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Coupon immersion tests were performed on 316L stainless steel in a simulated oilfield environment to evaluate the effect of H2S partial pressure on pit depth and density. Pitting was most significant at intermediate partial pressures of H2S, for which free H2S in the pit solution is maximised. Inhibition of pitting at higher partial pressures is attributed to blocking of the pit surface by metal sulphide phases. The key role of pH in the pit solution is to determine the solubility of metal sulphides and the availability of free H2S to adsorb on the reacting pit surface and sustain activity.
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When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when 'on-task' under demanding conditions and 'off-task' in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC.
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Cognición/fisiología , Corteza Prefrontal/fisiología , Descanso/psicología , Pensamiento/fisiología , Adolescente , Mapeo Encefálico , Femenino , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Corteza Prefrontal/diagnóstico por imagen , Adulto JovenRESUMEN
Plasma discharges with a negative triangularity (δ=-0.4) shape have been created in the DIII-D tokamak with a significant normalized beta (ß_{N}=2.7) and confinement characteristic of the high confinement mode (H_{98y2}=1.2) despite the absence of an edge pressure pedestal and no edge localized modes (ELMs). These inner-wall-limited plasmas have a similar global performance as a positive triangularity (δ=+0.4) ELMing H-mode discharge with the same plasma current, elongation and cross sectional area. For cases both of dominant electron cyclotron heating with T_{e}/T_{i}>1 and dominant neutral beam injection heating with T_{e}/T_{i}=1, turbulent fluctuations over radii 0.5<ρ<0.9 were reduced by 10-50% in the negative triangularity shape compared to the matching positive triangularity shape, depending on the radius and conditions.
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In this study, we present the translational modeling used in the discovery of AZD1979, a melanin-concentrating hormone receptor 1 (MCHr1) antagonist aimed for treatment of obesity. The model quantitatively connects the relevant biomarkers and thereby closes the scaling path from rodent to man, as well as from dose to effect level. The complexity of individual modeling steps depends on the quality and quantity of data as well as the prior information; from semimechanistic body-composition models to standard linear regression. Key predictions are obtained by standard forward simulation (e.g., predicting effect from exposure), as well as non-parametric input estimation (e.g., predicting energy intake from longitudinal body-weight data), across species. The work illustrates how modeling integrates data from several species, fills critical gaps between biomarkers, and supports experimental design and human dose-prediction. We believe this approach can be of general interest for translation in the obesity field, and might inspire translational reasoning more broadly.
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Fármacos Antiobesidad/administración & dosificación , Azetidinas/administración & dosificación , Modelos Biológicos , Obesidad/tratamiento farmacológico , Oxadiazoles/administración & dosificación , Receptores de la Hormona Hipofisaria/antagonistas & inhibidores , Investigación Biomédica Traslacional , Animales , Fármacos Antiobesidad/farmacocinética , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Azetidinas/farmacocinética , Azetidinas/farmacología , Azetidinas/uso terapéutico , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Ingestión de Energía/efectos de los fármacos , Femenino , Humanos , Masculino , Ratones , Obesidad/metabolismo , Oxadiazoles/farmacocinética , Oxadiazoles/farmacología , Oxadiazoles/uso terapéutico , Ratas , Receptores de la Hormona Hipofisaria/metabolismo , Proyectos de InvestigaciónRESUMEN
PurposeTo ascertain ophthalmology trainee confidence in managing posterior capsule rupture (PCR) and vitreous loss.MethodsAn electronic survey was distributed to ophthalmology trainees in a single UK postgraduate training Deanery. Data collected included the stage of training, number of completed cataract operations, cumulative PCR rate, number of PCRs personally managed by the trainee, previous vitrectomy experience during vitreoretinal rotations, and attendance at advanced phacoemulsification courses. Trainees self-evaluated their confidence in managing PCR with vitreous loss, including the management of specific aspects of the procedure.ResultsAcross training grades, only 9.1% (2/22) felt confident managing PCR without senior support. Respondents were most confident with fluidic parameters and IOL considerations, but 77.3% (17/22) lacked confidence in avoiding a dropped nucleus. Eleven respondents had completed >350 cases (mean 576; range 383-1087). In this subgroup, mean cumulative PCR rate was 2.1% (range 0.9-4.9%), and trainees personally managed a mean 3.5 cases of PCR (range 1-7). Only 18.2% felt they could manage PCR and vitreous loss without senior support, and 45.5% stated they were not confident in avoiding a dropped nucleus. The most experienced trainee (1087 cases) had personally managed PCR just six times, and three trainees with >350 cases had only managed PCR once each.ConclusionsThe Royal College of Ophthalmologists' requirement of 350 completed cases appears insufficient for independent cataract surgery, as opportunities to manage complications as a trainee are scarce. A competency-based assessment framework may be preferable, with a more targeted approach to training incorporating surgical simulation within the formal curriculum.
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Competencia Clínica/normas , Oftalmopatías/cirugía , Oftalmólogos/normas , Oftalmología/educación , Ruptura de la Cápsula Posterior del Ojo/cirugía , Especialización , Cuerpo Vítreo/cirugía , Extracción de Catarata/educación , Educación de Postgrado en Medicina/normas , Encuestas de Atención de la Salud , Investigación sobre Servicios de Salud , Humanos , Internado y Residencia , Implantación de Lentes Intraoculares/educación , Reino UnidoRESUMEN
The phosphatidylinositol-3-kinase pathway plays an important role in proliferation, migration and survival in breast cancer and may play a role in resistance to endocrine therapy. Pathway activation occurs as a result of mutations in PIK3CA or loss of functional PTEN. Matched primary and recurrent samples from 120 breast cancer patients treated with endocrine therapy were profiled with a qPCR-based mutation assay covering eight mutational hotspots in PIK3CA. PTEN was assayed by immunohistochemistry. Samples were well characterized with respect to anatomic location of recurrence (metastatic nodal or local recurrence as opposed to contralateral or ipsilateral new primary cancers). In total, 43 % of patients had at least one PIK3CA mutation at diagnosis, and 41 % had a mutation at the time of recurrence. Only 8 % of patients with local recurrence, metastatic disease or progression on primary endocrine treatment changed their PIK3CA mutation status (four gains, two losses, total 76). The most common changes in PIK3CA mutation status were seen in patients who developed a new cancer either in the treated or contralateral breast (64 %, three gains, four losses, total 11). PIK3CA mutation status does not change in the majority of patients with breast cancer and the acquisition of mutations in PIK3CA is not responsible for the development of endocrine resistance. PTEN loss at diagnosis is associated with a significantly shorter time to progression compared with tumours in which PTEN was retained. These are the most comprehensive data currently available correlating PIK3CA status, site of recurrence and endocrine resistance.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/genética , Mutación/genética , Recurrencia Local de Neoplasia/genética , Neoplasias Hormono-Dependientes/genética , Fosfatidilinositol 3-Quinasas/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/secundario , Carcinoma Intraductal no Infiltrante/tratamiento farmacológico , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/mortalidad , Carcinoma Intraductal no Infiltrante/secundario , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/genética , Carcinoma Lobular/mortalidad , Carcinoma Lobular/secundario , Fosfatidilinositol 3-Quinasa Clase I , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/mortalidad , Neoplasias Hormono-Dependientes/secundario , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/secundario , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasa/genética , Pronóstico , Tasa de SupervivenciaRESUMEN
Magnetic feedback control of the resistive-wall mode has enabled the DIII-D tokamak to access stable operation at safety factor q(95) = 1.9 in divertor plasmas for 150 instability growth times. Magnetohydrodynamic stability sets a hard, disruptive limit on the minimum edge safety factor achievable in a tokamak, or on the maximum plasma current at a given toroidal magnetic field. In tokamaks with a divertor, the limit occurs at q(95) = 2, as confirmed in DIII-D. Since the energy confinement time scales linearly with current, this also bounds the performance of a fusion reactor. DIII-D has overcome this limit, opening a whole new high-current regime not accessible before. This result brings significant possible benefits in terms of fusion performance, but it also extends resistive-wall mode physics and its control to conditions never explored before. In present experiments, the q(95) < 2 operation is eventually halted by voltage limits reached in the feedback power supplies, not by intrinsic physics issues. Improvements to power supplies and to control algorithms have the potential to further extend this regime.
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We describe a three generation family in whom multiple individuals are variably affected due to a PHOX2B non-polyalanine repeat mutation. This family demonstrates extreme phenotypic variability and autosomal dominant transmission over three generations not previously reported in the wider literature. Novel findings also inclue a history of recurrent second trimester miscarriage. Pediatr Pulmonol. 2014; 49:E140-E143. © 2014 Wiley Periodicals, Inc.
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Proteínas de Homeodominio/genética , Hipoventilación/congénito , Mutación , Apnea Central del Sueño/genética , Factores de Transcripción/genética , Aborto Habitual/genética , Femenino , Humanos , Hipoventilación/genética , Lactante , Masculino , Linaje , EmbarazoRESUMEN
AIM: To assess whether there are any significant differences in the film-reading histories of interval or screen-detected cancers, and whether this affects stage at diagnosis. MATERIALS AND METHODS: The rates of screen-detected and interval cancers (overall and by radiological categorization) were observed from 268,067 women screened in the East Midlands Breast Screening Programme over 2004-2007 to assess whether there were differences in incidence based on previous film-reading history. Cancers detected at the subsequent screen and film-reading history were analysed to assess whether this affected stage at diagnosis. Analysis undertaken involved cancer detection rates, confidence intervals, and chi-square tests with Monte Carlo simulation. RESULTS: Rates of interval cancers were similar in all groups where at least one reader had indicated recall to assessment (6.1-7.7/1000) and were significantly higher in comparison to women whose previous film-reading outcome was unanimous routine rescreen (2.9/1000; p < 0.001). Four point one percent of interval cancers with no previous recall outcomes were false negatives, which was significantly lower compared to the groups where at least one reader had indicated recall (10.9%; p = 0.005). Cancers detected at the subsequent screen demonstrated no significant difference in prognosis dependent on previous film-reading history (p = 0.503). CONCLUSION: The prognosis of screen-detected cancers was similar and few cancers were false negatives regardless of film-reading history at the previous screen.
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Neoplasias de la Mama/diagnóstico por imagen , Detección Precoz del Cáncer , Mamografía , Programas Nacionales de Salud , Garantía de la Calidad de Atención de Salud , Intensificación de Imagen Radiográfica/normas , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Detección Precoz del Cáncer/métodos , Inglaterra/epidemiología , Reacciones Falso Negativas , Femenino , Estudios de Seguimiento , Humanos , Mamografía/métodos , Mamografía/normas , Tamizaje Masivo , Persona de Mediana Edad , Garantía de la Calidad de Atención de Salud/normas , Estándares de Referencia , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To describe the anterior segment optical coherence tomography (AS-OCT) characteristics of patients with ocular manifestations of mucopolysaccharidoses type I (Hurler), II (Hunter), and VI (Maroteaux-Lamy). METHODS: Prospective, observational study of nine consecutive patients with variants of mucopolysaccharidosis (MPS) attending the Paediatric Ophthalmology service at Manchester Royal Eye Hospital, UK. All patients underwent Visante AS-OCT imaging as part of their ophthalmic assessment. RESULTS: Ocular involvement tended to be symmetrical. Angle-to-angle distance was significantly lower in MPS VI than in MPS I (P=0.04). Anterior chamber depth, angle opening distance, trabecular-iris space area, and scleral spur angle tended to be lower in MPS VI than in MPS I, but did not reach statistical significance. Corneal thickness in the central 0-2 mm zone was greater in MPS VI than in MPS I, approaching but not attaining statistical significance (P=0.07). The 2-5 and 5-7 mm zones were significantly thicker in MPS VI than MPS I (P=0.04, P=0.04). There was no difference in corneal thickness between MPS I and MPS VI in the peripheral 7-10 mm zone (P=0.57). Measurements of the patient with MPS II resembled the mean values of the MPS I group. CONCLUSION: AS-OCT is valuable in quantifying anterior segment pathology in MPS. It suggests more crowded anterior segments and greater corneal thickness in patients with MPS VI than MPS I. AS-OCT is useful in evaluating the risk and mechanism of glaucoma in MPS patients, and may improve our assessment of the efficacy of systemic treatment.
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Segmento Anterior del Ojo/patología , Mucopolisacaridosis II/diagnóstico , Mucopolisacaridosis I/diagnóstico , Mucopolisacaridosis VI/diagnóstico , Tomografía de Coherencia Óptica , Adolescente , Niño , Preescolar , Paquimetría Corneal , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
Femtosecond laser-assisted cataract surgery (FLACS) represents a potential paradigm shift in cataract surgery, but it is not without controversy. Advocates of the technology herald FLACS as a revolution that promises superior outcomes and an improved safety profile for patients. Conversely, detractors point to the large financial costs involved and claim that similar results are achievable with conventional small-incision phacoemulsification. This review provides a balanced and comprehensive account of the development of FLACS since its inception. It explains the physiology and mechanics underlying the technology, and critically reviews the outcomes and implications of initial studies. The benefits and limitations of using femtosecond laser accuracy to create corneal incisions, anterior capsulotomy, and lens fragmentation are explored, with reference to the main platforms, which currently offer FLACS. Economic considerations are discussed, in addition to the practicalities associated with the implementation of FLACS in a healthcare setting. The influence on surgical training and skills is considered and possible future applications of the technology introduced. While in its infancy, FLACS sets out the exciting possibility of a new level of precision in cataract surgery. However, further work in the form of large scale, phase 3 randomised controlled trials are required to demonstrate whether its theoretical benefits are significant in practice and worthy of the necessary huge financial investment and system overhaul. Whether it gains widespread acceptance is likely to be influenced by a complex interplay of scientific and socio-economic factors in years to come.
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Extracción de Catarata/métodos , Terapia por Láser/métodos , Cápsula del Cristalino/cirugía , Cristalino/cirugía , HumanosRESUMEN
BACKGROUND: Family quality of life (FQOL) has emerged as an important outcome of service delivery for individuals with disabilities and their families. The purpose of this review was to explore the disparity of scale development approaches between families with children with disabilities and families from other populations and identify strengths to serve as a source of recommendations to improve the measurements of FQOL in the disability field. METHOD: We conducted a keyword search of 25 databases. Sixteen measurement tools on FQOL, family well-being and family satisfaction currently used in the disability field, healthcare field and general family studies published in journals from 1980 to 2009 were included in the analysis. RESULTS: Three themes emerged from the detailed analysis and comparisons of the instruments: (1) description of the primary purpose and theoretical basis; (2) identification of the tool's respondents, domains, response formats and scoring strategies to assess family systems; and (3) summarisation of available psychometric information. CONCLUSIONS: As family researchers continue their mission to conceptualise and theorise about FQOL, they should also promote the refinement of FQOL measurements and consider the implications from family instruments used in the healthcare and general family fields from the following aspects: (1) domains of FQOL; (2) units of analysis; (3) response format; (4) scoring choice; and (5) psychometric evaluation.
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Salud de la Familia , Estado de Salud , Discapacidad Intelectual/psicología , Psicometría/métodos , Calidad de Vida/psicología , Bases de Datos Factuales , Evaluación de la Discapacidad , Humanos , Investigación CualitativaAsunto(s)
Neumología/tendencias , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/terapia , Asma/terapia , Enfermedad Crónica , Unión Europea , Femenino , Promoción de la Salud/métodos , Humanos , Masculino , Neumonía/terapia , Enfermedad Pulmonar Obstructiva Crónica/terapia , Neumología/métodos , Enfermedades Respiratorias/epidemiología , Infecciones del Sistema Respiratorio/terapia , Fumar/efectos adversosRESUMEN
The authors report the case of an 8-year-old girl of Caucasian origin who attended the Emergency Eye Clinic with a 3-week history of a red, light sensitive left eye during the month of April. Her Snellen visual acuities were 6/5 right and 6/9 left. Examination revealed perilimbal injection and anterior chamber inflammation in the left eye consistent with an anterior uveitis. Inferior stromal haze and fine keratic precipitates were noted in the left cornea. Intraocular pressures were normal, with no vitritis and healthy looking discs, maculae and peripheral retina. Systemic examination revealed a papular rash over the face consistent with previously diagnosed Hydroa vaccineforme. With intensive topical steroids the inflammation gradually resolved.
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Hidroa Vacciniforme/complicaciones , Queratitis/etiología , Uveítis Anterior/etiología , Niño , Femenino , HumanosRESUMEN
In life-threatening cases of Acute Asthma the administration of epinephrine may be given as part of the initial management by paramedics. Concurrent infection is a frequent precipitant of an asthma exacerbation and consequently a leucocytosis is often found in such a situation. This case illustrates that marked leucocytosis can occur without an underlying infective process following epinphrine use.