Metric to quantify white matter damage on brain magnetic resonance images

PURPOSE: Quantitative assessment of white matter hyperintensities (WMH) on structural Magnetic Resonance Imaging (MRI) is challenging. It is important to harmonise results from different software tools considering not only the volume but also the signal intensity. Here we propose and evaluate a metric of white matter (WM) damage that addresses this need. METHODS: We obtained WMH and normal-appearing white matter (NAWM) volumes from brain structural MRI from community dwelling older individuals and stroke patients enrolled in three different studies, using two automatic methods followed by manual editing by two to four observers blind to each other. We calculated the average intensity values on brain structural fluid-attenuation inversion recovery (FLAIR) MRI for the NAWM and WMH. The white matter damage metric is calculated as the proportion of WMH in brain tissue weighted by the relative image contrast of the WMH-to-NAWM. The new metric was evaluated using tissue microstructure parameters and visual ratings of small vessel disease burden and WMH: Fazekas score for WMH burden and Prins scale for WMH change. RESULTS: The correlation between the WM damage metric and the visual rating scores (Spearman ρ > =0.74, p  =0.72, p < 0.0001). The repeatability of the WM damage metric was better than WM volume (average median difference between measurements 3.26% (IQR 2.76%) and 5.88% (IQR 5.32%) respectively). The follow-up WM damage was highly related to total Prins score even when adjusted for baseline WM damage (ANCOVA, p < 0.0001), which was not always the case for WMH volume, as total Prins was highly associated with the change in the intense WMH volume (p = 0.0079, increase of 4.42 ml per unit change in total Prins, 95%CI [1.17 7.67]), but not with the change in less-intense, subtle WMH, which determined the volumetric change. CONCLUSION: The new metric is practical and simple to calculate. It is robust to variations in image processing methods and scanning protocols, and sensitive to subtle and severe white matter damage

Environment and Rural Affairs Monitoring & Modelling Programme - ERAMMP Report-60: ERAMMP Integrated Modelling Platform (IMP) Land Use Scenarios

Six scenarios consisting of changes in farm-gate prices (T1 to T6) have been applied to the ERAMMP Integrated Modelling Platform (IMP) to simulate impacts on land use change, biodiversity and ecosystem services (carbon, water quality and air quality). The scenarios were based on discussions held between stakeholders in the Evidence and Scenario subgroup (Roundtable Wales and Brexit1) and Welsh Government (WG) policy officials. These discussions took place in late 2020 before the arrangements for the UK leaving the EU were agreed, therefore are based on broad assumptions around the detail of the trade agreement with the EU as well as other third countries including Australia, New Zeland and USA. It is important to note that the outputs of these discussions which were used as inputs into the ERAMMP IMP may therefore not accurately reflect the outcomes achieved within the finalised trade agreements. The T1 scenario assumes no EU trade deal and trade liberalisation, with no tariffs applied to imported products and T2 an EU trade deal with no change to the trade arrangements with third countries. These two scenarios used the changes to farm-gate prices modelled by FAPRI2. The assumptions used in the T3 to T6 scenarios were based on expert opinion from the stakeholder group, and include impacts on farm-gate prices which potentially could have resulted from different combinations of trade deals with New Zealand, Australia and USA. Scenarios which include “no EU deal” options (T1 and T4) are no longer relevant. In no way whatsoever do T1, T3, T4, T5 and T6 represent a WG position; our understanding of the nature and impact of new and emerging trade deals has evolved significantly and the WG Trade Policy Team lead in this area. The objective of this work was to gain an early understanding of how changes in farm-gate prices potentially resulting from trading relationships may influence land use and subsequently effect entry into the Sustainable Farming Scheme. We note that many other factors are also likely to influence Welsh farmgate prices, such as (but not limited to), currency exchange rates, energy prices and extreme weather events in other parts of the world. This report provides an overview of the land use implications of all these scenarios, but focuses on the T2 scenario, which represents an EU Trade Deal. This T2 scenario is being used as the counterfactual scenario against which the costs and benefits of the land use implications of the proposed Sustainable Farming Scheme will be assessed in the Regulatory Impact Assessment for the proposed Agricultural Bill. This includes the estimated environmental outcomes of the EU Trade Deal scenario and, where the ERAMMP IMP has attached monetary valuations to these, the value of these outcomes to society. In the Cost Benefit Analysis, these monetary values will inform the overall estimated Net Present Value (NPV) of this business-as-usual counterfactual. The IMP involves many assumptions and these need to be borne in mind when interpreting and using its outcomes. By necessity, all models are a simplification of the real situation, but can still provide very useful insights if applied for a specific purpose and with caution. The collaborative and iterative consortium-based approach to co-designing the IMP has meant that Welsh Government and IMP teams have clear, open channels of communication for asking questions. This ensures that the modelling represents government aspirations as well as possible and the limits of the approach are well understood. IMP outputs for the T2 scenario show that some simulated full-time farms (>1 FTE labour) come under economic pressure (7%) and are simulated to be unable to produce a sufficient Farm Business Income to be economically viable. For these farm types, no options to transition to a more alternative profitable farm type are available and they are assumed to leave full-time agriculture. A greater number of farms transition to dairying resulting in a 75% increase in the number of dairy farms. This is associated with large increases in the number of dairy cattle (73%) and reductions in sheep (-34%). A general intensification of grassland systems is simulated resulting from the farm type transitions, with a 66% increase in temporary grasslands and a 21% decrease in permanent grasslands. Overall, these changes in agriculture and land use are simulated to lead to mixed, but predominantly negative, effects on biodiversity, increases in GHG emissions and deterioration in air and water quality. The T2 scenario predicts the least change in agriculture out of the six scenarios. T1 simulates the greatest impacts on agriculture due to significant farm-gate price reductions across dairy, beef and sheep systems, with a large number of full-time farms leaving agriculture. This leads to large increases in woodland area and generally positive effects on biodiversity and ecosystem services. T3 and T4 also simulate large impacts on agriculture. These are associated with significant farm transitions to dairy (due to increases in milk prices and significant decreases in beef and lamb prices) resulting in larger increases in GHG emissions and greater declines in air and water quality, compared to the T2 scenario. The T5 and T6 scenarios fall between these extremes, with T6 projecting the second greatest impacts on agriculture (after T1) in terms of farms under pressure. These simulated changes in agriculture are associated with net benefits for air and water quality, but net costs for GHG emissions; although these costs are lower than for scenarios T3-T5

Environment and Rural Affairs Monitoring & Modelling Programme ERAMMP - Report-32: National Forest in Wales - Evidence Review

This review was commissioned by Welsh Government (WG) from the Environment and Rural Affairs Monitoring and Modelling Programme (ERAMMP) to provide key evidence of potential benefits and disbenefits of woodland creation, woodland expansion and managing undermanaged woodland, to provide an evidence base to inform the development of a National Forest for Wales. During the commissioning process, WG emphasised that the evidence provided must reflect the collective views of the community by reviewing the literature in an objective way highlighting where evidence is contradictory or weak. Within the time available, evidence of causality of impacts, the likely timescales and magnitude of these impacts should be also be presented, for both positive and negative impacts of woodland expansion and management of undermanaged woodlands. This Evidence Pack should also build on the evidence put forward in the ERAMMP Sustainable Farm Scheme (SFS) (https://erammp.wales/en/resources) which included a range of assessments of the value of intervention measures which promoted trees within a landscape setting for a range of environmental, economic and social outcomes. The required rapid production of the review in four months meant an expert approach of key evidence was expected rather than a systematic review. Key topics to cover were selected, in partnership with WG, focussing on issues that could fundamentally change decision-making going forward. The final agreed list was arranged under a series of high-level subject headings, and the individual reviews published as ERAMMP Reports 33 to 38 and include; Biodiversity; Managing Undermanaged Woodland; Future-proofing our Woodland; Climate Change Mitigation; Ecosystem Services, and Economics and Natural Capital Accounting. An Integrated Assessment was also commissioned to provide a synthesis of cross-cutting themes and dependencies between topics. These ERAMMP reports are all provided as Annexes to this report

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Subcortical volumes across the lifespan: data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.Education and Child Studie

Podocarpaceae in tropical forests: A synthesis

The Podocarpaceae comprises 18 genera and about 173 species of evergreen, coniferous trees and shrubs. It is the most successful gymnosperm family in angiosperm-dominated tropical forests (Brodribb, this volume). Podocarps are distributed mainly in the Southern Hemisphere, with populations also extending as far north as China and Japan and to Mexico and the Caribbean in the neotropics (Dalling et al., this volume; Enright and Jaffré, this volume; Adie and Lawes, this volume)

Spectroscopic and Computational Studies of Spin States of Iron IV Nitrido and Imido Complexes

High-oxidation-state metal complexes with multiply bonded ligands are of great interest for both their reactivity as well as their fundamental bonding properties. This paper reports a combined spectroscopic and theoretical investigation into the effect of the apical multiply bonded ligand on the spin-state preferences of threefold symmetric iron­(IV) complexes with tris­(carbene) donor ligands. Specifically, singlet (<i>S</i> = 0) nitrido [{PhB­(Im^R)₃}­FeN], R = ^tBu (<b>1</b>), Mes (mesityl, <b>2</b>) and the related triplet (<i>S</i> = 1) imido complexes, [{PhB­(Im^R)₃}­Fe­(NR′)]⁺, R = Mes, R′ = 1-adamantyl (<b>3</b>), ^tBu (<b>4</b>), were investigated by electronic absorption and Mössbauer effect spectroscopies. For comparison, two other Fe­(IV) nitrido complexes, [(TIMEN^Ar)­FeN]⁺ (TIMEN^Ar = <i><b>t</b></i>ris­[2-(3-aryl-<i><b>im</b></i>idazol-2-ylidene)<i><b>e</b></i>thyl]­ami<i><b>n</b></i>e; Ar = Xyl (xylyl), Mes), were investigated by ⁵⁷Fe Mössbauer spectroscopy, including applied-field measurements. The paramagnetic imido complexes <b>3</b> and <b>4</b> were also studied by magnetic susceptibility measurements (for <b>3</b>) and paramagnetic resonance spectroscopy: high-frequency and -field electron paramagnetic resonance (for <b>3</b> and <b>4</b>) and frequency-domain Fourier-transform (FD-FT) terahertz electron paramagnetic resonance (for <b>3</b>), which reveal their zero-field splitting parameters. Experimentally correlated theoretical studies comprising ligand-field theory and quantum chemical theory, the latter including both density functional theory and ab initio methods, reveal the key role played by the Fe 3d_<i>z</i>² (a₁) orbital in these systems: the nature of its interaction with the nitrido or imido ligand dictates the spin-state preference of the complex. The ability to tune the spin state through the energy and nature of a <i>single orbital</i> has general relevance to the factors controlling spin states in complexes with applicability as single molecule devices