A model to estimate the lifetime health outcomes of patients with Type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68)

<i>Aims/hypothesis</i> The aim of this study was to develop a simulation model for Type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime, in order to calculate health economic outcomes such as quality-adjusted life expectancy. <i>Methods</i> Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospective Diabetes Study (UKPDS). After examining the internal validity, the UKPDS Outcomes Model was used to simulate the mean difference in expected quality-adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control. <i>Results</i> The models forecasts fell within the 95% confidence interval for the occurrence of observed events during the UKPDS follow-up period. When the model was used to simulate event history over patients lifetimes, those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality-adjusted life years, and those receiving treatment with intensive glucose control could expect 16.62 quality-adjusted life years, a difference of 0.27 (95% CI: –0.48 to 1.03). <i>Conclusions/interpretations</i> The UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients lifetimes. Its validity in estimating outcomes in other groups of patients, however, remains to be evaluated. The model allows simulation of a range of long-term outcomes, which should assist in informing future economic evaluations of interventions in Type 2 diabetes

Strain balancing of MOVPE InAs/GaAs quantum dots using GaAs0.8P0.2

MOVPE growth of stacked InAs/ GaAs QDs with and without GaAs 0.8 P 0.2 strain balancing layers has been studied. The GaAsP layers reduce the accumulated strain whilst maintaining the electrical characteristics. This should enable closer stacking of QD layers leading to higher gain and improved laser performance

Strain Balancing of Metal-Organic Vapour Phase Epitaxy InAs/GaAs Quantum Dot Lasers

Incorporation of a GaAs0.8P0.2 layer allows strain balancing to be achieved in self-assembled InAs/GaAs quantum dots (QDs) grown by metal organic vapor phase epitaxy. Tuneable wavelength and high density are obtained through growth parameter optimization, with emission at 1.27 μm and QD layer density 3 × 10 10 cm-2. Strain balancing allows close vertical stacking (30 nm) of the QD layers, giving the potential for increased optical gain. Modeling and device characterization indicates minimal degradation in the optical and electrical characteristics unless the phosphorus percentage is increased above 20%. Laser structures are fabricated with a layer separation of 30 nm, demonstrating low temperature lasing with a threshold current density of 100 A/cm2 at 130 K without any facet coating

Distinct migratory and non-migratory ecotypes of an endemic New Zealand eleotrid (Gobiomorphus cotidianus) – implications for incipient speciation in island freshwater fish species

Background: Many postglacial lakes contain fish species with distinct ecomorphs. Similar evolutionary scenarios might be acting on evolutionarily young fish communities in lakes of remote islands. One process that drives diversification in island freshwater fish species is the colonization of depauperate freshwater environments by diadromous (migratory) taxa, which secondarily lose their migratory behaviour. The loss of migration limits dispersal and gene flow between distant populations, and, therefore, is expected to facilitate local morphological and genetic differentiation. To date, most studies have focused on interspecific relationships among migratory species and their non-migratory sister taxa. We hypothesize that the loss of migration facilitates intraspecific morphological, behavioural, and genetic differentiation between migratory and non-migratory populations of facultatively diadromous taxa, and, hence, incipient speciation of island freshwater fish species. Results: Microchemical analyses of otolith isotopes (Sr-88, Ba-137 and Ca-43) differentiated migratory and non-migratory stocks of the New Zealand endemic Gobiomorphus cotidianus McDowall (Eleotridae). Samples were taken from two rivers, one lake and two geographically-separated outgroup locations. Meristic analyses of oculoscapular lateral line canals documented a gradual reduction of these structures in the non-migratory populations. Amplified fragment length polymorphism (AFLP) fingerprints revealed considerable genetic isolation between migratory and non-migratory populations. Temporal differences in reproductive timing (migratory = winter spawners, non-migratory = summer spawners; as inferred from gonadosomatic indices) provide a prezygotic reproductive isolation mechanism between the two ecotypes. Conclusion: This study provides a holistic look at the role of diadromy in incipient speciation of island freshwater fish species. All four analytical approaches (otolith microchemistry, morphology, spawning timing, population genetics) yield congruent results, and provide clear and independent evidence for the existence of distinct migratory and non-migratory ecotypes within a river in a geographically confined range. The morphological changes within the non-migratory populations parallel interspecific patterns observed in all non-migratory New Zealand endemic Gobiomorphus species and other derived gobiid taxa, a pattern suggesting parallel evolution. This study indicates, for the first time, that distinct ecotypes of island freshwater fish species may be formed as a consequence of loss of migration and subsequent diversification. Therefore, if reproductive isolation persists, these processes may provide a mechanism to facilitate speciation

Impact of simulated nitrogen pollution on heathland microfauna, mesofauna and plants

Deposition of reactive nitrogen derived from intensive agriculture and industrial processes is a major threat to biodiversity and ecosystem services around the world; however our knowledge of the impacts of nitrogen is restricted to a very limited range of organisms. Here we examine the response of groups of microfauna (testate amoebae), mesofauna (enchytraeid worms) and plants to ammonium nitrate application in the Ruabon heathland long-term experiment. Plant data showed significant differences between treatments, particularly characterised by a loss of bryophytes in nitrogen-treated plots, by contrast enchytraeids showed a non-significant increase in abundance in response to treatment. Testate amoebae showed no significant changes in abundance or inferred biomass but significant changes in community structure with a reduced abundance of Corythion dubium, interpreted as a response to the loss of bryophytes. Our results suggest that simple indices of plant community may have value for bioindication while the bioindication value of testate amoebae and enchytraeids is not clearly demonstrated

Candidates for detecting exoplanetary radio emissions generated by magnetosphere-ionosphere coupling

In this paper we consider the magnetosphere-ionosphere (M-I) coupling at Jupiter-like exoplanets with internal plasma sources such as volcanic moons, and we have determined the best candidates for detection of these radio emissions by estimating the maximum spectral flux density expected from planets orbiting stars within 25 pc using data listed in the NASA/IPAC/NExScI Star and Exoplanet Database (NStED). In total we identify 91 potential targets, of which 40 already host planets and 51 have stellar X-ray luminosity 100 times the solar value. In general, we find that stronger planetary field strength, combined with faster rotation rate, higher stellar XUV luminosity, and lower stellar wind dynamic pressure results in higher radio power. The top two targets for each category are $\epsilon$ Eri and HIP 85523, and CPD-28 332 and FF And.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society Letter

Egg development, hatching rhythm and moult patterns in Paralomos spinosissima (Decapoda: Anomura: Paguroidea: Lithodidae) from South Georgia waters (Southern Ocean)

Larval release, hatching rhythms and moult patterns were examined in a captive population of the subantarctic lithodid, Paralomis spinosissima from the South Georgia and Shag Rocks region. Larvae hatched throughout the year with the majority of females starting to release larvae at the end of the austral summer and beginning of autumn. Larval release continued over a period of up to 9 weeks with high variability in the numbers that hatched each day. A similar seasonal pattern to hatching was evident in the moulting of females. Intermoult period for two adult females (CL = 63 and 85 mm) ranged from 894 to 1,120 days while an intermoult period for males was estimated to be in excess of 832 days. The results are consistent with other species of Paralomis and are discussed in relation to physiological and environmental adaptations to the cold-water conditions south of the Antarctic Convergence

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u