Neuroinflammation is a key part of the etio-pathogenesis of Alzheimer's disease (AD). We tested the relationship between neuroinflammation and the disruption of functional connectivity in large-scale ...networks, and their joint influence on cognitive impairment. We combined
CPK11195 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in 28 patients (12 females/16 males) with clinical diagnosis of probable AD or mild cognitive impairment with positive PET biomarker for amyloid, and 14 age-, sex-, and education-matched healthy controls (8 females/6 males). Source-based "inflammetry" was used to extract principal components of
CPK11195 PET signal variance across all participants. rs-fMRI data were preprocessed via independent component analyses to classify neuronal and non-neuronal signals. Multiple linear regression models identified sources of signal covariance between neuroinflammation and brain connectivity profiles, in relation to the diagnostic group (patients, controls) and cognitive status.Patients showed significantly higher
CPK11195 binding relative to controls, in a distributed spatial pattern including the hippocampus, frontal, and inferior temporal cortex. Patients with enhanced loading on this
CPK11195 binding distribution displayed diffuse abnormal functional connectivity. The expression of a stronger association between such abnormal connectivity and higher levels of neuroinflammation correlated with worse cognitive deficits.Our study suggests that neuroinflammation relates to the pathophysiological changes in network function that underlie cognitive deficits in Alzheimer's disease. Neuroinflammation, and its association with functionally-relevant reorganization of brain networks, is proposed as a target for emerging immunotherapeutic strategies aimed at preventing or slowing the emergence of dementia.
Neuroinflammation is an important aspect of Alzheimer's disease (AD), but it was not known whether the influence of neuroinflammation on brain network function in humans was important for cognitive deficit. Our study provides clear evidence that
neuroinflammation in AD impairs large-scale network connectivity; and that the link between neuro inflammation and functional network connectivity is relevant to cognitive impairment. We suggest that future studies should address how neuroinflammation relates to network function as AD progresses, and whether the neuroinflammation in AD is reversible, as the basis of immunotherapeutic strategies to slow the progression of AD.
We determine the low-redshift field galaxy stellar mass function (GSMF) using an area of 143 deg2 from the first three years of the Galaxy And Mass Assembly (GAMA) survey. The magnitude limits of ...this redshift survey are r < 19.4 mag over two-thirds and 19.8 mag over one-third of the area. The GSMF is determined from a sample of 5210 galaxies using a density-corrected maximum volume method. This efficiently overcomes the issue of fluctuations in the number density versus redshift. With H
0= 70 km s−1 Mpc−1, the GSMF is well described between 108 and 1011.5 M⊙ using a double Schechter function with
,
, α1=−0.35,
and α2=−1.47. This result is more robust to uncertainties in the flow-model corrected redshifts than from the shallower Sloan Digital Sky Survey main sample (r < 17.8 mag). The upturn in the GSMF is also seen directly in the i-band and K-band galaxy luminosity functions. Accurately measuring the GSMF below 108 M⊙ is possible within the GAMA survey volume but as expected requires deeper imaging data to address the contribution from low surface-brightness galaxies.
A poly(2-(dimethylamino)ethyl methacrylate) (PDMA) chain transfer agent (CTA) is used for the reversible addition–fragmentation chain transfer (RAFT) alcoholic dispersion polymerization of benzyl ...methacrylate (BzMA) in ethanol at 70 °C. THF GPC analysis indicated a well-controlled polymerization with molecular weight increasing linearly with conversion. GPC traces also showed high blocking efficiency with no homopolymer contamination apparent and M w/M n values below 1.35 in all cases. 1H NMR studies confirmed greater than 98% BzMA conversion for a target PBzMA degree of polymerization (DP) of up to 600. The PBzMA block becomes insoluble as it grows, leading to the in situ formation of sterically stabilized diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA). Fixing the mean DP of the PDMA stabilizer block at 94 units and systematically varying the DP of the PBzMA block enabled a series of spherical nanoparticles of tunable diameter to be obtained. These nanoparticles were characterized by TEM, DLS, MALLS, and SAXS, with mean diameters ranging from 35 to 100 nm. The latter technique was particularly informative: data fits to a spherical micelle model enabled calculation of the core diameter, surface area occupied per copolymer chain, and the mean aggregation number (N agg). The scaling exponent derived from a double-logarithmic plot of core diameter vs PBzMA DP suggests that the conformation of the PBzMA chains is intermediate between the collapsed and fully extended state. This is in good agreement with 1H NMR studies, which suggest that only 5−13% of the BzMA residues of the core-forming chains are solvated. The N agg values calculated from SAXS and MALLS are in good agreement and scale approximately linearly with PBzMA DP. This suggests that spherical micelles grow in size not only as a result of the increase in copolymer molecular weight during the PISA synthesis but also by exchange of individual copolymer chains between micelles and/or by sphere–sphere fusion events.
A
bstract
We present results for Higgs boson pair production with variations of the trilinear Higgs boson self coupling at next-to-leading order (NLO) in QCD including the full top quark mass ...dependence. Differential results for the LHC at 14 TeV are presented and we discuss the implications of anomalous trilinear couplings as well as differences between the Pythia and Herwig parton showers in combination with POWHEG. The implementation of the NLO QCD calculation with variable Higgs boson self coupling is made publicly available in the POWHEG-BOX-V2 Monte Carlo framework. A simple method for using the new implementation to study also variations of the top quark Yukawa coupling is described.
This review considers the origins of the errorless learning (EL) concept, its application in memory rehabilitation, the evidence for its effectiveness, and the theoretical basis for the observed ...findings. The evidence suggests that EL offers valuable benefits for at least some people with memory impairments when teaching certain types of tasks. However, the benefits are not evident for all groups, some findings are equivocal, and there are some limitations associated with this approach. We discuss methodological issues impacting on these mixed findings, consider which theoretical explanations might account for the findings regarding benefits and limitations of EL, and comment on the implications for rehabilitation practitioners of the current state of evidence in this area.
Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the ...association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort.
In this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures-bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration-were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was β = -0.11 (95% confidence interval -0.13 to -0.10, p = 3 × 10-56, FDR = 6 × 10-55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry.
In this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.
The Southern Parkes Large-Area Survey in Hydroxyl (SPLASH) is a sensitive, unbiased, and fully sampled survey of the southern Galactic plane and Galactic Centre in all four ground-state transitions ...of the hydroxyl (OH) radical. The survey provides a deep census of 1612-, 1665-, 1667-, and 1720-MHz OH absorption and emission from the Galactic interstellar medium, and is also an unbiased search for maser sources in these transitions. We present here first results from the SPLASH pilot region, which covers Galactic longitudes 334° to 344° and latitudes ±2°. Diffuse OH is widely detected in all four transitions, with optical depths that are always small (averaged over the Parkes beam), and with departures from local thermodynamic equilibrium common even in the 1665- and 1667-MHz main lines. To a 3σ sensitivity of ∼30 mK, we find no evidence of OH envelopes extending beyond the CO-bright regions of molecular cloud complexes, and conclude that the similarity of the OH excitation temperature and the level of the continuum background is at least partly responsible for this. We detect masers and maser candidates in all four transitions, approximately 50 per cent of which are new detections. This implies that SPLASH will produce a substantial increase in the known population of ground-state OH masers in the southern Galactic plane.
•Sensory gating ratio negatively correlates with fluid intelligence.•Sensory gating correlates with continuous performance and latent inhibition tasks.•Sensory gating reflects identification and ...inhibition of irrelevant stimuli.•Possible evidence for bottom-up and top-down influences on sensory gating.
Sensory gating is a neurophysiological measure of inhibition that is characterised by a reduction in the P50 event-related potential to a repeated identical stimulus. The objective of this work was to determine the cognitive mechanisms that relate to the neurological phenomenon of auditory sensory gating. Sixty participants underwent a battery of 10 cognitive tasks, including qualitatively different measures of attentional inhibition, working memory, and fluid intelligence. Participants additionally completed a paired-stimulus paradigm as a measure of auditory sensory gating. A correlational analysis revealed that several tasks correlated significantly with sensory gating. However once fluid intelligence and working memory were accounted for, only a measure of latent inhibition and accuracy scores on the continuous performance task showed significant sensitivity to sensory gating. We conclude that sensory gating reflects the identification of goal-irrelevant information at the encoding (input) stage and the subsequent ability to selectively attend to goal-relevant information based on that previous identification.
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