206 research outputs found
Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum
Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology
The Imprint of Galaxy Formation on X-ray Clusters
It is widely believed that structure in the Universe evolves hierarchically,
as primordial density fluctuations, amplified by gravity, collapse and merge to
form progressively larger systems. The structure and evolution of X-ray
clusters, however, seems at odds with this hierarchical scenario for structure
formation. Poor clusters and groups, as well as most distant clusters detected
to date, are substantially fainter than expected from the tight relations
between luminosity, temperature and redshift predicted by these models. Here we
show that these discrepancies arise because, near the centre, the entropy of
the hot, diffuse intracluster medium (ICM) is higher tha possible if the ICM
is heated at modest redshift (z \ltsim 2) but prior to cluster collapse,
indicating that the formation of galaxies precedes that of clusters and that
most clusters have been assembled very recently.Comment: 5 pages, plus 2 postscript figures (one in colour), accepted for
publication in Natur
Underdiagnosis and referral bias of autism in ethnic minorities
This study examined (1) the distribution of ethnic minorities among children referred to autism institutions and (2) referral bias in pediatric assessment of autism in ethnic minorities. It showed that compared to the known community prevalence, ethnic minorities were under-represented among 712 children referred to autism institutions. In addition, pediatricians (n = 81) more often referred to autism when judging clinical vignettes of European majority cases (Dutch) than vignettes including non-European minority cases (Moroccan or Turkish). However, when asked explicitly for ratings of the probability of autism, the effect of ethnic background on autism diagnosis disappeared. We conclude that the use of structured ratings may decrease the likelihood of ethnic bias in diagnostic decisions of autis
Impact of T‐cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party
We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti‐thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14‐0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35‐0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA
Identifying the science and technology dimensions of emerging public policy issues through horizon scanning
Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security
Over-expression of the IGI1 leading to altered shoot-branching development related to MAX pathway in Arabidopsis
Shoot branching and growth are controlled by phytohormones such as auxin and other components in Arabidopsis. We identified a mutant (igi1) showing decreased height and bunchy branching patterns. The phenotypes reverted to the wild type in response to RNA interference with the IGI1 gene. Histochemical analysis by GUS assay revealed tissue-specific gene expression in the anther and showed that the expression levels of the IGI1 gene in apical parts, including flowers, were higher than in other parts of the plants. The auxin biosynthesis component gene, CYP79B2, was up-regulated in igi1 mutants and the IGI1 gene was down-regulated by IAA treatment. These results indicated that there is an interplay regulation between IGI1 and phytohormone auxin. Moreover, the expression of the auxin-related shoot branching regulation genes, MAX3 and MAX4, was down-regulated in igi1 mutants. Taken together, these results indicate that the overexpression of the IGI1 influenced MAX pathway in the shoot branching regulation
Dark Matter in 3D
We discuss the relevance of directional detection experiments in the
post-discovery era and propose a method to extract the local dark matter phase
space distribution from directional data. The first feature of this method is a
parameterization of the dark matter distribution function in terms of integrals
of motion, which can be analytically extended to infer properties of the global
distribution if certain equilibrium conditions hold. The second feature of our
method is a decomposition of the distribution function in moments of a model
independent basis, with minimal reliance on the ansatz for its functional form.
We illustrate our method using the Via Lactea II N-body simulation as well as
an analytical model for the dark matter halo. We conclude that O(1000) events
are necessary to measure deviations from the Standard Halo Model and constrain
or measure the presence of anisotropies.Comment: 36 pages, 13 figure
Semantic Dementia: a specific network-opathy
Semantic dementia (SD) is a unique syndrome in the frontotemporal lobar degeneration spectrum. Typically presenting as a progressive, fluent anomic aphasia, SD is the paradigmatic disorder of semantic memory with a characteristic anatomical profile of asymmetric, selective antero-inferior temporal lobe atrophy. Histopathologically, most cases show a specific pattern of abnormal deposition of protein TDP-43. This relatively close clinical, anatomical and pathological correspondence suggests SD as a promising target for future therapeutic trials. Here, we discuss outstanding nosological and neurobiological challenges posed by the syndrome and propose a pathophysiological model of SD based on sequential, regionally determined disintegration of a vulnerable neural network
Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners.
Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016
Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism
Normally, neutrophil pools are maintained by homeostatic mechanisms that require
the transcription factor C/EBPα. Inflammation, however, induces neutrophilia
through a distinct pathway of “emergency” granulopoiesis that is
dependent on C/EBPβ. Here, we show in mice that alum triggers emergency
granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R
neutralization impairs proliferative responses of hematopoietic stem and
progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM
neutrophils, raising the possibility that HSPC responses to inflammation are an
indirect result of the exhaustion of BM neutrophil stores. The induction of
neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1,
elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic
responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ,
thought to be necessary for enhanced generative capacity of BM, is dispensable
for increased proliferation of HSPC to alum or neutropenia, but plays a role in
terminal neutrophil differentiation during granulopoietic recovery. We conclude
that alum elicits a transient increase in G-CSF production via IL-1RI for the
mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF
for accelerated granulopoiesis
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