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Alzheimer’s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging – Alzheimer’s Association (NIA-AA) research framework.
Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models.
1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = −.58, p < .001). Word List Delayed Recall (β = −.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = −1.13, p < .001) and 4 (β = −2.23, p < .001).
We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
The identity, richness, and abundance of true flies (Diptera) from the nests of three cavity-nesting raptors (Aves) were investigated in northern Nova Scotia, Canada. After fledging, flies were extracted from the nest material using Berlese funnels within an emergence chamber. Thirty-one species/morphospecies from 14 families were collected, including eight new records for Nova Scotia and two new records for eastern North America.
This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.
The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.
Terrestrial plant macrofossils from the sedimentary record of Lake Suigetsu, Japan, provide the only quasi-continuous direct atmospheric record of radiocarbon (14C) covering the last 50 ka cal BP (Bronk Ramsey et al. 2012). Since then, new high precision data have become available on U-Th dated speleothems from Hulu Cave China, covering the same time range (Cheng et al. 2018). In addition, an updated varve-based chronology has also been published for the 2006 core from Lake Suigetsu (SG06) based on extended microscopic analysis of the sediments and improved algorithms for interpolation (Schlolaut et al. 2018). Here we reanalyze the radiocarbon dataset from Suigetsu based on the new varve counting information and the constraints imposed by the speleothem data. This enables the new information on the calendar age scale of the Suigetsu dataset to be used in the construction of the consensus IntCal calibration curve. Comparison of the speleothem and plant macrofossil records provides insight into the mechanisms underlying the incorporation of carbon into different types of record and the relative strengths of different types of archive for calibration purposes.
At Guy's King's and St Thomas’ School of Medicine, a unique initiative is the Psychiatry Early Experience Programme (PEEP), which allows students to shadow psychiatry trainees at work several times a year. The students’ attitudes towards psychiatry and the scheme are regularly assessed and initial results are already available.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
A computational study was performed both of a single agglomerate and of the collision of two agglomerates in a shear flow. The agglomerates were extracted from a direct numerical simulation of a turbulent agglomeration process, and had the loosely packed fractal structure typical of agglomerate structures formed in turbulent agglomeration processes. The computation was performed using a discrete-element method for adhesive particles with four-way coupling, accounting both for forces between the fluid and the particles (and vice versa) as well as force transmission directly between particles via particle collisions. In addition to understanding and characterizing the particle dynamics, the study focused on illuminating the fluid flow field induced by the agglomerate in the presence of a background shear and the effect of collisions on this particle-induced flow. Perhaps the most interesting result of the current work was the observation that the flow field induced by a particle agglomerate rotating in a shear flow has the form of two tilted vortex rings with opposite-sign circulation. These rings are surrounded by a sea of stretched vorticity from the background shear flow. The agglomerate rotates in the shear flow, but at a slower rate than the ambient fluid elements. In the computations with two colliding agglomerates, we observed cases resulting in agglomerate merger, bouncing and fragmentation. However, the bouncing cases were all observed to also result in an exchange of particles between the two colliding agglomerates, so that they were influenced both by elastic rebound of the agglomerate structures as well as by tearing away of particulate matter between the agglomerates. Overall, the problems of agglomerate–flow interaction and of the collision of two agglomerates in a shear flow are considerably richer in physical phenomena and more complex than can be described by the common approximation that represents each agglomerate by an ‘equivalent sphere’.
Polyphenol oxidase (PPO) in red clover (RC) has been shown to reduce both lipolysis and proteolysis in silo and implicated (in vitro) in the rumen. However, all in vivo comparisons have compared RC with other forages, typically with lower levels of PPO, which brings in other confounding factors as to the cause for the greater protection of dietary nitrogen (N) and C18 polyunsaturated fatty acids (PUFA) on RC silage. This study compared two RC silages which when ensiled had contrasting PPO activities (RC+ and RC−) against a control of perennial ryegrass silage (PRG) to ascertain the effect of PPO activity on dietary N digestibility and PUFA biohydrogenation. Two studies were performed the first to investigate rumen and duodenal flow with six Hereford×Friesian steers, prepared with rumen and duodenal cannulae, and the second investigating whole tract N balance using six Holstein-Friesian non-lactating dairy cows. All diets were offered at a restricted level based on animal live weight with each experiment consisting of two 3×3 Latin squares using big bale silages ensiled in 2010 and 2011, respectively. For the first experiment digesta flow at the duodenum was estimated using a dual-phase marker system with ytterbium acetate and chromium ethylenediaminetetraacetic acid as particulate and liquid phase markers, respectively. Total N intake was higher on the RC silages in both experiments and higher on RC− than RC+. Rumen ammonia-N reflected intake with ammonia-N per unit of N intake lower on RC+ than RC−. Microbial N duodenal flow was comparable across all silage diets with non-microbial N higher on RC than the PRG with no difference between RC+ and RC−, even when reported on a N intake basis. C18 PUFA biohydrogenation was lower on RC silage diets than PRG but with no difference between RC+ and RC−. The N balance trial showed a greater retention of N on RC+ over RC−; however, this response is likely related to the difference in N intake over any PPO driven protection. The lack of difference between RC silages, despite contrasting levels of PPO, may reflect a similar level of protein-bound-phenol complexing determined in each RC silage. Previously this complexing has been associated with PPOs protection mechanism; however, this study has shown that protection is not related to total PPO activity.
We study a combinatorial problem that recently arose in the context of shape optimization: among all triangles with vertices
and fixed area, which one encloses the most lattice points from
? Moreover, does its shape necessarily converge to the isosceles triangle
as the area becomes large? Laugesen and Liu suggested that, in contrast to similar problems, there might not be a limiting shape. We prove that the limiting set is indeed non-trivial and contains infinitely many elements. We also show that there exist “bad” areas where no triangle is particularly good at capturing lattice points and show that there exists an infinite set of slopes
such that any associated triangle captures more lattice points than any other fixed triangle for infinitely many (and arbitrarily large) areas; this set of slopes is a fractal subset of
and has Minkowski dimension of at most
Developing countries are experiencing an increase in total demand for livestock commodities, as populations and per capita demands increase. Increased production is therefore required to meet this demand and maintain food security. Production increases will lead to proportionate increases in greenhouse gas (GHG) emissions unless offset by reductions in the emissions intensity (Ei) (i.e. the amount of GHG emitted per kg of commodity produced) of livestock production. It is therefore important to identify measures that can increase production whilst reducing Ei cost-effectively. This paper seeks to do this for smallholder agro-pastoral cattle systems in Senegal; ranging from low input to semi-intensified, they are representative of a large proportion of the national cattle production. Specifically, it identifies a shortlist of mitigation measures with potential for application to the various herd systems and estimates their GHG emissions abatement potential (using the Global Livestock Environmental Assessment Model) and cost-effectiveness. Limitations and future requirements are identified and discussed. This paper demonstrates that the Ei of meat and milk from livestock systems in a developing region can be reduced through measures that would also benefit food security, many of which are likely to be cost-beneficial. The ability to make such quantification can assist future sustainable development efforts.
Chondrichthyan teeth from a new locality in the Scottish Borders supply additional evidence of Early Carboniferous chondrichthyans in the UK. The interbedded dolostones and siltstones of the Ballagan Formation exposed along Whitrope Burn are interpreted as representing a restricted lagoonal environment that received significant amounts of land-derived sediment. This site is palynologically dated to the latest Tournaisian–early Viséan. The diverse dental fauna documented here is dominated by large crushing holocephalan toothplates, with very few, small non-crushing chondrichthyan teeth. Two new taxa are named and described. Our samples are consistent with worldwide evidence that chondrichthyan crushing faunas are common following the Hangenberg extinction event. The lagoonal habitat represented by Whitrope Burn may represent a temporary refugium that was host to a near-relict fauna dominated by large holocephalan chondrichthyans with crushing dentitions. Many of these had already become scarce in other localities by the Viséan and become extinct later in the Carboniferous. This fauna provides evidence of early endemism or niche separation within European chondrichthyan faunas at this time. This evidence points to a complex picture in which the diversity of durophagous chondrichthyans is controlled by narrow spatial shifts in niche availability over time.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
We investigated how different models of HIV transmission, and assumptions regarding the distribution of unprotected sex and syringe-sharing events (‘risk acts’), affect quantitative understanding of HIV transmission process in people who inject drugs (PWID). The individual-based model simulated HIV transmission in a dynamic sexual and injecting network representing New York City. We constructed four HIV transmission models: model 1, constant probabilities; model 2, random number of sexual and parenteral acts; model 3, viral load individual assigned; and model 4, two groups of partnerships (low and high risk). Overall, models with less heterogeneity were more sensitive to changes in numbers risk acts, producing HIV incidence up to four times higher than that empirically observed. Although all models overestimated HIV incidence, micro-simulations with greater heterogeneity in the HIV transmission modelling process produced more robust results and better reproduced empirical epidemic dynamics.
Recent Fabry-Pérot observations towards the galaxy NGC 1325 with the Southern African Large Telescope (SALT) led to the serendipitous discovery of an emission feature centered at 661.3 nm arising from material in the interstellar medium (ISM) of our Galaxy; this emission feature lies at the wavelength of one of the sharper and stronger diffuse bands normally seen in absorption. The flux of the feature is 4.2 ± 0.5 × 10−18 es−1 cm−2 arcsec−2. It appears that this is the first observation of emission from a diffuse band carrier in the ISM, excited in this case by the interstellar radiation field. We present the discovery spectra and describe follow-up measurements proposed for SALT.
Laboratory-based surveillance data is essential for monitoring trends in the incidence of enteric disease. Current Canadian human enteric surveillance systems report only confirmed cases of human enteric disease and are often unable to capture the number of negative test results. Data from 9116 hospital stool specimens from the Waterloo Region in Canada, with a mixed urban and rural population of about 500 000 were analysed to investigate the use of stool submission data and its role in reporting bias when determining the incidence of enteric disease. The proportion of stool specimens positive for Campylobacter spp. was highest in the 15–29 years age group, and in the 5–14 years age group for Salmonella spp. and E. coli O157:H7. By contrast, the age-specific incidence rates were highest for all three pathogens in the 0–4 years age group which also had the highest stool submission rate. This suggests that variations in age-specific stool submission rates are influencing current interpretation of surveillance data.
The jet of BL Lac displays transverse patterns that propagate downstream superluminally. We suggest that they are transverse Alfvén waves propagating on the longitudinal component of a helical magnetic field. The speed of the wave adds relativistically to the speed of the beam, and the apparent speed of the pattern is greater than the beam speed. Models for the jet and the MHD waves give values for the Lorentz factor of the beam of 3–4.4 and pitch angle of the helical magnetic field of 43° - 65°. These are consistent with other estimates, if the beam and pattern speeds are allowed to differ.