Massive Stars in the Quintuplet Cluster

We present near-infrared photometry and K-band spectra of newly-identified massive stars in the Quintuplet Cluster, one of the three massive clusters projected within 50 pc of the Galactic Center. We find that the cluster contains a variety of massive stars, including more unambiguously identified Wolf-Rayet stars than any cluster in the Galaxy, and over a dozen stars in earlier stages of evolution, i.e., LBV, Ofpe/WN9, and OB supergiants. One newly identified star is the second ``Luminous Blue Variable'' in the cluster, after the ``Pistol Star.'' Given the evolutionary stages of the identified stars, the cluster appears to be about 4 \pm 1 Myr old, assuming coeval formation. The total mass in observed stars is \sim 10^3 \Msun, and the implied mass is \sim 10^4 \Msun, assuming a lower mass cutoff of 1 \Msun and a Salpeter initial mass function. The implied mass density in stars is at least a few thousand \Msun pc^{-3}. The newly-identified stars increase the estimated ionizing flux from this cluster by about an order of magnitude with respect to earlier estimates, to 10^{50.9} photons/s, or roughly what is required to ionize the nearby ``Sickle'' HII region (G0.18 - 0.04). The total luminosity from the massive cluster stars is $\approx 10^{7.5}$ \Lsun, enough to account for the heating of the nearby molecular cloud, M0.20 - 0.033. We propose a picture which integrates most of the major features in this part of the sky, excepting the non-thermal filaments. We compare the cluster to other young massive clusters and globular clusters, finding that it is unique in stellar content and age, except, perhaps, for the young cluster in the central parsec of the Galaxy. In addition, we find that the cluster is comparable to small ``super star clusters.'

Identification and prioritisation of sustainability issues for the UK precast concrete industry

As part of its strategy for more sustainable construction, the UK Government has been encouraging sector representative bodies and trade associations to develop sector sustainability strategies. A four-year research programme aimed at developing such a strategy for the precast concrete industry was therefore established by the British Precast Concrete Federation in 2004, in collaboration with the Department of Civil and Building Engineering at Loughborough University. In accordance with best practice, the research began with the identification and prioritisation of sustainability issues for the precast industry. A facilitated workshop with key practitioners from the industry identified a series of key business issues for the industry and demonstrated that sustainability was intrinsically linked to the profitability and competitiveness of the industry. A questionnaire survey was then conducted to verify and prioritise these issues across the wider industry. Whilst the survey verified the issues, priorities were found to vary between groups of companies as a result of them being in different phases of a corporate sustainability model. The research has enabled priorities for the precast sector sustainability strategy to be identified which will facilitate progress towards a more sustainable precast concrete industry in the UK

Healthcare recommendations for Joubert syndrome

Joubert syndrome (JS) is a recessive neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation recognizable on axial brain magnetic resonance imaging as the "Molar Tooth Sign". Although defined by the neurological features, JS is associated with clinical features affecting many other organ systems, particularly progressive involvement of the retina, kidney, and liver. JS is a rare condition; therefore, many affected individuals may not have easy access to subspecialty providers familiar with JS (e.g., geneticists, neurologists, developmental pediatricians, ophthalmologists, nephrologists, hepatologists, psychiatrists, therapists, and educators). Expert recommendations can enable practitioners of all types to provide quality care to individuals with JS and know when to refer for subspecialty care. This need will only increase as precision treatments targeting specific genetic causes of JS emerge. The goal of these recommendations is to provide a resource for general practitioners, subspecialists, and families to maximize the health of individuals with JS throughout the lifespan

Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine

Genotype-phenotype correlation at codon 1740 ofSETD2

The SET domain containing 2, histone lysine methyltransferase encoded by SETD2 is a dual-function methyltransferase for histones and microtubules and plays an important role for transcriptional regulation, genomic stability, and cytoskeletal functions. Specifically, SETD2 is associated with trimethylation of histone H3 at lysine 36 (H3K36me3) and methylation of α-tubulin at lysine 40. Heterozygous loss of function and missense variants have previously been described with Luscan-Lumish syndrome (LLS), which is characterized by overgrowth, neurodevelopmental features, and absence of overt congenital anomalies. We have identified 15 individuals with de novo variants in codon 1740 of SETD2 whose features differ from those with LLS. Group 1 consists of 12 individuals with heterozygous variant c.5218C>T p.(Arg1740Trp) and Group 2 consists of 3 individuals with heterozygous variant c.5219G>A p.(Arg1740Gln). The phenotype of Group 1 includes microcephaly, profound intellectual disability, congenital anomalies affecting several organ systems, and similar facial features. Individuals in Group 2 had moderate to severe intellectual disability, low normal head circumference, and absence of additional major congenital anomalies. While LLS is likely due to loss of function of SETD2, the clinical features seen in individuals with variants affecting codon 1740 are more severe suggesting an alternative mechanism, such as gain of function, effects on epigenetic regulation, or posttranslational modification of the cytoskeleton. Our report is a prime example of different mutations in the same gene causing diverging phenotypes and the features observed in Group 1 suggest a new clinically recognizable syndrome uniquely associated with the heterozygous variant c.5218C>T p.(Arg1740Trp) in SETD2