Barmah Forest virus (BFV) literature in relation to potential implications for future disease in tropical ...northern Australia. Ross River virus infection is the most common and most widespread arboviral disease in Australia, with an average of 4,800 national notifications annually. Of recent concern is the sudden rise in BFV infections; the 2005-2006 summer marked the largest BFV epidemic on record in Australia, with 1,895 notifications. Although not life-threatening, infection with either virus can cause arthritis, myalgia, and fatigue for 6 months or longer, resulting in substantial morbidity and economic impact. The geographic distribution of mosquito species and their seasonal activity is determined in large part by temperature and rainfall. Predictive models can be useful tools in providing early warning systems for epidemics of RRV and BFV infection. Various models have been developed to predict RRV outbreaks, but these appear to be mostly only regionally valid, being dependent on local ecological factors. Difficulties have arisen in developing useful models for the tropical northern parts of Australia, and to date no models have been developed for the Northern Territory. Only one model has been developed for predicting BFV infections using climate and tide variables. It is predicted that the exacerbation of current greenhouse conditions will result in longer periods of high mosquito activity in the tropical regions where RRV and BFV are already common. In addition, the endemic locations may expand further within temperate regions, and epidemics may become more frequent in those areas. Further development of predictive models should benefit public health planning by providing early warning systems of RRV and BFV infection outbreaks in different geographical locations.
There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic ...correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10
FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.
Mitochondrial DNA (mtDNA) analysis has proved useful in studies of recent human evolution and the genetic affinities of human groups of different geographical regions. As part of an extensive survey ...of mtDNA diversity in present-day Pacific populations, we obtained sequence information of the hypervariable mtDNA control region of 452 individuals from various localities in the western Pacific. The mtDNA types fell into three major groups which reflect the settlement history of the area. Interestingly, we detected an extremely rare point mutation at high frequency in the small island of Nguna in the Melanesian archipelago of Vanuatu. Phylogenetic analysis of the mtDNA data indicated that the mutation was present in individuals of separate mtDNA lineages. We propose that the multiple occurrence of a rare mutation event in one isolated locality is highly improbable, and that recombination between different mtDNA types is a more likely explanation for our observation. If correct, this conclusion has important implications for the use of mtDNA in phylogenetic and evolutionary studies.
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