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1.
Mol Ther ; 28(1): 328-340, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31628051

RESUMO

ß-globin lentiviral vectors (ß-LV) have faced challenges in clinical translation for gene therapy of sickle cell disease (SCD) due to low titer and sub-optimal gene transfer to hematopoietic stem and progenitor cells (HSPCs). To overcome the challenge of preserving efficacious expression while increasing vector performance, we used published genomic and epigenomic data available through ENCODE to redefine enhancer element boundaries of the ß-globin locus control region (LCR) to construct novel ENCODE core sequences. These novel LCR elements were used to design a ß-LV of reduced proviral length, termed CoreGA-AS3-FB, produced at higher titers and possessing superior gene transfer to HSPCs when compared to the full-length parental ß-LV at equal MOI. At low vector copy number, vectors containing the ENCODE core sequences were capable of reversing the sickle phenotype in a mouse model of SCD. These studies provide a ß-LV that will be beneficial for gene therapy of SCD by significantly reducing the cost of vector production and extending the vector supply.

2.
J Phys Chem Lett ; 10(14): 4003-4009, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31264874

RESUMO

Photolytic aging has been proposed as a major mass loss mechanism for atmospheric secondary organic aerosol (SOA). However, estimated mass loss rates vary by orders of magnitude, and their impacts on modeled SOA loadings and properties are highly uncertain. In this study, photolysis rates and composition changes of α-pinene SOA are analyzed in situ over multiple days in an environmental chamber. After an initial exponential decay (τ ∼ 22 h), the mass loss rate slows dramatically, with more than ∼70-90% of the SOA particulate mass undergoing an essentially negligible photolytic degradation. Scaled to ambient conditions, SOA undergoes rapid photolysis over only its first day in the atmosphere; beyond this, the remaining SOA is photo-recalcitrant, and photolysis ceases to be a major sink compared to wet deposition time scales. Thus, extrapolation of the initial photolysis loss rate to the entire aerosol mass may significantly overestimate the role of photolysis in the removal of atmospheric SOA.

3.
EBioMedicine ; 46: 423-430, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31311721

RESUMO

BACKGROUND: The POP Trial was a phase 1, open-label, rising-dose, randomised study that explored the safety and tolerability of calmangafodipir (superoxide dismutase mimetic) co-treatment with n-acetylcysteine (NAC) for paracetamol overdose. METHODS: Patients were recruited at the Royal Infirmary of Edinburgh (8th June 2017-10th May 2018). Inclusion criterion: adults within 24 h of a paracetamol overdose that required NAC. Within each of 3 sequential cohorts, participants were randomly assigned, with concealed allocation, to NAC and a single intravenous calmangafodipir dose (n = 6) or NAC alone (n = 2). Calmangafodipir doses were 2, 5, or 10 µmol/kg. Participants, study and clinical teams were not blinded. The primary outcome was safety and tolerability. Secondary outcomes were alanine transaminase (ALT), international normalised ratio (INR), keratin-18, caspase-cleaved keratin-18 (ccK18), microRNA-122, and glutamate dehydrogenase (GLDH). (Clinicaltrials.gov:NCT03177395). FINDINGS: All 24 participants received their allocated drug doses and were analysed. Primary endpoints: all participants experienced ≥1 adverse event (AE), most commonly gastrointestinal. Patients experiencing ≥1 serious adverse event (SAE): NAC alone, 2/6; NAC + calmangafodipir (2 µmol/kg), 4/6; NAC + calmangafodipir (5 µmol/kg), 2/6; NAC + calmangafodipir (10 µmol/kg), 3/6. No AEs or SAEs were probably or definitely calmangafodipir-related. Secondary safety outcomes demonstrated no differences between groups. With NAC alone, 2/6 had ALT > 100 U/L; with NAC + calmangafodipir, 0/18. No INR difference. Keratin-18 and ccK18 increased in the NAC alone group more than with calmangafodipir (baseline to 20 h fold change, NAC + calmangafodipir (5 µmol/kg) compared to NAC alone: 0.48 (95%CI 0.28-0.83)). microRNA-122 changes were similar to K18, GLDH was frequently undetected. INTERPRETATION: Calmangafodipir was tolerated when combined with NAC and may reduce biomarkers of paracetamol toxicity.


Assuntos
Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Acetilcisteína/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ácido Edético/análogos & derivados , Substâncias Protetoras/uso terapêutico , Fosfato de Piridoxal/análogos & derivados , Adulto , Biomarcadores , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Interações de Medicamentos , Overdose de Drogas , Ácido Edético/uso terapêutico , Feminino , Humanos , Masculino , Fosfato de Piridoxal/uso terapêutico , Fatores de Tempo , Adulto Jovem
4.
Environ Sci Technol ; 53(13): 7604-7612, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31184875

RESUMO

Characterizing the chemical composition of organic aerosols can elucidate aging mechanisms as well as the chemical and physical properties of the aerosol. However, the high chemical complexity and often low atmospheric abundance present a difficult analytical challenge. Milligrams or more of material may be needed for speciated spectroscopic analysis. In contrast, mass spectrometry provides a very sensitive platform but limited structural information. Here, we combine the strengths of mass spectrometry and infrared (IR) action spectroscopy to generate characteristic IR spectra of individual, mass-isolated ion populations. Soft ionization combined with in situ infrared ion spectroscopy, using the tunable free-electron laser FELIX, provides detailed information on molecular structures and functional groups. We apply this technique, along with quantum mechanical modeling, to characterize organic molecules in secondary organic aerosol (SOA) formed from the ozonolysis of α-pinene. Spectral overlap with a standard is used to identify cis-pinonic acid. We also demonstrate the characterization of isomers for multiple SOA products using both quantum mechanical computations and analyses of fragment ion spectra. These results demonstrate the detailed structural information on isolated ions obtained by combining mass spectrometry with fingerprint IR spectroscopy.


Assuntos
Poluentes Atmosféricos , Monoterpenos , Aerossóis , Íons , Espectrometria de Massas
5.
EClinicalMedicine ; 8: 37-46, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31193636

RESUMO

Background: Patients with palpitations and pre-syncope commonly present to Emergency Departments (EDs) but underlying rhythm diagnosis is often not possible during the initial presentation. This trial compares the symptomatic rhythm detection rate of a smartphone-based event recorder (AliveCor) alongside standard care versus standard care alone, for participants presenting to the ED with palpitations and pre-syncope with no obvious cause evident at initial consultation. Methods: Multi-centre open label, randomised controlled trial. Participants ≥ 16 years old presenting to 10 UK hospital EDs were included. Participants were randomised to either (a) intervention group; standard care plus the use of a smartphone-based event recorder or (b) control group; standard care alone. Primary endpoint was symptomatic rhythm detection rate at 90 days. Trial registration number NCT02783898 (ClinicalTrials.gov). Findings: Two hundred forty-three participants were recruited over an 18-month period. A symptomatic rhythm was detected at 90 days in 69 (n = 124; 55.6%; 95% CI 46.9-64.4%) participants in the intervention group versus 11 (n = 116; 9.5%; 95% CI 4.2-14.8) in the control group (RR 5.9, 95% CI 3.3-10.5; p < 0.0001). Mean time to symptomatic rhythm detection in the intervention group was 9.5 days (SD 16.1, range 0-83) versus 42.9 days (SD 16.0, range 12-66; p < 0.0001) in the control group. The commonest symptomatic rhythms detected were sinus rhythm, sinus tachycardia and ectopic beats. A symptomatic cardiac arrhythmia was detected at 90 days in 11 (n = 124; 8.9%; 95% CI 3.9-13.9%) participants in the intervention group versus 1 (n = 116; 0.9%; 95% CI 0.0-2.5%) in the control group (RR 10.3, 95% CI 1.3-78.5; p = 0.006). Interpretation: Use of a smartphone-based event recorder increased the number of patients in whom an ECG was captured during symptoms over five-fold to more than 55% at 90 days. This safe, non-invasive and easy to use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. Funding: This study was funded by research awards from Chest, Heart and Stroke Scotland (CHSS) and British Heart Foundation (BHF) which included funding for purchasing the devices. MR was supported by an NHS Research Scotland Career Researcher Clinician award.

6.
Trials ; 19(1): 711, 2018 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-30594256

RESUMO

BACKGROUND: Palpitations and pre-syncope are together responsible for 300,000 annual Emergency Department (ED) attendances in the United Kingdom (UK). Diagnosis of the underlying rhythm is difficult as many patients are fully recovered on ED arrival; and examination and presenting electrocardiogram (ECG) are commonly normal. The only way to establish the underlying heart rhythm is to capture an ECG during symptoms. Recent technology advances have led to several novel ECG monitoring devices appearing on the market. This trial aims to compare the symptomatic rhythm detection rate at 90 days of one such smart phone-based event recorder (AliveCor Heart Monitor and AliveECG) with standard care for participants presenting to the ED with palpitations and pre-syncope and no obvious cause in the ED. METHODS/DESIGN: This is a multi-centre hospital ED / Acute Medical Unit (AMU) open label, randomised controlled trial. Participants will be recruited in 10 tertiary and district general hospitals in the UK. Participants aged ≥ 16 years presenting with an episode of palpitations or pre-syncope with no obvious cause and whose underlying ECG rhythm during these episodes remains undiagnosed after clinical assessment will be included. Participants will be randomised to either: (1) the intervention arm, standard care plus the use of a smart phone-based event recorder; or (2) the control arm, standard care. Primary endpoint will be symptomatic rhythm detection rate at 90 days. A number of secondary clinical, process and cost-effectiveness endpoints will be collected and analysed. Analysis will be on an intention-to-treat basis. DISCUSSION: The Investigation of Palpitations in the ED (IPED) study aims to recruit 242 participants across 10 hospital sites. It will be the first study to investigate the ability of a smart phone-based event recorder to detect symptomatic cardiac rhythms compared to standard care for ED patients with palpitations and pre-syncope with no obvious cause in the ED. This smart phone event recorder will allow ED patients who have presented with palpitations or pre-syncope to record their ECG tracing if they have a further episode and may increase the rate of underlying rhythm diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02783898 . Registered on 26 May 2016.


Assuntos
Arritmias Cardíacas/diagnóstico , Eletrocardiografia Ambulatorial/instrumentação , Serviço Hospitalar de Emergência , Frequência Cardíaca , Aplicativos Móveis , Smartphone , Síncope/diagnóstico , Telemetria/instrumentação , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Humanos , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Síncope/fisiopatologia , Síncope/terapia , Fatores de Tempo , Reino Unido
7.
Lancet ; 392(10151): 919-928, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30170853

RESUMO

BACKGROUND: High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome. METHODS: In this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6-12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123. FINDINGS: Between June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620). INTERPRETATION: Use of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. FUNDING: The British Heart Foundation.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Síndrome Coronariana Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Valor Preditivo dos Testes
8.
Nat Chem ; 10(4): 462-468, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29483638

RESUMO

The evolution of atmospheric organic carbon as it undergoes oxidation has a controlling influence on concentrations of key atmospheric species, including particulate matter, ozone and oxidants. However, full characterization of organic carbon over hours to days of atmospheric processing has been stymied by its extreme chemical complexity. Here we study the multigenerational oxidation of α-pinene in the laboratory, characterizing products with several state-of-the-art analytical techniques. Although quantification of some early generation products remains elusive, full carbon closure is achieved (within measurement uncertainty) by the end of the experiments. These results provide new insights into the effects of oxidation on organic carbon properties (volatility, oxidation state and reactivity) and the atmospheric lifecycle of organic carbon. Following an initial period characterized by functionalization reactions and particle growth, fragmentation reactions dominate, forming smaller species. After approximately one day of atmospheric aging, most carbon is sequestered in two long-lived reservoirs-volatile oxidized gases and low-volatility particulate matter.

9.
Diagn Progn Res ; 2: 18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31093566

RESUMO

Background: In recent years, there has been increasing focus on the earlier detection of deterioration in the clinical condition of hospital patients with the aim of instigating earlier treatment to reverse this deterioration and prevent adverse outcomes. This is especially important in the ED, a dynamic environment with large volumes of undifferentiated patients, which carries inherent patient risk. SNAP40 is an innovative medical-grade device that can be worn on the upper arm that continuously monitors patients' vital signs including relative changes in systolic blood pressure, respiratory rate, heart rate, movement, blood oxygen saturation and temperature. It uses automated risk analysis to potentially allow clinical staff to easily and quickly identify high-risk patients. The aim of this study is to investigate whether the SNAP40 device is able to identify deterioration in the vital sign physiology of an ED patient earlier than current standard monitoring and observation charting techniques. Methods/design: Single centre, teaching hospital ED open label, prospective, observational cohort study recruiting 250 high acuity participants aged 16 years or over presenting to the ED. Participants will be approached and enrolled in the ED and after consent will have the SNAP40 wearable monitoring device attached which will be used alongside standard care monitoring. Participants will be observed throughout their time in the ED. Any SNAP40 device alarm, standard monitoring alarms or standard practice vital sign observations indicating a deterioration in a patient's vital sign physiology (defined as an increase in NEWS score) will be recorded. Primary outcome is time to detection of deterioration. Secondary outcomes include staff time spent performing observations and responding to standard monitoring alarms, clinical escalation of care when deterioration is detected and participants and staff rating of experience of both SNAP40 and current monitoring. Discussion: The SNAP40-ED study aims to recruit 250 patients. It will be the first study to compare the ability of a novel ambulatory monitoring device to detect deterioration compared to standard care in the ED. It may allow the earlier detection of deterioration in the clinical condition of ED patients and therefore earlier treatment to reverse this deterioration and prevent adverse outcomes. Trial registration: NCT03179267 ClinicalTrials.gov. Registered on June 17, 2017.

10.
BMC Musculoskelet Disord ; 18(1): 315, 2017 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-28732491

RESUMO

BACKGROUND: Inflammatory arthritis leads to work disability, absenteeism and presenteeism (i.e. at-work productivity loss) at high cost to individuals, employers and society. A trial of job retention vocational rehabilitation (VR) in the United States identified this helped people keep working. The effectiveness of this VR in countries with different socioeconomic policies and conditions, and its impact on absenteeism, presenteeism and health, are unknown. This feasibility study tested the acceptability of this VR, modified for the United Kingdom, compared to written advice about managing work problems. To help plan a randomized controlled trial, we tested screening, recruitment, intervention delivery, response rates, applicability of the control intervention and identified the relevant primary outcome. METHODS: A feasibility randomized controlled trial with rheumatoid, psoriatic or inflammatory arthritis patients randomized to receive either job retention VR or written information only (the WORK-IA trial). Following three days VR training, rheumatology occupational therapists provided individualised VR on a one to one basis. VR included work assessment, activity diaries and action planning, and (as applicable) arthritis self-management in the workplace, ergonomics, fatigue and stress management, orthoses, employment rights and support services, assistive technology, work modifications, psychological and disclosure support, workplace visits and employer liaison. RESULTS: Fifty five (10%) people were recruited from 539 screened. Follow-up response rates were acceptable at 80%. VR was delivered with fidelity. VR was more acceptable than written advice only (7.8 versus 6.7). VR took on average 4 h at a cost of £135 per person. Outcome assessment indicated VR was better than written advice in reducing presenteeism (Work Limitations Questionnaire (WLQ) change score mean: VR = -12.4 (SD 13.2); control = -2.5 (SD 15.9), absenteeism, perceived risk of job loss and improving pain and health status, indicating proof of concept. The preferred primary outcome measure was the WLQ, a presenteeism measure. CONCLUSIONS: This brief job retention VR is a credible and acceptable intervention for people with inflammatory arthritis with concerns about continuing to work due to arthritis. TRIAL REGISTRATION: ISRCTN 76777720 . Registered 21.9.12.


Assuntos
Absenteísmo , Artrite/epidemiologia , Artrite/reabilitação , Presenteísmo , Reabilitação Vocacional/métodos , Adulto , Artrite/diagnóstico , Emprego/métodos , Estudos de Viabilidade , Feminino , Seguimentos , Inquéritos Epidemiológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Presenteísmo/métodos , Reino Unido/epidemiologia
11.
Faraday Discuss ; 200: 165-194, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28574555

RESUMO

Anthropogenic and biogenic gas emissions contribute to the formation of secondary organic aerosol (SOA). When present, soot particles from fossil fuel combustion can acquire a coating of SOA. We investigate SOA-soot biogenic-anthropogenic interactions and their impact on ice nucleation in relation to the particles' organic phase state. SOA particles were generated from the OH oxidation of naphthalene, α-pinene, longifolene, or isoprene, with or without the presence of sulfate or soot particles. Corresponding particle glass transition (Tg) and full deliquescence relative humidity (FDRH) were estimated using a numerical diffusion model. Longifolene SOA particles are solid-like and all biogenic SOA sulfate mixtures exhibit a core-shell configuration (i.e. a sulfate-rich core coated with SOA). Biogenic SOA with or without sulfate formed ice at conditions expected for homogeneous ice nucleation, in agreement with respective Tg and FDRH. α-pinene SOA coated soot particles nucleated ice above the homogeneous freezing temperature with soot acting as ice nuclei (IN). At lower temperatures the α-pinene SOA coating can be semisolid, inducing ice nucleation. Naphthalene SOA coated soot particles acted as ice nuclei above and below the homogeneous freezing limit, which can be explained by the presence of a highly viscous SOA phase. Our results suggest that biogenic SOA does not play a significant role in mixed-phase cloud formation and the presence of sulfate renders this even less likely. However, anthropogenic SOA may have an enhancing effect on cloud glaciation under mixed-phase and cirrus cloud conditions compared to biogenic SOA that dominate during pre-industrial times or in pristine areas.

12.
Emerg Med J ; 34(7): 454-456, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28473529

RESUMO

Defining research priorities in a specialty as broad as emergency medicine is a significant challenge. In order to fund and complete the most important research projects, it is imperative that we identify topics that are important to all clinicians, society and to our patients. We have undertaken a priority setting partnership to establish the most important questions facing emergency medicine. The top 10 questions reached through a consensus process are discussed.


Assuntos
Consenso , Medicina de Emergência/organização & administração , Medicina de Emergência/tendências , Pesquisa/organização & administração , Comportamento Cooperativo , Humanos , Inquéritos e Questionários , Recursos Humanos
13.
Trials ; 17(1): 579, 2016 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-27923390

RESUMO

BACKGROUND: Emergency department attendances with chest pain requiring assessment for acute coronary syndrome (ACS) are a major global health issue. Standard assessment includes history, examination, electrocardiogram (ECG) and serial troponin testing. Computerised tomography coronary angiography (CTCA) enables additional anatomical assessment of patients for coronary artery disease (CAD) but has only been studied in very low-risk patients. This trial aims to investigate the effect of early CTCA upon interventions, event rates and health care costs in patients with suspected/confirmed ACS who are at intermediate risk. METHODS/DESIGN: Participants will be recruited in about 35 tertiary and district general hospitals in the UK. Patients ≥18 years old with symptoms with suspected/confirmed ACS with at least one of the following will be included: (1) ECG abnormalities, e.g. ST-segment depression >0.5 mm; (2) history of ischaemic heart disease; (3) troponin elevation above the 99th centile of the normal reference range or increase in high-sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' of myocardial infarction (MI). The early use of ≥64-slice CTCA as part of routine assessment will be compared to standard care. The primary endpoint will be 1-year all-cause death or recurrent type 1 or type 4b MI at 1 year, measured as the time to such event. A number of secondary clinical, process and safety endpoints will be collected and analysed. Cost effectiveness will be estimated in terms of the lifetime incremental cost per quality-adjusted life year gained. We plan to recruit 2424 (2500 with ~3% drop-out) evaluable patients (1212 per arm) to have 90% power to detect a 20% versus 15% difference in 1-year death or recurrent type 1 MI or type 4b MI, two-sided p < 0.05. Analysis will be on an intention-to-treat basis. The relationship between intervention and the primary outcome will be analysed using Cox proportional hazard regression adjusted for study site (used to stratify the randomisation), age, baseline Global Registry of Acute Coronary Events score, previous CAD and baseline troponin level. The results will be expressed as a hazard ratio with the corresponding 95% confidence intervals and p value. DISCUSSION: The Rapid Assessment of Potential Ischaemic Heart Disease with CTCA (RAPID-CTCA) trial will recruit 2500 participants across about 35 hospital sites. It will be the first study to investigate the role of CTCA in the early assessment of patients with suspected or confirmed ACS who are at intermediate risk and including patients who have raised troponin measurements during initial assessment. TRIAL REGISTRATION: ISRCTN19102565 . Registered on 3 October 2014. ClinicalTrials.gov: NCT02284191.


Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Protocolos Clínicos , Doença da Artéria Coronariana/economia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , Circulação Coronária , Vasos Coronários/fisiopatologia , Análise Custo-Benefício , Serviços Médicos de Emergência , Custos Hospitalares , Humanos , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Fatores de Tempo , Reino Unido
14.
Environ Sci Technol ; 50(10): 5172-80, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27088454

RESUMO

Quantifying how atmospheric particles interact with water vapor is critical for understanding the effects of aerosols on climate. We present a novel method to measure the mass-based hygroscopicity of particles while characterizing their elemental and carbon functional group compositions. Since mass-based hygroscopicity is insensitive to particle geometry, it is advantageous for probing the hygroscopic behavior of atmospheric particles, which can have irregular morphologies. Combining scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDX), scanning transmission X-ray microscopy (STXM) analysis, and in situ STXM humidification experiments, this method was validated using laboratory-generated, atmospherically relevant particles. Then, the hygroscopicity and elemental composition of 15 complex atmospheric particles were analyzed by leveraging quantification of C, N, and O from STXM, and complementary elemental quantification from SEM/EDX. We found three types of hygroscopic responses, and correlated high hygroscopicity with Na and Cl content. The mixing state of 158 other particles from the sample broadly agreed with those of the humidified particles, indicating the potential to infer atmospheric hygroscopic behavior from a selected subset of particles. These methods offer unique quantitative capabilities to characterize and correlate the hygroscopicity and chemistry of individual submicrometer atmospheric particles.


Assuntos
Tamanho da Partícula , Molhabilidade , Aerossóis/química , Carbono , Microscopia Eletrônica de Varredura
15.
Emerg Nurse ; 23(7): 26, 28-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26542924

RESUMO

Conducting research in emergency departments is relatively new, and there are a number of ethical and practical challenges to recruiting patients in these settings. In 2008, the Emergency Medicine Research Group Edinburgh (EMERGE) was set up at the Royal Infirmary of Edinburgh emergency department to support researchers and encourage the growth of research in emergency medicine. As part of a review of their working methods, the group's clinical nurse researchers undertook a small study to identify participant recruitment times. The results showed a significant difference between perceived and actual recruitment times, which has implications for planning staff numbers and budgets. This article describes the evaluation process and methods of data collection, and discusses the results.


Assuntos
Pesquisa Biomédica/métodos , Coleta de Dados/métodos , Serviço Hospitalar de Emergência , Seleção de Pacientes , Projetos de Pesquisa , Adulto , Humanos , Escócia , Fatores de Tempo
16.
Environ Sci Technol ; 49(8): 4995-5002, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25850933

RESUMO

Atmospheric aerosols can undergo phase transitions including liquid-liquid phase separation (LLPS) while responding to changes in the ambient relative humidity (RH). Here, we report results of chemical imaging experiments using environmental scanning electron microscopy (ESEM) and scanning transmission X-ray microscopy (STXM) to investigate the LLPS of micrometer-sized particles undergoing a full hydration-dehydration cycle. Internally mixed particles composed of ammonium sulfate (AS) and either: limonene secondary organic carbon (LSOC), α, 4-dihydroxy-3-methoxybenzeneaceticacid (HMMA), or polyethylene glycol (PEG-400) were studied. Events of LLPS were observed for all samples with both techniques. Chemical imaging with STXM showed that both LSOC/AS and HMMA/AS particles were never homogeneously mixed for all measured RH's above the deliquescence point and that the majority of the organic component was located in the outer phase. The outer phase composition was estimated as 65:35 organic: inorganic in LSOC/AS and as 50:50 organic: inorganic for HMMA/AS. PEG-400/AS particles showed fully homogeneous mixtures at high RH and phase separated below 89-92% RH with an estimated 70:30% organic to inorganic mix in the outer phase. These two chemical imaging techniques are well suited for in situ analysis of the hygroscopic behavior, phase separation, and surface composition of collected ambient aerosol particles.


Assuntos
Aerossóis/química , Modelos Químicos , Sulfato de Amônio/química , Cicloexenos/química , Limoneno , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Material Particulado/química , Transição de Fase , Polietilenoglicóis/química , Terpenos/química
17.
J Phys Chem A ; 119(19): 4498-508, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25386912

RESUMO

Constituents of secondary organic carbon (SOC) in atmospheric aerosols are often mixed with inorganic components and compose a significant mass fraction of fine particulate matter in the atmosphere. Interactions between SOC and other condensed-phase species are not well understood. Here, we investigate the reactions of liquid-like and semisolid SOC from ozonolysis of limonene (LSOC) and α-pinene (PSOC) with NaCl using a set of complementary microspectroscopic analyses. These reactions result in chloride depletion in the condensed phase, release of gaseous HCl, and formation of organic salts. The reactions attributed to acid displacement by SOC acidic components are driven by the high volatility of HCl. Similar reactions can take place in SOC/NaNO3 particles. The results show that an increase in SOC mass fraction in the internally mixed SOC/NaCl particles leads to higher chloride depletion. Glass transition temperatures and viscosity of PSOC were estimated for atmospherically relevant conditions. Data show that the reaction extent depends on SOC composition, particle phase state and viscosity, mixing state, temperature, relative humidity (RH), and reaction time. LSOC shows slightly higher potential to deplete chloride than PSOC. Higher particle viscosity at low temperatures and RH can hinder these acid displacement reactions. Formation of organic salts from these overlooked reactions can alter particle physiochemical properties and may affect their reactivity and ability to act as cloud condensation and ice nuclei. The release and potential recycling of HCl and HNO3 from reacted aerosol particles may have important implications for atmospheric chemistry.


Assuntos
Aerossóis/química , Atmosfera/química , Carbono/química , Cloretos/química , Nitratos/química , Cicloexenos/química , Difusão , Gases/química , Vidro/química , Umidade , Limoneno , Monoterpenos/química , Terpenos/química , Fatores de Tempo , Temperatura de Transição , Viscosidade
18.
Musculoskeletal Care ; 11(2): 99-105, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23703966

RESUMO

People with inflammatory arthritis rapidly develop work disability, yet there is limited provision of vocational rehabilitation (VR) in rheumatology departments. As part of a randomized, controlled trial, ten occupational therapists (OTs) were surveyed to identify their current VR provision and training needs. As a result, a VR training course for OTs was developed which included both taught and self-directed learning. The course included: employment and health and safety legislation, work assessment and practical application of ergonomic principles at work. Pre-, immediately post- and two months post-training, the ten OTs completed a questionnaire about their VR knowledge and confidence On completion, they reported a significant increase (p < 0.01)in their knowledge and confidence when delivering vocational rehabilitation. They rated the course as very or extremely relevant, although seven recommended more practical sessions. The preference for practical sessions was highlighted, in that the aspects they felt most beneficial were role-playing assessments and sharing ideas through discussion and presentations. In conclusion, the course was considered effective in increasing both knowledge and confidence in using VR as an intervention, but, due to time constraints within the working day, some of the self-directed learning should be incorporated into the training days.


Assuntos
Artrite/reabilitação , Terapia Ocupacional/educação , Reabilitação Vocacional/estatística & dados numéricos , Ensaios Clínicos como Assunto , Humanos , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Reumatologia
19.
Surgeon ; 9(5): 245-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21843817

RESUMO

OBJECTIVE: To identify predictors, and clinical consequences, of postoperative wound infection after peripheral vascular surgery. MATERIALS AND METHODS: Retrospective cohort study. Potential predictors of wound infection were sought among patient related factors and procedure related factors. Patient outcome was then analysed according to the incidence of wound infection. RESULTS: Following 209 procedures, 20 (9.6%) patients suffered a wound infection. On univariate analysis, infrainguinal surgery, use of vein graft, and tissue loss were associated with wound infection. On multivariate regression, however, only the association with use of a vein graft remained (OR = 4.2; 95%CI = 1.2-14.1; P = .022): the incidence of wound infection was 16/96 (17%; 95%CI = 9.2-24.1) when a vein graft was used and 4/113 (3.5%; 95%CI = .1-7%) when a prosthetic or no graft was used. Wound infection was associated with increased mortality (4/20 versus 9/189; P = .025) but not limb loss (2/20 versus 7/189; P = .208). Median (IQR) postoperative hospital stay in patients with wound infection was 22 (15-45) days and 8 (5-15) days in those without wound infection (P = .001). CONCLUSIONS: In lower limb arterial surgery, wound infection is associated with the use of vein grafts, and results in delayed recovery and increased mortality. Measures to reduce wound infection should be focussed on such patients.


Assuntos
Artérias/cirurgia , Extremidade Inferior/irrigação sanguínea , Infecções Relacionadas à Prótese/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Veias/transplante , Idoso , Idoso de 80 Anos ou mais , Prótese Vascular/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/etiologia , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia
20.
Mem Cognit ; 31(5): 715-27, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12956236

RESUMO

A recent study showed that the pronunciation of the definite article in English (as either a reduced "thuh" or an unreduced "thee") depends on a number of different factors, including the pronunciation, spelling, and stress assignment of the following word (Raymond, Fisher, & Healy, 2002). However, it is not clear from previous research whether these factors influenced performance implicitly in normal speech production or whether explicit knowledge of the object of the experiment was relied on. In Experiment 1, we examined implicit performance on pronunciation of the definite article and found more systematic behavior than had previously been observed but, again, an influence of the pronunciation, spelling, and stress assignment of the following word. In Experiment 2, we tested the influence of the following word on definite article production during language development for two groups of children 8 and 10 years of age. This experiment showed increasing use of the unreduced form during development and a further influence of orthography. We interpret these results in terms of an interaction between perception and production in which the production system makes use of generalizations on the basis of both phonological and orthographic representations generated in perception.


Assuntos
Linguística , Fala , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Psicolinguística/métodos , Medida da Produção da Fala
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