PurposeIn addition to environmental causes such as TORCH infection, trauma and drug or chemical exposure, childhood cataracts (CC) frequently have a genetic basis. They may be isolated or syndromic ...and have been associated with mutations in over 110 genes. We have recently demonstrated that next-generation sequencing (NGS), a high throughput sequencing technique that enables the parallel sequencing of multiple genes, is ideally suited to the investigation of bilateral CC. This study assesses the diagnostic outcomes of traditional routine investigations and compares this with outcomes of NGS testing.MethodsA retrospective review of the medical records of 27 consecutive patients with bilateral CC presenting in 2010-2012 was undertaken. The outcomes of routine investigations in these patients, including TORCH screen, urinalysis, karyotyping, and urinary and plasma organic amino acids, were collated. The success of routine genetic investigations undertaken over 10 years (2000-2010) was also assessed.ResultsBy April 2014, the underlying cause of bilateral CC had been identified in just one of 27 patients despite 44% (n=12) receiving a full 'standard' investigative work-up and 22% (n=6) investigations in addition to the standard work-up. Fifteen of these patients underwent NGS testing and nine (60%) of these received a diagnosis for their CC.ConclusionThe frequency of patients receiving a diagnosis for their CC after standard care and the time taken to diagnosis was disappointing. NGS testing improved diagnostic rates and time to diagnosis, as well as changing clinical management. These data serve as a baseline for future evaluation of novel diagnostic modalities.
Context. R Coronae Borealis stars (RCBs) are rare, hydrogen-deficient, carbon-rich supergiant variable stars that are likely the evolved merger products of pairs of CO and He white dwarfs. Only 55 ...RCB stars have been found in our galaxy and their distribution on the sky is weighted heavily by microlensing survey field positions. A less biased wide-area survey would enable us to test competing evolutionary scenarios, understand the population or populations that produce RCBs, and constrain their formation rate. Aims. The ASAS-3 survey monitored the sky south of declination +28 deg between 2000 and 2010 to a limiting magnitude of V = 14. We searched ASAS-3 for RCB variables using several different methods to ensure that the probability of RCB detection was as high as possible and to reduce selection biases based on luminosity, temperature, dust production activity and shell brightness. Methods. Candidates whose light curves were visually inspected were pre-selected based on their infrared (IR) excesses due to warm dust in their circumstellar shells using the WISE and/or 2MASS catalogues. Criteria on light curve variability were also applied when necessary to minimise the number of objects. Initially, we searched for RCB stars among the ASAS-3 ACVS1.1 variable star catalogue, then among the entire ASAS-3 south source catalogue, and finally directly interrogated the light curve database for objects that were not catalogued in either of those. We then acquired spectra of 104 stars to determine their real nature using the SSO/WiFeS spectrograph. Results. We report 21 newly discovered RCB stars and 2 new DY Per stars. Two previously suspected RCB candidates were also spectroscopically confirmed. Our methods allowed us to extend our detection efficiency to fainter magnitudes that would not have been easily accessible to discovery techniques based on light curve variability. The overall detection efficiency is about 90% for RCBs with maximum light brighter than V ~ 13. Conclusions. With these new discoveries, 76 RCBs are now known in our Galaxy and 22 in the Magellanic Clouds. This growing sample is of great value to constrain the peculiar and disparate atmosphere composition of RCBs. Most importantly, we show that the spatial distribution and apparent magnitudes of Galactic RCB stars is consistent with RCBs being part of the Galactic bulge population.
Aims.In order to gain new insight into the unidentified identity of the diffuse interstellar band (DIB) carriers, this paper describes research into possible links between the shape of the ...interstellar extinction curve (including the 2175 Å bump and far-UV rise), the presence or absence of DIBs, and physical and chemical conditions of the diffuse interstellar medium (gas and dust) in the Small Magellanic Cloud (SMC). Methods.We searched for DIB absorption features in VLT/UVES spectra of early-type stars in the SMC whose reddened lines-of-sight probe the diffuse interstellar medium of the SMC. Apparent column density profiles of interstellar atomic species (Na i, K i, Ca ii and Ti ii) are constructed to provide information on the distribution and conditions of the interstellar gas. Results.The characteristics of eight DIBs detected toward the SMC wing target AzV 456 are studied and upper limits are derived for the DIB equivalent widths toward the SMC stars AzV 398, AzV 214, AzV 18, AzV 65 and Sk 191. The amount of reddening is derived for these SMC sightlines, and, using RV and the H i column density, converted into a gas-to-dust ratio. From the atomic column density ratios we infer an indication of the strength of the interstellar radiation field, the titanium depletion level and a relative measure of turbulence/quiescence. The presence or absence of DIBs appears to be related to the shape of the extinction curve, in particular with respect to the presence or absence of the 2175 Å feature. Our measurements indicate that the DIB characteristics depend on the local physical conditions and chemical composition of the interstellar medium of the SMC, which apparently determine the rate of formation (and/or) destruction of the DIB carriers. The UV radiation field (via photoionisation and photo-destruction) and the metallicity (i.e. carbon abundance) are important factors in determining diffuse band strengths which can differ greatly both between and within galaxies.
ABSTRACT
Core-collapse supernovae (CCSNe) are capable of producing large quantities of dust, with strong evidence that ejecta dust masses can grow significantly over extended periods of time. ...Red–blue asymmetries in the broad emission lines of CCSNe can be modelled using the Monte Carlo radiative transfer code damocles, to determine ejecta dust masses. To facilitate easier use of damocles, we present a Tkinter graphical user interface (GUI) running damocles. The GUI was tested by high school students through the Original Research By Young Twinkle Students programme, who used it to measure the dust masses formed at two epochs in Type IIP CCSNe, SN 2012aw and iPTF14hls, demonstrating that a wide range of people can contribute to scientific advancement. Bayesian methods quantified uncertainties on our model parameters. From the red scattering wing in the day 1863 Hα profile of SN 2012aw, we constrained the dust composition to large (radius >0.1 μm) silicate grains, with a dust mass of $6.0^{+21.9}_{-3.6}\times 10^{-4}~\mathrm{ M}_\odot$. From the day 1158 Hα profile of SN 2012aw, we found a dust mass of $3.0^{+14}_{-2.5}\times 10^{-4}$ M⊙. For iPTF14hls, we found a day 1170 dust mass of 8.1$^{+81}_{-7.6}\times 10^{-5}$ M⊙ for a dust composition consisting of 50 per cent amorphous carbon and 50 per cent astronomical silicate. At 1000 d post-explosion, SN 2012aw and iPTF14hls have formed less dust than the peculiar Type II SN 1987A, suggesting that SN 1987A may have formed a larger dust mass than typical Type IIP’s.
Deriving the physical properties of red supergiants (RSGs) depends on accurate corrections for reddening by dust. We use our recent modeling of the optical spectra of RSGs to address this topic. ...First, we find that previous broadband studies have underestimated the correction for extinction in the visible, and hence the luminosities (if derived from V); the shift in the effective wavelengths of the standard B and V bandpasses necessitates using an effective value of the ratio R'V = 4.2 to correct broadband photometry of RSGs if R sub(V) = 3.1 for early-type stars viewed through the same dust, where we have assumed the standard reddening law of Cardelli and coauthors. Use of the Fitzpatrick reddening law would lead to R'V = 3.8, as well as slightly lower values of extinction derived from spectrophotometry, but results in slightly poorer fits. Second, we find that a significant fraction of RSGs in Galactic OB associations and clusters show up to several magnitudes of excess visual extinction compared to OB stars in the same regions; we argue that this is likely due to circumstellar dust around the RSGs. We also show that the RSG dust production rate (as indicated by the 12 km excess) is well correlated with bolometric luminosity, contrary to what has been found by earlier studies. The stars with the highest amount of extra visual extinction also show significant near-UV (NUV) excesses compared to the stellar models reddened by the standard reddening law. This NUV excess is likely due to scattering of the star's light by the dust and/or a larger average grain size than that typical of grains found in the diffuse interstellar medium. Similar excesses have been attributed to circumstellar dust around R Coronae Borealis stars. Finally, we estimate that the RSGs contribute dust grains at the rate of 3 x 10 super(-8) M sub(z) yr super(-1) kpc super(-2) in the solar neighborhood, comparable to what we estimate for late-type WCs, 1 x 10 super(-7) M sub(z) yr super(-1) kpc super(-2). In the solar neighborhood this represents only a few percent of the dust production (which is dominated by low-mass AGBs), but we note that in low-metallicity starbursts, dust production by RSGs would likely dominate over other sources.
3-M syndrome is a primordial growth disorder caused by mutations in CUL7, OBSL1 or CCDC8. 3-M patients typically have a modest response to GH treatment, but the mechanism is unknown. Our aim was to ...screen 13 clinically identified 3-M families for mutations, define the status of the GH-IGF axis in 3-M children and using fibroblast cell lines assess signalling responses to GH or IGF1. Eleven CUL7, three OBSL1 and one CCDC8 mutations in nine, three and one families respectively were identified, those with CUL7 mutations being significantly shorter than those with OBSL1 or CCDC8 mutations. The majority of 3-M patients tested had normal peak serum GH and normal/low IGF1. While the generation of IGF binding proteins by 3-M cells was dysregulated, activation of STAT5b and MAPK in response to GH was normal in CUL7(-/-) cells but reduced in OBSL1(-/-) and CCDC8(-/-) cells compared with controls. Activation of AKT to IGF1 was reduced in CUL7(-/-) and OBSL1(-/-) cells at 5 min post-stimulation but normal in CCDC8(-/-) cells. The prevalence of 3-M mutations was 69% CUL7, 23% OBSL1 and 8% CCDC8. The GH-IGF axis evaluation could reflect a degree of GH resistance and/or IGF1 resistance. This is consistent with the signalling data in which the CUL7(-/-) cells showed impaired IGF1 signalling, CCDC8(-/-) cells showed impaired GH signalling and the OBSL1(-/-) cells showed impairment in both pathways. Dysregulation of the GH-IGF-IGF binding protein axis is a feature of 3-M syndrome.
Individuals born of consanguineous union have segments of their genomes that are homozygous as a result of inheriting identical ancestral genomic segments through both parents. One consequence of ...this is an increased incidence of recessive disease within these sibships. Theoretical calculations predict that 6% (1/16) of the genome of a child of first cousins will be homozygous and that the average homozygous segment will be 20 cM in size. We assessed whether these predictions held true in populations that have preferred consanguineous marriage for many generations. We found that in individuals with a recessive disease whose parents were first cousins, on average, 11% of their genomes were homozygous (n=38; range 5%–20%), with each individual bearing 20 homozygous segments exceeding 3 cM (n=38; range of number of homozygous segments 7–32), and that the size of the homozygous segment associated with recessive disease was 26 cM (n=100; range 5–70 cM). These data imply that prolonged parental inbreeding has led to a background level of homozygosity increased ∼5% over and above that predicted by simple models of consanguinity. This has important clinical and research implications.
Background
Chronic pustular dermatoses are severe and debilitating autoinflammatory conditions that can have a monogenic basis. Their clinical features are, however, complex with considerable ...overlap. Null and missense mutations in the genes encoding interleukin (IL)‐1 family (IL‐1 and IL‐36) anti‐inflammatory receptor antagonist (Ra) cytokines can underlie the development of severe pustular dermatoses.
Objective
We present a clinical and genetic study of four children of Pakistani descent with similar clinical presentations and treatment course, each of whom suffers from a severe pustular dermatosis, initially described as a pustular variant of psoriasis. We use DNA sequencing to refine the diagnosis of two of the children studied.
Methods
Bidirectional Sanger sequencing was performed on the coding regions of the IL‐1Ra and IL‐36Ra genes (IL1RN and IL36RN, respectively), for the four affected children and their parents.
Results
We identified a novel homozygous missense mutation in IL36RN in two siblings, and showed the molecular basis of the condition to be both distinct from psoriasis and distinct between the two families studied.
Conclusions
We describe a novel mutation which underpins the diagnosis of childhood pustular dermatosis. Molecular diagnostics can be used to aid the clinical diagnosis and potential treatment of autoinflammatory conditions.
Using Spitzer Space Telescope and Hubble Space Telescope observations of the superbubble N51D, we have identified three young stellar objects (YSOs) in dust globules and made the first detection of a ...Herbig-Haro object outside the Galaxy. The spectral energy distributions of these YSOs suggest young massive stars with disk, envelope, and outflow cavities. The interstellar conditions are used to assess whether the star formation was spontaneous or induced by external pressure.
We are investigating the formation and evolution of dust around the hydrogen-deficient supergiants known as R Coronae Borealis (RCB) stars. We aim to determine the connection between the probable ...merger past of these stars and their current dust-production activities.
We carried out high angular resolution interferometric observations of three RCB stars, namely RY Sgr, V CrA and V854 Cen, with the mid-infrared interferometer (MIDI) on the Very Large Telescope Interferometer (VLTI), using two telescope pairs. The baselines ranged from 30 to 60 m, allowing us to probe the dusty environment at very small spatial scales (∼50 mas or 400R
★). The observations of the RCB star dust environments were interpreted using both geometrical models and one-dimensional radiative transfer codes.
From our analysis, we find that asymmetric circumstellar material is apparent in RY Sgr, may also exist in V CrA and is possible for V854 Cen. Overall, we find that our observations are consistent with dust forming in clumps ejected randomly around the RCB star so that over time they create a spherically symmetric distribution of dust. However, we conclude that the determination of whether there is a preferred plane of dust ejection must wait until a time series of observations are obtained.
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