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1.
J Cardiovasc Magn Reson ; 26(1): 101039, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38521391

RESUMEN

BACKGROUND: Cardiovascular magnetic resonance (CMR) is an important imaging modality for the assessment and management of adult patients with congenital heart disease (CHD). However, conventional techniques for three-dimensional (3D) whole-heart acquisition involve long and unpredictable scan times and methods that accelerate scans via k-space undersampling often rely on long iterative reconstructions. Deep-learning-based reconstruction methods have recently attracted much interest due to their capacity to provide fast reconstructions while often outperforming existing state-of-the-art methods. In this study, we sought to adapt and validate a non-rigid motion-corrected model-based deep learning (MoCo-MoDL) reconstruction framework for 3D whole-heart MRI in a CHD patient cohort. METHODS: The previously proposed deep-learning reconstruction framework MoCo-MoDL, which incorporates a non-rigid motion-estimation network and a denoising regularization network within an unrolled iterative reconstruction, was trained in an end-to-end manner using 39 CHD patient datasets. Once trained, the framework was evaluated in eight CHD patient datasets acquired with seven-fold prospective undersampling. Reconstruction quality was compared with the state-of-the-art non-rigid motion-corrected patch-based low-rank reconstruction method (NR-PROST) and against reference images (acquired with three-or-four-fold undersampling and reconstructed with NR-PROST). RESULTS: Seven-fold undersampled scan times were 2.1 ± 0.3 minutes and reconstruction times were ∼30 seconds, approximately 240 times faster than an NR-PROST reconstruction. Image quality comparable to the reference images was achieved using the proposed MoCo-MoDL framework, with no statistically significant differences found in any of the assessed quantitative or qualitative image quality measures. Additionally, expert image quality scores indicated the MoCo-MoDL reconstructions were consistently of a higher quality than the NR-PROST reconstructions of the same data, with the differences in 12 of the 22 scores measured for individual vascular structures found to be statistically significant. CONCLUSION: The MoCo-MoDL framework was applied to an adult CHD patient cohort, achieving good quality 3D whole-heart images from ∼2-minute scans with reconstruction times of ∼30 seconds.


Asunto(s)
Aprendizaje Profundo , Cardiopatías Congénitas , Interpretación de Imagen Asistida por Computador , Valor Predictivo de las Pruebas , Humanos , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/fisiopatología , Reproducibilidad de los Resultados , Adulto , Masculino , Femenino , Adulto Joven , Imagenología Tridimensional , Factores de Tiempo , Imagen por Resonancia Magnética , Imagen por Resonancia Cinemagnética
2.
Nature ; 557(7705): 392-395, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29769675

RESUMEN

A fundamental quest of modern astronomy is to locate the earliest galaxies and study how they influenced the intergalactic medium a few hundred million years after the Big Bang1-3. The abundance of star-forming galaxies is known to decline4,5 from redshifts of about 6 to 10, but a key question is the extent of star formation at even earlier times, corresponding to the period when the first galaxies might have emerged. Here we report spectroscopic observations of MACS1149-JD1 6 , a gravitationally lensed galaxy observed when the Universe was less than four per cent of its present age. We detect an emission line of doubly ionized oxygen at a redshift of 9.1096 ± 0.0006, with an uncertainty of one standard deviation. This precisely determined redshift indicates that the red rest-frame optical colour arises from a dominant stellar component that formed about 250 million years after the Big Bang, corresponding to a redshift of about 15. Our results indicate that it may be possible to detect such early episodes of star formation in similar galaxies with future telescopes.

3.
Clin Infect Dis ; 75(1): e525-e528, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35271729

RESUMEN

ß-d-N4-hydroxycytidine (NHC), the parent nucleoside of molnupiravir, a COVID-19 antiviral, was quantified at SARS-CoV-2 transmission sites in 12 patients enrolled in AGILE Candidate-Specific Trial-2. Saliva, nasal, and tear NHC concentrations were 3%, 21%, and 22% that of plasma. Saliva and nasal NHC were significantly correlated with plasma (P < .0001). Clinical Trials Registration. NCT04746183.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Profármacos , Antivirales/uso terapéutico , Citidina/análogos & derivados , Humanos , Hidroxilaminas , Nucleósidos , Padres , Profármacos/uso terapéutico , SARS-CoV-2
4.
Chem Rev ; 120(10): 4455-4533, 2020 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-32363864

RESUMEN

This comprehensive critical review combines, for the first time, recent advances in nanoscale surface chemistry, surface science, DFT, adsorption calorimetry, and in situ XRD and TEM to provide new insights into catalyst sintering. This work provides qualitative and quantitative estimates of the extent and rate of sintering as functions of nanocrystal (NC) size, temperature, and atmosphere. This review is unique in that besides summarizing important, useful data from previous studies, it also advances the field through addition of (i) improved or new models, (ii) new data summarized in original tables and figures, and (iii) new fundamental perspectives into sintering of supported metals and particularly of chemical sintering of supported Co during Fischer-Tropsch synthesis. We demonstrate how the two widely accepted sintering mechanisms are largely sequential with some overlap and highly NC-size dependent, i.e., generally, small NCs sinter rapidly by Ostwald ripening, while larger NCs sinter slowly by crystallite migration and coalescence. In addition, we demonstrate how accumulated knowledge, principles, and recent advances, discussed in this review, can be utilized in the design of supported metal NCs highly resistant to sintering. Recommendations for improving the design of sintering experiments and for new research are addressed.

5.
J Antimicrob Chemother ; 76(12): 3286-3295, 2021 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-34450619

RESUMEN

OBJECTIVES: AGILE is a Phase Ib/IIa platform for rapidly evaluating COVID-19 treatments. In this trial (NCT04746183) we evaluated the safety and optimal dose of molnupiravir in participants with early symptomatic infection. METHODS: We undertook a dose-escalating, open-label, randomized-controlled (standard-of-care) Bayesian adaptive Phase I trial at the Royal Liverpool and Broadgreen Clinical Research Facility. Participants (adult outpatients with PCR-confirmed SARS-CoV-2 infection within 5 days of symptom onset) were randomized 2:1 in groups of 6 participants to 300, 600 and 800 mg doses of molnupiravir orally, twice daily for 5 days or control. A dose was judged unsafe if the probability of 30% or greater dose-limiting toxicity (the primary outcome) over controls was 25% or greater. Secondary outcomes included safety, clinical progression, pharmacokinetics and virological responses. RESULTS: Of 103 participants screened, 18 participants were enrolled between 17 July and 30 October 2020. Molnupiravir was well tolerated at 300, 600 and 800 mg doses with no serious or severe adverse events. Overall, 4 of 4 (100%), 4 of 4 (100%) and 1 of 4 (25%) of the participants receiving 300, 600 and 800 mg molnupiravir, respectively, and 5 of 6 (83%) controls, had at least one adverse event, all of which were mild (≤grade 2). The probability of ≥30% excess toxicity over controls at 800 mg was estimated at 0.9%. CONCLUSIONS: Molnupiravir was safe and well tolerated; a dose of 800 mg twice daily for 5 days was recommended for Phase II evaluation.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Teorema de Bayes , Humanos , Proyectos de Investigación , Resultado del Tratamiento
6.
Lancet ; 391(10121): 700-708, 2018 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-29054555

RESUMEN

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief.


Asunto(s)
Brotes de Enfermedades , Medicina Basada en la Evidencia/métodos , Fiebre Hemorrágica Ebola/epidemiología , Aceptación de la Atención de Salud/psicología , África Occidental/epidemiología , Manejo de la Enfermedad , Instituciones de Salud , Fiebre Hemorrágica Ebola/psicología , Hospitalización , Humanos , Monitoreo Fisiológico , Manejo del Dolor , Guías de Práctica Clínica como Asunto
7.
N Engl J Med ; 371(22): 2092-100, 2014 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-25353969

RESUMEN

BACKGROUND: Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014. METHODS: We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase-polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients. RESULTS: Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient. CONCLUSIONS: The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.).


Asunto(s)
Ebolavirus/genética , Epidemias , Fiebre Hemorrágica Ebola/epidemiología , Dolor Abdominal , Adulto , Animales , Diarrea , Ebolavirus/aislamiento & purificación , Femenino , Fiebre , Fiebre Hemorrágica Ebola/complicaciones , Fiebre Hemorrágica Ebola/terapia , Fiebre Hemorrágica Ebola/virología , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sierra Leona/epidemiología , Carga Viral , Vómitos
8.
Crit Care ; 20(1): 217, 2016 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-27468829

RESUMEN

As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa.EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death.Males and females have been equally affected, with children (0-14 years of age) accounting for 19 %, young adults (15-44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40-90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission.While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes.


Asunto(s)
Fiebre Hemorrágica Ebola , Adulto , África Occidental/epidemiología , Anciano , Cuidados Críticos/métodos , Cuidados Críticos/normas , Enfermedad Crítica/mortalidad , Países en Desarrollo , Ebolavirus/patogenicidad , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad
9.
J Trauma Stress ; 29(4): 283-92, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27254474

RESUMEN

There is little information available on the mental health effects of exposure to shared community violence such as the August 2014 violence that occurred in Ferguson, Missouri. This study sought to examine the relationship between proximity to community violence and mental health in both community members and police officers. We recruited 565 adults (community, n = 304, and police, n = 261) exposed to the violence in Ferguson to complete measures of proximity to violence, posttraumatic stress, depression, and anger. Using structural equation modeling, we assessed aspects of proximity to violence-connectedness, direct exposure, fear from exposure, media exposure, reactions to media, and life interruption-as correlates of posttraumatic stress disorder (PTSD) symptoms, depression, and anger. The final model yielded (n = 432), χ(2) (d = 12) = 7.4, p = .830; comparative fit index = 1.0, root mean square error of approximation = 0 [0, .04]. All aspects of proximity except direct exposure were associated with mental health outcomes. There was no moderation as a function of community versus police. Race moderated the relationship between life interruptions and negative outcomes; interruption was related to distress for White, but not Black community members. Based on group comparisons, community members reported more symptoms of PTSD and depression than law enforcement (ηp (2) = .06 and .02, respectively). Black community members reported more PTSD and depression than White community members (ηp (2) = .05 and .02, respectively). Overall, distress was high, and mental health interventions are likely indicated for some individuals exposed to the Ferguson events.


Asunto(s)
Exposición a la Violencia/psicología , Aplicación de la Ley , Policia/psicología , Características de la Residencia/estadística & datos numéricos , Trastornos por Estrés Postraumático/etiología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Ira , Estudios Transversales , Depresión/etiología , Depresión/psicología , Femenino , Humanos , Masculino , Medios de Comunicación de Masas , Persona de Mediana Edad , Missouri , Policia/estadística & datos numéricos , Trastornos por Estrés Postraumático/psicología , Encuestas y Cuestionarios , Factores de Tiempo , Población Blanca/estadística & datos numéricos
10.
Clin Infect Dis ; 61(5): 795-8, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-25991466

RESUMEN

Patients with febrile illnesses presenting to an Ebola treatment unit in Sierra Leone had a wide range of diagnoses other than Ebola virus disease. Rapid diagnostic tests were useful in confirming these diagnoses, reducing the length of patient stay with valuable consequences. These alternative diagnoses should assist in future planning.


Asunto(s)
Fiebre/epidemiología , Fiebre/etiología , Adulto , Brotes de Enfermedades , Femenino , Fiebre/diagnóstico , Fiebre Hemorrágica Ebola , Humanos , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Estudios Retrospectivos , Sierra Leona/epidemiología , Adulto Joven
11.
N Engl J Med ; 376(7): 700, 2017 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-28207206
12.
Am J Respir Crit Care Med ; 190(7): 733-7, 2014 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25166884

RESUMEN

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.


Asunto(s)
Cuidados Críticos/métodos , Fiebre Hemorrágica Ebola/terapia , Atención al Paciente/métodos , África Occidental/epidemiología , Enfermedad Crítica , Brotes de Enfermedades/estadística & datos numéricos , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Cuidados Paliativos/métodos
13.
Proc Biol Sci ; 281(1788): 20140703, 2014 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-24943377

RESUMEN

From their earliest origins, fishes have developed a suite of adaptations for locomotion in water, which determine performance and ultimately fitness. Even without data from behaviour, soft tissue and extant relatives, it is possible to infer a wealth of palaeobiological and palaeoecological information. As in extant species, aspects of gross morphology such as streamlining, fin position and tail type are optimized even in the earliest fishes, indicating similar life strategies have been present throughout their evolutionary history. As hydrodynamical studies become more sophisticated, increasingly complex fluid movement can be modelled, including vortex formation and boundary layer control. Drag-reducing riblets ornamenting the scales of fast-moving sharks have been subjected to particularly intense research, but this has not been extended to extinct forms. Riblets are a convergent adaptation seen in many Palaeozoic fishes, and probably served a similar hydrodynamic purpose. Conversely, structures which appear to increase skin friction may act as turbulisors, reducing overall drag while serving a protective function. Here, we examine the diverse adaptions that contribute to drag reduction in modern fishes and review the few attempts to elucidate the hydrodynamics of extinct forms.


Asunto(s)
Peces/anatomía & histología , Peces/fisiología , Fósiles/anatomía & histología , Hidrodinámica , Natación , Adaptación Fisiológica , Animales , Evolución Biológica
14.
J Infect ; 88(3): 106115, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38309308

RESUMEN

OBJECTIVES: Glycosylation motifs shape antibody structure, stability and antigen affinity and play an important role in antibody localization and function. Serum IgG glycosylation profiles are significantly altered in infectious diseases, including tuberculosis (TB), but have not been studied in the context of progression from latent to active TB. METHODS: We performed a longitudinal study of paired bulk IgG glycosylation and transcriptomic profiling in blood from individuals with active TB (ATB) or latent TB infection (LTBI) before and after treatment. RESULTS: We identified that a combination of two IgG1 glycosylation traits were sufficient to distinguish ATB from LTBI with high specificity and sensitivity, prior to, and after treatment. Importantly, these two features positively correlated with previously defined cellular and RNA signatures of ATB risk in LTBI, namely monocyte to lymphocyte ratio and the expression of interferon (IFN)-associated gene signature of progression (IFN-risk signature) in blood prior to treatment. Additional glycosylation features at higher prevalence in LTBI individuals with high expression of the IFN-risk signature prior to treatment included fucosylation on IgG1, IgG2 and IgG3. CONCLUSIONS: Together, our results demonstrate that bulk IgG glycosylation features could be useful in stratifying the risk of LTBI reactivation and progression to ATB.


Asunto(s)
Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis , Humanos , Glicosilación , Estudios Longitudinales , Inmunoglobulina G , Biomarcadores
15.
PLoS Negl Trop Dis ; 18(1): e0011931, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38277403

RESUMEN

BACKGROUND: Gastrointestinal parasite (GIP) infections are a major cause of global morbidity, infecting hundreds of millions of people each year and potentially leading to lifelong infection and serious complications. Few data exist on screening for GIP infections in migrants entering the UK or on the current performance of different traditional diagnostic approaches. This study aimed to describe the prevalence of GIP infections in Nepalese Gurkha recruits screened on arrival in the UK. METHODOLOGY/PRINCIPAL FINDINGS: We present a retrospective analysis of data from screening male adults (18-21 years) who arrived in the UK from Nepal between 2012 and 2020. Three separate faecal samples were obtained from participants at weekly intervals and processed for formalin-ethyl acetate (FEA) concentration/light microscopy and charcoal culture. Serum samples were analysed for IgG antibodies to Strongyloides stercoralis by ELISA. Results were available from 2,263 participants, of whom 463 (20.5%, 95% CI 18.8%-22.2%) had a positive diagnostic test for at least one GIP infection. A total of 525 potential infections were identified. Giardia duodenalis was most common (231/2263, 10.2%), followed by S. stercoralis (102/2263, 4.5%), and hookworm species (86/2263, 3.8%). Analysis (microscopy and culture) of the initial stool sample diagnosed only 244/427 (57.1%) faecally identified pathogens, including 41/86 (47.7%) hookworm infections. The proportion of participants infected with any GIP showed a downward trend over the study period. Log-binomial regression showed risk of infection decreasing by 6.1% year-on-year (95% CI 3.2% - 9.0%). This was driven predominantly by a fall in hookworm, S. stercoralis and Trichuris trichiura prevalence. CONCLUSIONS/SIGNIFICANCE: The level of potentially pathogenic GIP infection in young Nepalese men migrating to the UK is high (20.5%) and requires a combined diagnostic approach including serology and analysis of multiple stool samples incorporating specialised parasitological methods. Advances in molecular approaches may optimise and simplify the intensive screening strategy required.


Asunto(s)
Enfermedades Transmisibles , Enfermedades Gastrointestinales , Parasitosis Intestinales , Parásitos , Strongyloides stercoralis , Estrongiloidiasis , Humanos , Adulto , Animales , Masculino , Estrongiloidiasis/epidemiología , Nepal/epidemiología , Estudios Retrospectivos , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/parasitología , Ancylostomatoidea , Heces/parasitología , Prevalencia
16.
Open Forum Infect Dis ; 11(1): ofae001, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38250201

RESUMEN

Background: We report clinical, epidemiological, and laboratory features of a large diarrhea outbreak caused by a novel Cryptosporidium hominis subtype during British military training in Kenya between February and April 2022. Methods: Data were collated from diarrhea cases, and fecal samples were analyzed on site using the multiplex polymerase chain reaction (PCR) BioFire FilmArray. Water was tested using Colilert kits (IDEXX, UK). DNA was extracted from feces for molecular characterization of Cryptosporidium A135, Lib13, ssu rRNA, and gp60 genes. Results: One hundred seventy-two of 1200 (14.3%) personnel at risk developed diarrhea over 69 days. One hundred six primary fecal samples were tested, and 63/106 (59.4%; 95% CI, 0.49%-0.69%) were positive for Cryptosporidium spp. Thirty-eight had Cryptosporidium spp. alone, and 25 had Cryptosporidium spp. with ≥1 other pathogen. A further 27/106 (25.5%; 95% CI, 0.18%-0.35%) had non-Cryptosporidium pathogens only, and 16/106 (15.1%; 95% CI, 0.09%-0.23%) were negative. C. hominis was detected in 58/63 (92.1%) Cryptosporidium spp.-positive primary samples, but the others were not genotypable. Twenty-seven C. hominis specimens were subtypable; 1 was gp60 subtype IeA11G3T3, and 26 were an unusual subtype, ImA13G1 (GenBank accession OP699729), supporting epidemiological evidence suggesting a point source outbreak from contaminated swimming water. Diarrhea persisted for a mean (SD) of 7.6 (4.6) days in Cryptosporidium spp. cases compared with 2.3 (0.9) days in non-Cryptosporidium cases (P = .001). Conclusions: Real-time multiplex PCR fecal testing was vital in managing this large cryptosporidiosis outbreak. The etiology of a rare C. hominis gp60 subtype emphasizes the need for more genotypic surveillance to identify widening host and geographic ranges of novel C. hominis subtypes.

17.
Lancet Infect Dis ; 23(2): 183-195, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36272432

RESUMEN

BACKGROUND: The antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19. METHODS: This randomised, placebo-controlled, double-blind, phase 2 trial (AGILE CST-2) was done at five National Institute for Health and Care Research sites in the UK. Eligible participants were adult (aged ≥18 years) outpatients with PCR-confirmed, mild-to-moderate SARS-CoV-2 infection who were within 5 days of symptom onset. Using permuted blocks (block size 2 or 4) and stratifying by site, participants were randomly assigned (1:1) to receive either molnupiravir (orally; 800 mg twice daily for 5 days) plus standard of care or matching placebo plus standard of care. The primary outcome was the time from randomisation to SARS-CoV-2 PCR negativity on nasopharyngeal swabs and was analysed by use of a Bayesian Cox proportional hazards model for estimating the probability of a superior virological response (hazard ratio [HR]>1) for molnupiravir versus placebo. Our primary model used a two-point prior based on equal prior probabilities (50%) that the HR was 1·0 or 1·5. We defined a priori that if the probability of a HR of more than 1 was more than 80% molnupiravir would be recommended for further testing. The primary outcome was analysed in the intention-to-treat population and safety was analysed in the safety population, comprising participants who had received at least one dose of allocated treatment. This trial is registered in ClinicalTrials.gov, NCT04746183, and the ISRCTN registry, ISRCTN27106947, and is ongoing. FINDINGS: Between Nov 18, 2020, and March 16, 2022, 1723 patients were assessed for eligibility, of whom 180 were randomly assigned to receive either molnupiravir (n=90) or placebo (n=90) and were included in the intention-to-treat analysis. 103 (57%) of 180 participants were female and 77 (43%) were male and 90 (50%) participants had received at least one dose of a COVID-19 vaccine. SARS-CoV-2 infections with the delta (B.1.617.2; 72 [40%] of 180), alpha (B.1.1.7; 37 [21%]), omicron (B.1.1.529; 38 [21%]), and EU1 (B.1.177; 28 [16%]) variants were represented. All 180 participants received at least one dose of treatment and four participants discontinued the study (one in the molnupiravir group and three in the placebo group). Participants in the molnupiravir group had a faster median time from randomisation to negative PCR (8 days [95% CI 8-9]) than participants in the placebo group (11 days [10-11]; HR 1·30, 95% credible interval 0·92-1·71; log-rank p=0·074). The probability of molnupiravir being superior to placebo (HR>1) was 75·4%, which was less than our threshold of 80%. 73 (81%) of 90 participants in the molnupiravir group and 68 (76%) of 90 participants in the placebo group had at least one adverse event by day 29. One participant in the molnupiravir group and three participants in the placebo group had an adverse event of a Common Terminology Criteria for Adverse Events grade 3 or higher severity. No participants died (due to any cause) during the trial. INTERPRETATION: We found molnupiravir to be well tolerated and, although our predefined threshold was not reached, we observed some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this evidence is not conclusive. FUNDING: Ridgeback Biotherapeutics, the UK National Institute for Health and Care Research, the Medical Research Council, and the Wellcome Trust.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Adolescente , Adulto , Femenino , Humanos , Masculino , Antivirales , Teorema de Bayes , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Método Doble Ciego , SARS-CoV-2 , Resultado del Tratamiento , Reino Unido
19.
Front Cardiovasc Med ; 9: 1009131, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36204566

RESUMEN

Magnetic resonance fingerprinting (MRF) is a fast MRI-based technique that allows for multiparametric quantitative characterization of the tissues of interest in a single acquisition. In particular, it has gained attention in the field of cardiac imaging due to its ability to provide simultaneous and co-registered myocardial T1 and T2 mapping in a single breath-held cardiac MRF scan, in addition to other parameters. Initial results in small healthy subject groups and clinical studies have demonstrated the feasibility and potential of MRF imaging. Ongoing research is being conducted to improve the accuracy, efficiency, and robustness of cardiac MRF. However, these improvements usually increase the complexity of image reconstruction and dictionary generation and introduce the need for sequence optimization. Each of these steps increase the computational demand and processing time of MRF. The latest advances in artificial intelligence (AI), including progress in deep learning and the development of neural networks for MRI, now present an opportunity to efficiently address these issues. Artificial intelligence can be used to optimize candidate sequences and reduce the memory demand and computational time required for reconstruction and post-processing. Recently, proposed machine learning-based approaches have been shown to reduce dictionary generation and reconstruction times by several orders of magnitude. Such applications of AI should help to remove these bottlenecks and speed up cardiac MRF, improving its practical utility and allowing for its potential inclusion in clinical routine. This review aims to summarize the latest developments in artificial intelligence applied to cardiac MRF. Particularly, we focus on the application of machine learning at different steps of the MRF process, such as sequence optimization, dictionary generation and image reconstruction.

20.
Front Public Health ; 10: 1101817, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36711341

RESUMEN

Introduction: Outbreaks of SARS-CoV-2 onboard maritime platforms spread rapidly and have high attack rates. The aim of the COVID-19 Risk, Attitudes and Behaviour (CRAB) study was to investigate the knowledge, attitudes, and practises in the Royal Navy in relation to COVID-19 prevention. Methods: The CRAB study was a cross-sectional survey, using a census sampling method, conducted in May and June 2021. An online questionnaire was distributed to all serving Royal Navy regular personnel using either the MyNavy application or via a QR code through email for a continuous 14 day period. The questionnaire was based on an existing validated questionnaire used for avian influenza epidemics. Questions investigated individual perceptions of COVID-19 seriousness, compliance with prevention methods, explored vaccination intention and vaccine hesitancy (unvaccinated individuals who declined or were unsure about receiving a COVID-19 vaccine). The chi-squared test of best fit was used to compare the demographic responses against the whole organisation, with p-value < 0.05 deemed significant. Odds ratios were used to investigate associations between demographic groups and responses to questions, with an odds ratio crossing 1.0 deemed non-significant. Results: The response rate was 6% (2,080/33,200), with 315 responses collated in the pilot phase and 1,765 in the main study phase. Male participants were less likely to rate COVID-19 as serious (OR 0.34; 95% CI: 0.23-0.49). BAME ethnicity (OR 2.41; 95% CI: 1.12-5.17) rated it as more serious. At the time of the study 62% of respondents had received one dose of a COVID-19 vaccine. In the 797 unvaccinated personnel, vaccine hesitancy accounted for 24.2% (193/797), of whom 136 were white males. Those who had a higher COVID-19 serious rating, the most significant factor for non-adherence to COVID-19 prevention measures in both vaccinated (OR 1.61 [95%CI: 1.20-2.17]) and vaccine-hesitant (OR 3.24 [95%CI: 1.63-6.41]) individuals was colleagues' non-adherence. The most trusted source of information on vaccines was provided by the Defence Medical Services (77.2% [1,606/2,080]). Conclusion: This study has identified reasons for COVID-19 protective measure adherence, sources of information trusted by respondents and vaccine hesitancy, in the Royal Navy. The questionnaire can be used to investigate attitudes and behaviours in future emerging infectious diseases.


Asunto(s)
COVID-19 , Animales , Masculino , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , SARS-CoV-2
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