Mechanisms of network changes in cognitive impairment in multiple sclerosis

Background and objectives: Cognitive impairment in multiple sclerosis (MS) is associated with functional connectivity abnormalities. While there have been calls to use functional connectivity measures as biomarkers, there remains to be a full understanding of why they are affected in MS. In this cross-sectional study, we tested the hypothesis that functional network regions may be susceptible to disease-related "wear and tear" and that this can be observable on co-occurring abnormalities on other magnetic resonance metrics. We tested whether functional connectivity abnormalities in cognitively impaired patients with MS co-occur with (1) overlapping, (2) local, or (3) distal changes in anatomic connectivity and cerebral blood flow abnormalities. Methods: Multimodal 3T MRI and assessment with the Brief Repeatable Battery of Neuropsychological tests were performed in 102 patients with relapsing-remitting MS and 27 healthy controls. Patients with MS were classified as cognitively impaired if they scored ≥1.5 SDs below the control mean on ≥2 tests (n = 55) or as cognitively preserved (n = 47). Functional connectivity was assessed with Independent Component Analysis and dual regression of resting-state fMRI images. Cerebral blood flow maps were estimated, and anatomic connectivity was assessed with anatomic connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomic connectivity were assessed within resting-state networks that showed functional connectivity abnormalities in cognitively impaired patients with MS. Results: Functional connectivity was significantly decreased in the anterior and posterior default mode networks and significantly increased in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients with MS (threshold-free cluster enhancement corrected at p ≤ 0.05, 2 sided). Networks showing functional abnormalities showed altered cerebral blood flow and anatomic connectivity locally and distally but not in overlapping locations. Discussion: We provide the first evidence that functional connectivity abnormalities are accompanied by local cerebral blood flow and structural connectivity abnormalities but also demonstrate that these effects do not occur in exactly the same location. Our findings suggest a possibly shared pathologic mechanism for altered functional connectivity in brain networks in MS

From site-focused intervention towards landscape-scale surface water management using Synthetic Stream Networks and Rapid Scenario Screening

This is the final version. Available on open access from IWA Publishing via the DOI in this recordData availability statement: All relevant data are included in the paper or its Supplementary InformationThis research addresses the need to transform success in technical understanding and practical implementation of surface water management (SWM) interventions at a site-scale towards integrated landscape-scale management. We achieve this through targeting the informative preliminary stages of strategic design, where broad, early and effective exploration of opportunities can enhance and direct a regional SWM perspective. We present a new method, ‘Synthetic Stream Networks’ (SSN), capable of meeting these requirements by taking advantage of easily accessible data, likely to be available during regional screening. We find that results from the SSN are validated by existing, ‘downstream’ focused data (90% of the river network is within 30 m of an associated SSN flow path), with the added advantage of extending understanding of surface water exceedance flow paths and watersheds into the upper catchment, thus establishing a foundational and physically based sub-catchment management unit exploring surface water connectivity at a catchment and landscape scale. We also demonstrate collaborative advantages of twinning the new SSN method with ‘Rapid Scenario Screening’ (RSS) to develop a novel approach for identifying, exploring and evaluating SWM interventions. Overall, we find that this approach addresses challenges of integrating understanding from sub-catchment, catchment and landscape perspectives within surface water management.Engineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC

First measurement of the Head-Tail directional nuclear recoil signature at energies relevant to WIMP dark matter searches

We present first evidence for the so-called Head-Tail asymmetry signature of neutron-induced nuclear recoil tracks at energies down to 1.5 keV/amu using the 1m^3 DRIFT-IIc dark matter detector. This regime is appropriate for recoils induced by Weakly Interacting Massive Particle (WIMPs) but one where the differential ionization is poorly understood. We show that the distribution of recoil energies and directions induced here by Cf-252 neutrons matches well that expected from massive WIMPs. The results open a powerful new means of searching for a galactic signature from WIMPs.Comment: 4 pages, 6 figures, 1 tabl

The DRIFT Dark Matter Experiments

The current status of the DRIFT (Directional Recoil Identification From Tracks) experiment at Boulby Mine is presented, including the latest limits on the WIMP spin-dependent cross-section from 1.5 kg days of running with a mixture of CS2 and CF4. Planned upgrades to DRIFT IId are detailed, along with ongoing work towards DRIFT III, which aims to be the world's first 10 m3-scale directional Dark Matter detector.Comment: Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 201

Wholescape assessment of Water Quality status, drivers and impacts in the Exe Estuary Catchment and implications for ecosystem health and services including Shellfish Aquaculture

This is the author accepted manuscript. The final version is available from SWEEP via the URL in this recordThe appendices to this report are available in ORE at http://hdl.handle.net/10871/131805The specific aims of this investigation are to provide an assessment of the current water quality of the Exe Estuary catchment, including tributaries of the Exe Estuary (Figure 1), assessing the drivers for water quality impairment, and impacts of this on estuarine and coastal bivalve shellfish aquaculture (farming of mussels, oysters and clams). This was done through a detailed evaluation of publicly available data and information. The investigation follows a receptor-pathway-source approach to back-track from designated shellfish waters in Lyme Bay and the Exe Estuary to potential upstream sources of contaminants in the Exe Estuary catchment. When reviewing information on potential sources and drivers of water quality issues, we highlight where there are significant data gaps. This report also provides a summary of activities and actions already underway within the wider catchment designed to achieve water quality improvements and discusses potential future catchment management interventions.Natural Environment Research Council (NERC

Low Energy Electron and Nuclear Recoil Thresholds in the DRIFT-II Negative Ion TPC for Dark Matter Searches

Understanding the ability to measure and discriminate particle events at the lowest possible energy is an essential requirement in developing new experiments to search for weakly interacting massive particle (WIMP) dark matter. In this paper we detail an assessment of the potential sensitivity below 10 keV in the 1 m^3 DRIFT-II directionally sensitive, low pressure, negative ion time projection chamber (NITPC), based on event-by-event track reconstruction and calorimetry in the multiwire proportional chamber (MWPC) readout. By application of a digital smoothing polynomial it is shown that the detector is sensitive to sulfur and carbon recoils down to 2.9 and 1.9 keV respectively, and 1.2 keV for electron induced events. The energy sensitivity is demonstrated through the 5.9 keV gamma spectrum of 55Fe, where the energy resolution is sufficient to identify the escape peak. The effect a lower energy sensitivity on the WIMP exclusion limit is demonstrated. In addition to recoil direction reconstruction for WIMP searches this sensitivity suggests new prospects for applications also in KK axion searches

WIMP-nucleon cross-section results from the second science run of ZEPLIN-III

We report experimental upper limits on WIMP-nucleon elastic scattering cross sections from the second science run of ZEPLIN-III at the Boulby Underground Laboratory. A raw fiducial exposure of 1,344 kg.days was accrued over 319 days of continuous operation between June 2010 and May 2011. A total of eight events was observed in the signal acceptance region in the nuclear recoil energy range 7-29 keV, which is compatible with background expectations. This allows the exclusion of the scalar cross-section above 4.8E-8 pb near 50 GeV/c^2 WIMP mass with 90% confidence. Combined with data from the first run, this result improves to 3.9E-8 pb. The corresponding WIMP-neutron spin-dependent cross-section limit is 8.0E-3 pb. The ZEPLIN programme reaches thus its conclusion at Boulby, having deployed and exploited successfully three liquid xenon experiments of increasing reach