Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

Proactive and politically skilled professionals: What is the relationship with affective occupational commitment?

The aim of this study is to extend research on employee affective commitment in three ways: (1) instead of organizational commitment the focus is on occupational commitment; (2) the role of proactive personality on affective occupational commitment is examined; and (3) occupational satisfaction is examined as a mediator and political skills as moderator in the relationship between proactive personality and affective occupational commitment. Two connected studies, one in a hospital located in the private sector and one in a university located in the public sector, are carried out in Pakistan, drawing on a total sample of over 400 employees. The results show that proactive personality is positively related to affective occupational commitment, and that occupational satisfaction partly mediates the relationship between proactive personality and affective occupational commitment. No effect is found for a moderator effect of political skills in the relationship between proactive personality and affective occupational commitment. Political skills however moderate the relationship between proactive personality and affective organizational commitment

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Results from a randomised controlled pilot study of the Better Conversations with Primary Progressive Aphasia (BCPPA) communication partner training program for people with PPA and their communication partners

BACKGROUND: There has been a growing focus on functional communication interventions for primary progressive aphasia (PPA). These interventions aim to support individuals to participate in life situations. One such intervention, communication partner training (CPT) aims to change conversation behaviours in both the person with PPA and their communication partner (CP). CPT has a growing evidence base in stroke aphasia; however, these programmes are not designed to meet the needs of people with progressive communication difficulties. To address this, the authors developed a CPT program entitled Better Conversations with PPA (BCPPA) and undertook a pilot trial to establish for a future full trial; predicted recruitment rates, acceptability, an assessment of treatment fidelity and an appropriate primary outcome measure. METHODOLOGY: This was a single-blind, randomised controlled pilot study comparing BCPPA to no treatment, delivered across 11 National Health Service Trusts in the UK. A random sample of eight recordings of local collaborators delivering the intervention were analysed to examine fidelity. Participants completed feedback forms reporting on acceptability. Pre- and post-intervention measures targeted conversation behaviours, communication goals and quality of life. RESULTS: Eighteen people with PPA and their CPs (9 randomised to BCPPA, 9 randomised to no treatment) completed the study. Participants in the intervention group rated BCPPA positively. Treatment fidelity was 87.2%. Twenty-nine of 30 intervention goals were achieved or over-achieved and 16 of 30 coded conversation behaviours demonstrated change in the intended direction. The Aphasia Impact Questionnaire was identified as the preferred outcome measure. CONCLUSION: The first randomised controlled UK pilot study of a CPT program for people with PPA and their families demonstrates BCPPA is a promising intervention. The intervention was acceptable, treatment fidelity high and an appropriate measure identified. Results of this study indicate a future RCT of BCPPA is feasible. TRIAL REGISTRATION: Registered 28/02/2018 ISRCTN10148247

Speech and language therapy for primary progressive aphasia: Referral patterns and barriers to service provision across the UK

Objective: To assess the extent of UK speech and language therapy engagement in assessment and management of primary progressive aphasia, determine the factors contributing to any shortfall and explore a gap in the research literature on current speech and language therapy practices with people with primary progressive aphasia. // Methods: A 37-item, pilot-tested survey was distributed electronically via clinical networks and through the Royal College of Speech and Language Therapists. Survey items included questions on intervention approaches, referral numbers and demographics, referral sources and access to services. // Results: One hundred and five speech and language therapists completed the survey. Over the previous 24 months, respondents reported seeing a total of 353 people with primary progressive aphasia (an average of 3.27 per speech and language therapist). Neurologists were the most commonly reported referrers to speech and language therapy (22.5%). Seventy-eight percent of respondents reported that people with primary progressive aphasia experienced barriers to accessing speech and language therapy. Key barriers were a lack of referrer awareness of a speech and language therapist’s role, and restrictive eligibility criteria for services. // Conclusions: This study highlighted inequities in access to speech and language therapy for people with primary progressive aphasia. The medical and speech and language therapy professions need to develop appropriate care pathways for people with primary progressive aphasia. Speech and language therapists have a duty to develop a relevant evidence base for speech and language interventions for people with primary progressive aphasia

Ultrafast isomerization initiated by X-ray core ionization

Rapid proton migration is a key process in hydrocarbon photochemistry. Charge migration and subsequent proton motion can mitigate radiation damage when heavier atoms absorb X-rays. If rapid enough, this can improve the fidelity of diffract-before-destroy measurements of biomolecular structure at X-ray-free electron lasers. Here we study X-ray-initiated isomerization of acetylene, a model for proton dynamics in hydrocarbons. Our time-resolved measurements capture the transient motion of protons following X-ray ionization of carbon K-shell electrons. We Coulomb-explode the molecule with a second precisely delayed X-ray pulse and then record all the fragment momenta. These snapshots at different delays are combined into a ‘molecular movie’ of the evolving molecule, which shows substantial proton redistribution within the first 12 fs. We conclude that significant proton motion occurs on a timescale comparable to the Auger relaxation that refills the K-shell vacancy

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

Sharing vocabularies: towards horizontal alignment of values-driven business functions

This paper highlights the emergence of different ‘vocabularies’ that describe various values-driven business functions within large organisations and argues for improved horizontal alignment between them. We investigate two established functions that have long-standing organisational histories: Ethics and Compliance (E&C) and Corporate Social Responsibility (CSR). By drawing upon research on organisational alignment, we explain both the need for and the potential benefit of greater alignment between these values-driven functions. We then examine the structural and socio-cultural dimensions of organisational systems through which E&C and CSR horizontal alignment can be coordinated to improve synergies, address tensions, and generate insight to inform future research and practice in the field of Business and Society. The paper concludes with research questions that can inform future scholarly research and a practical model to guide organizations’ efforts towards inter-functional, horizontal alignment of values-driven organizational practice

Connectivity precedes function in the development of the visual word form area

What determines the cortical location at which a given functionally specific region will arise in development? We tested the hypothesis that functionally specific regions develop in their characteristic locations because of pre-existing differences in the extrinsic connectivity of that region to the rest of the brain. We exploited the visual word form area (VWFA) as a test case, scanning children with diffusion and functional imaging at age 5, before they learned to read, and at age 8, after they learned to read. We found the VWFA developed functionally in this interval and that its location in a particular child at age 8 could be predicted from that child's connectivity fingerprints (but not functional responses) at age 5. These results suggest that early connectivity instructs the functional development of the VWFA, possibly reflecting a general mechanism of cortical development.National Institutes of Health (U.S.) (Grant F32HD079169)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant F32HD079169)National Institutes of Health (U.S.) (Grant R01HD067312)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant R01HD067312

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012