Two-decade change in prevalence of cognitive impairment in the UK.

Identification of individuals at high risk of dementia has usually focused attention on the clinical concept of mild cognitive impairment (MCI), which captures an intermediate state between normal cognitive ageing and dementia. In many countries age specific risk of dementia has declined, but whether this is also the case for subclinical cognitive impairment is unknown. This has important implications for prevention, planning and policy. Here we describe subclinical cognitive impairment and mild dementia prevalence changes, in the UK, over 2 decades. The Cognitive Function and Ageing Studies have examined the full spectrum of cognition, from normal to dementia, in representative populations of people aged ≥ 65 years in the UK over the last 2 decades 7635 participants were interviewed in CFAS I in Cambridgeshire, Newcastle, and Nottingham in 1991, with 1457 being diagnostically assessed. In the same geographical areas, the CFAS II investigators interviewed 7796 individuals in 2011. Using established criteria, the population was categorised into seven groups: no cognitive impairment, Mild cognitive Impairment (defined using consensus criteria), other cognitive impairment no dementia without functional impairment, OCIND with functional impairment, cognitive impairment (MMSE < 24 and no functional impairment), mild dementia (MMSE < 24 with functional impairment, not captured by CFAS dementia criteria), and CFAS dementia criteria. Multinomial logistic regression, adjusted for age and sex, was used to estimate the prevalence of impairment in both studies. Results were standardized to the age-sex specific UK and global population. There is a clear increase in the prevalence of other cognitive Impairment no Dementia (without functional impairment), with the purer MCI remaining stable. In the UK, mild dementia is estimated to fall from 520,704 cases (5.7%, 95% CI 3.8, 8.1) in 1991 to 315,142 (3.0%, 95% CI 2.4, 3.8) in 2011, cognitive impairment, has fallen from 1,225,984 (13.5%, 95% CI 10.1, 17.5) to 654,436 (6.3%, 95% CI 5.4, 7.3) cases. Using additional categories which reflect the continuum of cognitive decline and impairment in populations we see that the mildest dementia declines, but that there is stability in estimates of those who meet MCI criteria. Increases were found in the Other Cognitive Impairment no Dementia group. The decline observed in severe impairment thus seems to have resulted in larger proportions of the population in milder forms, seen alongside physical illnesses

Probing CO and N_2 Snow Surfaces in Protoplanetary Disks with N_2H^+ Emission

Snowlines of major volatiles regulate the gas and solid C/N/O ratios in the planet-forming midplanes of protoplanetary disks. Snow surfaces are the 2D extensions of snowlines in the outer disk regions, where radiative heating results in an increasing temperature with disk height. CO and N_2 are two of the most abundant carriers of C, N, and O. N_2H^+ can be used to probe the snow surfaces of both molecules, because it is destroyed by CO and formed from N_2. Here we present Atacama Large Millimeter/submillimeter Array (ALMA) observations of N_2H^+ at ~0.”2–0.”4 resolution in the disks around LkCa 15, GM Aur, DM Tau, V4046 Sgr, AS 209, and IM Lup. We find two distinctive emission morphologies: N_2H^+ is either present in a bright, narrow ring surrounded by extended tenuous emission, or in a broad ring. These emission patterns can be explained by two different kinds of vertical temperature structures. Bright, narrow N_2H^+ rings are expected in disks with a thick Vertically Isothermal Region above the Midplane (VIRaM) layer (LkCa 15, GM Aur, DM Tau) where the N_2H^+ emission peaks between the CO and N_2 snowlines. Broad N_2H^+ rings come from disks with a thin VIRaM layer (V4046 Sgr, AS 209, IM Lup). We use a simple model to extract the first sets of CO and N_2 snowline pairs and corresponding freeze-out temperatures toward the disks with a thick VIRaM layer. The results reveal a range of N_2 and CO snowline radii toward stars of similar spectral type, demonstrating the need for empirically determined snowlines in disks

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Drivers of column-average CO_2 variability at Southern Hemispheric Total Carbon Column Observing Network sites

We investigate factors that drive the variability in total column CO_2 at the Total Carbon Column Observing Network sites in the Southern Hemisphere using fluxes tagged by process and by source region from the CarbonTracker analysed product as well as the Simple Biosphere model. We show that the terrestrial biosphere is the largest driver of variability in the Southern Hemisphere column CO_2. However, it does not dominate in the same fashion as in the Northern Hemisphere. Local- and hemispheric-scale biomass burning can also play an important role, particularly at the tropical site, Darwin. The magnitude of seasonal variability in the column-average dry-air mole fraction of CO_2, X_CO_2, is also much smaller in the Southern Hemisphere and comparable in magnitude to the annual increase. Comparison of measurements to the model simulations highlights that there is some discrepancy between the two time series, especially in the early part of the Darwin data record. We show that this mismatch is most likely due to erroneously estimated local fluxes in the Australian tropical region, which are associated with enhanced photosynthesis caused by early rainfall during the tropical monsoon season

Complementarity of Spike- and Rate-Based Dynamics of Neural Systems

Relationships between spiking-neuron and rate-based approaches to the dynamics of neural assemblies are explored by analyzing a model system that can be treated by both methods, with the rate-based method further averaged over multiple neurons to give a neural-field approach. The system consists of a chain of neurons, each with simple spiking dynamics that has a known rate-based equivalent. The neurons are linked by propagating activity that is described in terms of a spatial interaction strength with temporal delays that reflect distances between neurons; feedback via a separate delay loop is also included because such loops also exist in real brains. These interactions are described using a spatiotemporal coupling function that can carry either spikes or rates to provide coupling between neurons. Numerical simulation of corresponding spike- and rate-based methods with these compatible couplings then allows direct comparison between the dynamics arising from these approaches. The rate-based dynamics can reproduce two different forms of oscillation that are present in the spike-based model: spiking rates of individual neurons and network-induced modulations of spiking rate that occur if network interactions are sufficiently strong. Depending on conditions either mode of oscillation can dominate the spike-based dynamics and in some situations, particularly when the ratio of the frequencies of these two modes is integer or half-integer, the two can both be present and interact with each other

Towards a Comprehensive View of Accretion, Inner Disks, and Extinction in Classical T Tauri Stars: An ODYSSEUS Study of the Orion OB1b Association

The coevolution of T Tauri stars and their surrounding protoplanetary disks dictates the timescales of planet formation. In this paper, we present magnetospheric accretion and inner disk wall model fits to near-UV (NUV) to near-IR (NIR) spectra of nine classical T Tauri stars in Orion OB1b as part of the Outflows and Disks around Young Stars: Synergies for the Exploration of ULLYSES Spectra (ODYSSEUS) survey. Using NUV-optical spectra from the Hubble UV Legacy Library of Young Stars as Essential Standards (ULLYSES) Director's Discretionary Program and optical-NIR spectra from the PENELLOPE VLT Large Programme, we find that the accretion rates of these targets are relatively high for the region's intermediate age of 5.0 Myr; rates are in the range of (0.5-17.2) x 10(-8) M-circle dot yr(-1), with a median value of 1.2 x 10(-8) M-circle dot yr(-1). The NIR excesses can be fit with 1200-1800 K inner disk walls located at 0.05-0.10 au from the host stars. We discuss the significance of the choice in extinction law, as the measured accretion rate depends strongly on the adopted extinction value. This analysis will be extended to the complete sample of T Tauri stars being observed through ULLYSES to characterize accretion and inner disks in star-forming regions of different ages and stellar populations