A Femtosecond Neutron Source

The possibility to use the ultrashort ion bunches produced by circularly polarized laser pulses to drive a source of fusion neutrons with sub-optical cycle duration is discussed. A two-side irradiation of a thin foil deuterated target produces two countermoving ion bunches, whose collision leads to an ultrashort neutron burst. Using particle-in-cell simulations and analytical modeling, it is evaluated that, for intensities of a few $10^{19} W cm^{-2}$, more than $10^3$ neutrons per Joule may be produced within a time shorter than one femtosecond. Another scheme based on a layered deuterium-tritium target is outlined.Comment: 15 pages, 3 figure

Activation of mGlu3 Receptors Stimulates the Production of GDNF in Striatal Neurons

Metabotropic glutamate (mGlu) receptors have been considered potential targets for the therapy of experimental parkinsonism. One hypothetical advantage associated with the use of mGlu receptor ligands is the lack of the adverse effects typically induced by ionotropic glutamate receptor antagonists, such as sedation, ataxia, and severe learning impairment. Low doses of the mGlu2/3 metabotropic glutamate receptor agonist, LY379268 (0.25–3 mg/kg, i.p.) increased glial cell line-derived neurotrophic factor (GDNF) mRNA and protein levels in the mouse brain, as assessed by in situ hybridization, real-time PCR, immunoblotting, and immunohistochemistry. This increase was prominent in the striatum, but was also observed in the cerebral cortex. GDNF mRNA levels peaked at 3 h and declined afterwards, whereas GDNF protein levels progressively increased from 24 to 72 h following LY379268 injection. The action of LY379268 was abrogated by the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.), and was lost in mGlu3 receptor knockout mice, but not in mGlu2 receptor knockout mice. In pure cultures of striatal neurons, the increase in GDNF induced by LY379268 required the activation of the mitogen-activated protein kinase and phosphatidylinositol-3-kinase pathways, as shown by the use of specific inhibitors of the two pathways. Both in vivo and in vitro studies led to the conclusion that neurons were the only source of GDNF in response to mGlu3 receptor activation. Remarkably, acute or repeated injections of LY379268 at doses that enhanced striatal GDNF levels (0.25 or 3 mg/kg, i.p.) were highly protective against nigro-striatal damage induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice, as assessed by stereological counting of tyrosine hydroxylase-positive neurons in the pars compacta of the substantia nigra. We speculate that selective mGlu3 receptor agonists or enhancers are potential candidates as neuroprotective agents in Parkinson's disease, and their use might circumvent the limitations associated with the administration of exogenous GDNF

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

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of Italian general practitioners.

OBJECTIVE: Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. RESULTS: Of the 995 asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had asthma alone. The latter, compared to those with R+A, showed significantly lower prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%, and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5% of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5% emergency department visits, 26.7% hospitalization, and 62.5% limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with R+A than in those with asthma alone. CONCLUSIONS: This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of Italian general practitioners.

OBJECTIVE: Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. RESULTS: Of the 995 asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had asthma alone. The latter, compared to those with R+A, showed significantly lower prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%, and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5% of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5% emergency department visits, 26.7% hospitalization, and 62.5% limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with R+A than in those with asthma alone. CONCLUSIONS: This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting