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1.
Plant Dis ; 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38764340

RESUMEN

Quinoa downy mildew, caused by Peronospora variabilis, is the most devastating disease of quinoa globally. Rapid, sensitive diagnostic methods are needed to detect and quantify this pathogen in seeds and plant tissue. A hydrolysis probe-based quantitative real-time PCR (qPCR) assay including a competitive internal control was developed for P. variabilis detection. This assay could detect as low as 20 ag of DNA or approximately 25 internal transcribed spacer (ITS) copies per reaction with efficiencies ranging from 93.9 to 98.2%. No non-target amplification was observed when tested against DNA from other downy mildew pathogens and related oomycetes. Peronospora variabilis strains from multiple countries were detected using this assay. The assay was successfully applied to quantify the pathogen in quinoa seeds from a field trial conducted in Washington State. Downy mildew disease was recorded on all 14 genotypes with the genotypes 104.88 and 106.49 recording the highest area under the disease progress values (3,236 ± 303 SE and 2,851 ± 198, respectively) while J6 and Dutchess recorded the lowest (441 ± 107 and 409 ± 129, respectively). Seed washes obtained from field samples were subjected to the qPCR assay, and the pathogen was detected in all samples. The highest pathogen ITS copy number recorded with 106.49 (194,934 ± 38,171 SE), while the lowest was observed in Pasto (5,971 ± 1,435) and Riobamba (9,954 ± 4,243). This qPCR assay could lead to improved detection and quantification of P. variabilis as well as increased understanding of quinoa-P. variabilis interactions and epidemiology.

2.
Plant Dis ; 107(9): 2673-2678, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36774576

RESUMEN

Corky root rot is an important disease in tomato production systems and is caused by Pseudopyrenochaeta terrestris and P. lycopersici (formerly Pyrenochaeta lycopersici Types 1 and 2, respectively). The corky root rot pathogens are slow growing and difficult to isolate and quantify in soil and plant tissue. A multiplex hydrolysis probe-based qPCR assay was designed to allow for simultaneous detection and quantification of P. lycopersici and P. terrestris with a competitive internal control to indicate if qPCR inhibitors are present. Single species and multiplex assays for Pseudopyrenochaeta spp. detected DNA levels above 0.013 pg of DNA per reaction. These highly specific assays had no nontarget amplification of other fungal and oomycete pathogens or rhizosphere-associated fungi of tomatoes that were tested. This assay can be used to quantify Pseudopyrenochaeta populations in roots and soils in tomato production systems to better determine the impacts of disease management strategies on Pseudopyrenochaeta spp. and provides a tool to study the biology of Pseudopyrenochaeta spp.


Asunto(s)
Solanum lycopersicum , Enfermedades de las Plantas/microbiología , Reacción en Cadena de la Polimerasa , ADN
3.
J Theor Biol ; 512: 110536, 2021 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-33186594

RESUMEN

We build a parsimonious Crump-Mode-Jagers continuous time branching process of COVID-19 propagation based on a negative binomial process subordinated by a gamma subordinator. By focusing on the stochastic nature of the process in small populations, our model provides decision making insight into mitigation strategies as an outbreak begins. Our model accommodates contact tracing and isolation, allowing for comparisons between different types of intervention. We emphasize a physical interpretation of the disease propagation throughout which affords analytical results for comparison to simulations. Our model provides a basis for decision makers to understand the likely trade-offs and consequences between alternative outbreak mitigation strategies particularly in office environments and confined work-spaces. Combining the asymptotic limit of our model with Bayesian hierarchical techniques, we provide US county level inferences for the reproduction number from cumulative case count data over July and August of this year.


Asunto(s)
COVID-19 , Modelos Biológicos , Pandemias , SARS-CoV-2 , Teorema de Bayes , COVID-19/epidemiología , COVID-19/transmisión , Humanos
4.
J Chem Phys ; 155(5): 054108, 2021 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-34364347

RESUMEN

Here, we present a concise model that can predict the photoluminescent properties of a given compound from first principles, both within and beyond the Franck-Condon approximation. The formalism required to compute fluorescence, Internal Conversion (IC), and Inter-System Crossing (ISC) is discussed. The IC mechanism, in particular, is a difficult pathway to compute due to difficulties associated with the computation of required bosonic configurations and non-adiabatic coupling elements. Here, we offer a discussion and breakdown on how to model these pathways at the Density Functional Theory (DFT) level with respect to its computational implementation, strengths, and current limitations. The model is then used to compute the photoluminescent quantum yield (PLQY) of a number of small but important compounds: anthracene, tetracene, pentacene, diketo-pyrrolo-pyrrole (DPP), and Perylene Diimide (PDI) within a polarizable continuum model. Rate constants for fluorescence, IC, and ISC compare well for the most part with respect to experiment, despite triplet energies being overestimated to a degree. The resulting PLQYs are promising with respect to the level of theory being DFT. While we obtained a positive result for PDI within the Franck-Condon limit, the other systems require a second order correction. Recomputing quantum yields with Herzberg-Teller terms yields PLQYs of 0.19, 0.08, 0.04, 0.70, and 0.99 for anthracene, tetracene, pentacene, DPP, and PDI, respectively. Based on these results, we are confident that the presented methodology is sound with respect to the level of quantum chemistry and presents an important stepping stone in the search for a tool to predict the properties of larger coupled systems.

5.
Clin Radiol ; 75(8): 599-605, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32593409

RESUMEN

AIM: To determine the incidence of possible COVID-19-related lung changes on preoperative screening computed tomography (CT) for COVID-19 and how their findings influenced decision-making. To also to determine whether the patients were managed as COVID-19 patients after their imaging findings, and the proportion who had SARS-CoV2 reverse transcriptionpolymerase chain reaction (RT-PCR) testing. MATERIALS AND METHODS: A retrospective study was undertaken of consecutive patients having imaging prior to urgent elective surgery (n=156) or acute abdominal imaging (n=283). Lung findings were categorised according to the British Society of Thoracic Imaging (BSTI) guidelines. RT-PCR testing, management, and outcomes were determined from the electronic patient records. RESULTS: 3% (13/439) of CT examinations demonstrated findings of classic/probable COVID-19 pneumonia, whilst 4% (19/439) had findings indeterminate for COVID-19. Of the total cohort, 1.6% (7/439) subsequently had confirmed RT-PCR-positive COVID-19. Importantly, all the patients with a normal chest or alternative diagnoses on CT who had PCR testing within the next 7 days, had a negative RT-PCR (92/407). There was a change in surgical outcome in 6% (10/156) of the elective surgical cohort with no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery (2/283). CONCLUSION: There was a 7% (32/439) incidence of potential COVID-19-related lung changes in patients having preoperative CT. Although this altered surgical management in the elective surgical cohort, no change to surgical management was demonstrated in the acute abdominal emergency cohort requiring surgery.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Cuidados Preoperatorios/métodos , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Procedimientos Quirúrgicos Electivos , Servicio de Urgencia en Hospital , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Reino Unido , Adulto Joven
6.
Psychiatr Psychol Law ; 26(1): 97-109, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31984067

RESUMEN

The number of older inmates in New South Wales prisons has increased over the past ten years but it is unclear whether corrective services can cater for the increase. The current study reports the results of a qualitative study about ageing in prison. Eight prison chaplains from four corrective facilities in NSW were interviewed using a semi-structured interview schedule. The results of a thematic analysis revealed four main themes: the system, the services, the environment and the inmate. The themes reveal a system that is not designed to cope with an ageing population. Inmates become resentful of what has happened to them rather than for the damage they have done to somebody else. The system lacks processes and programmes to enable proper rehabilitation. The issues raised by the chaplains in terms of services, the environment and the inmates decrease the possibility that an older inmate will adapt to the environment and successfully age in place.

7.
Int J Behav Nutr Phys Act ; 15(1): 21, 2018 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-29482617

RESUMEN

BACKGROUND: Sedentary behaviour is a public health concern that requires surveillance and epidemiological research. For such large scale studies, self-report tools are a pragmatic measurement solution. A large number of self-report tools are currently in use, but few have been validated against an objective measure of sedentary time and there is no comparative information between tools to guide choice or to enable comparison between studies. The aim of this study was to provide a systematic comparison, generalisable to all tools, of the validity of self-report measures of sedentary time against a gold standard sedentary time objective monitor. METHODS: Cross sectional data from three cohorts (N = 700) were used in this validation study. Eighteen self-report measures of sedentary time, based on the TAxonomy of Self-report SB Tools (TASST) framework, were compared against an objective measure of postural sitting (activPAL) to provide information, generalizable to all existing tools, on agreement and precision using Bland-Altman statistics, on criterion validity using Pearson correlation, and on data loss. RESULTS: All self-report measures showed poor accuracy compared with the objective measure of sedentary time, with very wide limits of agreement and poor precision (random error > 2.5 h). Most tools under-reported total sedentary time and demonstrated low correlations with objective data. The type of assessment used by the tool, whether direct, proxy, or a composite measure, influenced the measurement characteristics. Proxy measures (TV time) and single item direct measures using a visual analogue scale to assess the proportion of the day spent sitting, showed the best combination of precision and data loss. The recall period (e.g. previous week) had little influence on measurement characteristics. CONCLUSION: Self-report measures of sedentary time result in large bias, poor precision and low correlation with an objective measure of sedentary time. Choice of tool depends on the research context, design and question. Choice can be guided by this systematic comparative validation and, in the case of population surveillance, it recommends to use a visual analog scale and a 7 day recall period. Comparison between studies and improving population estimates of average sedentary time, is possible with the comparative correction factors provided.


Asunto(s)
Ejercicio Físico , Conducta Sedentaria , Autoinforme/normas , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Recuerdo Mental , Persona de Mediana Edad , Vigilancia de la Población , Postura , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Televisión , Tiempo
8.
Geophys Res Lett ; 45(19): 10738-10745, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30778268

RESUMEN

Cloud optical properties are determined not only by the number density n d and mean radius r ¯ of cloud droplets but also by the shape of the droplet size distribution. The change in cloud optical depth with changing n d , due to the change in distribution shape, is known as the dispersion effect. Droplet relative dispersion is defined as d = σ r / r ¯ . For the first time, a commonly used effective radius parameterization is tested in a controlled laboratory environment by creating a turbulent cloud. Stochastic condensation growth suggests d independent of n d for a nonprecipitating cloud, hence nearly zero albedo susceptibility due to the dispersion effect. However, for size-dependent removal, such as in a laboratory cloud or highly clean atmospheric conditions, stochastic condensation produces a weak dispersion effect. The albedo susceptibility due to turbulence broadening has the same sign as the Twomey effect and augments it by order 10%.

9.
J Hum Nutr Diet ; 31(6): 773-780, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29926996

RESUMEN

BACKGROUND: Weight-loss programmes requiring intermittent energy restriction offer an alternative to continuous energy restriction programmes that typically have low adherence. We reported greater weight loss, better adherence and spontaneous reduced energy intake on healthy eating days with intermittent as opposed to continuous energy restriction. The present study aims to explore why intermittent energy restriction diets exert these positive effects. METHODS: Semi-structured interviews were carried out with 13 women aged 39-62 years, who followed a 4-month intermittent energy restriction (2 days of low energy/low carbohydrate, 5 days of healthy eating). Nine of the 13 women successfully lost >5% of their total body weight. Data were analysed using thematic analysis. RESULTS: The intermittent regimen redefined the meaning of dieting and normal eating. Women reconceptualised dieting as only two low energy days per week, even though this often differed from their pre-diet eating patterns. Women reported that they could adhere more closely to the rules of the intermittent diet compared to previously attempted continuous diets. They found that the intermittent diet was less cognitively demanding because the restrictive and clear rules of the intermittent diet were easier to understand and easier to follow than with continuous dieting. CONCLUSIONS: Many participants found intermittent dieting preferable to previous experiences of continuous dieting. The findings provide some insight into the ways in which intermittent dieting is successful, and why it could be considered a viable alternative to continuous energy restriction for weight loss.


Asunto(s)
Neoplasias de la Mama/prevención & control , Restricción Calórica , Dieta Reductora/métodos , Ingestión de Energía , Obesidad/dietoterapia , Satisfacción del Paciente , Programas de Reducción de Peso/métodos , Adulto , Peso Corporal , Neoplasias de la Mama/etiología , Comprensión , Dieta Baja en Carbohidratos , Ayuno , Conducta Alimentaria , Femenino , Humanos , Persona de Mediana Edad , Obesidad/complicaciones , Cooperación del Paciente , Pérdida de Peso
10.
Clin Otolaryngol ; 43(1): 223-229, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28734109

RESUMEN

OBJECTIVES: To estimate the total costs of treating head and neck cancers, specifically oropharyngeal, laryngeal and oral cavity cancer, in secondary care facilities in England during the period 2006/2007 to 2010/2011. DESIGN: Patient records were extracted from an English hospital database to estimate the number of patients treated for oropharyngeal, laryngeal and oral cavity cancer in England. Identified resource use was linked to published United Kingdom cost estimates to quantify the reimbursement of treatment through the Payment by Results system. SETTING: Retrospective hospital data analysis. PARTICIPANTS: From the hospital data, patient records of patients treated for oropharyngeal, laryngeal and oral cavity cancer were selected. MAIN OUTCOME MEASURES: Annual total costs of treatment, stratified by inpatient and outpatient setting and by male and female patients. RESULTS: From 2006/2007 to 2010/2011, total costs of treatment across the three head and neck cancer sites were estimated to be approximately £309 million, with 90% attributable to inpatient care (bundled costs). Oropharyngeal cancer accounted for 37% of total costs. Costs and patient numbers increased over time, largely due to a rise in oropharyngeal cancer, where total costs increased from £17.21 million to £30.32 million, with over 1400 (52%) more inpatients treated in 2010/11 compared to 2006/07. CONCLUSIONS: In 4 years, the number of patients with oropharyngeal cancer receiving some form of inpatient care increased by more than half, and associated costs increased by three quarters. This reinforces the case for prevention and early detection strategies to help contain this epidemiological and economic burden.


Asunto(s)
Costo de Enfermedad , Gastos en Salud/tendencias , Neoplasias Orofaríngeas/economía , Terapia Combinada/economía , Bases de Datos Factuales , Inglaterra , Humanos , Neoplasias Orofaríngeas/terapia , Estudios Retrospectivos
11.
Clin Otolaryngol ; 43(3): 846-853, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29341454

RESUMEN

OBJECTIVES: The aim of this longitudinal study was to examine the distribution of head and neck cancer (HANC) disease burden across the region comparing it to national trends. DESIGN: We undertook a retrospective study of routine data combining it with indicators of deprivation and lifestyle at small geographical areas within the 9 Local Authorities (LAs) of Merseyside and Cheshire Network (MCCN) for head and neck cancers. Data from the North West of England and England were used as comparator regions. SETTING: This research was undertaken by the Cheshire and Merseyside Public Health Collaborative, UK. PARTICIPANTS: The Merseyside and Cheshire region serves a population of 2.2 million. Routine data allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and C30-C32 within 3 cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis. MAIN OUTCOME MEASURES: Directly age-standardised incidence rates and directly age-standardised mortality rates in the LAs and comparator regions were measured. Lifestyle and deprivation indicators were plotted against them and measured by Pearson's correlation coefficients. RESULTS: The incidence of head and neck cancer has increased across the region from 1998-2000 to 2008-2010 with a peak incidence for Liverpool males at 35/100 000 population. Certain Middle Super Output Areas contribute disproportionately to the significant effect of incidence and mortality within LAs. Income deprivation had the strongest correlation with incidence (r = .59) and mortality (r = .53) of head and neck cancer. CONCLUSION: Our study emphasises notable geographical variations within the region which need to be addressed through public health measures.


Asunto(s)
Costo de Enfermedad , Neoplasias de Cabeza y Cuello/epidemiología , Disparidades en el Estado de Salud , Factores Socioeconómicos , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Inglaterra/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Distribución por Sexo , Tasa de Supervivencia
12.
Clin Otolaryngol ; 42(6): 1141-1152, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28130927

RESUMEN

BACKGROUND: Fibrin sealants (FS) are commercially available products used in surgical wounds as adjuncts to haemostasis and closure of dead space. The role of FS in soft tissue head and neck surgery has not been established. OBJECTIVES: To assess whether FS improves wound-related outcomes in patients undergoing soft tissue surgery of the head and neck anatomical region that would commonly require a drain. TYPE OF REVIEW: Systematic review and meta-analysis of randomised controlled trials (RCTs). SEARCH STRATEGY: MEDLINE (1946-2016), EMBASE (1974-2016), PubMed (2016), CENTRAL (2016), ClinicalTrials.gov (2016), WHO International Clinical Trials Registry and Platform (2016), Research Gate (2016). EVALUATION METHOD: Two independent reviewers screened and selected studies. Included studies were assessed for risk of bias and data extracted using a predetermined data collection form. RESULTS: Of the 421 studies that were screened, 11 RCTs met the inclusion criteria. There were two RCTs on thyroidectomy, three on "surgery involving neck dissection" (central or lateral), five on rhytidectomy and one on parotidectomy. There was a tendency for FS to reduce "mean total drainage volume" (mean difference -26.86 mL, 95% CI -43.41 to -10.31, I2 =97%, P=.001). Subgroup analysis of thyroidectomy (mean difference -36.36 mL, 95% CI -72.82 to 0.10, I2 =79%, P=.05), "surgery involving neck dissection" (mean difference -33.21 mL, 95% CI -70.01 to 3.59, I2 =94%, P=.08) and rhytidectomy (mean difference -13.79 mL, 95% CI -17.57 to -10.01, I2 =0%, P < .00001) concurred with the overall analysis. There was a suggestion that FS may reduce "mean retention time of drains" by 1.24 days (95% CI -3.32 to 0.85, I2 =99%, P=.25) and "hospital length of stay" by 2.09 days (95% CI -5.18 to 0.99, I2 =97%, P=.18), but this was not statistically significant. There was also a suggestion that FS may protect against adverse events (RR 0.69, 95% CI 0.35 to 1.38, I2 =0%, P=.29) and haematoma/seroma formation (RR 0.49, 95% CI 0.22 to 1.07, I2 =0%, P=0.07). CONCLUSIONS: There was considerable heterogeneity within the RCTs included in this study, thus restricting definitive conclusions. FS has however shown a definite benefit in rhytidectomy and potential benefit in other soft tissue head and neck surgical procedures. Further pragmatic trials are required particularly in the field of lateral neck dissection.


Asunto(s)
Adhesivo de Tejido de Fibrina/uso terapéutico , Disección del Cuello/efectos adversos , Glándula Parótida/cirugía , Complicaciones Posoperatorias/prevención & control , Ritidoplastia/efectos adversos , Tiroidectomía/efectos adversos , Drenaje , Humanos , Complicaciones Posoperatorias/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
Clin Genet ; 89(4): 478-483, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25693842

RESUMEN

Genetic testing for non-specific intellectual disability (ID) presents challenges in daily clinical practice. Historically, the focus of the genetic elucidation of non-specific ID has been on genes on the X chromosome, and recent research has brought attention to the growing contribution of autosomal genes. In addition, next-generation sequencing (NGS) has greatly improved the ability to simultaneously analyze multiple genetic loci, making large panel testing a practical approach to testing for non-specific ID. We performed NGS analysis of a total of 90 genes implicated in non-specific ID. The 90 genes included 56 X-linked genes and 34 autosomal genes. Pathogenic variants were identified in 11 of 52 (21%) patient samples. Nine of the eleven cases harbored mutations in autosomal genes including AP4B1, STXB1, SYNGAP1, TCF4 and UBE3A. Our mutation-positive cases provide further evidence supporting the prevalence of autosomal mutations in patients referred for non-specific ID testing and the utility of their inclusion in multi-gene panel analysis.

14.
BMC Vet Res ; 11: 218, 2015 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-26289208

RESUMEN

BACKGROUND: Following the recent development of a new approach to quantitative analysis of IgG concentrations in bovine serum using transmission infrared spectroscopy, the potential to measure IgG levels using technology and a device better designed for field use was investigated. A method using attenuated total reflectance infrared (ATR) spectroscopy in combination with partial least squares (PLS) regression was developed to measure bovine serum IgG concentrations. ATR spectroscopy has a distinct ease-of-use advantage that may open the door to routine point-of-care testing. Serum samples were collected from calves and adult cows, tested by a reference RID method, and ATR spectra acquired. The spectra were linked to the RID-IgG concentrations and then randomly split into two sets: calibration and prediction. The calibration set was used to build a calibration model, while the prediction set was used to assess the predictive performance and accuracy of the final model. The procedure was repeated for various spectral data preprocessing approaches. RESULTS: For the prediction set, the Pearson's and concordance correlation coefficients between the IgG measured by RID and predicted by ATR spectroscopy were both 0.93. The Bland Altman plot revealed no obvious systematic bias between the two methods. ATR spectroscopy showed a sensitivity for detection of failure of transfer of passive immunity (FTPI) of 88 %, specificity of 100 % and accuracy of 94 % (with IgG <1000 mg/dL as the FTPI cut-off value). CONCLUSION: ATR spectroscopy in combination with multivariate data analysis shows potential as an alternative approach for rapid quantification of IgG concentrations in bovine serum and the diagnosis of FTPI in calves.


Asunto(s)
Inmunoglobulina G/sangre , Espectrofotometría Infrarroja/veterinaria , Animales , Bovinos , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Inmunidad Materno-Adquirida , Análisis Multivariante , Espectrofotometría Infrarroja/métodos
16.
BMC Med Educ ; 15: 86, 2015 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-25964102

RESUMEN

BACKGROUND: Failing a high-stakes assessment at medical school is a major event for those who go through the experience. Students who fail at medical school may be more likely to struggle in professional practice, therefore helping individuals overcome problems and respond appropriately is important. There is little understanding about what factors influence how individuals experience failure or make sense of the failing experience in remediation. The aim of this study was to investigate the complexity surrounding the failure experience from the student's perspective using interpretative phenomenological analysis (IPA). METHODS: The accounts of three medical students who had failed final re-sit exams, were subjected to in-depth analysis using IPA methodology. IPA was used to analyse each transcript case-by-case allowing the researcher to make sense of the participant's subjective world. The analysis process allowed the complexity surrounding the failure to be highlighted, alongside a narrative describing how students made sense of the experience. RESULTS: The circumstances surrounding students as they approached assessment and experienced failure at finals were a complex interaction between academic problems, personal problems (specifically finance and relationships), strained relationships with friends, family or faculty, and various mental health problems. Each student experienced multi-dimensional issues, each with their own individual combination of problems, but experienced remediation as a one-dimensional intervention with focus only on improving performance in written exams. What these students needed to be included was help with clinical skills, plus social and emotional support. Fear of termination of the their course was a barrier to open communication with staff. CONCLUSIONS: These students' experience of failure was complex. The experience of remediation is influenced by the way in which students make sense of failing. Generic remediation programmes may fail to meet the needs of students for whom personal, social and mental health issues are a part of the picture.


Asunto(s)
Escolaridad , Estudiantes de Medicina/psicología , Emociones , Femenino , Humanos , Masculino , Investigación Cualitativa , Aislamiento Social/psicología
17.
Br J Cancer ; 111(11): 2114-21, 2014 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-25268377

RESUMEN

BACKGROUND: Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available. METHODS: In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan-Meier survival analysis. RESULTS: Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95%; SMA: 82%; combination: 81%). CONCLUSION: A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.


Asunto(s)
Actinas/análisis , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Inhibidor 1 de Activador Plasminogénico/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/mortalidad , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Pronóstico
18.
Br J Cancer ; 111(8): 1590-604, 2014 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-25121956

RESUMEN

BACKGROUND: This study evaluated soluble serum proteins as biomarkers to subset patients with metastatic colorectal cancer (mCRC) treated with chemotherapy±cediranib, a vascular endothelial growth factor (VEGF) signalling inhibitor (VEGFi). Exploring biomarkers at pre- and on-treatment may identify patient subgroups showing clinical benefit on cediranib combination. METHODS: Two hundred and seven serum proteins were analysed in 588 mCRC patients at pre- and on-treatment with chemotherapy (FOLFOX/CAPOX)±cediranib 20 mg. Patients were enrolled in the phase III trial HORIZON II. We correlated baseline biomarker signatures and pharmacodynamic (PD) biomarkers with PFS and OS. RESULTS: We identified a baseline signature (BS) of 47 biomarkers that included VEGFA, VEGFD, VEGFR2, VEGFR3 and TIE-2, which defined two distinct subgroups of patients. Patients treated with chemotherapy plus cediranib who had 'high' BS had shorter PFS (HR=1.82, P=0.003) than patients with 'low' BS. This BS did not correlate with PFS of the patients treated with chemotherapy plus placebo. In addition, we identified a profile of 16 PD proteins on treatment associated with PFS (HR=0.58, P<0.001) and OS (HR=0.52, P<0.001) in patients treated with chemotherapy plus cediranib. This PD profile did not correlate with PFS and OS in patients treated with chemotherapy plus placebo. CONCLUSIONS: Serum proteins may represent relevant biomarkers to predict the outcome of patients treated with VEGFi-based therapies. We report a BS and PD biomarkers that may identify mCRC patients showing increased benefit of combining cediranib with chemotherapy. These exploratory findings need to be validated in future prospective studies.


Asunto(s)
Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Proteínas Sanguíneas/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Quinazolinas/uso terapéutico , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/fisiopatología , Humanos , Resultado del Tratamiento
19.
Phys Rev Lett ; 113(23): 235701, 2014 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-25526136

RESUMEN

It has been conjectured that roughness plays a role in surface nucleation, the tendency for freezing to begin preferentially at the liquid-gas interface. Using high speed imaging, we sought evidence for freezing at the contact line on catalyst substrates with imposed characteristic length scales (texture). Length scales consistent with the critical nucleus size and with δ∼τ/σ, where τ is a relevant line tension and σ is the surface tension, range from nanometers to micrometers. It is found that nanoscale texture causes a shift in the nucleation of ice in supercooled water to the three-phase contact line, while microscale texture does not.

20.
Heredity (Edinb) ; 112(1): 13-20, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23715015

RESUMEN

The additive genetic variance with respect to absolute fitness, VA(W), divided by mean absolute fitness, , sets the rate of ongoing adaptation. Fisher's key insight yielding this quantitative prediction of adaptive evolution, known as the Fundamental Theorem of Natural Selection, is well appreciated by evolutionists. Nevertheless, extremely scant information about VA(W) is available for natural populations. Consequently, the capacity for fitness increase via natural selection is unknown. Particularly in the current context of rapid environmental change, which is likely to reduce fitness directly and, consequently, the size and persistence of populations, the urgency of advancing understanding of immediate adaptive capacity is extreme. We here explore reasons for the dearth of empirical information about VA(W), despite its theoretical renown and critical evolutionary role. Of these reasons, we suggest that expectations that VA(W) is negligible, in general, together with severe statistical challenges of estimating it, may largely account for the limited empirical emphasis on it. To develop insight into the dynamics of VA(W) in a changing environment, we have conducted individual-based genetically explicit simulations. We show that, as optimizing selection on a trait changes steadily over generations, VA(W) can grow considerably, supporting more rapid adaptation than would the VA(W) of the base population. We call for direct evaluation of VA(W) and in support of prediction of rates adaptive evolution, and we advocate for the use of aster modeling as a rigorous basis for achieving this goal.


Asunto(s)
Adaptación Biológica/genética , Evolución Molecular , Aptitud Genética , Sitios de Carácter Cuantitativo/genética , Interacción Gen-Ambiente , Variación Genética , Modelos Teóricos , Selección Genética
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