Finite state stochastic games - Existence theorems and computational procedures

Existence theorems and computational procedures for finite state stochastic game

Immunity and AAV-Mediated Gene Therapy for Muscular Dystrophies in Large Animal Models and Human Trials

Adeno-associated viral (AAV) vector-mediated gene replacement for the treatment of muscular dystrophy represents a promising therapeutic strategy in modern medicine. One major obstacle in using AAV vectors for in vivo gene delivery is the development of host immune responses to the viral capsid protein and transgene products as evidenced in animal models and human trials for a range of genetic diseases. Here, we review immunity against AAV vector and transgene in the context of gene delivery specific to muscles for treating muscular dystrophies and non-muscle diseases in large animal models and human trials, factors that influence the intensity of the immune responses, and immune modulatory strategies to prevent unwanted immune responses and induce tolerance to the vector and therapeutic gene for a successful gene therapy

The hearing of fitness to practice cases by the General Medical Council: Current trends and future research agendas

Over the last three decades a risk-based model of medical regulation has emerged in the United Kingdom. To promote a risk-averse operational culture of transparency and professional accountability the regulatory state has intervened in medical governance and introduced best-evidenced practice frameworks, audit and performance appraisal, Against this background the paper analyses descriptive statistical data pertaining to the General Medical Council’s management of the process by which fitness to practice complaints against doctors are dealt with from initial receipt through to subsequent investigative and adjudication stages. Statistical trends are outlined regarding complaint data in relation to a doctor’s gender and race and ethnicity. The data shows that there has been an increase in rehabilitative and/or punitive action against doctors. In light of its findings the paper considers what the long-term consequences may be, for both patients and doctors, of the increasing use of risk-averse administrative systems to reform medical regulation and ensure professional accountability

Movements of Translocated and Nontranslocated Canada Geese in Georgia Estimated Using Band Recoveries

Overabundant populations of resident Canada geese (Branta canadensis) are an increasing source of human-wildlife complaints throughout the species’ range. Many resident geese exploit urban areas, and translocation is one method of reducing nuisance problems associated with resident Canada geese. Translocated geese have similar harvest rates but lower survival rates than nontranslocated geese. To examine relationships between distance moved and the age, sex, and status of geese, we evaluated distances from banding sites to recovery sites for resident geese banded in Georgia, USA, during 2001–2015. We assessed potential differences in movements between rural and urban, and nontranslocated and translocated geese, by examining the distribution of band recoveries spatially. Rural and urban geese traveled similar distances; however, distances traveled by translocated geese were significantly farther than nontranslocated geese, and adults traveled significantly farther than juveniles. Our findings suggest that distances moved by resident geese are most often localized, and harvested birds were mostly recovered in-state

The night-sky at the Calar Alto Observatory II: The sky at the near infrared

We present here the characterization of the night sky-brightness at the near-infrared, the telescope seeing, and the fraction of useful time at the Calar Alto observatory. For this study we have collected a large dataset comprising 7311 near-infrared images taken regularly along the last four years for the ALHAMBRA survey (J, H and Ks-bands), together with a more reduced dataset of additional near-infrared images taken for the current study. In addition we collected the information derived by the meteorological station at the observatory during the last 10 years, together with the results from the cloud sensor for the last ~2 years. We analyze the dependency of the near-infrared night sky-brightness with the airmass and the seasons, studying its origins and proposing a zenithal correction. A strong correlation is found between the night sky-brightness in the Ks-band and the air temperature, with a gradient of ~ -0.08 mag per 1 C degree. The typical (darkest) night sky-brightness in the J, H and Ks-band are 15.95 mag (16.95 mag), 13.99 mag (14.98 mag) and 12.39 mag (13.55 mag), respectively. These values show that Calar Alto is as dark in the near-infrared as most of the other astronomical astronomical sites in the world that we could compare with. Only Mauna Kea is clearly darker in the Ks-band. The typical telescope seeing at the 3.5m is ~1.0" when converted to the V-band, being only slightly larger than the atmospheric seeing measured at the same time by the seeing monitor, ~0.9". Finally we estimate the fraction of useful time based on the relative humidity, gust wind speed and presence of clouds. This fraction, ~72%, is very similar to the one derived in Paper I, based on the fraction of time when the extinction monitor is working.Comment: 15 pages, 6 figures, accepted to be published in PAS

Immune Responses to rAAV6: The Influence of Canine Parvovirus Vaccination and Neonatal Administration of Viral Vector

Recombinant adeno-associated viral (rAAV) vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV). rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV-vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, 1 month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice