RESUMEN
OBJECTIVE: To determine whether the ratio of cerebrospinal fluid (CSF) immunoglobulin kappa to lambda light chains at time of multiple sclerosis (MS) diagnosis predicts disease progression and whether this was intrinsic to CSF plasmablasts. METHODS: CSF and peripheral blood were obtained from patients undergoing elective diagnostic lumbar puncture and included clinically isolated syndrome (CIS) (n=43), relapsing remitting MS (RRMS; n=50), primary progressive MS (PPMS; n=20) and other neurological disease controls, both inflammatory (ONID; n=23) and non-inflammatory (OND; n=114). CSF samples were assayed for free and immunoglobulin-associated light chains and on B cells and plasmablasts. Clinical follow-up data were collected during a 5-year follow-up period where available. RESULTS: There was an increased median CSF κ:λ free light chain (FLC) in all MS groups (CIS: 18.2, 95% CI 6.8 to 30.3; RRMS: 4.4, 95% CI 2.7 to 11.4; PPMS: 12.0, 95% CI 3.6 to 37.1) but not controls (OND: 1.61, 95% CI 1.4 to 1.9; ONID: 1.7, 95% CI 1.3 to 2.2; p<0.001). This ratio predicted Expanded Disability Status Scores (EDSS) progression at 5 years, with a lower median EDSS in the group with high (>10) CSF κ:λ FLC (0.0, 95% CI 0 to 2.5 vs 2.5, 95% CI 0 to 4, high vs low; p=0.049). CSF κ:λ FLC correlated with CSF IgG1 κ:λ (r=0.776; p<0.0001) and was intrinsic to CSF plasmablasts (r=0.65; p=0.026). CONCLUSIONS: These data demonstrate that CSF immunoglobulin κ:λ ratios, determined at the time of diagnostic lumbar puncture, predict MS disease progression and may therefore be useful prognostic markers for early therapeutic stratification.
Asunto(s)
Cadenas Ligeras de Inmunoglobulina/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/líquido cefalorraquídeo , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/líquido cefalorraquídeo , Adulto JovenRESUMEN
Introduction: Formal farm safety education/training should be tailored, in terms of the approach, content and delivery, to students undertaking agriculture education and training to enhance Farm-related Injury Risk Perception (FIRP). To this end, this paper assesses factor(s) explaining or predicting levels of FIRP amongst students studying for a degree in agriculture science. Methods: A cross-sectional online survey was conducted with a nationally representative sample of Bachelor of Agriculture Science (BAgrSc) students (N = 417) (aged 18-20) in Ireland. Descriptive [frequency and cross-tabulations) and inferential (Ordinal Logistic Regression (OLR)] analyses were applied to evaluate the effects of social influences, experience (of farming, of a near-miss or injury), and awareness (of others who were injured or killed on the farm) on FIRP. Results: The study found that social influences negatively affected FIRP (P < 0.05). A relatively small number of students reported experiencing an injury (n = 56, 13.4%) that resulted in them being unable to participate in educational or social activities. A quarter of the respondents did, however, record experiencing a near-miss/close call (n = 106, 25.4%). A notable proportion (n = 144, 34.5%) of students had personal connections to someone who died as a consequence of a farm-related incident and 56.4% (n = 235) knew someone who was moderately or severely injured. OLR findings established that experiencing a severe injury, having a near-miss or close call, and awareness of a farm-related death or injury positively affects FIRP (P < 0.05). Conclusions: Perception of farm risks amongst students in Ireland is low. Students who recorded higher levels of risk perception were, however, more likely to report experiencing a near-miss, close call or severe injury, or knowing someone who experienced a farm-related injury or fatality. Farmers, family or friends were found to negatively impact the FIRP and this reflects previous research findings. Our findings highlight the need for education and training programs to enhance opportunities for student peer-to-peer learning through sharing of experiences and/or knowledge of farm injuries and/or fatalities. Such activities will enhance awareness and understanding amongst the general population of students leading to increased FIRP and contribute to a reduction in risk-taking.
Asunto(s)
Agricultura , Estudiantes , Humanos , Granjas , Irlanda/epidemiología , Estudios Transversales , PercepciónRESUMEN
Identification of occupational workplace injury risk factors is dependent on gaining sufficient and reliable data on both injury occurrence and associated workplace factors. Assessing workplace injury risk factors associated with farming is challenged by non-collection, non-reporting, or under-reporting by farmers, particularly those operating family farms in a self-employed manner. A supplementary (or add-on) farm operator (FO) workplace injury survey was undertaken in association with the Irish National Farm Survey (NFS), which is responsible for provision of Irish farm-level data to the European Commission (EC) Farm Accountancy Data Network (FADN). Data from this add-on survey were analyzed in association with farm and socio-economic data routinely collected by NFS as a component of the FADN. The combined data-set was analyzed using both descriptive and inferential statistical techniques including multivariate logistic regression to identify risk factors for occurrence of farm operator workplace injuries (FOWI). FOWI levels were significantly higher on farms where both the FO and their spouse engaged in Off Farm Employment (OFE). More generally, FO injury levels were associated with farm workload and investment levels. The study demonstrates how FADN farm and socio-economic data can be combined with additional FO workplace injury data to identify workplace injury risk factors. The study identifies a risk factor for FOWI occurrence where both FO and spouse engaged in OFE. More generally, it indicates that farm workplace injuries are associated with farm management-related factors.
Asunto(s)
Agricultores , Lugar de Trabajo , Agricultura , Granjas , Humanos , Irlanda/epidemiología , Factores de RiesgoRESUMEN
Patients often present to the emergency department with a wide variety of nontraumatic infectious, inflammatory, and neoplastic conditions of the head and neck. Because the use of cervical and neck computed tomography (CT) has become routine in the emergency setting, knowledge of the imaging findings of common acute conditions of the head and neck is essential to ensure an accurate diagnosis of these potentially life-threatening conditions, which include oral cavity infections, tonsillitis and peritonsillar abscess, sialadenitis, parotiditis, diskitis, thrombophlebitis, periorbital and orbital cellulitis, infectious cervical lymphadenopathy, and various neoplasms. Less common conditions that require rapid diagnosis and treatment include epiglottitis, invasive fungal sinusitis, angioedema, and deep neck abscess. Familiarity with these conditions enables the radiologist to make a prompt diagnosis, assess the extent of disease, and evaluate for potential complications. CT is the first-line imaging modality in the emergency setting; however, magnetic resonance imaging plays an important secondary role.
Asunto(s)
Servicios Médicos de Urgencia/métodos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Cabeza/diagnóstico por imagen , Cuello/diagnóstico por imagen , Infecciones de los Tejidos Blandos/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , HumanosRESUMEN
BACKGROUND: This study was performed to test the hypothesis that there exists a correlation between the Butler-Leggett (BL) criterion for right ventricular hypertrophy on the electrocardiogram and the Qp/Qs shunt ratio in adults with ostium secundum atrial septal defects (ASDs). METHODS: Demographic, cardiac catheterization, ASD closure, and electrocardiographic data were acquired on 70 patients with secundum ASDs closed percutaneously. Simple linear regression and logistic regression models were created to test the hypothesis. RESULTS: The mean Qp/Qs ratio and BL criterion value were 1.61 +/- 0.46 and 0.11 +/- 0.41, respectively. The BL criterion values correlated with shunt ratios (r(2) = 0.11 and P = .004). A BL criterion value greater than 0 mV predicted a significant shunt ratio (Qp/Qs > or = 1.5) (odds ratio, 4.8; 95% confidence interval, 1.3, 18.1; P = or <.0001) with a sensitivity of 0.68 and specificity of 0.65. CONCLUSION: Our results indicate that there is limited utility of the BL criterion at detecting right ventricular volume overload, although a BL criterion value greater than 0 mV being used to identify patients with significant intracardiac shunts yielded a sensitivity of 0.68 and specificity of 0.65.
Asunto(s)
Algoritmos , Diagnóstico por Computador/métodos , Electrocardiografía/métodos , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico , Hipertrofia Ventricular Derecha/complicaciones , Hipertrofia Ventricular Derecha/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVES: This article describes levels of implementation of occupational health and safety (OHS) controls on a sample of Irish farms following completion of a risk assessment document (RAD) made available as part of a statutory code of practice (COP) for the agriculture sector. The article describes the legislation mandating the COP and the operation of a prevention initiative (PI) among key stakeholders to develop and promote farmer use of the COP and RAD. METHODS: RADs were collected for farmers (N = 475) and the number and type of OHS controls listed for action were tabulated. A farm audit of OHS standards and of implementation of controls listed for action in the RAD was undertaken among a randomly selected sample of farms (N = 94) where the RAD was completed. RESULTS: The study data indicates that farmers used the RAD to a limited extent, and that their focus in its use was on identifying physical rather than organizational controls. An association was found between farmers who actively implemented controls and positive OHS standards. Farm OHS standards were also associated with farmer attitude to OHS, farm enterprise, farmer age category, and work time needed to operate the farm. CONCLUSIONS: Overall, the study data suggests that standards of farm management are a crucial determinant of OHS standards. The study data also indicates that having knowledge of required OHS controls does not ensure implementation. Development of social learning in groups is considered as a significant means of increasing OHS farm adoption.
Asunto(s)
Granjas/normas , Salud Laboral/normas , Agricultores/psicología , Humanos , Irlanda , Medición de Riesgo , Seguridad , Encuestas y Cuestionarios , Recursos HumanosRESUMEN
In patients with pulmonary arterial hypertension (PAH), right ventricular mass (RVM) correlates linearly with pulmonary artery pressure, and decreases with successful treatment. Accurate measurement of RVM currently requires cardiovascular magnetic resonance (CMR) imaging. We therefore tested the relationship between RVM and a simple, 12 lead ECG-derived value, the Butler-Leggett (BL) score. This has previously been validated in patients with RV hypertrophy (RVH) due to mitral stenosis. We also tested the diagnostic accuracy of the BL score in detecting RVH. The Scottish Pulmonary Vascular Unit database was reviewed retrospectively. Twenty-eight patients with PAH were identified, in whom CMR and ECG data had been recorded no more than 28 days apart. All had completed a comprehensive clinical assessment, including right heart catheterization. CMR-derived absolute RVM and RV mass index (RVMI=RV mass/LV mass) were correlated against BL score. The ability of this score to detect RVH was tested using 2 x 2 contingency tables. RVM and RVMI correlated with BL score (r=0.77, P<0.001 and r=0.78, P<0.001, respectively). A BL score >0.7 mV proved a highly specific but insensitive indicator of RVH, based on either absolute RVM (sensitivity 74%, specificity 100%) or a high RVMI (sensitivity 61%, specificity 100%). The BL score, which can be defined using a standard 12-lead ECG, correlates with RVM and RVMI in patients with PAH. A score >0.7 mV was a highly specific but insensitive indicator of RVH in these patients.
RESUMEN
Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy of photoreceptor-based diseases. Previous studies have demonstrated that rAAV serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and dogs, and it can target rods, but not cones in primates. Here we report that using a human cone-specific enhancer and promoter to regulate expression of a green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully targeted expression of the reporter gene to primate cones, and the time course of GFP expression was able to be monitored in a living animal using the RetCam II digital imaging system.
Asunto(s)
Adenoviridae/genética , Expresión Génica/fisiología , Marcación de Gen/métodos , Técnicas de Transferencia de Gen , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células Fotorreceptoras Retinianas Conos/metabolismo , Animales , Proteínas Recombinantes/metabolismo , Retina/metabolismo , SciuridaeRESUMEN
Allosteric control of Na(+)/H(+) exchange by intracellular protons ensures rapid and accurate regulation of the intracellular pH. Although this allosteric effect was heretofore thought to occur almost instantaneously, we report here the occurrence of a slower secondary activation of the epithelial Na(+)/H(+) exchanger (NHE)-3 isoform. This slow activation mode developed over the course of minutes and was unique to NHE3 and the closely related isoform NHE5, but was not observed in NHE1 or NHE2. Activation of NHE3 was not due to increased density of exchangers at the cell surface, nor was it accompanied by detectable changes in phosphorylation. The association of NHE3 with the cytoskeleton, assessed by its retention in the detergent-insoluble fraction, was similarly unaffected by acidification. In contrast to the slow progressive activation elicited by acidification, deactivation occurred very rapidly upon restoration of the physiological pH. We propose that NHE3 undergoes a slow pH-dependent transition from a less active to a more active state, likely by changing its conformation or state of association.