Spectroscopic Survey of the Galaxy with Gaia II. The expected science yield from the Radial Velocity Spectrometer

The Gaia mission is designed as a Galaxy explorer, and will measure simultaneously, in a survey mode, the five or six phase space parameters of all stars brighter than 20th magnitude, as well as providing a description of their astrophysical characteristics. These measurements are obtained by combining an astrometric instrument with micro-arcsecond capabilities, a photometric system giving the magnitudes and colours in 15 bands and a medium resolution spectrograph named the Radial Velocity Spectrometer (RVS). The latter instrument will produce spectra in the 848 to 874 nm wavelength range, with a resolving power R = 11 500, from which radial velocities, rotational velocities, atmospheric parameters and abundances can be derived. A companion paper (Katz et al. 2004) presents the characteristics of the RVS and its performance. This paper details the outstanding scientific impact of this important part of the Gaia satellite on some key open questions in present day astrophysics. The unbiased and simultaneous acquisition of multi-epoch radial velocities and individual abundances of key elements in parallel with the astrometric parameters is essential for the determination of the dynamical state and formation history of our Galaxy. Moreover, for stars brighter than V=15, the resolving power of the RVS will give information about most of the effects which influence the position of a star in the Hertzsprung-Russell diagram, placing unprecedented constraints on the age, internal structure and evolution of stars of all types. Finally, the RVS multi-epoch observations are ideally suited to the identification, classification and characterisation of the many types of double, multiple and variable stars.Comment: 33 pages, 11 figures, in press at MNRAS. Figs 1, 3 and 9 included at reduced resolution; available in full resolution at http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1365-2966.2005.09012.

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Pair-Bonding and the Evolutionary Trajectory of Homo: Disease Avoidance as an Adaptive Trait

As the ancestors of both the great apes and humans began to separate into two lineages, several distinctions emerged and solidified for the separate genera. It is suggested here that the sequelae to sexually transmitted diseases (STDs) and subsequent behavioral tendencies to avoid sexually transmitted diseases played an important role in forging the unique character of the Australopithecine/Homo line. In particular, the advantage of pair-bonding versus promiscuity in avoiding STDs would facilitate the crystallization of both the nascent nuclear family and the man-to-child affiliative bond. In addition, the unexpectedly small sexual dimorphism of Homo is suggested to be a partial consequence of replacing (physical) dominance acquisition as a reproductive strategy with the ability and motivation to form an on-going pair-bond. The capacity of males to send and the capacity of females to receive communication signals of male reliance and competence are suggested to be a key dynamic in the separation of the hominid line from the pongids

Perspectives on Human Attachment (Pair Bonding): Eve's Unique Legacy of a Canine Analogue

The mother-child bond is undoubtedly homologous with that of other primates (and mammals). However, the man-woman pair bond and man(to)child pair bond are not paralleled by any terrestrial primate nor many mammals. Hence, knowledge of primate behavior would not be predictive of the pan-human (i) social father and (ii) the extended pair bond between a man and woman (with the cultural overlay of marriage). It is suggested that female choice of mating partner shifted in the direction of a canid analogue in which men's motivations to share resources with the female and to exhibit paternalistic behaviors were positively selected. Accordingly, it would be predicted that, compared to other terrestrial primates, the neuro-hormonal bases for the mother-child affiliative bond would be similar, but the bases of man-woman affiliative bond and the man(to)child affiliative bond would be dissimilar