Dyskeratosis congenita: natural history of the disease through the study of a cohort of patients diagnosed in childhood

Aplastic anaemia; Dyskeratosis congenita; Multisystem diseaseAnemia aplásica; Disqueratosis congénita; Enfermedad multisistémicaAnèmia aplàstica; Disceratosi congènita; Malaltia multisistèmicaBackground: Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time. Material and methods: Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020). Results: Fourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3–18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2–24 years]. Six patients died, the median age was 13 years [range, 6–24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6–32 years]. None of them have developed myeloblastic syndrome or cancer. Conclusions: DC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential

Energy distribution of individual quasars from far-UV to X-rays: I. Intrinsic UV hardness and dust opacities

Using Chandra and HST archival data, we have studied the individual Spectral Energy Distribution (SED) of 11 quasars. All UV spectra show a spectral break around 1100A. 5 X-ray spectra show the presence of a ``soft excess'' and 7 spectra showed an intrinsic absorption. We found that for most quasars a simple extrapolation of the far-UV powerlaw into the X-ray domain generally lies below the X-ray data and that the big blue bump and the soft X-ray excess do not share a common physical origin. We explore the issue of whether the observed SED might be dust absorbed in the far and near-UV. We fit the UV break, assuming a powerlaw that is absorbed by cubic nanodiamond dust grains. We then explore the possibility of a universal SED (with a unique spectral index) by including further absorption from SMC-like extinction. Using this approach, satisfactory fits to the spectra can be obtained. The hydrogen column densities required by either nanodiamonds or amorphous dust models are all consistent, except for one object, with the columns deduced by our X-ray analysis, provided that the C depletion is ~0.6. Because dust absorption implies a flux recovery in the extreme UV (<700A), our modeling opens the possibility that the intrinsic quasar SED is much harder and more luminous in the extreme UV than inferred from the near-UV data, as required by photoionization models of the broad emission line region. We conclude that the intrinsic UV SED must undergo a sharp turn-over before the X-ray domain.Comment: 49 pages, 11 figures, accepted for publication in Ap

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Dyskeratosis congenita: natural history of the disease through the study of a cohort of patients diagnosed in childhood

BackgroundDyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time.Material and methodsMulticenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020).ResultsFourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3–18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2–24 years]. Six patients died, the median age was 13 years [range, 6–24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6–32 years]. None of them have developed myeloblastic syndrome or cancer.ConclusionsDC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential

The Spectral Energy Distribution of Fermi bright blazars

(Abridged) We have conducted a detailed investigation of the broad-band spectral properties of the \gamma-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi gamma-ray spectra with Swift, radio, infra-red, optical and other hard X-ray/gamma-ray data, collected within three months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous Spectral Energy Distributions (SED) for 48 LBAS blazars.The SED of these gamma-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual Log $\nu$ - Log $\nu$ F$_\nu$ representation, the typical broad-band spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SEDs to characterize the peak intensity of both the low and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broad-band colors (i.e. the radio to optical and optical to X-ray spectral slopes) and from the gamma-ray spectral index. Our data show that the synchrotron peak frequency $\nu_p^S$ is positioned between 10$^{12.5}$ and 10$^{14.5}$ Hz in broad-lined FSRQs and between $10^{13}$ and $10^{17}$ Hz in featureless BL Lacertae objects.We find that the gamma-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron - inverse Compton scenarios. However, simple homogeneous, one-zone, Synchrotron Self Compton (SSC) models cannot explain most of our SEDs, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. (...)Comment: 85 pages, 38 figures, submitted to Ap

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Search for the standard model Higgs boson decaying to a bbˉb\bar{b} pair in events with no charged leptons and large missing transverse energy using the full CDF data set

We report on a search for the standard model Higgs boson produced in association with a vector boson in the full data set of proton-antiproton collisions at $\sqrt{s} = 1.96$ TeV recorded by the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45 fb$^{-1}$. We consider events having no identified charged lepton, a transverse energy imbalance, and two or three jets, of which at least one is consistent with originating from the decay of a $b$ quark. We place 95% credibility level upper limits on the production cross section times standard model branching fraction for several mass hypotheses between 90 and $150 \mathrm{GeV}/c^2$. For a Higgs boson mass of $125 \mathrm{GeV}/c^2$, the observed (expected) limit is 6.7 (3.6) times the standard model prediction.Comment: Accepted by Phys. Rev. Let

Search for the standard model Higgs boson decaying to a bb pair in events with one charged lepton and large missing transverse energy using the full CDF data set

We present a search for the standard model Higgs boson produced in association with a W boson in sqrt(s) = 1.96 TeV p-pbar collision data collected with the CDF II detector at the Tevatron corresponding to an integrated luminosity of 9.45 fb-1. In events consistent with the decay of the Higgs boson to a bottom-quark pair and the W boson to an electron or muon and a neutrino, we set 95% credibility level upper limits on the WH production cross section times the H->bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125 GeV/c2 we observe (expect) a limit of 4.9 (2.8) times the standard model value.Comment: Submitted to Phys. Rev. Lett (v2 contains clarifications suggested by PRL

Search for the standard model Higgs boson decaying to a bb pair in events with two oppositely-charged leptons using the full CDF data set

We present a search for the standard model Higgs boson produced in association with a Z boson in data collected with the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45/fb. In events consistent with the decay of the Higgs boson to a bottom-quark pair and the Z boson to electron or muon pairs, we set 95% credibility level upper limits on the ZH production cross section times the H -> bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125 GeV/c^2 we observe (expect) a limit of 7.1 (3.9) times the standard model value.Comment: To be submitted to Phys. Rev. Let

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO