Children with Reading Disability Show Brain Differences in Effective Connectivity for Visual, but Not Auditory Word Comprehension

Background: Previous literature suggests that those with reading disability (RD) have more pronounced deficits during semantic processing in reading as compared to listening comprehension. This discrepancy has been supported by recent neuroimaging studies showing abnormal activity in RD during semantic processing in the visual but not in the auditory modality. Whether effective connectivity between brain regions in RD could also show this pattern of discrepancy has not been investigated. Methodology/Principal Findings: Children (8- to 14-year-olds) were given a semantic task in the visual and auditory modality that required an association judgment as to whether two sequentially presented words were associated. Effective connectivity was investigated using Dynamic Causal Modeling (DCM) on functional magnetic resonance imaging (fMRI) data. Bayesian Model Selection (BMS) was used separately for each modality to find a winning family of DCM models separately for typically developing (TD) and RD children. BMS yielded the same winning family with modulatory effects on bottom-up connections from the input regions to middle temporal gyrus (MTG) and inferior frontal gyrus(IFG) with inconclusive evidence regarding top-down modulations. Bayesian Model Averaging (BMA) was thus conducted across models in this winning family and compared across groups. The bottom-up effect from the fusiform gyrus (FG) to MTG rather than the top-down effect from IFG to MTG was stronger in TD compared to RD for the visual modality. The stronge

The “Flexi-Chamber”: A Novel Cost-Effective In Situ Respirometry Chamber for Coral Physiological Measurements

Coral reefs are threatened worldwide, with environmental stressors increasingly affecting the ability of reef-building corals to sustain growth from calcification (G), photosynthesis (P) and respiration (R). These processes support the foundation of coral reefs by directly influencing biogeochemical nutrient cycles and complex ecological interactions and therefore represent key knowledge required for effective reef management. However, metabolic rates are not trivial to quantify and typically rely on the use of cumbersome in situ respirometry chambers and/or the need to remove material and examine ex situ, thereby fundamentally limiting the scale, resolution and possibly the accuracy of the rate data. Here we describe a novel low-cost in situ respirometry bag that mitigates many constraints of traditional glass and plexi-glass incubation chambers. We subsequently demonstrate the effectiveness of our novel "Flexi-Chamber" approach via two case studies: 1) the Flexi-Chamber provides values of P, R and G for the reef-building coral Siderastrea cf. stellata collected from reefs close to Salvador, Brazil, which were statistically similar to values collected from a traditional glass respirometry vessel; and 2) wide-scale application of obtaining P, R and G rates for different species across different habitats to obtain inter- and intra-species differences. Our novel cost-effective design allows us to increase sampling scale of metabolic rate measurements in situ without the need for destructive sampling and thus significantly expands on existing research potential, not only for corals as we have demonstrated here, but also other important benthic groups

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue

CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R-/-) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R-/- mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Tracking economic deprivation in New Deal for Communities areas

The objects of research are lattice dynamics in fcc systems; austenitic stainless steels, hydrogenated austenitic stainless steels and superionic conductor Cu2-δSe. The thesis can be divided into three parts: modelling of lattice dynamics in austenitic stainless steels with different composition; modelling of optic modes of hydrogen vibrations in austenitic stainless steels with variation in alloying composition and hydrogen contents; investigation of structure and lattice dynamics of copper selenide Cu2-δSe compounds with different compositions. Firstly were investigated non-hydrogenated austenitic stainless steels. The experimental data phonon dispersion curves for the steels Fe-18Cr-12Ni-2Mo and Fe-18Cr-16Ni-10Mn are very similar. The Born-von-Karman model calculation together with the generalized force matrices (5 neighbouring shells) fits well to the experimental data. Using the Born-von Karman model with only two neighbouring shells and introducing the electron gas contribution instead, a significant improvement of the fit can be achieved. With this approach a satisfactory fitting with only few fitting parameters was obtained. In the further work INS study was performed on hydrogenated austenitic stainless steels. The experimental data for inelastic neutron scattering in highly hydrogenated austenitic stainless steels show significantly different results from the samples with medium and low hydrogen content. The fully hydrogenated samples have obviously a two peak structure due to the hydrogen-hydrogen interaction. In this system is used Born-von-Karman model(2 neighbour shell). In the samples with medium and low hydrogen content only one non-symmetric peak exists. Dominant term in this samples is due to influence of different alloying elements. The model which fit experimental data well is model of Einstein oscillators. The structure in α-copper selenide is determined as a function of composition . In Cu1.75Se, Cu1.78Se and Cu1.8Se at room temperature the cations occupy tetrahedral and octahedral interstices within the fcc anion sublattice. In Cu1.85Se and Cu2Se at elevated temperature no octahedral occupation has been detected, although considerable copper density is localised near the tetrahedral-octahedral boundary. The phase diagram of the system Cu-Se is not completely determined yet, especially on the low and high temperature regions. Diffraction studies gave indication that exsolution of copper in copper selenide occurs