Induced gravitational collapse at extreme cosmological distances: the case of GRB 090423

CONTEXT: The induced gravitational collapse (IGC) scenario has been introduced in order to explain the most energetic gamma ray bursts (GRBs), Eiso=10^{52}-10^{54}erg, associated with type Ib/c supernovae (SNe). It has led to the concept of binary-driven hypernovae (BdHNe) originating in a tight binary system composed by a FeCO core on the verge of a SN explosion and a companion neutron star (NS). Their evolution is characterized by a rapid sequence of events: [...]. AIMS: We investigate whether GRB 090423, one of the farthest observed GRB at z=8.2, is a member of the BdHN family. METHODS: We compare and contrast the spectra, the luminosity evolution and the detectability in the observations by Swift of GRB 090423 with the corresponding ones of the best known BdHN case, GRB 090618. RESULTS: Identification of constant slope power-law behavior in the late X-ray emission of GRB 090423 and its overlapping with the corresponding one in GRB 090618, measured in a common rest frame, represents the main result of this article. This result represents a very significant step on the way to using the scaling law properties, proven in Episode 3 of this BdHN family, as a cosmological standard candle. CONCLUSIONS: Having identified GRB 090423 as a member of the BdHN family, we can conclude that SN events, leading to NS formation, can already occur already at z=8.2, namely at 650 Myr after the Big Bang. It is then possible that these BdHNe originate stem from 40-60 M_{\odot} binaries. They are probing the Population II stars after the completion and possible disappearance of Population III stars.Comment: 9 pages, 9 figures, to appear on A&

Disease characteristics of MCT8 deficiency : an international, retrospective, multicentre cohort study

Background Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. Methods We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1–3 years (defined as a bodyweight-for-age Z score <–2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. Findings Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3–61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76–8·34; log-rank test p=0·0041). Patients who were underweight during age 1–3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26–17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. Interpretation Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies

Animal models of osteogenesis imperfecta: applications in clinical research

Tanya A Enderli,&nbsp;Stephanie R Burtch,&nbsp;Jara N Templet,&nbsp;Alessandra Carriero Department of Biomedical Engineering, Florida Institute of Technology, Melbourne, FL, USA Abstract: Osteogenesis imperfecta (OI), commonly known as brittle bone disease, is a genetic disease characterized by extreme bone fragility and consequent skeletal deformities. This connective tissue disorder is caused by mutations in the quality and quantity of the collagen that in turn affect the overall mechanical integrity of the bone, increasing its vulnerability to fracture. Animal models of the disease have played a critical role in the understanding of the pathology and causes of OI and in the investigation of a broad range of clinical therapies for the disease. Currently, at least 20 animal models have been officially recognized to represent the phenotype and biochemistry of the 17 different types of OI in humans. These include mice, dogs, and fish. Here, we describe each of the animal models and the type of OI they represent, and present their application in clinical research for treatments of OI, such as drug therapies (ie, bisphosphonates and sclerostin) and mechanical (ie, vibrational) loading. In the future, different dosages and lengths of treatment need to be further investigated on different animal models of OI using potentially promising treatments, such as cellular and chaperone therapies. A combination of therapies may also offer a viable treatment regime to improve bone quality and reduce fragility in animals before being introduced into clinical trials for OI patients. Keywords: OI, brittle bone, clinical research, mouse, dog, zebrafis

On binary-driven hypernovae and their nested late X-ray emission

Context. The induced gravitational collapse (IGC) paradigm addresses the very energetic (1052–1054 erg) long gamma-ray bursts (GRBs) associated to supernovae (SNe). Unlike the traditional “collapsar” model, an evolved FeCO core with a companion neutron star (NS) in a tight binary system is considered as the progenitor. This special class of sources, here named “binary-driven hypernovae” (BdHNe), presents a composite sequence composed of four different episodes with precise spectral and luminosity features. Aims. We first compare and contrast the steep decay, the plateau, and the power-law decay of the X-ray luminosities of three selected BdHNe (GRB 060729, GRB 061121, and GRB 130427A). Second, to explain the different sizes and Lorentz factors of the emitting regions of the four episodes, for definiteness, we use the most complete set of data of GRB 090618. Finally, we show the possible role of r-process, which originates in the binary system of the progenitor. Methods. We compare and contrast the late X-ray luminosity of the above three BdHNe. We examine correlations between the time at the starting point of the constant late power-law decay t*a, the average prompt luminosity ⟨ Liso ⟩, and the luminosity at the end of the plateau La. We analyze a thermal emission (~ 0.97–0.29 keV), observed during the X-ray steep decay phase of GRB 090618. Results. The late X-ray luminosities of the three BdHNe, in the rest-frame energy band 0.3–10 keV, show a precisely constrained “nested” structure. In a space–time diagram, we illustrate the different sizes and Lorentz factors of the emitting regions of the three episodes. For GRB 090618, we infer an initial dimension of the thermal emitter of ~ 7 × 1012 cm, expanding at Γ ≈ 2. We find tighter correlations than the Dainotti-Willingale ones. Conclusions. We confirm a constant slope power-law behavior for the late X-ray luminosity in the source rest frame, which may lead to a new distance indicator for BdHNe. These results, as well as the emitter size and Lorentz factor, appear to be inconsistent with the traditional afterglow model based on synchrotron emission from an ultra-relativistic (Γ ~ 102–103) collimated jet outflow. We argue, instead, for the possible role of r-process, originating in the binary system, to power the mildly relativistic X-ray source