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The purpose of this research is to identify how decision-makers within anchor institutions, using the context of higher education, determine the course of action in response to an improbable disaster event, such as the recent coronavirus disease 2019 (COVID-19) pandemic. A survey was conducted among higher education decision-makers during spring 2020 at the moment they were adapting to COVID-19. The survey aimed to identify policies and planning measures that may help Institutions of Higher Education learn from this experience to maintain continuity of operations should similar or unanticipated events occur in the future. With this knowledge, both assets and detriments contributing to community vulnerability can be better balanced to inform decision-making. The outcomes of the analysis and shared reflections inform the development of future policy and strengthen existing processes for preparedness and mitigation planning for unexpected events.
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COVID-19 , Toma de Decisiones , Planificación en Desastres , Pandemias , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Planificación en Desastres/organización & administración , Universidades , Encuestas y CuestionariosRESUMEN
BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18. METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity. FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p<0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p<0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival. INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID. FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Inmunodeficiencia Combinada Grave , Humanos , Recién Nacido , Trasplante de Células Madre Hematopoyéticas/métodos , Estudios Longitudinales , Tamizaje Neonatal , Modelos de Riesgos Proporcionales , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/terapia , Inmunodeficiencia Combinada Grave/genéticaRESUMEN
The association of obesity with cardiovascular disease is well established. However, the interplay of obesity and vascular dysfunction in peripheral tissues such as skeletal muscle, which plays a key in role metabolic homeostasis, requires further study. In particular, there is a paucity of data with regard to sex-differences. Therefore, using a murine model (C57BL/6) of high-fat diet-induced obesity and insulin resistance, we investigated changes in vascular function in gluteus maximus muscle of female and male mice. Diet-induced obesity resulted in alterations in microvascular function. Obese male mice displayed impaired vasoconstriction in second order arterioles compared to lean, male mice, whereas arterioles of obese, female mice displayed significant impairments of both vasodilation and vasoconstrictor responses compared to lean, female mice. Overall, this study identifies distinct differences in how obesity impacts the female and male murine response to skeletal muscle vascular function. This work advances our understanding of sex-specific risk of metabolic complications of obesity and indicates the need for expansion of this study as well as detailed investigation of sex-specific differences in obesity pathology in the future.
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BACKGROUND: Cervical membrane sweep is a mechanical method of cervical ripening at term gestation with the aim of avoiding prolonged pregnancy and reducing the need for labour induction for this indication. There is no published data on obstetric outcomes following membrane sweep in an Irish obstetric population or any studies on patient perception/recommendation of membrane sweep in the international literature. AIMS: This study is aimed at determining if cervical membrane sweep at term has an effect on duration of pregnancy and delivery outcome in an Irish population. Postnatally, patient perception of the experience of membrane sweep was evaluated as well as their recommendation of the procedure for other women. METHODS: A prospective multi-centre cohort study of women who had cervical membrane sweep at term was carried out which assesses labour and delivery outcomes as well as patient perceptions in women undergoing membrane sweep. RESULTS: Spontaneous labour occurred in 79% of women following membrane sweep. A quarter of nulliparae (25%) and 18% of multipara had labour induction despite membrane sweep. Three quarters of both nulliparae (73%) and multipara (76%) delivered within 7 days of membrane sweep. In the presence of a Bishop score greater than six, the rate of spontaneous labour was 97% in our patient cohort. Nine in ten women (91%) had previously heard of cervical membrane sweep. Two in three women (65%) thought that membrane sweep helped them to labour, and over 80% would recommend it to other pregnant women despite 63% of women reporting moderate discomfort with the procedure. CONCLUSIONS: Cervical membrane sweep is associated with spontaneous onset of labour within 7 days in the majority of patients, more so in the presence of higher Bishop score and better quality sweep. It has a high level of acceptability among patients and is highly recommended by them to other patients. The need for more than one membrane sweep is associated with less likelihood of spontaneous onset of labour.
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Cuello del Útero/patología , Parto Obstétrico/métodos , Adulto , Maduración Cervical , Estudios de Cohortes , Femenino , Humanos , Irlanda , Embarazo , Estudios ProspectivosRESUMEN
The human spliceosome is a large ribonucleoprotein complex that catalyzes pre-mRNA splicing. It consists of five snRNAs and more than 200 proteins. Because of this complexity, much work has focused on the Saccharomyces cerevisiae spliceosome, viewed as a highly simplified system with fewer than half as many splicing factors as humans. Nevertheless, it has been difficult to ascribe a mechanistic function to individual splicing factors or even to discern which are critical for catalyzing the splicing reaction. We have identified and characterized the splicing machinery from the red alga Cyanidioschyzon merolae, which has been reported to harbor only 26 intron-containing genes. The U2, U4, U5, and U6 snRNAs contain expected conserved sequences and have the ability to adopt secondary structures and form intermolecular base-pairing interactions, as in other organisms. C. merolae has a highly reduced set of 43 identifiable core splicing proteins, compared with â¼90 in budding yeast and â¼140 in humans. Strikingly, we have been unable to find a U1 snRNA candidate or any predicted U1-associated proteins, suggesting that splicing in C. merolae may occur without the U1 small nuclear ribonucleoprotein particle. In addition, based on mapping the identified proteins onto the known splicing cycle, we propose that there is far less compositional variability during splicing in C. merolae than in other organisms. The observed reduction in splicing factors is consistent with the elimination of spliceosomal components that play a peripheral or modulatory role in splicing, presumably retaining those with a more central role in organization and catalysis.
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Rhodophyta/metabolismo , Empalmosomas/metabolismo , Proteínas Algáceas/genética , Proteínas Algáceas/metabolismo , Emparejamiento Base/genética , Humanos , Inmunoprecipitación , Intrones/genética , Modelos Biológicos , Conformación de Ácido Nucleico , Precursores del ARN/genética , Precursores del ARN/metabolismo , Empalme del ARN/genética , Estabilidad del ARN/genética , ARN Nuclear Pequeño/química , ARN Nuclear Pequeño/genética , ARN Nuclear Pequeño/metabolismo , Rhodophyta/genéticaRESUMEN
Pre-mRNA splicing, the removal of introns from pre-messenger RNA, is an essential step in eukaryotic gene expression. In humans, it has been estimated that 60 % of noninfectious diseases are caused by errors in splicing, making the study of pre-mRNA splicing a high priority from a health perspective. Pre-mRNA splicing is also complicated: the molecular machine that catalyzes the reaction, the spliceosome, is composed of five small nuclear RNAs, and over 100 proteins, making splicing one of the most complex processes in the cell.An important tool for studying pre-mRNA splicing is the in vitro splicing assay. With an in vitro assay, it is possible to test the function of each splicing component by removing the endogenous version and replacing it (or reconstituting it) with a modified one. This assay relies on the ability to produce an extract-either whole cell or nuclear-that contains all of the activities required to convert pre-mRNA to mRNA. To date, splicing extracts have only been produced from human and S. cerevisiae (yeast) cells. We describe a method to produce whole cell extracts from yeast that support splicing with efficiencies up to 90 %. These extracts have been used to reconstitute snRNAs, screen small molecule libraries for splicing inhibitors, and purify a variety of splicing complexes.
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Extractos Celulares/aislamiento & purificación , Biología Molecular/métodos , Empalme del ARN/genética , Empalmosomas/genética , Humanos , Intrones , Precursores del ARN/genética , ARN Nuclear Pequeño/química , ARN Nuclear Pequeño/genética , Saccharomyces cerevisiae/genéticaRESUMEN
Background. No in-depth qualitative research exists about the effects of therapeutic massage with children hospitalized to undergo hematopoietic cell transplantation (HCT). The objective of this study is to describe parent caregivers' experience of the effects of massage/acupressure for their children undergoing HCT. Methods. We conducted a qualitative analysis of open-ended interviews with 15 parents of children in the intervention arm of a massage/acupressure trial. Children received both practitioner and parent-provided massage/acupressure. Results. Parents reported that their child experienced relief from pain and nausea, relaxation, and greater ease falling asleep. They also reported increased caregiver competence and closeness with their child as a result of learning and performing massage/acupressure. Parents supported a semistandardized massage protocol. Conclusion. Massage/acupressure may support symptom relief and promote relaxation and sleep among pediatric HCT patients if administered with attention to individual patients' needs and hospital routines and may relieve stress among parents, improve caregiver competence, and enhance the sense of connection between parent and child.
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Background. Pediatric hematopoietic cell transplant (HCT) is a lifesaving treatment that often results in physical and psychological discomfort. An acupressure-massage intervention may improve symptom management in this setting. Methods. This randomized controlled pilot trial compared a combined massage-acupressure intervention to usual care. Children were offered three practitioner-provided sessions per week throughout hospitalization. Parents were trained to provide additional acupressure as needed. Symptoms were assessed using nurses' reports and two questionnaires, the behavioral affective and somatic experiences scale and the Peds quality of life cancer module. Results. We enrolled 23 children, ages 5 to 18. Children receiving the intervention reported fewer days of mucositis (Hedges' g effect size ES = 0.63), lower overall symptom burden (ES = 0.26), feeling less tired and run-down (ES = 0.86), having fewer moderate/severe symptoms of pain, nausea, and fatigue (ES = 0.62), and less pain (ES = 0.42). The intervention group showed trends toward increasing contentness/serenity (ES = +0.50) and decreasing depression (ES = -0.45), but not decreased anxiety (ES = +0.42). Differences were not statistically significant. Discussion. Feasibility of studying massage-acupressure was established in children undergoing HCT. Larger studies are needed to test the efficacy of such interventions in reducing HCT-associated symptoms in children.
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U6 snRNA (small nuclear RNA), one of five RNA molecules that are required for the essential process of pre-mRNA splicing, is notable for its high level of sequence conservation and the important role it is thought to play in the splicing reaction. Nevertheless, the secondary structure of U6 in the free snRNP (small nuclear ribonucleoprotein) form has remained elusive, with predictions changing substantially over the years. In the present review we discuss the evidence for existing models and critically evaluate a fundamental assumption of these models, namely whether the important 3' ISL (3' internal stem-loop) is present in the free U6 particle, as well as in the active splicing complex. We compare existing models of free U6 with a newly proposed model lacking the 3' ISL and evaluate the implications of the new model for the structure and function of U6's base-pairing partner U4 snRNA. Intriguingly, the new model predicts a role for U4 that was unanticipated previously, namely as an activator of U6 for assembly into the splicing machinery.
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Conformación de Ácido Nucleico , Multimerización de Proteína/fisiología , ARN Nuclear Pequeño/química , Empalmosomas/metabolismo , Animales , Secuencia de Bases , Humanos , Modelos Biológicos , Datos de Secuencia Molecular , Complejos Multiproteicos/metabolismo , Empalme del ARN/fisiología , ARN Nuclear Pequeño/metabolismoRESUMEN
Metastasis is responsible for most deaths due to malignant melanoma. The clinical significance of micrometastases in the lymph is a hotly debated topic, but an improved understanding of the lymphatic spread of cancer remains important for improving cancer survival. Cellular magnetic resonance imaging (MRI) is a newly emerging field of imaging research that is expected to have a large impact on cancer research. In this study, we demonstrate the cellular MRI technology required to reliably image the lymphatic system in mice and to detect iron-labeled metastatic melanoma cells within the mouse lymph nodes. Melanoma cells were implanted directly into the inguinal lymph nodes in mice, and micro-MRI was performed using a customized 1.5-T clinical MRI system. We show cell detection of as few as 100 iron-labeled cells within the lymph node, with injections of larger cell numbers producing increasingly obvious regions of signal void. In addition, we show that cellular MRI allows monitoring of the fate of these cells over time as they develop into intranodal tumors. This technology will allow noninvasive investigations of cellular events in cancer metastasis within an entire animal and will facilitate progress in understanding the mechanisms of metastasis within the lymphatic system.
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Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodos , Melanoma Experimental/patología , Neoplasias Cutáneas/patología , Animales , Femenino , Metástasis Linfática , Melanoma Experimental/diagnóstico , Ratones , Ratones Endogámicos C57BL , Neoplasias Cutáneas/diagnósticoAsunto(s)
Madurez de los Órganos Fetales/efectos de los fármacos , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Enfermedades Pulmonares/prevención & control , Pulmón/efectos de los fármacos , Nacimiento Prematuro , Femenino , Edad Gestacional , Humanos , Recién Nacido , Enfermedades del Prematuro/prevención & control , Embarazo , Nacimiento Prematuro/epidemiología , Factores de RiesgoRESUMEN
PURPOSE: To determine the contribution of blood-derived macrophages to the signal loss observed in MR images of inflammatory lesions in experimental autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: A relapsing-remitting form of EAE was induced in transgenic mice that express enhanced green fluorescent protein (EGFP) specifically in hematopoietic cells of the myelomonocytic lineage. Animals were injected with Feridex, a superparamagnetic iron oxide (SPIO) nanoparticle, 24 hours prior to in vivo MRI. MRI was performed using a 1.5T whole-body scanner; a high-performance, custom-built gradient coil insert; and a 3D steady-state free precession (SSFP) imaging pulse sequence. Comparisons were made between MR images and corresponding anti-GFP and Perl's Prussian blue (PPB)-stained brain sections. RESULTS: MR images revealed the presence of discrete regions of signal loss throughout the brains of EAE animals that were administered Feridex. Histological staining showed that regions of signal loss on MR images corresponded anatomically with regions of PPB- and GFP-positive cells. CONCLUSION: This experiment provides the first direct evidence that macrophages of hematogenous origin are labeled with SPIO after intravenous administration of Feridex, and contribute to the regions of signal loss detected in MR images of EAE brain.
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Medios de Contraste/farmacocinética , Encefalomielitis Autoinmune Experimental/patología , Hierro/farmacocinética , Macrófagos/citología , Imagen por Resonancia Magnética/métodos , Óxidos/farmacocinética , Animales , Dextranos , Modelos Animales de Enfermedad , Femenino , Óxido Ferrosoférrico , Interpretación de Imagen Asistida por Computador , Nanopartículas de Magnetita , Ratones , Ratones Transgénicos , Microscopía Fluorescente , Reproducibilidad de los ResultadosRESUMEN
The ability to visualize the cellular inflammatory responses after experimental spinal cord injury (SCI) was investigated using a clinical 1.5-T magnetic resonance imaging scanner, a custom-built, high-strength gradient coil insert, a 3-D fast imaging employing steady-state acquisition (FIESTA) imaging sequence and a superparamagnetic iron oxide (SPIO) contrast agent. An "active labeling" approach was used, with SPIO administered intravenously at different time points following SCI. Our results show that this strategy can be used to visualize clusters of iron-labeled cells associated with the inflammatory response in SCI. Of particular importance for this application was the finding that in FIESTA images hemorrhage does not cause signal loss. In T2-weighted spin echo or T2*-weighted gradient-echo images, which are more commonly used to detect signal loss associated with SPIO, the signal loss associated with hemorrhage interferes with the detection of iron-induced signal loss. FIESTA, therefore, allowed us to discriminate between iron associated with blood products in hemorrhage that occurs in acute SCI and the iron associated with SPIO-labeled cells accumulating in the injured cord.
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Inflamación/patología , Imagen por Resonancia Magnética/métodos , Traumatismos de la Médula Espinal/patología , Animales , Medios de Contraste , Modelos Animales de Enfermedad , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/análisis , Hemorragia/patología , Inflamación/etiología , Inyecciones Intravenosas , Ratas , Ratas Wistar , Traumatismos de la Médula Espinal/complicacionesRESUMEN
OBJECTIVES: To compare (i) satisfaction levels among women who delivered vaginally after one previous caesarean (VBAC) with women delivered by caesarean after previous vaginal delivery (CSAVD) and (ii) to assess reasons why women may request caesarean delivery on subsequent pregnancies. STUDY DESIGN: We conducted a prospective questionnaire-based study of maternal satisfaction following both modes of delivery during an 8-month period. RESULTS: One hundred and forty women completed an early postnatal questionnaire, 70 each in VBAC and CSAVD cohorts. The vast majority in both groups were satisfied with their respective mode of delivery, but would opt for vaginal delivery in their next pregnancy (89% in VBAC versus 94% in CSAVD). The VBAC group experienced minimal pain after delivery and had felt better prepared for delivery (74% versus 41% in the CSAVD group). Reasons for dissatisfaction in the VBAC group included the physical stress of labour and inadequacy of analgesia. CONCLUSION: Maternal satisfaction with vaginal delivery is high. Those who have experienced both modes of delivery would prefer vaginal birth on future pregnancies. These findings are reassuring to women contemplating vaginal delivery.
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Cesárea/métodos , Parto Vaginal Después de Cesárea/métodos , Adolescente , Adulto , Cesárea/efectos adversos , Cesárea Repetida/efectos adversos , Cesárea Repetida/métodos , Femenino , Estudios de Seguimiento , Humanos , Edad Materna , Dimensión del Dolor , Satisfacción del Paciente , Periodo Posparto , Embarazo , Resultado del Embarazo , Probabilidad , Estudios Prospectivos , Medición de Riesgo , Encuestas y Cuestionarios , Parto Vaginal Después de Cesárea/efectos adversos , Cicatrización de Heridas/fisiologíaRESUMEN
The ability to visualize cell infiltration in experimental auto-immune encephalomyelitis (EAE), a well-known animal model for multiple sclerosis in humans, was investigated using a clinical 1.5-T magnetic resonance imaging (MRI) scanner, a custom-built, high-strength gradient coil insert, a 3-D fast imaging employing steady-state acquisition (FIESTA) imaging sequence and a superparamagnetic iron oxide (SPIO) contrast agent. An "active labeling" approach was used with SPIO administered intravenously during inflammation in EAE. Our results show that small, discrete regions of signal void corresponding to iron accumulation in EAE brain can be detected using FIESTA at 1.5 T. This work provides early evidence that cellular abnormalities that are the basis of diseases can be probed using cellular MRI and supports our earlier work which indicates that tracking of iron-labeled cells will be possible using clinical MR scanners.