Advances in neuroimaging in frontotemporal dementia

Frontotemporal dementia (FTD) is a clinically and neuroanatomically heterogeneous neurodegenerative disorder with multiple underlying genetic and pathological causes. Whilst initial neuroimaging studies highlighted the presence of frontal and temporal lobe atrophy or hypometabolism as the unifying feature in patients with FTD, more detailed studies have revealed diverse patterns across individuals, with variable frontal or temporal predominance, differing degrees of asymmetry, and the involvement of other cortical areas including the insula and cingulate, as well as subcortical structures such as the basal ganglia and thalamus. Recent advances in novel imaging modalities including diffusion tensor imaging, resting-state functional magnetic resonance imaging and molecular positron emission tomography imaging allow the possibility of investigating alterations in structural and functional connectivity and the visualisation of pathological protein deposition. This review will cover the major imaging modalities currently used in research and clinical practice, focusing on the key insights they have provided into FTD, including the onset and evolution of pathological changes and also importantly their utility as biomarkers for disease detection and staging, differential diagnosis and measurement of disease progression. Validating neuroimaging biomarkers that are able to accomplish these tasks will be crucial for the ultimate goal of powering upcoming clinical trials by correctly stratifying patient enrolment and providing sensitive markers for evaluating the effects and efficacy of disease-modifying therapies

Detailed volumetric analysis of the hypothalamus in behavioral variant frontotemporal dementia

Abnormal eating behaviors are frequently reported in behavioral variant frontotemporal dementia (bvFTD). The hypothalamus is the regulatory center for feeding and satiety but its involvement in bvFTD has not been fully clarified, partly due to its difficult identification on MR images. We measured hypothalamic volume in 18 patients with bvFTD (including 9 MAPT and 6 C9orf72 mutation carriers) and 18 cognitively normal controls using a novel optimized multimodal segmentation protocol, combining 3D T1 and T2-weighted 3T MRIs (intrarater intraclass correlation coefficients ≥0.93). The whole hypothalamus was subsequently segmented into five subunits: the anterior (superior and inferior), tuberal (superior and inferior), and posterior regions. The presence of abnormal eating behavior was assessed with the revised version of the Cambridge Behavioural Inventory (CBI-R). The bvFTD group showed a 17 % lower hypothalamic volume compared with controls (p < 0.001): mean 783 (standard deviation 113) versus 944 (73) mm(3) (corrected for total intracranial volume). In the hypothalamic subunit analysis, the superior parts of the anterior and tuberal regions and the posterior region were significantly smaller in the bvFTD group compared with controls. There was a trend for a smaller hypothalamic volume, particularly in the superior tuberal region, in those with severe eating disturbance scores on the CBI-R. Differences were seen between the two genetic subgroups with significantly smaller volumes in the MAPT but not the C9orf72 group compared with controls. In summary, bvFTD patients had lower hypothalamic volumes compared with controls. Different genetic mutations may have a differential impact on the hypothalamus

Anisotropic Structure of the Order Parameter in FeSe0.45Te0.55 Revealed by Angle Resolved Specific Heat

The symmetry and structure of the superconducting gap in the Fe-based superconductors are the central issue for understanding these novel materials. So far the experimental data and theoretical models have been highly controversial. Some experiments favor two or more constant or nearly-constant gaps, others indicate strong anisotropy and yet others suggest gap zeros ("nodes"). Theoretical models also vary, suggesting that the absence or presence of the nodes depends quantitatively on the model parameters. An opinion that has gained substantial currency is that the gap structure, unlike all other known superconductors, including cuprates, may be different in different compounds within the same family. A unique method for addressing this issue, one of the very few methods that are bulk and angle-resolved, calls for measuring the electronic specific heat in a rotating magnetic field, as a function of field orientation with respect to the crystallographic axes. In this Communication we present the first such measurement for an Fe-based high-Tc superconductor (FeBSC). We observed a fourfold oscillation of the specific heat as a function of the in-plane magnetic field direction, which allowed us to identify the locations of the gap minima (or nodes) on the Fermi surface. Our results are consistent with the expectations of an extended s-wave model with a significant gap anisotropy on the electron pockets and the gap minima along the \Gamma M (or Fe-Fe bond) direction.Comment: 32 pages, 7 figure

The role of Comprehension in Requirements and Implications for Use Case Descriptions

Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements. Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design

Actinopolyspora algeriensis sp. nov., a novel halophilic actinomycete isolated from a Saharan soil

A halophilic actinomycete strain designated H19T, was isolated from a Saharan soil in the Bamendil region (Ouargla province, South Algeria) and was characterized taxonomically by using a polyphasic approach. The morphological and chemotaxonomic characteristics of the strain were consistent with those of members of the genus Actinopolyspora, and 16S rRNA gene sequence analysis confirmed that strain H19T was a novel species of the genus Actinopolyspora. DNA–DNA hybridization value between strain H19T and the nearest Actinopolyspora species, A. halophila, was clearly below the 70 % threshold. The genotypic and phenotypic data showed that the organism represents a novel species of the genus Actinopolyspora for which the name Actinopolyspora algeriensis sp. nov. is proposed, with the type strain H19T (= DSM 45476T = CCUG 62415T)

STORIES Statement: publication standards for healthcare education evidence synthesis

Fully copy of the STORIES statement - a checklist of reporting guidance for health education evidence synthesis Structured approach for Reporting In health education of Evidence Synthesis Background Evidence synthesis techniques in healthcare education have been enhanced through the activities of experts in the field and the Best Evidence Medical Education (BEME) collaborative. Despite this, significant heterogeneity in techniques and reporting of healthcare education systematic review still exist and limit the usefulness of such reports. The aim of this project was to produce the STORIES (STructured apprOach to the Reporting In healthcare education of Evidence Synthesis) statement to offer a guide for reporting evidence synthesis in health education for use by authors and journal editors. Methods A review of existing published evidence synthesis consensus statements was undertaken. A modified Delphi process was used. In stage one, expert participants were asked to state whether common existing items identified were relevant, to suggest relevant texts and specify any items they feel should be included. The results were analysed and a second stage commenced where all synthesised items were presented and participants asked to state whether they should be included or amend as needed. After further analysis, the full statement was sent for final review and comment. Results Nineteen experts participated in the panel from 35 invitations. Thirteen text sources were proposed, six existing items amended and twelve new items synthesised. After stage two, 25 amended consensus items were proposed for inclusion. The final statement contains several items unique to this context, including description of relevant conceptual frameworks or theoretical constructs, description of qualitative methodologies with rationale for their choice and presenting the implications for educators in practice of the results obtained. Conclusions An international expert panel has agreed upon a consensus statement of 25 items for the reporting of evidence synthesis within healthcare education. This unique set of items is focused on context, rather than a specific methodology. This statement can be used for those writing for publication and reviewing such manuscripts to ensure reporting supports and best informs the wider healthcare education community

Economic and other barriers to adopting recommendations to prevent childhood obesity: results of a focus group study with parents

Abstract Background Parents are integral to the implementation of obesity prevention and management recommendations for children. Exploration of barriers to and facilitators of parental decisions to adopt obesity prevention recommendations will inform future efforts to reduce childhood obesity. Methods We conducted 4 focus groups (2 English, 2 Spanish) among a total of 19 parents of overweight (BMI &#8805; 85th percentile) children aged 5-17 years. The main discussion focused on 7 common obesity prevention recommendations: reducing television (TV) watching, removing TV from child's bedroom, increasing physically active games, participating in community or school-based athletics, walking to school, walking more in general, and eating less fast food. Parents were asked to discuss what factors would make each recommendation more difficult (barriers) or easier (facilitators) to follow. Participants were also asked about the relative importance of economic (time and dollar costs/savings) barriers and facilitators if these were not brought into the discussion unprompted. Results Parents identified many barriers but few facilitators to adopting obesity prevention recommendations for their children. Members of all groups identified economic barriers (time and dollar costs) among a variety of pertinent barriers, although the discussion of dollar costs often required prompting. Parents cited other barriers including child preference, difficulty with changing habits, lack of information, lack of transportation, difficulty with monitoring child behavior, need for assistance from family members, parity with other family members, and neighborhood walking safety. Facilitators identified included access to physical activity programs, availability of alternatives to fast food and TV which are acceptable to the child, enlisting outside support, dietary information, involving the child, setting limits, making behavior changes gradually, and parental change in shopping behaviors and own eating behaviors. Conclusions Parents identify numerous barriers to adopting obesity prevention recommendations, most notably child and family preferences and resistance to change, but also economic barriers. Intervention programs should consider the context of family priorities and how to overcome barriers and make use of relevant facilitators during program development.http://deepblue.lib.umich.edu/bitstream/2027.42/78270/1/1471-2431-9-81.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78270/2/1471-2431-9-81.pdfPeer Reviewe

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Meditation Awareness Training (MAT) for Work-related Wellbeing and Job Performance: A Randomised Controlled Trial

Due to its potential to concurrently improve work-related wellbeing (WRW) and job performance, occupational stakeholders are becoming increasingly interested in the applications of meditation. The present study conducted the first randomized controlled trial to assess the effects of meditation on outcomes relating to both WRW and job performance. Office-based middle-hierarchy managers (n = 152) received an eight-week meditation intervention (Meditation Awareness Training; MAT) or an active control intervention. MAT participants demonstrated significant and sustainable improvements (with strong effect sizes) over control-group participants in levels of work-related stress, job satisfaction, psychological distress, and employer-rated job performance. There are a number of novel implications: (i) meditation can effectuate a perceptual shift in how employees experience their work and psychological environment and may thus constitute a cost-effective WRW intervention, (ii) meditation-based (i.e., present-moment-focussed) working styles may be more effective than goal-based (i.e., future-orientated) working styles, and (iii) meditation may reduce the separation made by employees between their own interests and those of the organizations they work for