Two-Dimensional Helioseismic Power, Phase, and Coherence Spectra of {\it Solar Dynamics Observatory} Photospheric and Chromospheric Observables

While the {\it Helioseismic and Magnetic Imager} (HMI) onboard the {\it Solar Dynamics Observatory} (SDO) provides Doppler velocity [$V$], continuum intensity [$I_C$], and line-depth [$Ld$] observations, each of which is sensitive to the five-minute acoustic spectrum, the {\it Atmospheric Imaging Array} (AIA) also observes at wavelengths -- specifically the 1600 and 1700 Angstrom bands -- that are partly formed in the upper photosphere and have good sensitivity to acoustic modes. In this article we consider the characteristics of the spatio--temporal Fourier spectra in AIA and HMI observables for a 15-degree region around NOAA Active Region 11072. We map the spatio--temporal-power distribution for the different observables and the HMI Line Core [$I_L$], or Continuum minus Line Depth, and the phase and coherence functions for selected observable pairs, as a function of position and frequency. Five-minute oscillation power in all observables is suppressed in the sunspot and also in plage areas. Above the acoustic cut-off frequency, the behaviour is more complicated: power in HMI $I_C$ is still suppressed in the presence of surface magnetic fields, while power in HMI $I_L$ and the AIA bands is suppressed in areas of surface field but enhanced in an extended area around the active region, and power in HMI $V$ is enhanced in a narrow zone around strong-field concentrations and suppressed in a wider surrounding area. The relative phase of the observables, and their cross-coherence functions, are also altered around the active region. These effects may help us to understand the interaction of waves and magnetic fields in the different layers of the photosphere, and will need to be taken into account in multi-wavelength local helioseismic analysis of active regions.Comment: 18 pages, 15 figures, to be published in Solar Physic

Aggregates, Formational Emergence, and the Focus on Practice in Stone Artifact Archaeology

The stone artifact record has been one of the major grounds for investigating our evolution. With the predominant focus on their morphological attributes and technological aspects of manufacture, stone artifacts and their assemblages have been analyzed as explicit measures of past behaviors, adaptations, and population histories. This analytical focus on technological andmorphological appearance is one of the characteristics of the conventional approach for constructing inferences from this record. An equally persistent routine involves ascribing the emerged patterns and variability within the archaeological deposits directly to long-term central tendencies in human actions and cultural transmission. Here we re-evaluate this conventional approach. By invoking some of the known concerns and concepts about the formation of archaeological record, we introduce notions of aggregates and formational emergence to expand on the understanding of how artifacts accumulate, what these accumulations represent, and how the patterns and variability among them emerge. To infer behavior that could inform on past lifeways, we further promote a shift in the focus of analysis from the technological and morphological appearance of artifacts and assemblages to the practice of stone use. We argue for a more rigorous and multi-level inferential procedure in modeling behavioral adaptation and evolution

Major Fallacies Surrounding Stone Artifacts and Assemblages

While lithic objects can potentially inform us about past adaptations and behaviors, it is important to develop a comprehensive understanding of all of the various processes that influence what we recover from the archaeological record. We argue here that many assumptions used by archaeologists to derive behavioral inferences through the definition, conceptualization, and interpretation of both individual stone artifact forms and groups of artifacts identified as assemblages do not fit squarely with what we have learned from both ethnographic sources and analyses of archaeological materials. We discuss this in terms of two fallacies. The first is the fallacy of the “desired end product” in stone artifact manufacture, which also includes our ability to recognize such end products. The second fallacy has to do with the notions that lithic assemblages represent simple accumulations of contemporary behaviors and the degree to which the composition of the depositional units we study reliably match the kinds of activities that took place. Although it is beyond the scope of this paper to offer a comprehensive set of new methodologies and theoretical perspectives to solve these problems, our goal here is to stress the importance of rethinking some of our most basic assumptions regarding the nature of lithic objects and how they become part of the archaeological record. Such a revision is needed if we want to be able to develop research questions that can be addressed with the data we have available to us

Prominent microglial inclusions in transgenic mouse models of α-synucleinopathy that are distinct from neuronal lesions.

Alpha-synucleinopathies are a group of progressive neurodegenerative disorders, characterized by intracellular deposits of aggregated α-synuclein (αS). The clinical heterogeneity of these diseases is thought to be attributed to conformers (or strains) of αS but the contribution of inclusions in various cell types is unclear. The aim of the present work was to study αS conformers among different transgenic (TG) mouse models of α-synucleinopathies. To this end, four different TG mouse models were studied (Prnp-h[A53T]αS; Thy1-h[A53T]αS; Thy1-h[A30P]αS; Thy1-mαS) that overexpress human or murine αS and differed in their age-of-symptom onset and subsequent disease progression. Postmortem analysis of end-stage brains revealed robust neuronal αS pathology as evidenced by accumulation of αS serine 129 (p-αS) phosphorylation in the brainstem of all four TG mouse lines. Overall appearance of the pathology was similar and only modest differences were observed among additionally affected brain regions. To study αS conformers in these mice, we used pentameric formyl thiophene acetic acid (pFTAA), a fluorescent dye with amyloid conformation-dependent spectral properties. Unexpectedly, besides the neuronal αS pathology, we also found abundant pFTAA-positive inclusions in microglia of all four TG mouse lines. These microglial inclusions were also positive for Thioflavin S and showed immunoreactivity with antibodies recognizing the N-terminus of αS, but were largely p-αS-negative. In all four lines, spectral pFTAA analysis revealed conformational differences between microglia and neuronal inclusions but not among the different mouse models. Concomitant with neuronal lesions, microglial inclusions were already present at presymptomatic stages and could also be induced by seeded αS aggregation. Although nature and significance of microglial inclusions for human α-synucleinopathies remain to be clarified, the previously overlooked abundance of microglial inclusions in TG mouse models of α-synucleinopathy bears importance for mechanistic and preclinical-translational studies

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Rehabilitation of memory following brain injury (ReMemBrIn): study protocol for a randomised controlled trial

Background Impairments of memory are commonly reported by people with traumatic brain injuries (TBI). Such deficits are persistent, debilitating, and can severely impact quality of life. Currently, many do not routinely receive follow-up appointments for residual memory problems following discharge. Methods/Design This is a multi-centre, randomised controlled trial investigating the clinical and cost-effectiveness of a group-based memory rehabilitation programme. Three hundred and twelve people with a traumatic brain injury will be randomised from four centres. Participants will be eligible if they had a traumatic brain injury more than 3 months prior to recruitment, have memory problems, are 18 to 69 years of age, are able to travel to one of our centres and attend group sessions, and are able to give informed consent. Participants will be randomised in clusters of 4 to 6 to the group rehabilitation intervention or to usual care. Intervention groups will receive 10 weekly sessions of a manualised memory rehabilitation programme, which has been developed in previous pilot studies. The intervention will include restitution strategies to retrain impaired memory functions and compensation strategies to enable participants to cope with their memory problems. All participants will receive a follow-up postal questionnaire and an assessment by a research assistant at 6 and 12 months post-randomisation. The primary outcome is the Everyday Memory Questionnaire at 6 months. Secondary outcomes include the Rivermead Behavioural Memory Test-3, General Health Questionnaire-30, health related quality of life, cost-effectiveness analysis determined by the EQ-5D and a service use questionnaire, individual goal attainment, European Brain Injury Questionnaire (patient and relative versions), and the Everyday Memory Questionnaire-relative version. The primary analysis will be based on intention to treat. A mixed-model regression analysis of the Everyday Memory Questionnaire at 6 months will be used to estimate the effect of the group memory rehabilitation programme. Discussion The study will hopefully provide robust evidence regarding the clinical and cost-effectiveness of a group-based memory rehabilitation intervention for civilians and military personnel following TBI. We discuss our decision-making regarding choice of outcome measures and control group, and the unique challenges to recruiting people with memory problems to trials

A pleiotropic missense variant in SLC39A8 is associated with Crohn's disease and human gut microbiome composition

Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA)

A scoping study of interventions to increase the uptake of physical activity (PA) amongst individuals with mild-to-moderate depression (MMD)

Background - Depression is the largest contributor to disease burden globally. The evidence favouring physical activity as a treatment for mild-to-moderate depression is extensive and relatively uncontested. It is unclear, however, how to increase an uptake of physical activity amongst individuals experiencing mild-to-moderate depression. This leaves professionals with no guidance on how to help people experiencing mild-to-moderate depression to take up physical activity. The purpose of this study was to scope the evidence on interventions to increase the uptake of physical activity amongst individuals experiencing mild-to-moderate depression, and to develop a model of the mechanisms by which they are hypothesised to work. Methods - A scoping study was designed to include a review of primary studies, grey literature and six consultation exercises; two with individuals with experience of depression, two pre-project consultations with physical activity, mental health and literature review experts, one with public health experts, and one with community engagement experts. Results - Ten papers met the inclusion criteria and were included in the review. Consultation exercises provided insights into the mechanisms of an uptake of physical activity amongst individuals experiencing mild-to-moderate depression; evidence concerning those mechanisms is (a) fragmented in terms of design and purpose; (b) of varied quality; (c) rarely explicit about the mechanisms through which the interventions are thought to work. Physical, environmental and social factors that may represent mediating variables in the uptake of physical activity amongst people experiencing mild-to-moderate depression are largely absent from studies. Conclusions - An explanatory model was developed. This represents mild-to-moderate depression as interfering with (a) the motivation to take part in physical activity and (b) the volition that it is required to take part in physical activity. Therefore, both motivational and volitional elements are important in any intervention to increase physical activity in people with mild-to-moderate depression. Furthermore, mild-to-moderate depression-specific factors need to be tackled in any physical activity initiative, via psychological treatments such as Cognitive Behavioural Therapy. We argu

Challenges to undertaking randomised trials with looked after children in social care settings.

BACKGROUND: Randomised controlled trials (RCTs) are widely viewed as the gold standard for assessing effectiveness in health research; however many researchers and practitioners believe that RCTs are inappropriate and un-doable in social care settings, particularly in relation to looked after children. The aim of this article is to describe the challenges faced in conducting a pilot study and phase II RCT of a peer mentoring intervention to reduce teenage pregnancy in looked after children in a social care setting. METHODS: Interviews were undertaken with social care professionals and looked after children, and a survey conducted with looked after children, to establish the feasibility and acceptability of the intervention and research design. RESULTS: Barriers to recruitment and in managing the intervention were identified, including social workers acting as informal gatekeepers; social workers concerns and misconceptions about the recruitment criteria and the need for and purpose of randomisation; resource limitations, which made it difficult to prioritise research over other demands on their time and difficulties in engaging and retaining looked after children in the study. CONCLUSIONS: The relative absence of a research infrastructure and culture in social care and the lack of research support funding available for social care agencies, compared to health organisations, has implications for increasing evidence-based practice in social care settings, particularly in this very vulnerable group of young people

Tinnitus referral pathways within the National Health Service in England: a survey of their perceived effectiveness among audiology staff

<p>Abstract</p> <p>Background</p> <p>In the UK, audiology services deliver the majority of tinnitus patient care, but not all patients experience the same level of service. In 2009, the Department of Health released a Good Practice Guide to inform commissioners about key aspects of a quality tinnitus service in order to promote equity of tinnitus patient care in UK primary care, audiology, and in specialist multi-disciplinary centres. The purpose of the present research was to evaluate utilisation and opinions on pathways for the referral of tinnitus patients to and from English Audiology Departments.</p> <p>Methods</p> <p>We surveyed all audiology staff engaged in providing tinnitus services across England. A 36-item questionnaire was mailed to 351 clinicians in all 163 National Health Service (NHS) Trusts identified as having a tinnitus service. 138 clinicians responded. The results presented here describe experiences and opinions of the current patient pathways to and from the audiology tinnitus service.</p> <p>Results</p> <p>The most common referral pathway was from general practice to a hospital-based Ear, Nose & Throat department and from there to a hospital-based audiology department (64%). Respondents considered the NHS tinnitus referral process to be generally effective (67%), but expressed needs for improving GP referral and patients' access to services. 'Open access' to the audiology clinic was rarely an option for patients (9%), nor was the opportunity to access specialist counselling provided by clinical psychology (35%). To decrease the number of inappropriate referrals, 40% of respondents called for greater awareness by referrers about the audiology tinnitus service.</p> <p>Conclusions</p> <p>Respondents in the present survey were generally satisfied with the tinnitus referral system. However, they highlighted some potential targets for service improvement including 1] faster and more appropriate referral from GPs, to be achieved through education on tinnitus referral criteria, 2] improved access to psychological services through audiologist training, and 3] ongoing support from tinnitus support groups, national charities, or open access to the tinnitus clinic for existing patients.</p