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.
Evolution of the cosmic web Cautun, Marius; van de Weygaert, Rien; Jones, Bernard J. T ...
Monthly Notices of the Royal Astronomical Society,
07/2014, Letnik:
441, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The cosmic web is the largest scale manifestation of the anisotropic gravitational collapse of matter. It represents the transitional stage between linear and non-linear structures and contains ...easily accessible information about the early phases of structure formation processes. Here we investigate the characteristics and the time evolution of morphological components. Our analysis involves the application of the NEXUS Multiscale Morphology Filter technique, predominantly its NEXUS+ version, to high resolution and large volume cosmological simulations. We quantify the cosmic web components in terms of their mass and volume content, their density distribution and halo populations. We employ new analysis techniques to determine the spatial extent of filaments and sheets, like their total length and local width. This analysis identifies clusters and filaments as the most prominent components of the web. In contrast, while voids and sheets take most of the volume, they correspond to underdense environments and are devoid of group-sized and more massive haloes. At early times the cosmos is dominated by tenuous filaments and sheets, which, during subsequent evolution, merge together, such that the present-day web is dominated by fewer, but much more massive, structures. The analysis of the mass transport between environments clearly shows how matter flows from voids into walls, and then via filaments into cluster regions, which form the nodes of the cosmic web. We also study the properties of individual filamentary branches, to find long, almost straight, filaments extending to distances larger than 100 h
−1 Mpc. These constitute the bridges between massive clusters, which seem to form along approximatively straight lines.
Although a disease of low mortality, the global impact of foot and mouth disease (FMD) is colossal due to the huge numbers of animals affected. This impact can be separated into two components: (1) ...direct losses due to reduced production and changes in herd structure; and (2) indirect losses caused by costs of FMD control, poor access to markets and limited use of improved production technologies. This paper estimates that annual impact of FMD in terms of visible production losses and vaccination in endemic regions alone amount to between US$6.5 and 21 billion. In addition, outbreaks in FMD free countries and zones cause losses of >US$1.5 billion a year.
FMD impacts are not the same throughout the world:1.FMD production losses have a big impact on the world's poorest where more people are directly dependent on livestock. FMD reduces herd fertility leading to less efficient herd structures and discourages the use of FMD susceptible, high productivity breeds. Overall the direct losses limit livestock productivity affecting food security.2.In countries with ongoing control programmes, FMD control and management creates large costs. These control programmes are often difficult to discontinue due to risks of new FMD incursion.3.The presence, or even threat, of FMD prevents access to lucrative international markets.4.In FMD free countries outbreaks occur periodically and the costs involved in regaining free status have been enormous.
FMD is highly contagious and the actions of one farmer affect the risk of FMD occurring on other holdings; thus sizeable externalities are generated. Control therefore requires coordination within and between countries. These externalities imply that FMD control produces a significant amount of public goods, justifying the need for national and international public investment.
Equipping poor countries with the tools needed to control FMD will involve the long term development of state veterinary services that in turn will deliver wider benefits to a nation including the control of other livestock diseases.
Dementia with Lewy bodies (DLB) is increasingly recognized as a common cause of dementia in older people. However, its true frequency remains unclear, with previous studies reporting a prevalence ...range from zero to 22.8% of all dementia cases. This review aimed to establish the population prevalence and incidence for DLB and to compare this to its prevalence in secondary care settings.
A literature review of all relevant population and clinical studies was conducted using PubMed. Additional references from papers found during that process were added to this.
DLB accounted for 4.2% of all diagnosed dementias in the community. In secondary care this increased to 7.5%. The incidence of DLB was 3.8% of new dementia cases. There was a significant increase in DLB diagnoses when using the revised (2005) International Consensus Criteria (ICC) for DLB compared to the original (1996) criteria.
DLB currently accounts for around one in 25 dementia cases diagnosed in the community and one in 13 cases in secondary care. The significantly higher rates of DLB in secondary care may reflect enhanced diagnostic accuracy in specialist settings and/or the increased morbidity and carer burden of the DLB syndrome compared to other dementias. However, the true prevalence is likely to be much higher because DLB diagnoses are often missed, although there is evidence that new criteria aid case identification.
The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC) highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for association to schizophrenia. After ...follow-up in independent samples, seven loci attained genome-wide significance (GWS), but multi-locus tests suggested some SNPs that did not do so represented true associations. We tested 78 of the 81 SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar disorder, and 2878 controls. In CLOZUK, we obtained significant replication to the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs for which we had data that were reported as GWS by the PGC. After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support. In bipolar disorder, we also obtained significant evidence for association for 21% of the alleles that had been associated with schizophrenia in the PGC. Our study independently confirms association to three loci previously reported to be GWS in schizophrenia, and identifies the first GWS evidence in schizophrenia for a further three loci. Given the number of independent replications and the power of our sample, we estimate 98% (confidence interval (CI) 78-100%) of the original set of 78 SNPs represent true associations. We also provide strong evidence for overlap in genetic risk between schizophrenia and bipolar disorder.
Abstract
We use very long baseline interferometry to measure the proper motions of three black hole X-ray binaries (BHXBs). Using these results together with data from the literature and Gaia DR2 to ...collate the best available constraints on proper motion, parallax, distance, and systemic radial velocity of 16 BHXBs, we determined their three-dimensional Galactocentric orbits. We extended this analysis to estimate the probability distribution for the potential kick velocity (PKV) a BHXB system could have received on formation. Constraining the kicks imparted to BHXBs provides insight into the birth mechanism of black holes (BHs). Kicks also have a significant effect on BH–BH merger rates, merger sites, and binary evolution, and can be responsible for spin–orbit misalignment in BH binary systems. 75 per cent of our systems have potential kicks $\gt 70\, \rm {km\,s^{-1}}$. This suggests that strong kicks and hence spin–orbit misalignment might be common among BHXBs, in agreement with the observed quasi-periodic X-ray variability in their power density spectra. We used a Bayesian hierarchical methodology to analyse the PKV distribution of the BHXB population, and suggest that a unimodal Gaussian model with a mean of 107 $\pm \,\,16\, \rm {km\,s^{-1}}$ is a statistically favourable fit. Such relatively high PKVs would also reduce the number of BHs likely to be retained in globular clusters. We found no significant correlation between the BH mass and PKV, suggesting a lack of correlation between BH mass and the BH birth mechanism. Our python code allows the estimation of the PKV for any system with sufficient observational constraints.
A cosmic watershed: the WVF void detection technique Platen, Erwin; Van De Weygaert, Rien; Jones, Bernard J. T.
Monthly Notices of the Royal Astronomical Society,
09/2007, Letnik:
380, Številka:
2
Journal Article
Recenzirano
Odprti dostop
On megaparsec scales the Universe is permeated by an intricate filigree of clusters, filaments, sheets and voids, the cosmic web. For the understanding of its dynamical and hierarchical history it is ...crucial to identify objectively its complex morphological components. One of the most characteristic aspects is that of the dominant underdense voids, the product of a hierarchical process driven by the collapse of minor voids in addition to the merging of large ones. In this study we present an objective void finder technique which involves a minimum of assumptions about the scale, structure and shape of voids. Our void finding method, the watershed void finder (WVF), is based upon the watershed transform, a well-known technique for the segmentation of images. Importantly, the technique has the potential to trace the existing manifestations of a void hierarchy. The basic watershed transform is augmented by a variety of correction procedures to remove spurious structure resulting from sampling noise. This study contains a detailed description of the WVF. We demonstrate how it is able to trace and identify, relatively parameter free, voids and their surrounding (filamentary and planar) boundaries. We test the technique on a set of kinematic Voronoi models, heuristic spatial models for a cellular distribution of matter. Comparison of the WVF segmentations of low-noise and high-noise Voronoi models with the quantitatively known spatial characteristics of the intrinsic Voronoi tessellation shows that the size and shape of the voids are successfully retrieved. WVF manages to even reproduce the full void size distribution function.
The analgesic efficacy and adverse effects of a single perioperative dose of dexamethasone are unclear. We performed a systematic review to evaluate the impact of a single i.v. dose of dexamethasone ...on postoperative pain and explore adverse events associated with this treatment.
MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched for randomized, controlled studies that compared dexamethasone vs placebo or an antiemetic in adult patients undergoing general anaesthesia and reported pain outcomes.
Forty-five studies involving 5796 patients receiving dexamethasone 1.25–20 mg were included. Patients receiving dexamethasone had lower pain scores at 2 h {mean difference (MD) −0.49 95% confidence interval (CI): −0.83, −0.15} and 24 h MD −0.48 (95% CI: −0.62, −0.35) after surgery. Dexamethasone-treated patients used less opioids at 2 h MD −0.87 mg morphine equivalents (95% CI: −1.40 to −0.33) and 24 h MD −2.33 mg morphine equivalents (95% CI: −4.39, −0.26), required less rescue analgesia for intolerable pain relative risk 0.80 (95% CI: 0.69, 0.93), had longer time to first dose of analgesic MD 12.06 min (95% CI: 0.80, 23.32), and shorter stays in the post-anaesthesia care unit MD −5.32 min (95% CI: −10.49 to −0.15). There was no dose–response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h MD 0.39 mmol litre−1 (95% CI: 0.04, 0.74).
A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits.
NEXUS: tracing the cosmic web connection Cautun, Marius; van de Weygaert, Rien; Jones, Bernard J. T
Monthly Notices of the Royal Astronomical Society,
02/2013, Letnik:
429, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We introduce the NEXUS algorithm for the identification of cosmic web environments: clusters, filaments, walls and voids. This is a multiscale and automatic morphological analysis tool that ...identifies all the cosmic structures in a scale free way, without preference for a certain size or shape. We develop the NEXUS method to incorporate the density, tidal field, velocity divergence and velocity shear as tracers of the cosmic web. We also present the NEXUS+ procedure which, taking advantage of a novel filtering of the density in logarithmic space, is very successful at identifying the filament and wall environments in a robust and natural way.
To assess the algorithms we apply them to an N-body simulation. We find that all methods correctly identify the most prominent filaments and walls, while there are differences in the detection of the more tenuous structures. In general, the structures traced by the density and tidal fields are clumpier and more rugged than those present in the velocity divergence and velocity shear fields. We find that the NEXUS+ method captures much better the filamentary and wall networks and is successful in detecting even the fainter structures. We also confirm the efficiency of our methods by examining the dark matter particle and halo distributions.
PDF
