Abstract
The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi) shows long-lasting high-energy emission in many gamma-ray bursts (GRBs), similar to X-ray afterglows ...observed by the Neil Gehrels Swift Observatory (Swift). Some LAT light curves (LCs) show a late-time flattening reminiscent of X-ray plateaus. We explore the presence of plateaus in LAT temporally extended emission analyzing GRBs from the second Fermi-LAT GRB Catalog from 2008 to 2016 May with known redshifts, and check whether they follow closure relations corresponding to four distinct astrophysical environments predicted by the external forward shock model. We find that three LCs can be fit by the same phenomenological model used to fit X-ray plateaus and show tentative evidence for the existence of plateaus in their high-energy extended emission. The most favorable scenario is a slow-cooling regime, whereas the preferred density profile for each GRBs varies from a constant-density interstellar medium to an
r
−2
wind environment. We also compare the end time of the plateaus in
γ
-rays and X-rays using a statistical comparison with 222 Swift GRBs with plateaus and known redshifts from 2005 January to 2019 August. Within this comparison, the case of GRB 090510 shows an indication of chromaticity at the end time of the plateau. Finally, we update the 3D fundamental plane relation among the rest-frame end time of the plateau, its correspondent luminosity, and the peak prompt luminosity for 222 GRBs observed by Swift. We find that these three LAT GRBs follow this relation.
Long duration gamma-ray bursts may serve as standard candles to constrain cosmological parameters by probing the Hubble diagram well beyond the range of redshift currently accessible using SNe Ia. ...The standardization of gamma-ray bursts (GRBs) is based on phenomenological relations between two or more parameters found from spectral modeling, one of which is strongly dependent on the cosmological model. The Amati relation links the source-frame energy at which the prompt gamma-ray spectral energy distribution F peaks, and the isotropic-equivalent bolometric energy emitted during the prompt phase. We performed spectral analysis of 26 GRBs with known redshift that have been detected by the Fermi-Large Area Telescope (LAT) during its nine years of operations from 2008 July to 2017 September, thus extending the computation of Eiso to the 100 MeV range. Multiple components are required to fit the spectra of a number of GRBs. We found that the Amati relation is satisfied by the 25 LGRBs, with best-fit parameters similar to previous studies that used data from different satellite experiments, while the only short GRB with known redshift is an outlier. Using the Amati relation, we extend the Hubble diagram to redshift 4.35 and constrain the Hubble constant and dark-energy density in the ΛCDM model, with Fermi-LAT GRBs alone and together with another sample of 94 GRBs and with the latest Supernovae type-Ia data. Our results are consistent with the currently acceptable ranges of those cosmological parameters within errors.
Much evidence points towards that the photosphere in the relativistic outflow in GRBs plays an important role in shaping the observed MeV spectrum. However, it is unclear whether the spectrum is ...fully produced by the photosphere or whether a substantial part of the spectrum is added by processes far above the photosphere. Here we make a detailed study of the γ-ray emission from single pulse GRB110920A which has a spectrum that becomes extremely narrow towards the end of the burst. We show that the emission can be interpreted as Comptonization of thermal photons by cold electrons in an unmagnetized outflow at an optical depth of τ ∼ 20. The electrons receive their energy by a local dissipation occurring close to the saturation radius. The main spectral component of GRB110920A and its evolution is thus, in this interpretation, fully explained by the emission from the photosphere including localized dissipation at high optical depths.
The major intermediate cytoskeletal protein of astrocytes, glial fibrillary acidic protein (GFAP), and that of axons, neurofilament light protein (NFL), may both be released into the cerebrospinal ...fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). Patients with relapsing-remitting MS (RRMS,
n
= 15) or secondary progressive MS (SPMS,
n
= 10) and healthy control subjects (
n
= 28) were examined twice with an interval of 8–10 years apart. Neurological deficits were scored with the Expanded Disability Status Scale (EDSS). GFAP and NFL levels were determined in CSF by enzyme-linked immunosorbent assay (ELISA). GFAP levels and NFL levels correlated with age (
r
and
r
s
= 0.50,
p
= 0.006). Adjusting for age, MS patients had increased GFAP levels compared with controls (
p
= 0.03) and GFAP levels correlated with neurological disability (EDSS,
r
= 0.51,
p
< 0.05) and disease progression Multiple Sclerosis Severity Score (MSSS),
r
= 0.47,
p
< 0.05. The mean annual increase of GFAP was 6.5 ng/L for controls, 8.1 ng/L for RRMS patients, and 18.9 ng/L for SPMS patients. GFAP level at the first examination had predictive value for neurological disability 8–10 years later (EDSS,
r
= 0.45,
p
< 0.05) but not for EDSS increase between the examinations. NFL levels were not significantly increased in MS patients compared with controls and had no relationship to disability or progression and no prognostic value for disability development. GFAP, a marker for astrogliosis, is a potential biomarker for MS progression and may have a role in clinical trials for assessing the impact of therapies on MS progression.
Individuals with severe asthma often report poor Health-related quality of life (HRQoL) and more research is essential to increase understanding of how they may be helped to improve HRQoL. The main ...aim of the current paper is to evaluate HRQoL, and possible factors influencing HRQoL, in individuals with severe asthma. The aim is also to explore associations among anxiety, depression, beliefs of medication, self-efficacy, and HRQoL among individuals with severe and other asthma as well as those with no asthma.
Participants with severe asthma (
= 59), other asthma (
= 526), and no asthma (
= 902) were recruited from West Sweden Asthma Study, a population-based study, which includes both questionnaire surveys and clinical examinations.
Individuals with severe asthma had worse physical HRQoL (measured with SF-8) than those with other and no asthma (median 48.4, 51.9, and 54.3, respectively). They also had worse mental HRQoL (median 46.7) and reported higher anxiety and depression scores (measured using HADS, median 5.0 and 3.5, respectively) compared to no asthma (median 4.0 and 2.0, respectively). HRQoL was particularly affected among women with severe asthma. Individuals with severe asthma believed that their asthma medication was more necessary than those with other asthma, but they reported more concern for the medication. Asthma control and packyears predicted physical HRQoL and anxiety predicted mental HRQoL among individuals with severe asthma.
Efforts to improve asthma control and to reduce anxiety may improve HRQoL in individuals with severe asthma. Especially, women with severe asthma seem to need support to improve their HRQoL. Reducing concerns with asthma medication is most likely essential as high concerns may lead to poor adherence, which in turn may negatively affect asthma control and HRQoL.
Background and purpose
Breakthrough disease on first‐line injectables in relapsing‐remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different ...escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS.
Methods
Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder‐adjusted Cox proportional hazard models.
Results
A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2–5.6) for RTX and 3.4 (95% CI, 1.3–9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01–0.38) for RTX and 1.0 (95% CI, 0.6–1.7) for FGL vs. NTZ.
Conclusions
In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.
Background:
Serum neurofilament light (sNfL) reflects neuroaxonal damage and is now used as an outcome in treatment trials of relapsing-remitting multiple sclerosis (RRMS). However, the diagnostic ...properties of sNfL for monitoring disease activity in individual patients warrant further investigations.
Method:
Patients with suspected relapse and/or contrast-enhancing lesions (CELs) were consecutively included and performed magnetic resonance imaging (MRI) of the brain at baseline and weeks 28 and 48. Serum was obtained at baseline and 2, 4, 8, 16, 24, and 48 weeks. Neurofilament light concentration was measured using Single molecule array technology.
Results:
We included 44 patients, 40 with RRMS and 4 with clinically isolated syndrome. The median sNfL level peaked at 2 weeks post-baseline (14.6 ng/L, interquartile range (IQR); 9.3–31.6) and reached nadir at 48 weeks (9.1 ng/L, IQR; 5.5–15.0), equivalent to the median sNfL of controls (9.1 ng/L, IQR; 7.4–12). A baseline Z-score of more than 1.1 (area under the curve; 0.78, p < 0.0001) had a sensitivity of 81% and specificity of 70% to detect disease activity.
Conclusion:
One out of five patients with relapse and/or CELs did not change significantly in post-baseline sNfL levels. The utility of repeated sNfL measurements to monitor disease activity is complementary rather than a substitute for clinical and MRI measures.
Cementitious grouts are the most commonly used grouting material in the world. The general concept of grouting is to propagate the grout in a sufficiently large volume in the grouted medium and hence ...to have a controlled penetration. This study has been performed in order to determine and test the different mechanisms that result in stoppage of the penetration of cementitious grouts. This is performed as sand column tests in a laboratory study, coupled with grouting in the field. The result shows that three different stop mechanisms can be identified depending on the ratio between the grain size of the grout and the available opening. At an opening up to three times the size of the largest grout grains, penetration does not occur due to clogging of the grains. For an opening larger than five times the largest grain the penetration is unrestricted and stoppage occurs due to equilibrium between the driving and resistance forces. Between these ratios, a transition area exists where the water content determines the penetrability and the stoppage is governed by a filtration process for the grout grains. This implies that grouting with higher water-to-cement ratios results in a larger penetration area and hence by applying the mixture-thickening method during grouting an increased sealing efficiency can be obtained.
Objectives
The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90‐90‐90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of ...those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV‐1‐infected population in Sweden.
Methods
The Swedish InfCare HIV Cohort Study collects viral loads, CD4 counts, and viral sequences, along with demographic and clinical data, through an electronic clinical decision support system. Almost 100% of those diagnosed with HIV infection are included in the database, corresponding to 6946 diagnosed subjects living with HIV‐1 in Sweden by 31 December 2015.
Results
Using HIV surveillance data reported to the Public Health Agency of Sweden, it was estimated that 10% of all HIV‐infected subjects in Sweden remain undiagnosed. Among all diagnosed patients, 99.8% were linked to care and 97.1% of those remained in care. On 31 December 2015, 6605 of 6946 patients (95.1%) were on ART. A total of 6395 had been on treatment for at least 6 months and 6053 of those (94.7%) had a viral load < 50 HIV‐1 RNA copies/mL.
Conclusions
The 2014 UNAIDS/WHO 90‐90‐90 goals for HIV care means that > 73% of all patients living with HIV should be virologically suppressed by 2020. Sweden has already achieved this target, with 78% suppression, and is the first country reported to meet all the UNAIDS/WHO 90‐90‐90 goals.
Current guidelines primarily use medication levels to distinguish severe asthma from other types of asthma. In addition, severe asthma must also be uncontrolled at high-intensity treatment or become ...uncontrolled if treatment level is decreased. To date, only a few studies have used this definition to investigate the prevalence and clinical characteristics of severe asthma in population-based samples. Therefore, the aim of this study was to evaluate the prevalence and clinical characteristics of individuals with severe asthma in the population-representative West Sweden Asthma Study.
In this cross-sectional population-based study, a randomly selected sample (n=1172) and a separate asthma sample (n=744) underwent clinical examinations, completed a structured interview and responded to questionnaires. Severe asthma was defined as at least one feature of uncontrolled asthma despite treatment in line with the Global Initiative for Asthma (GINA) steps 4/5. This treatment level required a minimum medium dose of inhaled corticosteroids (ICS) plus a second controller or oral corticosteroids.
The prevalence of severe asthma was 1.1% in the adult random sample and 9.5% within the asthma sample. Individuals with severe asthma were older and had more symptoms, activity limitations, heart disease and blood neutrophils compared to those with other asthma. They also had lower lung function and despite these impairments, 32% did not have annual contact with a healthcare provider.
The prevalence of severe asthma was higher compared to previous studies, and many individuals with severe asthma did not have regular contact with healthcare providers. Due to the high burden of symptoms and impairments for individuals with severe asthma, it is important that the healthcare system implement strategies to improve follow-up and evaluate these patients according to existing guidelines.
PDF
