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The slow photoelectron spectrum of the ethynyl radical has been recorded for the first time by using the DESIRS beamline of the SOLEIL synchrotron facility. Ethynyl was generated using a microwave discharge flow tube. The observation of the X+Π3âXΣ+2 transition allowed the first direct measurement of the adiabatic ionization threshold of this radical (EI = 11.641(5) eV). The experimental results are supported by ab initio calculations. Our preliminary investigation of the cationic ground state potential energy surfaces predicts a non-negligible Renner-Teller effect which has not been discussed previously.
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We report the first experimental observations of X(+) (1)Σ(+)âX (2)Π and a(+) (3)ΠâX (2)Π single-photon ionization transitions of the CH radical performed on the DESIRS beamline at the SOLEIL synchrotron facility. The radical was produced by successive hydrogen-atom abstractions on methane by fluorine atoms in a continuous microwave discharge flow tube. Mass-selected ion yields and photoelectron spectra were recorded as a function of photon energy using a double imaging photoelectron/photoion coincidence spectrometer. The ion yield appears to be strongly affected by vibrational and electronic autoionizations, which allow the observation of high Rydberg states of the neutral species. The photoelectron spectra enable the first direct determinations of the adiabatic ionization potential and the energy of the first triplet state of the cation with respect to its singlet ground state. This work also brings valuable information on the complex electronic structure of the CH radical and its cation and adds new observations to complement our understanding of Rydberg states and autoionization processes.
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OBJECTIVE: To identify barriers to children's access to dental care. BASIC RESEARCH DESIGN: A cross-sectional health survey. SETTING: All residential census tracts in Genesee County, Michigan, USA. PARTICIPANTS: 498 adults who reported having children in their households, extracted from 2,932 randomly selected adult participants in the 2009 and 2011 surveys. MAIN MEASURES: Stepwise logistic regression was used to predict two dependent variables: children's lack of any visits to dentists' offices and unmet dental care needs (defined as needing dental care but not receiving it due to cost) in the previous year as reported by the adults. Independent variables included gender, age, education, race/ethnicity, financial planning, financial distress, fear of crime, stress, depressive symptoms, experiences of discrimination, and neighbourhood social capital. RESULTS: Of the 498 adults, 29.9% reported that they had children who had not visited a dentist in the past 12 months and 13% reported that they had household children with unmet dental care needs in the past year. Adults who reported higher depressive symptoms, lower neighbourhood social capital, greater financial distress, and who were younger were more likely to have household children who did not visit a dentist in the past year. Financial distress was the only significant predictor when controlling for other variables to predict unmet dental care needs. CONCLUSIONS: Factors beyond financial distress affect children's dental care; these include parental depressive symptoms and lower neighbourhood social capital. Interventions promoting parental mental health and social integration may increase dental care among children.
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Cuidadores , Atención Dental para Niños , Depresión/psicología , Accesibilidad a los Servicios de Salud , Clase Social , Medio Social , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Cuidadores/economía , Cuidadores/psicología , Niño , Preescolar , Crimen , Estudios Transversales , Escolaridad , Etnicidad , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , Renta , Masculino , Michigan , Persona de Mediana Edad , Prejuicio , Factores Sexuales , Estrés Psicológico/psicología , Adulto JovenRESUMEN
AIMS: To build a flexible and comprehensive long-term type 1 diabetes mellitus model incorporating the most up-to-date methodologies to allow a number of cost-effectiveness evaluations. METHODS: This paper describes the conceptual modelling, model implementation and model validation of the Sheffield type 1 diabetes policy model (version 1.0), developed through funding by the U.K. National Institute for Health Research as part of the Dose Adjustment for Normal Eating research programme. The model is an individual patient-level simulation model of type 1 diabetes and it includes long-term microvascular (retinopathy, neuropathy and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization and angina) diabetes-related complications and acute adverse events (severe hypoglycaemia and diabetic ketoacidosis). The occurrence of these diabetes-related complications in the model is linked to simulated individual patient-level risk factors, including HbA1c , age, duration of diabetes, lipids and blood pressure. Transition probabilities were modelled based on a combination of existing risk functions, published trials, epidemiological studies and individual-level data from the Dose Adjustment for Normal Eating research programme. RESULTS: The model takes a lifetime perspective, estimating the impact of interventions on costs, clinical outcomes, survival and quality-adjusted life years. Validation of the model suggested that, for almost all diabetes-related complications predicted, event rates were within 10% of the normalized rates reported in the studies used to build the model. CONCLUSIONS: The model is highly flexible and has broad potential application to evaluate the Dose Adjustment for Normal Eating research programme, other structured diabetes education programmes and other interventions for type 1 diabetes.
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Complicaciones de la Diabetes/economía , Diabetes Mellitus Tipo 1/economía , Análisis Costo-Beneficio , Complicaciones de la Diabetes/terapia , Diabetes Mellitus Tipo 1/terapia , Humanos , Modelos Económicos , Modelos Teóricos , Años de Vida Ajustados por Calidad de Vida , Resultado del TratamientoRESUMEN
AIMS: To determine the impact of structured education promoting flexible intensive insulin therapy on rates of diabetic ketoacidosis, and the costs associated with emergency treatment for severe hypoglycaemia and ketoacidosis in adults with Type 1 diabetes. METHODS: Using the Dose Adjustment For Normal Eating research database we compared the rates of ketoacidosis and severe hypoglycaemia during the 12 months preceding Dose Adjustment For Normal Eating training with the rates during the 12-month follow-up after this training. Emergency treatment costs were calculated for associated paramedic assistance, Accident and Emergency department attendance and hospital admissions. RESULTS: Complete baseline and 1-year data were available for 939/1651 participants (57%). The risk of ketoacidosis in the 12 months after Dose Adjustment For Normal Eating training, compared with that before training, was 0.39 (95% CI: 0.23 to 0.65, P < 0.001), reduced from 0.07 to 0.03 episodes/patient/year. For every 1 mmol/mol unit increase in HbA1c concentration, the risk of a ketoacidosis episode increased by 6% (95% CI: 5 to 7%; 88% for a 1% increase), and for each 5-year increase in diabetes duration, the relative risk reduced by 20% (95% CI: 19 to 22%). The number of emergency treatments decreased for ketoacidosis (P < 0.001), and also for severe hypoglycaemia, including paramedic assistance (P < 0.001), Accident and Emergency department attendance (P = 0.029) and hospital admission (P = 0.001). In the study cohort, the combined cost of emergency treatment for ketoacidosis and severe hypoglycaemia fell by 64%, from £119,470 to £42,948. CONCLUSIONS: Structured training in flexible intensive insulin therapy is associated with a 61% reduction in the risk of ketoacidosis and with 64% lower emergency treatment costs for ketoacidosis and severe hypoglycaemia.
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Diabetes Mellitus Tipo 1/complicaciones , Cetoacidosis Diabética/prevención & control , Tratamiento de Urgencia/estadística & datos numéricos , Hemoglobina Glucada/metabolismo , Hiperglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Autocuidado , Adulto , Análisis Costo-Beneficio , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Hiperglucemia/sangre , Hiperglucemia/epidemiología , Masculino , Educación del Paciente como Asunto , RiesgoRESUMEN
OBJECTIVE: Studies about cartilage repair in the hip and infant chondrocytes are rare. The aim of our study was to evaluate the use of infant articular hip chondrocytes for tissue engineering of scaffold-assisted cartilage grafts. METHOD: Hip cartilage was obtained from five human donors (age 1-10 years). Expanded chondrocytes were cultured in polyglycolic acid (PGA)-fibrin scaffolds. De- and re-differentiation of chondrocytes were assessed by histological staining and gene expression analysis of typical chondrocytic marker genes. In vivo, cartilage matrix formation was assessed by histology after subcutaneous transplantation of chondrocyte-seeded PGA-fibrin scaffolds in immunocompromised mice. RESULTS: The donor tissue was heterogenous showing differentiated articular cartilage and non-differentiated tissue and considerable expression of type I and II collagens. Gene expression analysis showed repression of typical chondrocyte and/or mesenchymal marker genes during cell expansion, while markers were re-induced when expanded cells were cultured in PGA-fibrin scaffolds. Cartilage formation after subcutaneous transplantation of chondrocyte loaded PGA-fibrin scaffolds in nude mice was variable, with grafts showing resorption and host cell infiltration or formation of hyaline cartilage rich in type II collagen. Addition of human platelet rich plasma (PRP) to cartilage grafts resulted robustly in formation of hyaline-like cartilage that showed type II collagen and regions with type X collagen. CONCLUSION: These results suggest that culture of expanded and/or de-differentiated infant hip cartilage cells in PGA-fibrin scaffolds initiates chondrocyte re-differentiation. The heterogenous donor tissue containing immature chondrocytes bears the risk of cartilage repair failure in vivo, which may be possibly overcome by the addition of PRP.
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Cartílago Articular/citología , Desdiferenciación Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Fibrina/farmacología , Articulación de la Cadera/citología , Ácido Poliglicólico/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Técnicas de Cultivo de Célula , Niño , Preescolar , Condrocitos/metabolismo , Condrocitos/trasplante , Colágeno Tipo I/efectos de los fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo II/efectos de los fármacos , Colágeno Tipo II/metabolismo , Humanos , Lactante , Ratones , Ratones Desnudos , Trasplante HeterólogoRESUMEN
AIMS: To estimate the cost-effectiveness of training in flexible intensive insulin therapy [as provided in the Dose Adjustment for Normal Eating (DAFNE) structured education programme] compared with no training for adults with Type 1 diabetes mellitus in the UK using the Sheffield Type 1 Diabetes Policy Model. METHODS: The Sheffield Type 1 Diabetes Policy Model was used to simulate the development of long-term microvascular and macrovascular diabetes-related complications and the occurrence of diabetes-related adverse events in 5000 adults with Type 1 diabetes. Total costs and quality-adjusted life years were estimated from a National Health Service perspective over a lifetime horizon, discounted at a rate of 3.5%. The treatment effectiveness of DAFNE was modelled as a reduction in HbA1c that affected the risk of developing long-term diabetes-related complications. Probabilistic and structural sensitivity analyses were conducted. RESULTS: DAFNE resulted in greater life expectancy and reduced incidence of some diabetes-related complications compared with no DAFNE. DAFNE was found to generate an average of 0.0294 additional quality-adjusted life years for an additional cost of £426 per patient, leading to an incremental cost-effectiveness ratio of £14 400 compared with no DAFNE. There was a 54% probability that DAFNE would be cost-effective at a willingness-to-pay threshold of £20 000 per quality-adjusted life year. CONCLUSIONS: The results of this study suggest that DAFNE is a cost-effective structured education programme for people with Type 1 diabetes and support its provision by the National Health Service in the UK.
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Diabetes Mellitus Tipo 1/economía , Angiopatías Diabéticas/economía , Hipoglucemiantes/economía , Insulina/economía , Educación del Paciente como Asunto/economía , Autocuidado , Medicina Estatal/economía , Adulto , Glucemia/metabolismo , Análisis Costo-Beneficio , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/terapia , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/prevención & control , Progresión de la Enfermedad , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Modelos Económicos , Años de Vida Ajustados por Calidad de Vida , Autocuidado/economía , Reino Unido/epidemiologíaRESUMEN
We report on the electrical transport properties of single multiwall carbon nanotubes with and without an iron filling as a function of temperature and magnetic field. For the iron filled nanotubes the magnetoresistance shows a magnetic behavior induced by iron, which can be explained by taking into account a contribution of s-d hybridization. In particular, ferromagnetic-like hysteresis loops were observed up to 50 K for the iron filled multiwall carbon nanotubes. The magnetoresistance shows quantum interference phenomena such as universal conductance fluctuations and weak localization effects.
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Hierro/química , Nanotubos de Carbono/química , Conductividad Eléctrica , Campos Magnéticos , Imanes/química , Nanotubos de Carbono/ultraestructura , TemperaturaRESUMEN
BACKGROUND: Humans and environmental organisms are constantly exposed to complex mixtures of chemicals. Extending our knowledge about the combined effects of chemicals is thus essential for assessing the potential consequences of these exposures. In this context, comprehensive molecular readouts as retrieved by omics techniques are advancing our understanding of the diversity of effects upon chemical exposure. This is especially true for effects induced by chemical concentrations that do not instantaneously lead to mortality, as is commonly the case for environmental exposures. However, omics profiles induced by chemical exposures have rarely been systematically considered in mixture contexts. OBJECTIVES: In this study, we aimed to investigate the predictability of chemical mixture effects on the whole-transcriptome scale. METHODS: We predicted and measured the toxicogenomic effects of a synthetic mixture on zebrafish embryos. The mixture contained the compounds diuron, diclofenac, and naproxen. To predict concentration- and time-resolved whole-transcriptome responses to the mixture exposure, we adopted the mixture concept of concentration addition. Predictions were based on the transcriptome profiles obtained for the individual mixture components in a previous study. Finally, concentration- and time-resolved mixture exposures and subsequent toxicogenomic measurements were performed and the results were compared with the predictions. RESULTS: This comparison of the predictions with the observations showed that the concept of concentration addition provided reasonable estimates for the effects induced by the mixture exposure on the whole transcriptome. Although nonadditive effects were observed only occasionally, combined, that is, multicomponent-driven, effects were found for mixture components with anticipated similar, as well as dissimilar, modes of action. DISCUSSION: Overall, this study demonstrates that using a concentration- and time-resolved approach, the occurrence and size of combined effects of chemicals may be predicted at the whole-transcriptome scale. This allows improving effect assessment of mixture exposures on the molecular scale that might not only be of relevance in terms of risk assessment but also for pharmacological applications. https://doi.org/10.1289/EHP7773.
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Contaminantes Químicos del Agua , Pez Cebra , Animales , Exposición a Riesgos Ambientales , Humanos , Toxicogenética , TranscriptomaRESUMEN
Structural pore models are generated for Vpu(1-32)WT from HIV-1 as well as for three mutants W23L, S24L and R31V. A computational methodology is employed which samples the whole conformational space of the pentameric assemblies of Vpu. The analysis of the related energy landscape reveals a small set of reasonable pore models, which are thoroughly investigated regarding their structural properties as well as their putative stability under native-like conditions. The models are also discussed in respect of earlier experimental findings about their channel activities. The study proposes functional pores reflecting the experimentally found conductance states of Vpu and its mutants.
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VIH-1/química , Proteínas del Virus de la Inmunodeficiencia Humana/química , Proteínas del Virus de la Inmunodeficiencia Humana/genética , Simulación de Dinámica Molecular , Mutación Missense , Proteínas Reguladoras y Accesorias Virales/química , Proteínas Reguladoras y Accesorias Virales/genética , VIH-1/genética , Cinética , Membrana Dobles de Lípidos/química , Fosfatidilcolinas/química , Conformación Proteica , Estructura Secundaria de ProteínaRESUMEN
BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a genetically complex disorder. The majority of mutations linked to FTLD families are found in the microtubule-associated protein tau (MAPT) and progranulin (PGRN) genes. Mutations in the chromatin-modifying protein 2B gene (CHMP2B) have been identified in a few families. However, CHMP2B has been showed to be a rare cause of FTLD. Our aim was to determine the frequency of CHMP2B mutations in a clinical series of patients with FTLD in Northern Finland. PATIENTS AND METHODS: We examined 72 (36 men) Finnish patients with FTLD. The mean age at onset was 58.9 (range 4380). Symptoms of motor neuron disease (FTLDMND) were present in 12 patients (17%). Positive family history was detected in 28% of the patients. Mutations in MAPT and PGRN were excluded from these patients. All exons and exonintron boundaries of the CHMP2B gene were sequenced. RESULTS: No pathogenic CHMP2B mutations were found. A rare polymorphism in the non-coding region of exon 1 (rs36098294) and three other previously reported polymorphisms were detected. CONCLUSIONS: Our results confirm that mutations in CHMP2B are not a common cause of FTLD. MAPT and PGRN mutations are also rare in Finnish population, suggesting that other, still unknown genetic factors may play a role in the pathogenesis of FTLD in Finnish population.
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Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Degeneración Lobar Frontotemporal/etiología , Degeneración Lobar Frontotemporal/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Análisis Mutacional de ADN/métodos , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genéticaRESUMEN
OBJECTIVE: To clarify whether the 'plane of minimal dimensions' of the levator hiatus on three-dimensional (3D) ultrasound accurately represents the minimal anatomical transverse hiatal dimension during a Valsalva maneuver. METHODS: In this retrospective study of 3D transperineal ultrasound and magnetic resonance (MR) imaging, datasets from 19 female participants were used to measure the transverse diameter of the levator hiatus using the plane of minimal dimensions on maximum Valsalva maneuver. The term 'apparent minimal transverse diameter' (aMTD) was used to define the transverse diameter measured using axial ultrasound and comparable axial or coronal MR images. Coronal MR images, using the plane of the vagina as a reference, were also obtained on maximum Valsalva. The transverse diameter measured between the caudal margin of the pubococcygeus/puborectalis on the MR coronal image is denoted by the term 'true minimal transverse diameter' (tMTD). Statistical comparisons between the aMTD and tMTD were made using Student's t-test. RESULTS: No significant difference was demonstrated between the aMTD as measured by ultrasonography and MRI. However, there were significant differences found between the aMTD measured by both ultrasound and MRI and the tMTD measured on coronal MR images (both P < 0.01), with mean ( ± SD) values of 4.36 ± 0.85, 4.13 ± 1.09 and 3.23 ± 0.49 cm, respectively. CONCLUSION: This study highlights the complexity and 3D nature of the levator hiatus and pelvic floor muscles. Investigators have previously assumed that the plane of minimal dimensions of the hiatus can be measured in a flat plane, however, the 3D nature of the hiatus means that the true levator hiatus occupies a warped (non-Euclidean) plane. Hiatal measurements on Valsalva may be subject to systematic error if performed in a single section, i.e. using a flat (Euclidean) plane.
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Diafragma Pélvico/diagnóstico por imagen , Perineo/diagnóstico por imagen , Prolapso Uterino/diagnóstico , Maniobra de Valsalva/fisiología , Adulto , Biometría , Femenino , Humanos , Imagenología Tridimensional/clasificación , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética , Diafragma Pélvico/anatomía & histología , Perineo/anatomía & histología , Estudios Retrospectivos , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Ectopic ureters (EUs) associated with varying combinations of urinary incontinence, hydronephrosis, and urinary tract infection have been identified in related North American Entlebucher Mountain Dogs. OBJECTIVES: To characterize the disease phenotype in affected dogs and evaluate possible modes of inheritance. ANIMALS: Twenty client-owned Entlebucher Mountain Dogs. Nine dogs had clinical signs of urinary tract disease. METHODS: Prospective case series in which 17 dogs were evaluated with excretory urography, ultrasonography, and urethrocystoscopy. Three additional dogs were evaluated by necropsy alone. Clinical and pedigree histories from 165 North American Entlebuchers were compiled for analysis. RESULTS: Eleven female and 2 male dogs were found to have EUs. Six females and 1 male were continent. Bilateral intravesicular ectopic ureters (IVEUs) were identified in 9 dogs, bilateral extravesicular ectopic ureters (EVEUs) in 3 dogs, and 1 dog had IVEU and EVEU. Hydronephrosis was identified in 5 dogs, 3 of which had bilateral IVEUs. Two necropsied dogs had bilateral hydronephrosis with presumed ureterovesical junction obstruction associated with chronic granulation tissue or lymphoplasmacytic inflammation. Twenty-six dogs with EUs were identified in the pedigree. Because of incomplete penetrance, mode of inheritance could not be determined. CONCLUSIONS AND CLINICAL IMPORTANCE: Ureteral ectopia is common in North American Entlebucher Mountain Dogs and clinical signs alone could not reliably predict disease phenotype. EVEUs were associated with urinary incontinence and occasionally hydronephrosis. IVEUs were clinically silent or associated with hydronephrosis. Further analyses are necessary to confirm and characterize the hereditary nature of the disorder.
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Enfermedades de los Perros/congénito , Enfermedades Ureterales/veterinaria , Incontinencia Urinaria/veterinaria , Animales , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , Perros , Femenino , Predisposición Genética a la Enfermedad , Masculino , Linaje , Enfermedades Ureterales/congénito , Enfermedades Ureterales/patología , Incontinencia Urinaria/genética , Incontinencia Urinaria/patologíaRESUMEN
BACKGROUND: There is a lack of data on the frequency and pattern of colorectal adenomas in sub-Saharan Africa to guide diagnostic and preventive strategies for colorectal cancer (CRC) in the region. OBJECTIVES: To describe polyp characteristics and adenoma frequency in patients at average risk of CRC, who are undergoing colonoscopy for bowel symptoms at a tertiary hospital in South Africa (SA). METHODS: Colonoscopy records from the prospective endoscopy database at Groote Schuur Hospital, Cape Town, SA, from August 2014 to February 2017, were retrieved. The presence of polyps, and their morphology, size, site and number in relation to ethnicity, symptoms and colonoscopy quality indicators were analysed. The histological type and grade were obtained from laboratory records and analysed. The primary endpoint was the adenoma detection rate (ADR). Age, gender, ethnicity, symptoms, bowel preparation and caecal intubation rates were also compared between patients with adenomas and those without. RESULTS: Of 1 334 colonoscopies, 342 were performed in patients at increased risk of premalignant lesions; these were excluded from the analysis. Polyps were identified in 172 of the remaining 992 patients (17.3%), whose self-declared ethnicity was mixed race (76%), white (12%), black African (11%) or Asian (1%). The quality of bowel preparation and caecal intubation rate were similar between patients with polyps and those without. Patients with polyps were older than those without polyps (mean age 61.5 (standard deviation 12.9) v. 56.3 (17.4) years; p<0.002). On histological examination of these polyps, 119 were adenomas, 26 were hyperplastic and 27 were normal. The majority of the adenomas were tubular (80%), and there were only 6% with high-grade dysplasia. Half (51%) of the adenomas were in the proximal colon, and the overall ADR was 12%. The ADR (prevalence) was highest in white and Asian South Africans (18% each), followed by that in persons of mixed race (13%), but much lower in black Africans (5%). CONCLUSIONS: This study provides a benchmark ADR for our catchment population and potentially across Africa. There is evidence of a continuing differential colorectal neoplasia risk according to ethnicity, with fewer adenomas being detected in black South Africans.
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Adenoma/diagnóstico , Pólipos del Colon/diagnóstico , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Adenoma/epidemiología , Adulto , Anciano , Pólipos del Colon/epidemiología , Neoplasias Colorrectales/epidemiología , Estudios Transversales , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Indicadores de Calidad de la Atención de Salud , SudáfricaRESUMEN
Deep brain stimulation (DBS) is an established treatment for movement disorders such as Parkinson's disease or essential tremor. Currently, the selection of optimal stimulation settings is performed by iteratively adjusting the stimulation parameters and is a time consuming procedure that requires multiple clinic visits of several hours. Recently, computational models to predict and visualize the effect of DBS have been developed with the goal to simplify and accelerate this procedure by providing visual guidance and such models have been made available also on mobile devices. However, currently available visualization software still either lacks mobility, i.e., it is running on desktop computers and not easily available in clinical praxis, or flexibility, as the simulations that are visualized on mobile devices have to be precomputed. The goal of the pipeline presented in this paper is to close this gap: Using Duality, a newly developed software for the interactive visualization of simulation results, we implemented a pipeline that allows to compute DBS simulations in near-real time and instantaneously visualize the result on a tablet computer. Therefore, a client-server setup is used, so that the visualization and user interaction occur on the tablet computer, while the computations are carried out on a remote server. We present two examples for the use of Duality, one for postoperative programming and one for the planning of DBS surgery in a pre- or intraoperative setting. We carry out a performance analysis and present the results of a case study in which the pipeline for postoperative programming was applied.
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BACKGROUND AND PURPOSE: Mutations in the progranulin (PGRN) gene have recently been associated with frontotemporal lobar degeneration (FTLD). The frequency of these mutations varies between populations. The aim of this study was to determine mutations and genetic variations of the PGRN gene in Finnish patients with FTLD and FTLD with associated motor neuron disease (FTLD-MND). SUBJECTS AND METHODS: All exons of the PGRN gene were sequenced from 69 Finnish patients with FTLD. The FTLD-MND phenotype was present in 13 of the 69 patients. RESULTS: No pathogenic PGRN mutations were identified in the cohort. Eleven sequence variations were detected, of which IVS8 + 15C>T, IVS4-51_-52insAGTC and IVS11 + 25G>A have not been reported previously. At least one single-nucleotide polymorphism (SNP) of PGRN was detected in 83% of patients. CONCLUSIONS: We conclude that mutations in PGRN are rare among Finnish patients with FTLD and FTLD-MND. However, SNPs were frequent suggesting high genetic variability of the PGRN gene.
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Degeneración Lobar Frontotemporal/epidemiología , Degeneración Lobar Frontotemporal/genética , Péptidos y Proteínas de Señalización Intercelular/deficiencia , Péptidos y Proteínas de Señalización Intercelular/genética , Adulto , Anciano , Estudios de Cohortes , Comorbilidad , Femenino , Finlandia/epidemiología , Degeneración Lobar Frontotemporal/metabolismo , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/epidemiología , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/metabolismo , Mutación Puntual/genética , Prevalencia , ProgranulinasRESUMEN
OBJECTIVE: To describe structural and biochemical evidence from postmortem brains that implicates the reciprocal connections between the mediodorsal thalamic nucleus and the prefrontal cortex in cognitive symptoms of schizophrenia. METHOD: The estimation of the regional volumes and cell numbers was obtained using stereological methods. The biochemical analyses of molecular expression in postmortem brain involve quantitative measurement of transcripts and proteins by in-situ (RNA) or Western blot/autoradiography in brains from patients with schizophrenia and comparison subjects. RESULTS: Stereological studies in postmortem brain from patients with schizophrenia have reported divergent and often opposing findings in the total number of neurons and volume of the mediodorsal (MD) thalamic nucleus, and to a lesser degree in its reciprocally associated areas of the prefrontal cortex. Similarly, quantitative molecular postmortem studies have found large inter-subject and between-study variance at both the transcript and protein levels for receptors and their interacting molecules of several neurotransmitter systems in these interconnected anatomical regions. Combined, large variation in stereological and molecular studies indicates a complex and heterogeneous involvement of the MD thalamic-prefrontal loop in schizophrenia. CONCLUSION: Based on a considerable heterogeneity in patients suffering from schizophrenia, large variation in postmortem studies, including stereological and molecular postmortem studies of the MD thalamus and frontal cortex, might be expected and may in fact partly help to explain the variable endophenotypic traits associated with this severe psychiatric illness.
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Núcleo Talámico Mediodorsal/patología , Esquizofrenia/patología , Recuento de Células , Ácido Glutámico/fisiología , Humanos , Núcleo Talámico Mediodorsal/citología , Núcleo Talámico Mediodorsal/fisiopatología , Esquizofrenia/fisiopatología , Transmisión Sináptica/fisiología , Tálamo/patología , Tálamo/fisiologíaRESUMEN
The temperature and concentration dependence of the refractive index, nD(x, T), in ethanol-water mixtures agrees with previous data in the ethanol-rich concentration range. The refractive index versus concentration x determined at 20 degrees C shows the expected maximum at about 41 mol% water (22 mass% water). The temperature derivative of the refractive index, dnD/dT, shows anomalies at lower water concentrations at about 10 mol% water but no anomaly at 41 mol% water. Both anomalies are related to intermolecular interactions, the one in nD seems to be due to molecular segregation and cluster formation while the origin of the second one in dnD/dT is still not clear.
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Etanol/química , Refractometría , Temperatura , Agua/química , Simulación por Computador , Modelos Químicos , Soluciones/químicaRESUMEN
The non-equilibrium process of polymerization of reactive polymers can be accompanied by transition phenomena like gelation or the chemical glass transition. The sensitivity of the mechanical properties at hypersonic frequencies-including the generalized Cauchy relation-to these transition phenomena is studied for three different polyurethanes using Brillouin spectroscopy. As for epoxies, the generalized Cauchy relation surprisingly holds true for the non-equilibrium polymerization process and for the temperature dependence of polyurethanes. Neither the sol-gel transition nor the chemical and thermal glass transitions are visible in the representation of the generalized Cauchy relation. Taking into account the new results and combining them with general considerations about the elastic properties of the isotropic state, an improved physical foundation of the generalized Cauchy relation is proposed.
RESUMEN
The influence of Al(2)O(3) nanoparticles on the curing of an epoxy thermoset based on diglycidyl ether of bisphenol A was investigated using temperature-modulated differential scanning calorimetry (TMDSC) and rheology. Diethylene triamine was used as a hardener. TMDSC not only allows for a systematic study of the kinetics of cure but simultaneously gives access to the evolution of the specific heat capacities of the thermosets. The technique thus provides insight into the glass transition behaviour of the nanocomposites and hence makes it possible to shed some light on the interaction between the nanoparticles and the polymer matrix. The Al(2)O(3) fillers are shown to accelerate the growth of macromolecules upon isothermal curing. Several mechanisms which possibly could be responsible for the acceleration are described. As a result of the faster network growth chemical vitrification occurs at earlier times in the filled thermosets and the specific reaction heat decreases with increasing nanoparticle concentration. Rheologic measurements of the zero-shear viscosity confirm the faster growth of the macromolecules in the presence of the nanoparticles.