Dynamics around supermassive black holes

The dynamics of galactic nuclei reflects the presence of supermassive black holes (SBHs) in many ways. Single SBHs act as sinks, destroying a mass in stars equal to their own mass in roughly one relaxation time and forcing nuclei to expand. Formation of binary SBHs displaces a mass in stars roughly equal to the binary mass, creating low-density cores and ejecting hyper-velocity stars. Gravitational radiation recoil can eject coalescing binary SBHs from nuclei, resulting in offset SBHs and lopsided cores. We review recent work on these mechanisms and discuss the observable consequences.Comment: Invited talk. To appear in "2007 STScI Spring Symposium: Black Holes", eds. M. Livio & A. M. Koekemoer. (Cambridge University Press, in press) 26 pages, 12 figure

Molecular mechanisms underlying growth hormone insensitivity and idiopathic short stature

PhDShort stature can be due to several causes, including genetically transmitted insensitivity to the action of growth hormone (GHI). In approximately 80% of referred patients, no aetiology can be identified and they are classified as having idiopathic short stature (ISS). The overall aim of this thesis was to identify and characterise the molecular mechanisms of GHI and ISS. The genetic analysis of a large GHI population identified several novel defects in the GH receptor (GHR), the signal transducer and activator of transcription (STAT5b) and the acid-labile subunit (lGFALS) genes and a genotype/phenotype relationship between GHR defects and GHI severity. In approximately 20% of GHI patients a GHR splice mutation was present. An in vitro splicing assay was developed and showed to accurately identify nucleotide changes resulting in aberrant mRNA splicing. Among the splice mutations, was the one leading to the activation of a GHR pseudoexon. This defect was found to be a common cause of GHI and a translational approach using antisense oligonucleotides showed to effectively correct in vitro the aberrant GHR mRNA splicing. During the course of the project an algorithm for the search of alternative exons and pseudoexons, was developed and allowed the identification of several potential regions, two of which were demonstrated to be expressed in human liver cDNA. Identification and analysis of GHI patients with ALS deficiency caused by IGF ALS defects and the observation of short stature in their heterozygote parents, led us to hypothesise the involvement of IGF ALS in the pathogenesis of ISS. Genetic analysis of a large ISS population showed the presence of single heterozygous IGF ALS defects in 9.6% of patients and in their short stature family members. Identification of the genetic defects responsible for growth failure can shed new light on the physiology of longitudinal growth and guide therapy in children with short stature

Dynamical evolution of the young stars in the Galactic center

Recent observations of the Galactic center revealed a nuclear disk of young OB stars near the massive black hole (MBH), in addition to many similar outlying stars with higher eccentricities and/or high inclinations relative to the disk (some of them possibly belonging to a second disk). In addition, observations show the existence of young B stars (the 'S-cluster') in an isotropic distribution in the close vicinity of the MBH ($<0.04$ pc). We use extended N-body simulations to probe the dynamical evolution of these two populations. We show that the stellar disk could have evolved to its currently observed state from a thin disk of stars formed in a gaseous disk, and that the dominant component in its evolution is the interaction with stars in the cusp around the MBH. We also show that the currently observed distribution of the S-stars could be consistent with a capture origin through 3-body binary-MBH interactions. In this scenario the stars are captured at highly eccentric orbits, but scattering by stellar black holes could change their eccentricity distribution to be consistent with current observations.Comment: 5 pages, 2 figures. To appear in the proceedings of the Central Kiloparsec conference, 2008, Cret

Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis.

ObjectiveTo determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire (1)H-NMR and ultra high pressure liquid chromatography (UPLC)-MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that (1)H-NMR and UPLC-MS/MS may be promising tools for predicting response to rituximab

Leaner, Healthier, Happier Together&#8212;-A Family-Centred Approach to Weight Loss with the Overweight Dog and Her Caregivers

Obesity represents a one of the most significant healthcare issues facing human and companion animal populations worldwide. A complex relationship commonly exists between owners and their companion animal, particularly around feeding behaviour. Obese companion animals commonly live alongside caregivers who are also struggling with their own body weight. This case report highlights the importance of a family-centred approach to canine obesity as a way to engage with the pet’s caregivers to help maximize their compliance towards the successful implementation of a tailored weight loss programme. Lara, an overweight dog weighing 35 kilos with a body condition score (BCS) of 7–7.5/9, was referred for a nutritional assessment. A comprehensive, pro-active and multidisciplinary protocol, tailored towards a family-centred approach, was established. After a 16-week programme, Lara reached the target body weight. The caregivers’ compliance was assessed as being excellent; they also reassessed their individual lifestyle and were able to increase awareness towards their own nutritional issues and body weight perception, resulting in weight loss in all caregivers. Lara’s case report represents how a family-centred approach can lead to successful patient weight loss and to a modification in the caregivers’ way of thinking about nutrition and their own lifestyle, with the final goal of living a healthier and longer life together

Generalized Warped Disk Equations

The manner in which warps in accretion disks evolve depends on the magnitude of the viscosity. ... See full text for complete abstract

Designing game logics for dynamic Active Surfaces

This paper describes the development of a modular system of interactive tiles to support therapists’ in performing therapeutic activities together with impaired children in a swimming pool. Active Surfaces support mobile interactions and dynamic configuration of assemblies of tiles. Each tile represents an interactive unit, able to communicate with other tiles and to exchange data. The tiles can be assembled on a physical and logical service level to support activities of different complexity. This creates technical challenges where assemblies are re-created over time between devices with limited input and output capabilities. Furthermore, Active Surfaces challenge the concept of understandability and how users can make sense of assembled systems with no or limited output capabilities

Austerity, measles and mandatory vaccination: cross-regional analysis of vaccination in Italy 2000-14.

Background: Italy has experienced a resurgence in measles since 2015. Although much emphasis has been placed on the role of individuals opting out of vaccination, here we test the hypothesis that large budget reductions in public health spending were also a contributing factor. Methods: Multi-variate statistical models were used to assess the relationship between measles, mumps and rubella (MMR) coverage and real public health expenditure per-capita across Italy's 20 regions covering the period 2000-14. Results: Between 2010 and 2014 Italy's public health expenditure fell by over 2%, although varying among regions. Fixed effects models estimate that each 1% reduction in per-capita public health expenditure was associated with a decrease of 0.5 percentage points (95% CI: 0.36-0.65 percentage points) in MMR coverage, after adjusting for time and regional-specific time trends. The consequences can be illustrated by comparing two regions, Lazio, where public health spending fell by 5% and MMR coverage by over 3 percentage points, and Sardinia, a historically deprived region, where public health spending partly rose and MMR rates remained approximately steady. Conclusion: Adoption of austerity policies in the Italian health system was found to be significantly associated with declining vaccination rates for MMR. However, the recent introduction of mandatory vaccination for Italian children may help counteract this trend