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The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6
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The blood-brain barrier (BBB) presents a significant challenge for targeted drug delivery. A proposed method to improve drug delivery across the BBB is focused ultrasound (fUS), which delivers ultrasound waves to a targeted location in the brain and is hypothesized to open the BBB. Furthermore, stem cell-derived exosomes have been suggested as a possible anti-inflammatory molecule that may have neural benefits, if able to pass the BBB. In the present study, transcranial low-intensity focused ultrasound (LIFU), without the use of intravenous microbubbles, was assessed for both (1) its ability to influence the BBB, as well as (2) its ability to increase the localization of intravenously administered small molecules to a specific region in the brain. In vivo rat studies were conducted with a rodent-customized 2 MHz LIFU probe (peak pressure = 1.5 MPa), and injection of labeled stem cell-derived exosomes. The results suggested that LIFU (without microbubbles) did not appear to open the BBB after exposure times of 20, 40, or 60 min; instead, there appeared to be an increase in transcytosis of the dextran tracer. Furthermore, the imaging results of the exosome study showed an increase in exosome localization in the right hippocampus following 60 min of targeted LIFU.
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Exosomas , Ratas , Animales , Encéfalo/diagnóstico por imagen , Barrera Hematoencefálica/diagnóstico por imagen , Ultrasonografía , Sistemas de Liberación de Medicamentos/métodos , Microburbujas , Imagen por Resonancia MagnéticaRESUMEN
A chemiluminescent immunoassay is commonly employed to measure adrenocorticotrophic hormone (ACTH) concentrations to assist pituitary pars intermedia dysfunction diagnosis. In a previous study, seasonally-dependent assay cross-reactivity to endogenous equine corticotropin-like intermediate lobe peptide (CLIP, ACTH 18-39) was suspected. The present study aimed to demonstrate binding of endogenous equine CLIP to the capture antibody of the ACTH chemiluminescent immunoassay. Liquid chromatography - mass spectrometry (LCMS) methods were optimised to identify selected ions from synthetic human ACTH, α-melanocyte stimulating hormone (α-MSH, ACTH 1-17) and CLIP. Synthetic ACTH and CLIP bound to the capture antibody of the chemiluminescent ACTH assay, but α-MSH did not. Equine endogenous CLIP was detected by LCMS in pony plasma taken in the autumn and could be eluted from the capture antibody of the ACTH chemiluminescent immunoassay. Further research is required to enable quantification of CLIP. Equine CLIP may alter measured ACTH concentrations in vivo.
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Hormona Adrenocorticotrópica , alfa-MSH , Caballos , Animales , Humanos , Péptido de la Porción Intermedia de la Adenohipófisis Similar a la Corticotropina/metabolismo , alfa-MSH/metabolismo , Anticuerpos , Hipófisis/metabolismo , Hormonas Estimuladoras de los Melanocitos/metabolismoRESUMEN
When protons and neutrons (nucleons) are bound into atomic nuclei, they are close enough to feel significant attraction, or repulsion, from the strong, short-distance part of the nucleon-nucleon interaction. These strong interactions lead to hard collisions between nucleons, generating pairs of highly energetic nucleons referred to as short-range correlations (SRCs). SRCs are an important but relatively poorly understood part of nuclear structure1-3, and mapping out the strength and the isospin structure (neutron-proton (np) versus proton-proton (pp) pairs) of these virtual excitations is thus critical input for modelling a range of nuclear, particle and astrophysics measurements3-5. Two-nucleon knockout or 'triple coincidence' reactions have been used to measure the relative contribution of np-SRCs and pp-SRCs by knocking out a proton from the SRC and detecting its partner nucleon (proton or neutron). These measurements6-8 have shown that SRCs are almost exclusively np pairs, but they had limited statistics and required large model-dependent final-state interaction corrections. Here we report on measurements using inclusive scattering from the mirror nuclei hydrogen-3 and helium-3 to extract the np/pp ratio of SRCs in systems with a mass number of three. We obtain a measure of the np/pp SRC ratio that is an order of magnitude more precise than previous experiments, and find a marked deviation from the near-total np dominance observed in heavy nuclei. This result implies an unexpected structure in the high-momentum wavefunction for hydrogen-3 and helium-3. Understanding these results will improve our understanding of the short-range part of the nucleon-nucleon interaction.
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BACKGROUND: COVID-19 restrictions have significantly limited access to in-person educational and healthcare services for all, including individuals with intellectual and developmental disabilities (IDDs). The objectives of this online survey that included both national and international families were to capture changes in access to healthcare and educational services for individuals with IDDs that occurred shortly after restrictions were initiated and to survey families on resources that could improve services for these individuals. METHODS: This was an online survey for caregivers of individuals with (1) a genetic diagnosis and (2) a neurodevelopmental diagnosis, including developmental delay, intellectual disability, autism spectrum disorder or epilepsy. The survey assessed (1) demographics, (2) changes in access to educational and healthcare services and (3) available and preferred resources to help families navigate the changes in service allocation. RESULTS: Of the 818 responses (669 within the USA and 149 outside of the USA), most families reported a loss of at least some educational or healthcare services. Seventy-four per cent of parents reported that their child lost access to at least one therapy or education service, and 36% of respondents lost access to a healthcare provider. Only 56% reported that their child received at least some continued services through tele-education. Those that needed to access healthcare providers did so primarily through telemedicine. Telehealth (both tele-education and telemedicine) was reported to be helpful when available, and caregivers most often endorsed a need for an augmentation of these remote delivery services, such as 1:1 videoconference sessions, as well as increased access to 1:1 aides in the home. CONCLUSIONS: COVID-19 restrictions have greatly affected access to services for individuals with syndromic IDDs. Telehealth may provide opportunities for delivery of care and education in a sustainable way, not only as restrictions endure but also after they have been lifted.
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BACKGROUND: A variety of study designs are available to evaluate the accuracy of tests, but the terms used to describe these designs seem to lack clarity and standardization. We investigated if this was the case in the diagnostic guidance of the National Institute of Care and Health Excellence (NICE), an influential source of advice on the value of tests. OBJECTIVES: To describe the range of study design terms and labels used to distinguish study designs in NICE Diagnostic Guidance and the underlying evidence reports. METHODS: We carefully examined all NICE Diagnostic Guidance that has been developed from inception in 2011 until 2018 and the corresponding diagnostic assessment reports that summarized the evidence, focusing on guidance where tests were considered for diagnosis. We abstracted labels used to describe study designs and investigated what labels were used when studies were weighted differently because of their design (in terms of validity of evidence), in relevant sections. We made a descriptive analysis to assess the range of labels and also categorized labels by design features. RESULTS: From a total of 36 pieces of guidance, 20 (56%) were eligible and 17 (47%) were included in our analysis. We identified 53 unique design labels, of which 19 (36%) were specific to diagnostic test accuracy designs. These referred to a total of 12 study design features. Labels were used in assigning different weights to studies in seven of the reports (41%) but never in the guidance documents. CONCLUSION: Our study confirms a lack of clarity and standardization of test accuracy study design terms. There seems to be scope to reduce and harmonize the number of terms and still capture the design features that were deemed influential by those compiling the evidence reports. This should help decision makers in quickly identifying subgroups of included studies that should be weighted differently because their designs are more susceptible to bias.
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Studies in which single- and paired-pulse TMS was applied during motor task performance have shed considerable light on the functional relevance of popular TMS-derived neurophysiological biomarkers such as short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI). While it has become well established that corticospinal excitability and intracortical inhibition are modulated during the enactment and cancellation of actions, it has remained unclear as to whether interindividual differences in these neurophysiological markers were associated with an individual's actual ability to restrain and cancel actions. In this study, we found that individual differences in both SICI and LICI were positively associated with relevant performance metrics on the go/no-go task and stop-signal task. Specifically, we found that individuals with greater resting SICI and LICI were faster to respond on go trials of the go/no-go task and were also more accurate at inhibiting their manual responses on both go/no-go and stop-signal tasks. These results are in support of findings from our earlier study and also provide new evidence for a general relationship between individual differences in resting-state GABAergic intracortical inhibitory functioning and motor inhibition.
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Potenciales Evocados Motores/fisiología , Individualidad , Músculo Esquelético/fisiología , Inhibición Neural/fisiología , Adulto , Femenino , Humanos , Inhibición Psicológica , Masculino , Corteza Motora/fisiología , Descanso/fisiología , Estimulación Magnética Transcraneal/métodos , Adulto JovenRESUMEN
BACKGROUND: Several pasture management strategies have been proposed to avoid hypoglycin A (HGA) intoxication in horses, but their efficacy has never been investigated. OBJECTIVES: To evaluate the effect of mowing and herbicidal spraying on HGA content of sycamore seedlings and the presence of HGA in seeds and seedlings processed within haylage and silage. STUDY DESIGN: Experimental study. METHODS: Groups of seedlings were mowed (n = 6), sprayed with a dimethylamine-based (n = 2) or a picolinic acid-based herbicide (n = 1). Seedlings were collected before intervention, and at 48 h, 1 and 2 weeks after. Cut grass in the vicinity of mowed seedlings was collected pre-cutting and after 1 week. Seeds and seedling (n = 6) samples processed within haylage and silage were collected. HGA concentration in samples was measured using a validated LC-MS-based method. RESULTS: There was no significant decline in HGA content in either mowed or sprayed seedlings; indeed, mowing induced a temporary significant rise in HGA content of seedlings. HGA concentration increased significantly (albeit to low levels) in grass cut with the seedlings by 1 week. HGA was still present in sycamore material after 6-8 months storage within either hay or silage. MAIN LIMITATIONS: Restricted number of herbicide compounds tested. CONCLUSIONS: Neither mowing nor herbicidal spraying reduces HGA concentration in sycamore seedlings up to 2 weeks after intervention. Cross contamination is possible between grass and sycamore seedlings when mowed together. Mowing followed by collection of sycamore seedlings seems the current best option to avoid HGA toxicity in horses grazing contaminated pasture. Pastures contaminated with sycamore material should not be used to produce processed hay or silage as both seedlings and seeds present in the bales still pose a risk of intoxication.
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Acer/química , Enfermedades de los Caballos/inducido químicamente , Hipoglicinas/metabolismo , Plantones/química , Acer/crecimiento & desarrollo , Acer/metabolismo , Agricultura , Animales , Enfermedades de los Caballos/prevención & control , Caballos , Hipoglicinas/química , Hipoglicinas/toxicidad , Miotoxicidad/veterinaria , Plantones/crecimiento & desarrollo , Plantones/metabolismoRESUMEN
This study aimed to evaluate the 'inhibitory deficit' hypothesis of developmental coordination disorder (DCD). We adopted a multifaceted approach, investigating two distinct, yet complimentary facets of motor inhibition: action restraint and action cancellation. This was achieved using carefully constructed versions of the 'Go/No-go' and 'Stop-signal' tasks, respectively. The sample comprised 11 young adults with DCD aged between 18 and 30â¯years of age and 11 typically developing, age-matched controls. Participants completed both the 'Go/No-go' and 'Stop-signal' tasks to assess action restraint and action cancellation respectively. Individuals with DCD were less efficient than their typically developing peers at performing both action restraint and action cancellation, indicated by significantly reduced action restraint efficiency index scores on the 'Go/No-go' task and a trend towards longer stop-signal reaction times on the 'Stop-signal' task. This work clarifies disparate evidence speaking to the integrity of action restraint in DCD and provides the first account of action cancellation in DCD using a purpose-built measure. In support of the inhibitory deficit hypothesis of DCD, our results suggest that young adults with DCD experience broad difficulties with engaging inhibitory mechanisms during motor behaviour.
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Inhibición Psicológica , Trastornos de la Destreza Motora/fisiopatología , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Destreza Motora/fisiología , Adulto JovenRESUMEN
BACKGROUND: Primary care faecal calprotectin testing distinguishes inflammatory bowel disease (IBD) from functional gut disorder in young patients presenting with abdominal symptoms; however, previous evaluations have excluded patients with alarm symptoms. AIMS: We sought to evaluate the diagnostic accuracy of calprotectin to distinguish IBD from functional gut disorder in young adults in whom general practitioners (GPs) suspected IBD; including patients reporting gastrointestinal alarm symptoms. We hypothesised that calprotectin would reduce secondary care referrals and healthcare costs. METHODS: We undertook a prospective cohort study of 789 young adults (18-46 years old) presenting with gastrointestinal symptoms to 49 local general practices that had undergone calprotectin testing (1053 tests: between Jan 2014 and May 2016) because of suspected IBD. We considered calprotectin levels of ≥100 µg/g positive. Primary and secondary care records over 12 months from the point of calprotectin testing were used as the reference standard. RESULTS: Overall, 39% (308/789) patients reported gastrointestinal alarm symptoms and 6% (50/789) tested patients were diagnosed with IBD. The positive and negative predictive values of calprotectin testing for distinguishing IBD from functional gut disorder in patients with gastrointestinal alarm symptoms were 50% (95% CI 36%-64%) and 98% (96%-100%): and in patients without gastrointestinal alarm symptoms were 27% (16%-41%) and 99% (98%-100%), respectively. We estimate savings of 279 referrals and £160 per patient. CONCLUSIONS: Calprotectin testing of young adults with suspected IBD in primary care accurately distinguishes IBD from functional gut disorder, even in patients with gastrointestinal alarm symptoms and reduces secondary care referrals and diagnostic healthcare costs.
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Biomarcadores/análisis , Heces/química , Enfermedades Gastrointestinales/diagnóstico , Complejo de Antígeno L1 de Leucocito/análisis , Adolescente , Adulto , Diagnóstico Diferencial , Femenino , Médicos Generales , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Estudios Prospectivos , Derivación y Consulta , Atención Secundaria de Salud , Reino Unido , Adulto JovenRESUMEN
Recent neuroimaging studies have reported atypical neural activation in children with Developmental Coordination Disorder (DCD) during tasks assessing manual dexterity. However, small sample sizes and subtle differences in task parameters have led to inconsistent findings, rendering interpretation difficult. The aim of the present meta-analysis was to quantitatively summarize this body of evidence using activation likelihood estimation (ALE) analysis to identify reliable regions of differential neural activation in children with DCD, compared to age-matched controls. Seven studies that adopted fMRI to compare children with and without DCD during manual performance were identified following a literature search. All were included in the ALE analysis. Compared to controls, children with DCD showed reduced activation during a manual dexterity task in the middle frontal gyrus, superior frontal gyrus, cerebellum, supramarginal gyrus, and inferior parietal lobule. Children with DCD showed greater activation in parts of the thalamus. Findings provide much needed clarification into the possible neural contributors to atypical manual dexterity in DCD and highlight the need for neuroimaging studies to include manual performance outcomes.
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Encéfalo/fisiopatología , Trastornos de la Destreza Motora/fisiopatología , Destreza Motora/fisiología , Humanos , Funciones de Verosimilitud , Imagen por Resonancia Magnética , NeuroimagenRESUMEN
While a compelling body of behavioral research suggests that individuals with developmental coordination disorder (DCD) experience difficulties engaging motor imagery (MI), very little is known about the neural correlates of this deficit. Since corticospinal excitability is a predictor of MI proficiency in healthy adults, we reasoned that decreased MI efficiency in DCD may be paralleled by atypical primary motor cortex (PMC) activity. Participants were 29 young adults aged 18- 36 years: 8 with DCD (DCD) and 21 controls. Six participants with DCD and 15 controls showed behavioral profiles consistent with the use of a MI strategy (MI users) while performing a novel adaptation of the classic hand laterality task (HLT). Single-pulse transcranial magnetic stimulation (TMS) was administered to the hand node of the left PMC (hPMC) at 50ms, 400ms or 650ms post stimulus presentation during the HLT. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous (FDI) via electromyography. As predicted, MI users with DCD were significantly less efficient than MI using controls, shown by poorer performance on the HLT. Importantly, unlike healthy controls, no evidence of enhanced hPMC activity during MI was detected in our DCD group. Our data are consistent with the view that inefficient MI in DCD may be subserved by decreased hPMC activity. These findings are an important step towards clarifying the neuro-cognitive correlates of poor MI ability and motor skill in individuals with DCD.
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Potenciales Evocados Motores/fisiología , Mano , Imaginación/fisiología , Trastornos de la Destreza Motora , Destreza Motora/fisiología , Adaptación Fisiológica , Adulto , Electromiografía/métodos , Femenino , Lateralidad Funcional , Mano/fisiología , Mano/fisiopatología , Humanos , Masculino , Corteza Motora/fisiología , Trastornos de la Destreza Motora/diagnóstico , Trastornos de la Destreza Motora/fisiopatología , Trastornos de la Destreza Motora/psicología , Estimulación Magnética Transcraneal/métodosRESUMEN
The internal structure of nucleons (protons and neutrons) remains one of the greatest outstanding problems in modern nuclear physics. By scattering high-energy electrons off a proton we are able to resolve its fundamental constituents and probe their momenta and positions. Here we investigate the dynamics of quarks and gluons inside nucleons using deeply virtual Compton scattering (DVCS)-a highly virtual photon scatters off the proton, which subsequently radiates a photon. DVCS interferes with the Bethe-Heitler (BH) process, where the photon is emitted by the electron rather than the proton. We report herein the full determination of the BH-DVCS interference by exploiting the distinct energy dependences of the DVCS and BH amplitudes. In the regime where the scattering is expected to occur off a single quark, measurements show an intriguing sensitivity to gluons, the carriers of the strong interaction.
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We report the first longitudinal-transverse separation of the deeply virtual exclusive π^{0} electroproduction cross section off the neutron and coherent deuteron. The corresponding four structure functions dσ_{L}/dt, dσ_{T}/dt, dσ_{LT}/dt, and dσ_{TT}/dt are extracted as a function of the momentum transfer to the recoil system at Q^{2}=1.75 GeV^{2} and x_{B}=0.36. The edâedπ^{0} cross sections are found compatible with the small values expected from theoretical models. The enâenπ^{0} cross sections show a dominance from the response to transversely polarized photons, and are in good agreement with calculations based on the transversity generalized parton distributions of the nucleon. By combining these results with previous measurements of π^{0} electroproduction off the proton, we present a flavor decomposition of the u and d quark contributions to the cross section.
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Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes - processing speed, whole-brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3' untranslated region of voltage-gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia.
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Canal de Potasio KCNQ1/genética , Polimorfismo de Nucleótido Simple , Esquizofrenia/genética , Sustancia Blanca/metabolismo , Regiones no Traducidas 3' , Potenciales de Acción , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción , Esquizofrenia/fisiopatología , Sustancia Blanca/fisiopatologíaRESUMEN
The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-Z target. Positron polarization up to 82% have been measured for an initial electron beam momentum of 8.19 MeV/c, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community.
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We present deeply virtual π^{0} electroproduction cross-section measurements at x_{B}=0.36 and three different Q^{2} values ranging from 1.5 to 2 GeV^{2}, obtained from Jefferson Lab Hall A experiment E07-007. The Rosenbluth technique is used to separate the longitudinal and transverse responses. Results demonstrate that the cross section is dominated by its transverse component and, thus, is far from the asymptotic limit predicted by perturbative quantum chromodynamics. Nonetheless, an indication of a nonzero longitudinal contribution is provided by the measured interference term σ_{LT}. Results are compared with several models based on the leading-twist approach of generalized parton distributions (GPDs). In particular, a fair agreement is obtained with models in which the scattering amplitude includes convolution terms of chiral-odd (transversity) GPDs of the nucleon with the twist-3 pion distribution amplitude. This experiment, together with previous extensive unseparated measurements, provides strong support to the exciting idea that transversity GPDs can be accessed via neutral pion electroproduction in the high-Q^{2} regime.
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AIM: To assess the diagnostic accuracy of computed tomography coronary angiography (CTCA) using a combination of high-definition CT (HD-CTCA) and high level of reader experience, with invasive coronary angiography (ICA) as the reference standard, in high-risk patients for the investigation of coronary artery disease (CAD). MATERIALS AND METHODS: Three hundred high-risk patients underwent HD-CTCA and ICA. Independent experts evaluated the images for the presence of significant CAD, defined primarily as the presence of moderate (≥ 50%) stenosis and secondarily as the presence of severe (≥ 70%) stenosis in at least one coronary segment, in a blinded fashion. HD-CTCA was compared to ICA as the reference standard. RESULTS: No patients were excluded. Two hundred and six patients (69%) had moderate and 178 (59%) had severe stenosis in at least one vessel at ICA. The sensitivity, specificity, positive predictive value, and negative predictive value were 97.1%, 97.9%, 99% and 93.9% for moderate stenosis, and 98.9%, 93.4%, 95.7% and 98.3%, for severe stenosis, on a per-patient basis. CONCLUSION: The combination of HD-CTCA and experienced readers applied to a high-risk population, results in high diagnostic accuracy comparable to ICA. Modern generation CT systems in experienced hands might be considered for an expanded role.
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Riesgo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. METHODS: A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. FINDINGS: When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. INTERPRETATION: A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. FUNDING: National Institutes of Health.
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Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/genética , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Humanos , Números Necesarios a Tratar , Prevención Primaria , Recurrencia , Medición de Riesgo , Prevención Secundaria , Resultado del TratamientoRESUMEN
Double-spin asymmetries and absolute cross sections were measured at large Bjorken x (0.25≤x≤0.90), in both the deep-inelastic and resonance regions, by scattering longitudinally polarized electrons at beam energies of 4.7 and 5.9 GeV from a transversely and longitudinally polarized (3)He target. In this dedicated experiment, the spin structure function g(2)((3)He) was determined with precision at large x, and the neutron twist-3 matrix element d(2)(n) was measured at ⟨Q(2)⟩ of 3.21 and 4.32 GeV(2)/c(2), with an absolute precision of about 10(-5). Our results are found to be in agreement with lattice QCD calculations and resolve the disagreement found with previous data at ⟨Q(2)⟩=5 GeV(2)/c(2). Combining d(2)(n) and a newly extracted twist-4 matrix element f(2)(n), the average neutron color electric and magnetic forces were extracted and found to be of opposite sign and about 30 MeV/fm in magnitude.