2,544 research outputs found

    Deep convolutional filtering for spatio-temporal denoising and artifact removal in arterial spin labelling MRI

    Get PDF
    Arterial spin labelling (ASL) is a noninvasive imaging modality, used in the clinic and in research, which can give quantitative measurements of perfusion in the brain and other organs. However, because the signal-to-noise ratio is inherently low and the ASL acquisition is particularly prone to corruption by artifact, image processing methods such as denoising and artifact filtering are vital for generating accurate measurements of perfusion. In this work, we present a new simultaneous approach to denoising and artifact removal, using a novel deep convolutional joint filter architecture to learn and exploit spatio-temporal properties of the ASL signal. We proceed to show, using data from 15 healthy subjects, that our approach achieves state of the art performance in both denoising and artifact removal, improving peak signal-to-noise ratio by up to 50%. By allowing more accurate estimation of perfusion, even in challenging datasets, this technique offers an exciting new approach for ASL pipelines, and might be used both for improving individual images and to increase the power of research studies using ASL

    Characterization of the Prophage Repertoire of African Salmonella Typhimurium ST313 Reveals High Levels of Spontaneous Induction of Novel Phage BTP1

    Get PDF
    In the past 30 years,Salmonella bloodstream infections have become a significant health problem in sub-Saharan Africa and are responsible for the deaths of anestimated 390,000 people each year. The disease is predominantly caused by a recently described sequence type of SalmonellaTyphimurium: ST313, which has a distinctive set of prophage sequences. We have thoroughly characterized the ST313-associated prophages both genetically and experimentally. ST313 representative strain D23580 contains five full-length prophages: BTP1, Gifsy-2D23580, ST64BD23580, Gifsy-1D23580,and BTP5. We show that commonS.Typhimurium prophages Gifsy-2, Gifsy-1, andST64B are inactivated in ST313 by mutations. Prophage BTP1 was found to be a functional novel phage, and the first isolate of the proposed new species “Salmonellavirus BTP1”, belonging to the P22virusgenus. Surprisingly,∼109BTP1 virus particlesperml were detected in the supernatant of non-induced, stationary-phase culturesof strain D23580, representing the highest spontaneously induced phage titer so farreported for a bacterial prophage. High spontaneous induction is shown to be anintrinsic property of prophage BTP1, and indicates the phage-mediated lysis of around0.2% of the lysogenic population. The fact that BTP1 is highly conserved in ST313 poses interesting questions about the potential fitness costs and benefits of novel prophagesin epidemicS.Typhimurium ST313

    Domains of chronic low back pain and assessing treatment effectiveness : a clinical perspective

    Get PDF
    Nonspecific chronic low back pain (CLBP) is a common clinical condition that has impacts at both the individual and societal level. Pain intensity is a primary outcome used in clinical practice to quantify the severity of CLBP and the efficacy of its treatment; however, pain is a subjective experience that is impacted by a multitude of factors. Moreover, differences in effect sizes for pain intensity are not observed between common conservative treatments, such as spinal manipulative therapy, cognitive behavioral therapy, acupuncture, and exercise training. As pain science evolves, the biopsychosocial model is gaining interest in its application for CLBP management. The aim of this article is to discuss our current scientific understanding of pain and present why additional factors should be considered in conservative CLBP management. In addition to pain intensity, we recommend that clinicians should consider assessing the multidimensional nature of CLBP by including physical (disability, muscular strength and endurance, performance in activities of daily living, and body composition), psychological (kinesiophobia, fear-avoidance, pain catastrophizing, pain self-efficacy, depression, anxiety, and sleep quality), social (social functioning and work absenteeism), and health-related quality-of-life measures, depending on what is deemed relevant for each individual. This review also provides practical recommendations to clinicians for the assessment of outcomes beyond pain intensity, including information on how large a change must be for it to be considered "real" in an individual patient. This information can guide treatment selection when working with an individual with CLBP

    The Formulated Microbicide RC-101 Was Safe and Antivirally Active Following Intravaginal Application in Pigtailed Macaques

    Get PDF
    Background: RC-101 is a congener of the antiretroviral peptide retrocyclin, which we and others have reported is active against clinical HIV-1 isolates from all major clades, does not hemagglutinate, and is non-toxic and non-inflammatory in cervicovaginal cell culture. Herein, film-formulated RC-101 was assessed for its antiviral activity in vitro, safety in vivo, retention in the cervix and vagina, and ability to remain active against HIV-1 and SHIV after intravaginal application in macaques. Methodology/Principal Findings: RC-101 was formulated as a quick-dissolving film (2000 μg/film), retained complete activity in vitro as compared to unformulated peptide, and was applied intravaginally in six pigtailed macaques daily for four days. At one and four days following the final application, the presence of RC-101 was assessed in peripheral blood, cervicovaginal lavage, cytobrushed cervicovaginal cells, and biopsied cervical and vaginal tissues by quantitative western blots. One day following the last film application, cervical biopsies from RC-101-exposed and placebo-controlled macaques were collected and were subjected to challenge with RT-SHIV in an ex vivo organ culture model. RC-101 peptide was detected primarily in the cytobrush and biopsied cervical and vaginal tissues, with little to no peptide detected in lavage samples, suggesting that the peptide was associated with the cervicovaginal epithelia. RC-101 remained in the tissues and cytobrush samples up to four days post-application, yet was not detected in any sera or plasma samples. RC-101, extracted from cytobrushes obtained one day post-application, remained active against HIV-1 BaL. Importantly, cervical biopsies from RC-101-treated animals reduced RT-SHIV replication in ex vivo organ culture as compared to placebo-treated animals. Conclusions/Significance:Formulated RC-101 was stable in vivo and was retained in the mucosa. The presence of antivirally active RC-101 after five days in vivo suggests that RC-101 would be an important molecule to develop further as a topical microbicide to prevent HIV-1 transmission. © 2010 Cole et al

    “Couch-to-5k or Couch to Ouch to Couch!?” Who Takes Part in Beginner Runner Programmes in the UK and Is Non-Completion Linked to Musculoskeletal Injury?

    Get PDF
    Physical activity has mental and physical health benefits; however, globally, three-quarters of the population do not meet physical activity guidelines. The Couch-to-5k is a beginner runner programme aimed at increasing physical activity. However, this programme lacks an evidence base, and it is unclear who is attracted to the programme; running also has a high rate of musculoskeletal (MSK) injuries. The aims of this study were to identify the characteristics of people taking part and the incidence of MSK injuries as well as exploring the experiences of people who dropped out of a modified 9-week Couch-to-5k programme. A total of 110 runners (average age was 47.1 ± 13.7 years) participated in the study, which involved completion of questionnaires (running experience and footwear information, quality of life (EQ-5D-5L), physical activity level (IPAQ-short form), MSK injury history and knee condition (SNAPPS and KOOS-PS)) at the start, middle and end of the programme and collecting sociodemographic information (age, gender, social economic status, relationship status, education level), as well as body mass index, running experience, footwear information, quality of life, physical activity levels, MSK injuries and knee condition. Fifteen drop-outs were interviewed to explore experiences of the programme. Runners were mainly females (81.8%) with an average age 47.1 years, average body mass index of 28.1 kg.m2, mainly from high socio-economic levels, married and educated to degree level. In total, 64% of the sample had previous running experience and were classified as active. Half the sample self-reported pain/discomfort and 37.2% reported anxiety/depression at the start of the programme via the EQ-5D-5L scale. Self-reported health scores increased (p = 0.047) between baseline (73.1 ± 18.8 out of 100) and at the midpoint (81.2 ± 11.6), but there were no significant differences between any other time points (end point 79.7 ± 17.5, p > 0.05). Twenty-one injuries were reported during the programme (19%). Previous injury increased the risk of new injury (OR 7.56 95% CI from 2.06 to 27.75). Only 27.3% completed the programme. Three themes emerged from interviews; MSK injury, negative emotions linked to non-completion and design of the programme. The Couch-to-5k may not attract diverse inactive populations, but future work with larger sample sizes is needed to substantiate this finding. Dropping out was linked to MSK injury and progressive design, so future programmes should consider including injury prevention advice and more flexible designs

    Assessing connectivity between an overlying aquifer and a coal seam gas resource using methane isotopes, dissolved organic carbon and tritium

    Get PDF
    Coal seam gas (CSG) production can have an impact on groundwater quality and quantity in adjacent or overlying aquifers. To assess this impact we need to determine the background groundwater chemistry and to map geological pathways of hydraulic connectivity between aquifers. In south-east Queensland (Qld), Australia, a globally important CSG exploration and production province, we mapped hydraulic connectivity between the Walloon Coal Measures (WCM, the target formation for gas production) and the overlying Condamine River Alluvial Aquifer (CRAA), using groundwater methane (CH4) concentration and isotopic composition (δ13C-CH4), groundwater tritium (3H) and dissolved organic carbon (DOC) concentration. A continuous mobile CH4 survey adjacent to CSG developments was used to determine the source signature of CH4 derived from the WCM. Trends in groundwater δ13C-CH4 versus CH4 concentration, in association with DOC concentration and 3H analysis, identify locations where CH4 in the groundwater of the CRAA most likely originates from the WCM. The methodology is widely applicable in unconventional gas development regions worldwide for providing an early indicator of geological pathways of hydraulic connectivity

    Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

    Get PDF
    AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

    Identification of the regulatory circuit governing corneal epithelial fate determination and disease

    Get PDF
    The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells (LSCs), while the nontransparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human LSCs from the cornea and keratinocytes from the epidermis and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors (TFs) that define specific cell fates and established their regulatory hierarchy. Single-cell RNA-seq (scRNA-seq) analyses of the cornea and the epidermis confirmed these shared and cell type-specific TFs. Notably, the shared and LSC-specific TFs can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the LSC fate and its association with corneal opacity
    corecore