266 research outputs found

    Modified Early Warning Scores (MEWS) to support ambulance clinicians’ decisions to transport or treat at home

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    Introduction Modified Early Warning Scores (MEWS), calculated from patients’ vital signs, are used in hospital to identify patients who may benefit from admission or intensive care: higher MEWS indicates greater clinical risk. We aimed to evaluate MEWS to support paramedics’ decisions to transport patients to hospital or treat and leave them at home. Methods We used an interrupted time series design. We trained 19 volunteer paramedics to use MEWS to support decisions to transport or treat and leave at home. We used linear regression to evaluate differences in weekly transportation rates (percentage of patients attended and transported to hospital) and revisit rates (percentage of patients attended, treated at home and subsequently revisited within 7 days), comparing trends in rates 17 weeks prior (pre-MEWS) and 17 weeks post implementation of MEWS. Auto-calculated scores retrospectively applied to all data provided pre-MEWS and were compared with paramedic calculated scores post-MEWS. Results Of the 4140 patients attended, 2208 were excluded owing to missing values (n=1897), recording errors (n=21) or excluded clinical complaints (n=290). From the remaining data (n=1932) there were no significant differences in transportation rates (pre=55±6%; post=63±11%) by catering for the existing increasing trends where the confidence intervals of the regression slopes overlap (pre=0.15; 95%CI -0.51 to 0.80 vs. post=0.54; -0.58 to 1.65). Similarly, there were no significant difference in revisit rates (pre=4±4%; post=2±4%) catering for the similar trends (pre=-0.13; -0.53 to 0.27 vs. post=0.08; -0.33 to 0.49). Paramedic scores were incorrect 39% of the time (n=622). Conclusion MEWS had a minimal effect on transportation or revisit rates. Scores were frequently not calculated or recorded, or incorrectly calculated. Opportunities for ongoing training, clinical support and feedback were limited. A larger study, ensuring adequate ongoing support, is recommended before implementing MEWS on a wider scale

    An Efficient Method for Generating Poxvirus Recombinants in the Absence of Selection

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    The use of selectable markers (ecogpt) and selection pressures to aid in detection of poxvirus (Vaccinia, VV) recombinants has been implicated in the unintended introduction of second site mutations. We have reinvestigated the use of the helper virus system described by Scheiflinger et al. [1] and adapted by Yao and Evans [2] which produces recombinants at a high frequency in the absence of any selection, at a rate of 6–100%. Our system uses fowlpox virus (FPV) as the infectious helper virus which in infected cells provides the enzymatic apparatus for transcription and replication of a purified, transfected VV genome and for recombination with a second transfected PCR generated DNA fragment. To optimize the system, a PCR DNA fragment was generated that contained poxvirus promoter driven gfp and lacZ genes inserted within the coding sequences of the viral thymidine kinase gene. This PCR fragment was co-transfected together with VV genomic DNA. Recombinant VV was identified by plaquing the mixture on cells non-permissive for FPV and selection of green fluorescent or LacZ positive recombinant vaccinia plaques. The system was optimized using FPV permissive cells (CEF) and non-permissive cells (A549, CV-1) for both the initial infection/transfection and the subsequent selection. Up to 70% of the progeny vaccinia virus contained the gfp/LacZ insertion. In order to test for the presence of FPV/VV intertypic recombinants or other unintended mutations, recombinant wtVV (RwtVV) was regenerated from the gfp/LacZ viruses and evaluated by RFLP analysis and pathogenesis in animals. While all RwtVVs were viable in cell culture, in many of the RwtVV isolates, RFLP differences were noted and while some recombinant viruses exhibited wild type behavior in mice, a wide range of virulence indicative of unintended changes suggests that mutants created by “rescue” systems require careful analysis particularly before use for in vivo studies employing animal models

    Detection of Antibodies against Turkey Astrovirus in Humans

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    Astroviruses are a leading cause of gastroenteritis in mammals and birds worldwide. Although historically thought to be species-specific, increasing evidence suggests that astroviruses may cross species barriers. In this report, we used enzyme-linked immunosorbent assays to screen sera from three distinct human cohorts involved in influenza studies in Memphis, TN or Chapel Hill, NC, and Midwestern poultry abattoir workers for antibodies to turkey astrovirus type 2 (TAstV-2). Surprisingly, 26% of one cohort’s population was TAstV-2 positive as compared to 0 and 8.9% in the other cohorts. This cohort was composed of people with exposure to turkeys in the Midwestern United States including abattoir workers, turkey growers, and non-occupationally exposed participants. The odds of testing positive for antibodies against turkey astrovirus among abattoir workers were approximately 3 times higher than the other groups. These studies suggest that people with contact to turkeys can develop serological responses to turkey astrovirus. Further work is needed to determine if these exposures result in virus replication and/or clinical disease

    Going to sleep in the supine position is a modifiable risk factor for late pregnancy stillbirth; findings from the New Zealand multicentre stillbirth case-control study

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    Objective: Our objective was to test the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation). Methods: A multicentre case-control study was conducted in seven New Zealand health regions, between February 2012 and December 2015. Cases (n=164) were women with singleton pregnancies and late stillbirth, without congenital abnormality. Controls (n=569) were women with on-going singleton pregnancies, randomly selected and frequency matched for health region and gestation. The primary outcome was adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night. The last night was the night before the late stillbirth was thought to have occurred or the night before interview for controls. Going to- sleep position on the last night was categorised as: supine, left-side, right-side, propped or restless. Multivariable logistic regression adjusted for known confounders. Results: Supine going-to-sleep position on the last night was associated with increased late stillbirth risk (adjusted odds ratios (aOR) 3.67, 95% confidence interval (CI) 1.74 to 7.78) with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth (aOR, 95% CI) were: BMI (1.04, 1.01 to 1.08) per unit, maternal age ≥40 (2.88, 1.31 to 6.32), birthweight <10th customised centile (2.76, 1.59 to 4.80), and <6 hours sleep on the last night (1.81, 1.14 to 2.88). The risk associated with supine-going-to sleep position was greater for term (aOR 10.26, 3.00 to 35.04) than preterm stillbirths (aOR 3.12, 0.97 to 10.05). Conclusions: Supine going-to-sleep position is associated with a 3.7 fold increase in overall late stillbirth risk, independent of other common risk factors. A public health campaign encouraging women not to go-to-sleep supine in the third trimester has potential to reduce late stillbirth by approximately 9%

    Tyrosine Phosphorylation of the E3 Ubiquitin Ligase TRIM21 Positively Regulates Interaction with IRF3 and Hence TRIM21 Activity

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    Patients suffering from Systemic Lupus Erythematous (SLE) have elevated type I interferon (IFN) levels which correlate with disease activity and severity. TRIM21, an autoantigen associated with SLE, has been identified as an ubiquitin E3 ligase that targets the transcription factor IRF3 in order to turn off and limit type I IFN production following detection of viral and bacterial infection by Toll Like Receptors (TLRs). However, how the activity of TRIM21 is regulated downstream of TLRs is unknown. In this study we demonstrate that TRIM21 is tyrosine phosphorylated following TLR3 and TLR4 stimulation, suggesting that its activity is potentially regulated by tyrosine phosphorylation. Using Netphos, we have identified three key tyrosines that are strongly predicted to be phosphorylated, two of which are conserved between the human and murine forms of TRIM21, at residues 343, 388, and 393, all of which have been mutated from tyrosine to phenylalanine (Y343F, Y388F, and Y393F). We have observed that tyrosine phosphorylation of TRIM21 only occurs in the substrate binding PRY/SPRY domain, and that Y393, and to a lesser extent, Y388 are required for TRIM21 to function as a negative regulator of IFN-β promoter activity. Further studies revealed that mutating Y393 to phenylalanine inhibits the ability of TRIM21 to interact with its substrate, IRF3, thus providing a molecular explanation for the lack of activity of Y393 on the IFN-β promoter. Our data demonstrates a novel role for tyrosine phosphorylation in regulating the activity of TRIM21 downstream of TLR3 and TLR4. Given the pathogenic role of TRIM21 in systemic autoimmunity, these findings have important implications for the development of novel therapeutics

    Development of a lifestyle intervention using the MRC framework for diabetes prevention in people with impaired glucose regulation

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    A B S T R AC T Background We report development of a group-based lifestyle intervention, Let&apos;s Prevent, using the UK Medical Research Council (MRC) framework, and delivered by structured education to prevent type 2 diabetes mellitus (T2DM) in people with impaired glucose regulation (IGR) in a UK multi-ethnic population. Methods Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) is the first national T2DM programme that meets National Institute for Health and Care Excellence criteria and formed the basis for Let&apos;s Prevent. An iterative cycle of initial development, piloting, collecting and collating qualitative and quantitative data, and reflection and modification, was used to inform and refine lifestyle intervention until it was fit for evaluation in a definitive randomized controlled trial (RCT). The programme encouraged IGR self-management using simple, non-technical language and visual aids. Results Qualitative and quantitative data suggested that intervention resulted in beneficial short-term behaviour change such as healthier eating patterns, improved health beliefs and greater participant motivation and empowerment. We also demonstrated that recruitment strategy and data collection methods were feasible for RCT implementation. Conclusions Let&apos;s Prevent was developed following successful application of MRC framework criteria and the subsequent RCT will determine whether it is feasible, reliable and transferable from research into a real-world NHS primary healthcare setting. Trial Registration ISRCTN80605705. Keywords complex intervention, diabetes prevention, impaired glucose regulation, structured education Introduction Screening studies carried out in primary care in the UK 1 have shown that screening for type 2 diabetes mellitus (T2DM) will identify around 15% of middle aged adults with impaired glucose tolerance or impaired fasting glucose, collectively termed impaired glucose regulation (IGR) and also known as pre-diabetes mellitus. 2 IGR is considered to be a high-risk state for T2DM, cardiovascular disease (CVD) and increased mortality 3,4 and is now referred to as &apos;at high risk of developing diabetes&apos; under new guidelines on terminology. There is evidence that, in people with IGR, lifestyle modifications can substantially reduce the risk of developing T2DM. 6 Screening and lifestyle interventions are also likely to be costeffective. 7 The Diabetes Prevention Programme 8 and the Finnish Prevention study 9 showed that lifestyle programmes addressing weight loss, healthy diet and physical activity reduce the risk of developing T2DM in those with IGR by 58%. Successful lifestyle programmes have also been carried out in many other countries, including India, 10 China 11 and Japan. 12 There is limited evidence, however, regarding the feasibility of translating this research into practice. Many research-based prevention programmes have involved multiple one-to-one counselling sessions. The Diabetes Prevention Programme had a median of 20 individual counselling sessions over a 4-year period. 9 The intensity of such an intervention, even if cost-effective in the long term, is likely to place acute strain on healthcare resources in the short term. Even resource-rich countries, such as Germany and Finland, where diabetes prevention is a public health priority, have been unable to replicate the intensive nature of diabetes prevention programmes when implemented into clinical practice. 17 New guidelines from the National Institute for Health and Care Excellence (NICE) state that those identified with a moderate or high risk of developing T2DM should be offered culturally appropriate information or support, in a range of formats and languages, including structured education, to help them change their lifestyle. 5 Structured education refers to group-based patient-centred educational programmes that have a clear philosophy and a written curriculum with supporting resources, are underpinned by appropriate learning and psychological theory, and are evidence-based and delivered by trained, quality assessed educators. 19 Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) is the first national programme for T2DM that meets NICE criteria 20,21 and a randomized controlled trial (RCT) has demonstrated its effectiveness in improving weight, smoking behaviours and illness beliefs. 21 The DESMOND model is based on an empowerment philosophy that sees the participant as capable and responsible for their own health decisions and behaviours. The UK Medical Research Council (MRC) Framework for Complex Interventions to Improve Health has internationally recognized criteria to guide the development and evaluation of health behaviour change programmes. The most recent MRC guidance suggests including the following phases: development, feasibility and piloting, evaluation and implementation 23 There is an urgent need to design and test prevention programmes that meet the needs of ethnically diverse communities and are feasible, cost-effective and replicable in a real-world UK healthcare setting. The lifestyle intervention described was developed to meet this need and is currently being formally evaluated in an RCT. Methods Study design and recruitment The Let&apos;s Prevent intervention was developed by a core multidisciplinary team in collaboration with the DESMOND collaborative and the National Physical Activity Centre in Loughborough. It was designed as a group educational programme with a written curriculum suitable for the broadest range of participants, to be deliverable in a community setting for ease of access for patients, and to have the potential for integration into future routine clinical care. The session content was founded on a sound evidence base and guided by a review of the literature surrounding nutrition, exercise and educational principles with pragmatic decisions on best practice where the evidence was ambiguous, lacking or conflicting. Using the DESMOND model, the programme was 6 h long, deliverable in either one full day or as two half-day equivalents. It was designed to be facilitated by two trained healthcare professionals (educators) to a group of between 5 and 12 participants with IGR, who had the option of bringing an accompanying person. It was delivered as two versions. The first was broadly suitable for most White European groups, referred to as the Let&apos;s Prevent programme, and the second was adapted to suit SA patient groups and referred to as the SA Let&apos;s Prevent programme. Both versions of the educational intervention and the educator training programme were modelled and refined using an iterative process, including piloting, feedback, analysis, reflection and modification, based on a methodology previously developed for modifying an educational programme. 30 Key to the process was the collection and analysis of qualitative and quantitative data. A degree of objectivity and a high level of rigour were attained by involving academic researchers in this process. The Qualitative data were gathered to ascertain the experiences of both participants and educators of engaging in the programme. Data were collected via observation, telephone and face-to-face interviews and focus groups. Flexible topic guides were developed by trainers and qualitative researchers to inform and facilitate the qualitative data collection process. The SA Let&apos;s Prevent programme was developed concurrently to address the needs of the SA population living in the UK, many of whom do not speak English. Core educational messages were identical to Let&apos;s Prevent but changes were made to ensure that food and activity messages were culturally relevant. Teaching resources (images and models) were developed to ensure that the programme was not reliant on the written word. A previous action research project The nutritional goals from the Diabetes Prevention Programme 8 and the Finnish Prevention Study 9 and the physical activity goals from the PREPARE stud

    The Vehicle, Fall 1982

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    Vol. 24, No. 1 Table of Contents Winter SurveillanceB.L. Davidsonpage 3 The InvitationBecky Lawsonpage 4 Check In, Check OutSteve Sandstrompage 4 On The Front Porch StepKeila Tooleypage 5 Old Greek ManDevon Flesorpage 5 Exotic PassionsBecky Lawsonpage 6 PhotographLisa Owenspage 7 Beyond The ThornsBrook Wilsonpage 8 Ritual Of HeatB.L. Davidsonpage 11 The GamerBecky Lawsonpage 12 It\u27s OverKeila Tooleypage 13 DreamJohn Stockmanpage 14 Silver DollarGina J. Grillopage 15 The DancerJessica Lewispage 16 Snapshots Of Rural IllinoisIsabel M. Parrottpage 16 The Last SeasonTheresa Whitesidepage 17 DrawingKaren Haneypage 17 Rotary LuncheonJessica Lewispage 18 Factory TourLinda Fraembspage 18 The ImmigrantsD.L. Lewispage 19 At Shedd AquariumLinda Fraembspage 20 The GuardianBecky Lewispage 20 Digital LifeEverett Tackettpage 21 Full ServiceScott Graypage 22 Dust ShowLinda A. Brownpage 23 At SixMaureen Foertschpage 24 DrawingJean Imherrpage 24 ReflectionMaggie Kennedypage 25 Cat DefiningBecky Lawsonpage 26 Ode To An Unread NewspaperLinda Fraembspage 26 GumSteve Sandstrompage 27 The DancerChrystal Clarkpage 27 PoemD.L. Lewispage 28 For LucyStacey Flanniganpage 29 An AbortionDevon Flesorpage 29 ReveriesKeila Tooleypage 30 Sunday Morning After Tequila With LemonScott Graypage 33 Staging A Living Jewel BoxMichelle Mitchellpage 34 The Other WomanStacey Flanniganpage 35 The Natural LookMichelle Mitchellpage 35 Poem To A Girl Named SandalsJohn Stockmanpage 36 PhotographLisa Owenspage 37 In The Balcony Of The Bijou On A Saturday NightScott Graypage 38 The Canadian Soccer PlayerBecky Lawsonpage 39 The HealingJohn Stockmanpage 39 AppeasedDevon Flesorpage 40 CodaJohn Stockmanpage 40https://thekeep.eiu.edu/vehicle/1040/thumbnail.jp

    Use of quantitative PCR to assess the efficacy of albendazole against Necator americanus and Ascaris spp. in Manufahi District, Timor-Leste

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    BACKGROUND: Soil-transmitted helminths (STHs) including Ascaris lumbricoides, Necator americanus, Ancylostoma spp. and Trichuris trichiura are cause of significant global morbidity. To mitigate their disease burden, at-risk groups in endemic regions receive periodic mass drug administration using anthelmintics, most commonly albendazole and mebendazole. Assessing the efficacy of anthelmintic drugs is important for confirming that these regimens are working effectively and that drug resistance has not emerged. In this study we aimed to characterise the therapeutic efficacy of albendazole against Ascaris spp. and N. americanus in Timor-Leste, using a quantitative polymerase chain reaction (qPCR) method for parasite detection and quantification. RESULTS: A total of 314 participants from 8 communities in Timor-Leste provided stool samples before and 10-14 days after the administration of a single 400 mg dose of albendazole. Helminth infection status and infection intensity (measured in Ct-values and relative fluorescence units) were determined using qPCR. Efficacy was determined by examining the cure rates and infection intensity reduction rates. Albendazole was found to be highly efficacious against Ascaris spp., with a cure rate of 91.4% (95% CI: 85.9-95.2%) and infection intensity reduction rate of 95.6% (95% CI: 88.3-100%). The drug was less efficacious against N. americanus with a cure rate of 58.3% (95% CI: 51.4-64.9%) and infection intensity reduction rate of 88.9% (95% CI: 84.0-97.0%). CONCLUSIONS: The observed cure rates and infection intensity reduction rates obtained for Ascaris spp. and to a lower extent N. americanus, demonstrate the continued efficacy of albendazole against these species and its utility as a mass chemotherapy agent in Timor-Leste. Furthermore, this study demonstrates the usefulness of qPCR as a method to measure the efficacy of anthelminthic drugs. Additional research is necessary to translate Ct-values into eggs per gram in a systematic way
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