Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe

Dexamethasone; PrenatalDexametasona; PrenatalDexametasona; PrenatalObjective To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Design and methods A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN. Results Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4–5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France. Conclusions This study reveals a high international variability and discrepancy in the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence-based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH.This work was supported by the Deutsche Forschungsgemeinschaft (Heisenberg Professorship, 325768017 to N R and 314061271-TRR205 to N R and A H), the European Commission for funding EndoERN CHAFEA FPA grant no. 739527, the Eva Luise und Horst Köhler Stiftung & Else Kröner-Fresenius-Stiftung (2019_KollegSE.03 to H N) and the Stockholm County Council (Senior clinical research fellowship dnr RS 2019-1140 to S L), Stiftelsen Frimurare Barnhuset i Stockholm and Lisa and Johan Grönbergs Stiftelse

Isotopic ratios of H, C, N, O, and S in comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy)

The apparition of bright comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy) in March-April 2013 and January 2015, combined with the improved observational capabilities of submillimeter facilities, offered an opportunity to carry out sensitive compositional and isotopic studies of the volatiles in their coma. We observed comet Lovejoy with the IRAM 30m telescope between 13 and 26 January 2015, and with the Odin submillimeter space observatory on 29 January - 3 February 2015. We detected 22 molecules and several isotopologues. The H$_2^{16}$O and H$_2^{18}$O production rates measured with Odin follow a periodic pattern with a period of 0.94 days and an amplitude of ~25%. The inferred isotope ratios in comet Lovejoy are $^{16}$O/$^{18}$O = 499 $\pm$ 24 and D/H = 1.4 $\pm$ 0.4 $\times 10^{-4}$ in water, $^{32}$S/$^{34}$S = 24.7 $\pm$ 3.5 in CS, all compatible with terrestrial values. The ratio $^{12}$C/$^{13}$C = 109 $\pm$ 14 in HCN is marginally higher than terrestrial and $^{14}$N/$^{15}$N = 145 $\pm$ 12 in HCN is half the Earth ratio. Several upper limits for D/H or 12C/13C in other molecules are reported. From our observation of HDO in comet C/2014 Q2 (Lovejoy), we report the first D/H ratio in an Oort Cloud comet that is not larger than the terrestrial value. On the other hand, the observation of the same HDO line in the other Oort-cloud comet, C/2012 F6 (Lemmon), suggests a D/H value four times higher. Given the previous measurements of D/H in cometary water, this illustrates that a diversity in the D/H ratio and in the chemical composition, is present even within the same dynamical group of comets, suggesting that current dynamical groups contain comets formed at very different places or times in the early solar system.Comment: Accepted for publication in Astronomy and Astrophysic

Attention to speech and music in young children with bilateral cochlear implants: a pupillometry study

Early bilateral cochlear implants (CIs) may enhance attention to speech, and reduce cognitive load in noisy environments. However, it is sometimes difficult to measure speech perception and listening effort, especially in very young children. Behavioral measures cannot always be obtained in young/uncooperative children, whereas objective measures are either difficult to assess or do not reliably correlate with behavioral measures. Recent studies have thus explored pupillometry as a possible objective measure. Here, pupillometry is introduced to assess attention to speech and music in noise in very young children with bilateral CIs (N = 14, age: 17–47 months), and in the age-matched group of normally-hearing (NH) children (N = 14, age: 22–48 months). The results show that the response to speech was affected by the presence of background noise only in children with CIs, but not NH children. Conversely, the presence of background noise altered pupil response to music only in in NH children. We conclude that whereas speech and music may receive comparable attention in comparable listening conditions, in young children with CIs, controlling for background noise affects attention to speech and speech processing more than in NH children. Potential implementations of the results for rehabilitation procedures are discussed

Adattamento precoce dell’impianto cocleare in età pediatrica

L’impianto cocleare costituisce una valida opportunità per fornire l’accesso alla stimolazione uditiva nei casi di ipoacusia severa o profonda di origine cocleare. E’ stato ampiamente dimostrato che l’impianto cocleare è una soluzione sicura ed efficace e che la precocità nell’attivazione è associata a risultati migliori. E’ importante studiare le variabili e gli aspetti che possono interferire con un adattamento precoce e un adeguato accesso al mondo sonoro: caratteristiche del bambino, alleanza terapeutica con la famiglia, aspetti tecnici, medici e organizzativi. Obiettivo di questo lavoro è quello di proporre raccomandazioni utili per gli aspetti organizzativi-pratici relativi alle attivazioni precoci di impianto cocleare, attraverso un particolare modello di analisi SWOT e TOWS

Chaotic self-similar wave maps coupled to gravity

We continue our studies of spherically symmetric self-similar solutions in the SU(2) sigma model coupled to gravity. For some values of the coupling constant we present numerical evidence for the chaotic solution and the fractal threshold behavior. We explain this phenomenon in terms of horseshoe-like dynamics and heteroclinic intersections.Comment: 25 pages, 17 figure

Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin

AIMS/HYPOTHESIS: We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI). METHODS: This is a retrospective cohort study using the Scottish Care Information – Diabetes database for retinal screening outcomes and HbA(1c) changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan–Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA(1c), blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA(1c) and change in HbA(1c) on diabetic retinopathy progression was assessed within CSII and MDI cohorts. RESULTS: CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA(1c) and higher diastolic BP at baseline. There was a larger reduction in HbA(1c) at 1 year in those on CSII vs MDI (−6 mmol/mol [−0.6%] vs −2 mmol/mol [−0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA(1c) (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA(1c) at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group. CONCLUSIONS/INTERPRETATION: CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA(1c). Progression of diabetic retinopathy over 3 years was not associated with a change in HbA(1c). GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05456-w

Observational evidence of dissipative photospheres in gamma-ray bursts

The emission from a gamma-ray burst (GRB) photosphere can give rise to a variety of spectral shapes. The spectrum can retain the shape of a Planck function or it can be broadened and have the shape of a Band function. This fact is best illustrated by studying GRB090902B: The main gamma-ray spectral component is initially close to a Planck function, which can only be explained by emission from the jet photosphere. Later, the same component evolves into a broader Band function. This burst thus provides observational evidence that the photosphere can give rise to a non-thermal spectrum. We show that such a broadening is most naturally explained by subphotospheric dissipation in the jet. The broadening mainly depends on the strength and location of the dissipation, on the magnetic field strength, and on the relation between the energy densities of thermal photons and of the electrons. We suggest that the evolution in spectral shape observed in GRB090902B is due to a decrease of the bulk Lorentz factor of the flow, leading to the main dissipation becoming subphotospheric. Such a change in the flow parameters can also explain the correlation observed between the peak energy of the spectrum and low-energy power law slope, alpha, a correlation commonly observed in GRBs. We conclude that photospheric emission could indeed be a ubiquitous feature during the prompt phase in GRBs and play a decisive role in creating the diverse spectral shapes and spectral evolutions that are observed.Comment: Submitted to MNRAS, 14 pages, 7 figure

The INNODIA Type 1 Diabetes Natural History Study: a European cohort of newly diagnosed children, adolescents and adults

Aims/hypothesis: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual’s clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis. Methods: Data were collected from the large INNODIA cohort of individuals (aged 1.0–45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10–17 years; and ≥18 years. Results: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0–382.0) pmol/l (AUC 749.3 [466.2–1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001). Conclusions/interpretation: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline. Graphical Abstract

Early Fermi Gamma-ray Space Telescope Observations of the Quasar 3C 454.3

This is the first report of Fermi Gamma-ray Space Telescope observations of the quasar 3C 454.3, which has been undergoing pronounced long-term outbursts since 2000. The data from the Large Area Telescope (LAT), covering 2008 July 7 - October 6, indicate strong, highly variable gamma-ray emission with an average flux of ~3 x 10^{-6} photons cm^{-2} s^{-1}, for energies above 100 MeV. The gamma-ray flux is variable, with strong, distinct, symmetrically-shaped flares for which the flux increases by a factor of several on a time scale of about three days. This variability indicates a compact emission region, and the requirement that the source is optically thin to pair-production implies relativistic beaming with Doppler factor delta > 8, consistent with the values inferred from VLBI observations of superluminal expansion (delta ~ 25). The observed gamma-ray spectrum is not consistent with a simple power-law, but instead steepens strongly above ~2 GeV, and is well described by a broken power-law with photon indices of ~2.3 and ~3.5 below and above the break, respectively. This is the first direct observation of a break in the spectrum of a high luminosity blazar above 100 MeV, and it is likely direct evidence for an intrinsic break in the energy distribution of the radiating particles. Alternatively, the spectral softening above 2 GeV could be due to gamma-ray absorption via photon-photon pair production on the soft X-ray photon field of the host AGN, but such an interpretation would require the dissipation region to be located very close (less than 100 gravitational radii) to the black hole, which would be inconsistent with the X-ray spectrum of the source.Comment: Accepted by the Astrophysical Journal; corresponding authors: Greg Madejski ([email protected]) and Benoit Lott ([email protected]

Fermi Large Area Telescope Bright Gamma-ray Source List

Following its launch in June 2008, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in 3 months produced a deeper and better-resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than ~10-sigma) gamma-ray sources in these data. These are the best-characterized and best-localized point-like (i.e., spatially unresolved) gamma-ray sources in the early-mission data.Comment: Accepted by ApJS. Many helpful comments by referee incorporated 57 pages, 12 figure