Ultraviolet Observations of Super-Chandrasekhar Mass Type Ia Supernova Candidates with Swift UVOT

Among Type Ia supernovae (SNe~Ia) exist a class of overluminous objects whose ejecta mass is inferred to be larger than the canonical Chandrasekhar mass. We present and discuss the UV/optical photometric light curves, colors, absolute magnitudes, and spectra of three candidate Super-Chandrasekhar mass SNe--2009dc, 2011aa, and 2012dn--observed with the Swift Ultraviolet/Optical Telescope. The light curves are at the broad end for SNe Ia, with the light curves of SN~2011aa being amongst the broadest ever observed. We find all three to have very blue colors which may provide a means of excluding these overluminous SNe from cosmological analysis, though there is some overlap with the bluest of "normal" SNe Ia. All three are overluminous in their UV absolute magnitudes compared to normal and broad SNe Ia, but SNe 2011aa and 2012dn are not optically overluminous compared to normal SNe Ia. The integrated luminosity curves of SNe 2011aa and 2012dn in the UVOT range (1600-6000 Angstroms) are only half as bright as SN~2009dc, implying a smaller 56Ni yield. While not enough to strongly affect the bolometric flux, the early time mid-UV flux makes a significant contribution at early times. The strong spectral features in the mid-UV spectra of SNe 2009dc and 2012dn suggest a higher temperature and lower opacity to be the cause of the UV excess rather than a hot, smooth blackbody from shock interaction. Further work is needed to determine the ejecta and 56Ni masses of SNe 2011aa and 2012dn and fully explain their high UV luminosities.Comment: 12 pages, 8 figures Accepted for publication in the Astrophysical Journal Data available on the Swift supernova website http://swift.gsfc.nasa.gov/docs/swift/sne/swift_sn.htm

THE 1999aa-LIKE TYPE Ia SUPERNOVA IPTF14BDN IN THE ULTRAVIOLET AND OPTICAL

We present ultraviolet (UV) and optical photometry and spectra of the 1999aa-like supernova (SN) iPTF14bdn. The UV data were observed using the Swift Ultraviolet/Optical Telescope (UVOT) and constitute the first UV spectral series of a 1999aa-like SN. From the photometry we measure $\Delta m_{15}({\it B})\,=\,0.84 \pm0.05$ mag and blue UV colors at epochs earlier than $-5$ days. The spectra show that the early-time blue colors are the result of less absorption between $2800 - 3200 \,\AA~$ than is present in normal SNe Ia. Using model spectra fits of the data at $-10$ and $+10$ days, we identify the origin of this spectral feature to be a temperature effect in which doubly ionized iron group elements create an opacity 'window'. We determine that the detection of high temperatures and large quantities of iron group elements at early epochs imply the mixing of a high Ni mass into the outer layers of the SN ejecta. We also identify the source of the I-band secondary maximum in iPTF14bdn to be the decay of Fe III to Fe II, as is seen in normal SNe Ia.Comment: 10 pages, 11 figures, 4 tables. Accepted to Ap

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated with torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with AMC5-TOR1A have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with foetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71%, with higher mortality in males. Death occurred at a median age of 1.2 months (1 week-9 years), due to respiratory failure, cardiac arrest or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity

A Profile of the Global Auto Industry: Innovation and Dynamics

This is the first book on the global auto industry viewed through the lens of technology. It starts by tracing how innovation shaped the first century of its history, then it examines the industry’s shifting footprint in Europe and North America, and the rise of new producers, particularly China. Succeeding chapters emphasize the role of suppliers in what is now a high-tech industry. This book describes new forms of collaboration that challenge traditional supply chain relations, analyzing regulation as a driver of innovation, and the enabling role of the materials science revolution, such as the shift of steel from a commodity to a highly engineered product. It covers innovations in management, from computer-aided engineering, roadmapping, and just-in-time methods to the evolving role of workers and public policy. The authors finish with an overview of electric vehicles, shared mobility, and autonomous vehicles, concluding that they will not prove disruptive

The Illusion of Inclusion: Global Inclusion, Unconscious Bias, and the Bottom Line

We may say we want to be inclusive, but what if we really don’t? What if our brains are hard-wired for selfishness and similarity and not for diversity and altruism? Having a diverse workforce is no guarantee that the work environment is inclusive. Companies hire for diversity and manage for similarity. We hire people for their difference and then teach them directly and indirectly what they have to do to fit in to the corporate culture. The Illusion of Inclusion exposes a myriad of diverse reasons why people are not more fully engaged and offers you the key to unlock the “Geometry of Inclusion”. This book takes the lid off Pandora’s box and explores the complexity of inclusion; where affinity bias or “mini-me” syndrome and the need to fit in are unconsciously blocking our ability to be inclusive. It offers a road map and an easy to comprehend model on how to minimize the impact of unconscious and conscious biases in order to embed an inclusive organizational culture