An image-based model of brain volume biomarker changes in Huntington's disease

Objective: Determining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into the disease progression and a quantitative tool for patient stratification. Here, we construct and present a uniquely fine-grained model of temporal progression of Huntington's disease from premanifest through to manifest stages. Methods: We employ a probabilistic event-based model to determine the sequence of appearance of atrophy in brain volumes, learned from structural MRI in the Track-HD study, as well as to estimate the uncertainty in the ordering. We use longitudinal and phenotypic data to demonstrate the utility of the patient staging system that the resulting model provides. Results: The model recovers the following order of detectable changes in brain region volumes: putamen, caudate, pallidum, insula white matter, nonventricular cerebrospinal fluid, amygdala, optic chiasm, third ventricle, posterior insula, and basal forebrain. This ordering is mostly preserved even under cross-validation of the uncertainty in the event sequence. Longitudinal analysis performed using 6 years of follow-up data from baseline confirms efficacy of the model, as subjects consistently move to later stages with time, and significant correlations are observed between the estimated stages and nonimaging phenotypic markers. Interpretation: We used a data-driven method to provide new insight into Huntington's disease progression as well as new power to stage and predict conversion. Our results highlight the potential of disease progression models, such as the event-based model, to provide new insight into Huntington's disease progression and to support fine-grained patient stratification for future precision medicine in Huntington's disease

Statistically Significant Detection of Linguistic Change

We propose a new computational approach for tracking and detecting statistically significant linguistic shifts in the meaning and usage of words. Such linguistic shifts are especially prevalent on the Internet, where the rapid exchange of ideas can quickly change a word's meaning. Our meta-analysis approach constructs property time series of word usage, and then uses statistically sound change point detection algorithms to identify significant linguistic shifts. We consider and analyze three approaches of increasing complexity to generate such linguistic property time series, the culmination of which uses distributional characteristics inferred from word co-occurrences. Using recently proposed deep neural language models, we first train vector representations of words for each time period. Second, we warp the vector spaces into one unified coordinate system. Finally, we construct a distance-based distributional time series for each word to track it's linguistic displacement over time. We demonstrate that our approach is scalable by tracking linguistic change across years of micro-blogging using Twitter, a decade of product reviews using a corpus of movie reviews from Amazon, and a century of written books using the Google Book-ngrams. Our analysis reveals interesting patterns of language usage change commensurate with each medium.Comment: 11 pages, 7 figures, 4 table

Editorial: An ombar perspective on the united nations' decade of ocean science for sustainable development

The year 2021 saw the start of the UN Decade of Ocean Science for Sustainable Development. Ocean and coastal ecosystems play crucial roles in supporting our planet and our lives, from regulating climate and protecting shorelines, to providing food and employment. The UN estimates that billions of people rely on the ocean for their livelihoods. The First Global Integrated Marine Assessment (World Ocean Assessment I), published by the United Nations in 2016 (UN 2016), flagged that much of the ocean was severely degraded. The second (WOAII), released last year, suggests that the situation has not improved (UN 2021). The UN Climate Change Conference (COP26) in Glasgow demonstrated that the world’s oceans and its species and ecosystems are under immense pressure from climate change. The UN Decade of Ocean Science is a call to arms for scientists and others to deliver research to enable societal outcomes which include a clean ocean, a healthy and resilient ocean, a predicted ocean, a safe ocean, a sustainably harvested and productive ocean and a transparent and accessible ocean. These are lofty ambitions, but can they be realised in a ten-year programme that has no funding attached to it? This question is particularly relevant when one considers the starting point and how little progress has been made in addressing other major global environmental issues such as the climate crisis

How do MNC R&D laboratory roles affect employee international assignments?

Research and development (R&D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&D laboratories in which these employees work on the international assignments they undertake. We categorise R&D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

Do Harmonised Accounting Standards Lead to Harmonised

The objective of this paper is to investigate the level of harmonisation for IAS 39 Financial Instruments: Recognition and Measurement and to identify if different levels of harmonisation are associated with company-specific factors. Based on Rahman et al. (2002), we used the Jaccard (JACC) index to determine the level of harmonisation between IAS 39 and the financial reporting practice of a broad-based sample of European-listed companies in 2005.We applied regression analysis to identify companies’ specific characteristics that affect the level of convergence of the reporting practice of financial instruments. The results of this study show a high level of harmonisation between accounting practices of European companies included in our sample and IAS 39

Covariant Lagrange multiplier constrained higher derivative gravity with scalar projectors

We formulate higher derivative gravity with Lagrange multiplier constraint and scalar projectors. Its gauge-fixed formulation as well as vector fields formulation is developed and corresponding spontaneous Lorentz symmetry breaking is investigated. We show that the only propagating mode is higher derivative graviton while scalar and vector modes do not propagate. Despite to higher derivatives structure of the action, its first FRW equation is the first order differential equation which admits the inflationary universe solution.Comment: Physics Letters B published version. LaTeX 12 page

Using motivational techniques to reduce cardiometabolic risk factors in long term psychiatric inpatients: A naturalistic interventional study

Background People with severe mental illness have markedly reduced life expectancy; cardiometabolic disease is a major cause. Psychiatric hospital inpatients have elevated levels of cardiometabolic risk factors and are to a high degree dependent of the routines and facilities of the institutions. Studies of lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients are few. The current study aimed at assessing the feasibility and effects of a lifestyle intervention including Motivational Interviewing (MI) on physical activity levels, cardiometabolic risk status and mental health status in psychotic disorder inpatients. Methods Prospective naturalistic intervention study of 83 patients at long term inpatient psychosis treatment wards in South-Eastern Norway. Patients were assessed 3–6 months prior to, at start and 6 months after a life-style intervention program including training of staff in MI, simple changes in routines and improvements of facilities for physical exercise. Assessments were done by clinical staff and included level of physical activity, motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as well as anthropometric and biochemical markers of cardiometabolic risk. A mixed model was applied to analyze change over time. Results A total of 88% of patients received MI interventions, with a mean of 2.5 MI interventions per week per patient. The physical activity level was not increased, but activity level was positively associated with motivation and negatively associated with positive symptoms. Triglyceride levels and number of smokers were significantly reduced and a significant decrease in symptom levels was observed. Conclusions The current results suggest that a simple, low cost life-style intervention program focusing on motivational change is feasible and may reduce symptoms and improve lifestyle habits in psychosis patients in long term treatment facilities. Similar programs may easily be implemented in other psychiatric hospitals.submittedVersio

Metal-Organic Nanosheets Formed via Defect-Mediated Transformation of a Hafnium Metal-Organic Framework

We report a hafnium-containing MOF, hcp UiO-67(Hf), which is a ligand-deficient layered analogue of the face-centered cubic fcu UiO-67(Hf). hcp UiO-67 accommodates its lower ligand:metal ratio compared to fcu UiO-67 through a new structural mechanism: the formation of a condensed "double cluster" (Hf$_{12}$O$_{8}$(OH)$_{14}$), analogous to the condensation of coordination polyhedra in oxide frameworks. In oxide frameworks, variable stoichiometry can lead to more complex defect structures, e.g., crystallographic shear planes or modules with differing compositions, which can be the source of further chemical reactivity; likewise, the layered hcp UiO-67 can react further to reversibly form a two-dimensional metal-organic framework, hxl UiO-67. Both three-dimensional hcp UiO-67 and two-dimensional hxl UiO-67 can be delaminated to form metal-organic nanosheets. Delamination of hcp UiO-67 occurs through the cleavage of strong hafnium-carboxylate bonds and is effected under mild conditions, suggesting that defect-ordered MOFs could be a productive route to porous two-dimensional materials.M.J.C. was supported by Sidney Sussex College, Cambridge; M.J.C., J.A.H., and A.L.G. were supported by the European Research Council (279705); and J.L., A.C.F., E.C.-M., and C.P.G. were supported by the Engineering and Physical Sciences Research Council (U.K.) under the Supergen Consortium and Grant (EP/N001583/1). D.F.-J. thanks the Royal Society for funding through a University Research Fellowship. The Diamond Light Source Ltd. (beamlines I11 (EE9940, EE15118), I12 (EE12554), and I15 (EE13681, EE13843) is thanked for providing beamtime. Via our membership of the UK’s HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202), this work used the ARCHER UK National Supercomputing Service (http://www.archer.ac.uk). Part of this work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council

Executive cash compensation and tax aggressiveness of Chinese firms

We examine the influence of corporate compensation policies on firms’ tax aggressiveness in an emerging market where executive compensation is primarily in cash form. Based on a hand-collected dataset of 958 firm-year observations of Chinese listed firms for the 2006-2012 period, we find that firms paying higher executive cash compensation are associated with lower tax aggressiveness. This relationship also holds for the excess cash compensation measures which control for executive shareholding, firm profitability, size, growth opportunity, and board independence. We further document that mutual funds ownership pressure firms paying higher compensation to reduce their tax aggressiveness, suggesting adverse selection by mutual funds on firms exhibiting risky tax avoidance activities. High leverage offsets the negative link between cash compensation and tax aggressiveness, indicating a complementary effect between debt and tax avoidance, and, hence, suggesting that creditor monitoring is weak. These results are robust to the system-GMM estimation, which simultaneously account for the endogeneity of executive compensation, tax aggressiveness, ownership and control, leverage, and corporate governance. Our findings on Chinese firms have important policy implications for developing countries around the world with concentrated ownership structure, weak institutional environment, widespread corruption, ineffective rule of law, and ongoing significant social and political transformation