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1.
J Med Genet ; 59(7): 632-643, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34844974

RESUMEN

BACKGROUND: Epithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention. METHODS: We developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively. RESULTS: Based on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%-10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk. CONCLUSION: This multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).


Asunto(s)
Neoplasias de la Mama , Neoplasias Ováricas , Carcinoma Epitelial de Ovario/epidemiología , Carcinoma Epitelial de Ovario/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Herencia Multifactorial/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Factores de Riesgo
2.
J Med Genet ; 59(12): 1206-1218, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36162851

RESUMEN

BACKGROUND: BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. METHODS: BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. RESULTS: BARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%-44% of these carriers would be reclassified to the near-population and 15%-22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of <5%, 5%-10% and >10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. CONCLUSIONS: These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.


Asunto(s)
Neoplasias de la Mama , Neoplasias Ováricas , Adulto , Femenino , Humanos , Incidencia , Predisposición Genética a la Enfermedad , Proteína BRCA1/genética , Neoplasias Ováricas/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/diagnóstico , Carcinoma Epitelial de Ovario , Factores de Riesgo , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/genética , Proteínas de Unión al ADN/genética
3.
Bioinformatics ; 34(6): 1069-1071, 2018 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-29095980

RESUMEN

Motivation: The collection, management and visualization of clinical pedigree (family history) data is a core activity in clinical genetics centres. However, clinical pedigree datasets can be difficult to manage, as they are time consuming to capture, and can be difficult to build, manipulate and visualize graphically. Several standalone graphical pedigree editors and drawing applications exist but there are no freely available lightweight graphical pedigree editors that can be easily configured and incorporated into web applications. Results: We developed 'pedigreejs', an interactive graphical pedigree editor written in JavaScript, which uses standard pedigree nomenclature. Pedigreejs provides an easily configurable, extensible and lightweight pedigree editor. It makes use of an open-source Javascript library to define a hierarchical layout and to produce images in scalable vector graphics (SVG) format that can be viewed and edited in web browsers. Availability and implementation: The software is freely available under GPL licence (https://ccge-boadicea.github.io/pedigreejs/). Contact: tjc29@cam.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online.


Asunto(s)
Anamnesis , Linaje , Programas Informáticos , Femenino , Humanos , Internet , Masculino , Navegador Web
5.
Genet Med ; 21(8): 1708-1718, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30643217

RESUMEN

PURPOSE: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs). METHODS: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information. RESULTS: Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th percentile, with 14.7% of women predicted to have a lifetime risk of ≥17-<30% (moderate risk according to National Institute for Health and Care Excellence [NICE] guidelines) and 1.1% a lifetime risk of ≥30% (high risk). CONCLUSION: This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualized, informed decision-making on prevention therapies and screening.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/patología , Quinasa de Punto de Control 2/genética , Proteína del Grupo de Complementación N de la Anemia de Fanconi/genética , Femenino , Humanos , Herencia Multifactorial/genética , Mutación/genética , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Polimorfismo de Nucleótido Simple/genética , Medición de Riesgo , Factores de Riesgo
6.
Genet Med ; 18(12): 1190-1198, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27464310

RESUMEN

PURPOSE: The proliferation of gene panel testing precipitates the need for a breast cancer (BC) risk model that incorporates the effects of mutations in several genes and family history (FH). We extended the BOADICEA model to incorporate the effects of truncating variants in PALB2, CHEK2, and ATM. METHODS: The BC incidence was modeled via the explicit effects of truncating variants in BRCA1/2, PALB2, CHEK2, and ATM and other unobserved genetic effects using segregation analysis methods. RESULTS: The predicted average BC risk by age 80 for an ATM mutation carrier is 28%, 30% for CHEK2, 50% for PALB2, and 74% for BRCA1 and BRCA2. However, the BC risks are predicted to increase with FH burden. In families with mutations, predicted risks for mutation-negative members depend on both FH and the specific mutation. The reduction in BC risk after negative predictive testing is greatest when a BRCA1 mutation is identified in the family, but for women whose relatives carry a CHEK2 or ATM mutation, the risks decrease slightly. CONCLUSIONS: The model may be a valuable tool for counseling women who have undergone gene panel testing for providing consistent risks and harmonizing their clinical management. A Web application can be used to obtain BC risks in clinical practice (http://ccge.medschl.cam.ac.uk/boadicea/).Genet Med 18 12, 1190-1198.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/genética , Neoplasias de la Mama/genética , Quinasa de Punto de Control 2/genética , Proteínas Nucleares/genética , Proteínas Supresoras de Tumor/genética , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/patología , Proteína del Grupo de Complementación N de la Anemia de Fanconi , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Persona de Mediana Edad , Mutación , Medición de Riesgo
7.
Front Psychol ; 14: 1298623, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38259528

RESUMEN

Climate change is the greatest threat humanity faces, and puts at risk the mental health and wellbeing of children and young people. Climate change education must equip children and young people with the knowledge, skills and resilience to live in an uncertain future, sustainably take relevant climate action and work in climate careers. As attention on climate change education grows, this is a critical moment for the mental health community to ensure mental health and wellbeing considerations are embedded. Critically, appropriate integration of mental health can enable these very necessary goals of equipping children and young people to live and work in a future where climate change looms large. This paper explores why promoting good mental health and wellbeing and building psychological resilience can help achieve climate change education outcomes, and why not doing so risks harming children and young people's mental health. It also explores how integrating discussions about emotions, mental health, and coping strategies within climate change education can be a route into wider discussions about mental health, to support children and young people in the context of rising mental health needs. Learning from an existing approach to promoting good mental health and wellbeing in schools (the 'whole school approach') provides the opportunity to explore one avenue through which such an integrated approach could be implemented in practice. Identifying appropriate mechanisms to integrate mental health into climate change education will require co-design and research with educators and young people, and addressing systemic barriers facing the schools sector.

8.
Br J Gen Pract ; 73(733): e586-e596, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37308304

RESUMEN

BACKGROUND: The CanRisk tool enables the collection of risk factor information and calculation of estimated future breast cancer risks based on the multifactorial Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. Despite BOADICEA being recommended in National Institute for Health and Care Excellence (NICE) guidelines and CanRisk being freely available for use, the CanRisk tool has not yet been widely implemented in primary care. AIM: To explore the barriers to and facilitators of the implementation of the CanRisk tool in primary care. DESIGN AND SETTING: A multi-methods study was conducted with primary care practitioners (PCPs) in the East of England. METHOD: Participants used the CanRisk tool to complete two vignette-based case studies; semi-structured interviews gained feedback about the tool; and questionnaires collected demographic details and information about the structural characteristics of the practices. RESULTS: Sixteen PCPs (eight GPs and eight nurses) completed the study. The main barriers to implementation included: time needed to complete the tool; competing priorities; IT infrastructure; and PCPs' lack of confidence and knowledge to use the tool. Main facilitators included: easy navigation of the tool; its potential clinical impact; and the increasing availability of and expectation to use risk prediction tools. CONCLUSION: There is now a greater understanding of the barriers and facilitators that exist when using CanRisk in primary care. The study has highlighted that future implementation activities should focus on reducing the time needed to complete a CanRisk calculation, integrating the CanRisk tool into existing IT infrastructure, and identifying appropriate contexts in which to conduct a CanRisk calculation. PCPs may also benefit from information about cancer risk assessment and CanRisk-specific training.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/prevención & control , Factores de Riesgo , Atención Primaria de Salud , Inglaterra , Estudios de Casos y Controles , Investigación Cualitativa
9.
Cancer Epidemiol Biomarkers Prev ; 32(3): 422-427, 2023 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-36649146

RESUMEN

BACKGROUND: The multifactorial risk prediction model BOADICEA enables identification of women at higher or lower risk of developing breast cancer. BOADICEA models genetic susceptibility in terms of the effects of rare variants in breast cancer susceptibility genes and a polygenic component, decomposed into an unmeasured and a measured component - the polygenic risk score (PRS). The current version was developed using a 313 SNP PRS. Here, we evaluated approaches to incorporating this PRS and alternative PRS in BOADICEA. METHODS: The mean, SD, and proportion of the overall polygenic component explained by the PRS (α2) need to be estimated. $\alpha $ was estimated using logistic regression, where the age-specific log-OR is constrained to be a function of the age-dependent polygenic relative risk in BOADICEA; and using a retrospective likelihood (RL) approach that models, in addition, the unmeasured polygenic component. RESULTS: Parameters were computed for 11 PRS, including 6 variations of the 313 SNP PRS used in clinical trials and implementation studies. The logistic regression approach underestimates $\alpha $, as compared with the RL estimates. The RL $\alpha $ estimates were very close to those obtained by assuming proportionality to the OR per 1 SD, with the constant of proportionality estimated using the 313 SNP PRS. Small variations in the SNPs included in the PRS can lead to large differences in the mean. CONCLUSIONS: BOADICEA can be readily adapted to different PRS in a manner that maintains consistency of the model. IMPACT: : The methods described facilitate comprehensive breast cancer risk assessment.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/genética , Medición de Riesgo/métodos , Estudios Retrospectivos , Factores de Riesgo , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple
10.
BMC Med Inform Decis Mak ; 12: 30, 2012 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-22490389

RESUMEN

BACKGROUND: In the past 20 years, society has witnessed the following landmark scientific advances: (i) the sequencing of the human genome, (ii) the distribution of software by the open source movement, and (iii) the invention of the World Wide Web. Together, these advances have provided a new impetus for clinical software development: developers now translate the products of human genomic research into clinical software tools; they use open-source programs to build them; and they use the Web to deliver them. Whilst this open-source component-based approach has undoubtedly made clinical software development easier, clinical software projects are still hampered by problems that traditionally accompany the software process. This study describes the development of the BOADICEA Web Application, a computer program used by clinical geneticists to assess risks to patients with a family history of breast and ovarian cancer. The key challenge of the BOADICEA Web Application project was to deliver a program that was safe, secure and easy for healthcare professionals to use. We focus on the software process, problems faced, and lessons learned. Our key objectives are: (i) to highlight key clinical software development issues; (ii) to demonstrate how software engineering tools and techniques can facilitate clinical software development for the benefit of individuals who lack software engineering expertise; and (iii) to provide a clinical software development case report that can be used as a basis for discussion at the start of future projects. RESULTS: We developed the BOADICEA Web Application using an evolutionary software process. Our approach to Web implementation was conservative and we used conventional software engineering tools and techniques. The principal software development activities were: requirements, design, implementation, testing, documentation and maintenance. The BOADICEA Web Application has now been widely adopted by clinical geneticists and researchers. BOADICEA Web Application version 1 was released for general use in November 2007. By May 2010, we had > 1200 registered users based in the UK, USA, Canada, South America, Europe, Africa, Middle East, SE Asia, Australia and New Zealand. CONCLUSIONS: We found that an evolutionary software process was effective when we developed the BOADICEA Web Application. The key clinical software development issues identified during the BOADICEA Web Application project were: software reliability, Web security, clinical data protection and user feedback.


Asunto(s)
Neoplasias de la Mama/genética , Sistemas de Apoyo a Decisiones Clínicas/organización & administración , Internet , Neoplasias Ováricas/genética , Diseño de Software , Algoritmos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/prevención & control , Simulación por Computador , Sistemas de Apoyo a Decisiones Clínicas/normas , Análisis de Falla de Equipo/métodos , Análisis de Falla de Equipo/normas , Femenino , Predisposición Genética a la Enfermedad , Humanos , Modelos Genéticos , Mutación , Neoplasias Ováricas/prevención & control , Proyectos Piloto , Medición de Riesgo/métodos , Medición de Riesgo/normas
11.
Cancer Epidemiol Biomarkers Prev ; 30(3): 469-473, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33335023

RESUMEN

BACKGROUND: The CanRisk Tool (https://canrisk.org) is the next-generation web interface for the latest version of the BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) state-of-the-art risk model and a forthcoming ovarian cancer risk model. METHODS: The tool captures information on family history, rare pathogenic variants in cancer susceptibility genes, polygenic risk scores, lifestyle/hormonal/clinical features, and imaging risk factors to predict breast and ovarian cancer risks and estimate the probabilities of carrying pathogenic variants in certain genes. It was implemented using modern web frameworks, technologies, and web services to make it extensible and increase accessibility to researchers and third-party applications. The design of the graphical user interface was informed by feedback from health care professionals and a formal evaluation. RESULTS: This freely accessible tool was designed to be user friendly for clinicians and to boost acceptability in clinical settings. The tool incorporates a novel graphical pedigree builder to facilitate collection of the family history data required by risk calculations. CONCLUSIONS: The CanRisk Tool provides health care professionals and researchers with a user-friendly interface to carry out multifactorial breast and ovarian cancer risk predictions. It is the first freely accessible cancer risk prediction program to carry the CE marking. IMPACT: There have been over 3,100 account registrations, and 98,000 breast and ovarian cancer risk calculations have been run within the first 9 months of the CanRisk Tool launch.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias Ováricas/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Internet , Factores de Riesgo
12.
Sci Rep ; 11(1): 15389, 2021 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-34321509

RESUMEN

Understanding seasonal human mobility at subnational scales has important implications across sciences, from urban planning efforts to disease modelling and control. Assessing how, when, and where populations move over the course of the year, however, requires spatially and temporally resolved datasets spanning large periods of time, which can be rare, contain sensitive information, or may be proprietary. Here, we aim to explore how a set of broadly available covariates can describe typical seasonal subnational mobility in Kenya pre-COVID-19, therefore enabling better modelling of seasonal mobility across low- and middle-income country (LMIC) settings in non-pandemic settings. To do this, we used the Google Aggregated Mobility Research Dataset, containing anonymized mobility flows aggregated over users who have turned on the Location History setting, which is off by default. We combined this with socioeconomic and geospatial covariates from 2018 to 2019 to quantify seasonal changes in domestic and international mobility patterns across years. We undertook a spatiotemporal analysis within a Bayesian framework to identify relevant geospatial and socioeconomic covariates explaining human movement patterns, while accounting for spatial and temporal autocorrelations. Typical pre-pandemic mobility patterns in Kenya mostly consisted of shorter, within-county trips, followed by longer domestic travel between counties and international travel, which is important in establishing how mobility patterns changed post-pandemic. Mobility peaked in August and December, closely corresponding to school holiday seasons, which was found to be an important predictor in our model. We further found that socioeconomic variables including urbanicity, poverty, and female education strongly explained mobility patterns, in addition to geospatial covariates such as accessibility to major population centres and temperature. These findings derived from novel data sources elucidate broad spatiotemporal patterns of how populations move within and beyond Kenya, and can be easily generalized to other LMIC settings before the COVID-19 pandemic. Understanding such pre-pandemic mobility patterns provides a crucial baseline to interpret both how these patterns have changed as a result of the pandemic, as well as whether human mobility patterns have been permanently altered once the pandemic subsides. Our findings outline key correlates of mobility using broadly available covariates, alleviating the data bottlenecks of highly sensitive and proprietary mobile phone datasets, which many researchers do not have access to. These results further provide novel insight on monitoring mobility proxies in the context of disease surveillance and control efforts through LMIC settings.


Asunto(s)
Dinámica Poblacional/estadística & datos numéricos , Teléfono Celular , Sistemas de Información Geográfica , Humanos , Kenia , Modelos Estadísticos , Factores de Riesgo , Estaciones del Año , Factores Socioeconómicos , Análisis Espacio-Temporal , Viaje/estadística & datos numéricos
13.
PLoS One ; 15(3): e0229999, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32142536

RESUMEN

BACKGROUND: There is a growing focus on the development of multi-factorial cancer risk prediction algorithms alongside tools that operationalise them for clinical use. BOADICEA is a breast and ovarian cancer risk prediction model incorporating genetic and other risk factors. A new user-friendly Web-based tool (CanRisk.org) has been developed to apply BOADICEA. This study aimed to explore the acceptability of the prototype CanRisk tool among two healthcare professional groups to inform further development, evaluation and implementation. METHOD: A multi-methods approach was used. Clinicians from primary care and specialist genetics clinics in England, France and Germany were invited to use the CanRisk prototype with two test cases (either face-to-face with a simulated patient or via a written vignette). Their views about the tool were examined via a semi-structured interview or equivalent open-ended questionnaire. Qualitative data were subjected to thematic analysis and organised around Sekhon's Theoretical Framework of Acceptability. RESULTS: Seventy-five clinicians participated, 21 from primary care and 54 from specialist genetics clinics. Participants were from England (n = 37), France (n = 23) and Germany (n = 15). The prototype CanRisk tool was generally acceptable to most participants due to its intuitive design. Primary care clinicians were concerned about the amount of time needed to complete, interpret and communicate risk information. Clinicians from both settings were apprehensive about the impact of the CanRisk tool on their consultations and lack of opportunities to interpret risk scores before sharing them with their patients. CONCLUSIONS: The findings highlight the challenges associated with developing a complex tool for use in different clinical settings; they also helped refine the tool. This prototype may not have been versatile enough for clinical use in both primary care and specialist genetics clinics where the needs of clinicians are different, emphasising the importance of understanding the clinical context when developing cancer risk assessment tools.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Personal de Salud/psicología , Neoplasias Ováricas/diagnóstico , Interfaz Usuario-Computador , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Riesgo , Autoeficacia
14.
Appl Opt ; 48(24): 4663-75, 2009 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-19696853

RESUMEN

The particulate backscattering ratio (b(bp)/b(p)) is a useful indicator of the angular scattering characteristics of natural waters. Recent studies have shown evidence both for and against significant spectral variability in b(bp)/b(p) in the visible domain, but most show significant variability in its magnitude. We present results from a case study in which both backscattering and scattering coefficients were measured at nine wavelengths in a region of UK coastal waters where optical scattering is strongly influenced by inorganic particles and where a wide range of turbidities is found in a small geographic area. Using a new approach based on regression analysis of in situ signals, it is shown that, for this study site, most of the apparent variability in the magnitude of the backscattering ratio can be attributed to measurement uncertainties. Regression analysis suggests that b(bp)/b(p) is wavelength dependent for these mineral-rich waters. This conclusion can only be avoided by positing the existence of undocumented, systematic, wavelength-dependent errors in backscattering measurements made by two independently calibrated sensors. These results are important for radiative transfer simulations in mineral-dominated waters where the backscattering ratio has often been assumed to be spectrally flat. Furthermore, spectral dependence also has profound implications for our understanding of the relationship between b(bp)/b(p) and particle size distributions in coastal waters since the commonly assumed power-law distribution is associated with a spectrally flat particulate backscattering ratio for nonabsorbing particles.

15.
J Community Genet ; 10(1): 61-71, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29508368

RESUMEN

The BOADICEA breast cancer (BC) risk assessment model and its associated Web Application v3 (BWA) tool are being extended to incorporate additional genetic and non-genetic BC risk factors. From an online survey through the BOADICEA website and UK, Dutch, French and Swedish national genetic societies, we explored the relationships between the usage frequencies of the BWA and six other common BC risk assessment tools and respondents' perceived importance of BC risk factors. Respondents (N = 443) varied in age, country and clinical seniority but comprised mainly genetics health professionals (82%) and BWA users (93%). Oncology professionals perceived reproductive, hormonal (exogenous) and lifestyle BC risk factors as more important in BC risk assessment compared to genetics professionals (p values < 0.05 to 0.0001). BWA was used more frequently by respondents who gave high weight to breast tumour pathology and low weight to personal BC history as BC risk factors. BWA use was positively related to the weight given to hormonal BC risk factors. The importance attributed to lifestyle and BMI BC risk factors was not associated with the use of BWA or any of the other tools. Next version of the BWA encompassing additional BC risk factors will facilitate more comprehensive BC risk assessment in genetics and oncology practice.

17.
Fam Cancer ; 17(1): 31-41, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28623477

RESUMEN

The 'BOADICEA' Web Application (BWA) used to assess breast cancer risk, is currently being further developed, to integrate additional genetic and non-genetic factors. We surveyed clinicians' perceived acceptability of the existing BWA v3. An online survey was conducted through the BOADICEA website, and the British, Dutch, French and Swedish genetics societies. Cross-sectional data from 443 participants who provided at least 50% responses were analysed. Respondents varied in age and, clinical seniority, but mainly comprised women (77%) and genetics professionals (82%). Some expressed negative opinions about the scientific validity of BOADICEA (9%) and BWA v3 risk presentations (7-9%). Data entry time (62%), clinical utility (22%) and ease of communicating BWA v3 risks (13-17%) received additional negative appraisals. In multivariate analyses, controlling for gender and country, data entry time was perceived as longer by genetic counsellors than clinical geneticists (p < 0.05). Respondents who (1) considered hormonal BC risk factors as more important (p < 0.01), and (2) communicated numerical risk estimates more frequently (p < 0.001), judged BWA v3 of lower clinical utility. Respondents who carried out less frequent clinical activity (p < 0.01) and respondents with '11 to 15 years' seniority (p < 0.01) had less favourable opinions of BWA v3 risk presentations. Seniority of '6 to 10 years' (p < 0.05) and more frequent numerical risk communication (p < 0.05) were associated with higher fear of communicating the BWA v3 risks to patients. The level of genetics training did not affect opinions. Further development of BWA should consider technological, genetics service delivery and training initiatives.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Pruebas Genéticas , Aplicaciones de la Informática Médica , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Humanos , Análisis Multivariante , Mutación , Medición de Riesgo/métodos
18.
Fam Cancer ; 17(3): 469, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29071503

RESUMEN

The article "Use of the BOADICEA Web Application in clinical practice: appraisals by clinicians from various countries" written by Anne Brédart · Jean­Luc Kop · Antonis C. Antoniou · Alex P. Cunningham · Antoine De Pauw ·Marc Tischkowitz · Hans Ehrencrona · Sylvie Dolbeault · Léonore Robieux · Kerstin Rhiem ·Douglas F. Easton · Peter Devilee · Dominique Stoppa­Lyonnet· Rita Schmutlzer, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 16th June 2017 without open access.

19.
Appl Opt ; 46(31): 7720-9, 2007 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-17973016

RESUMEN

It has been suggested that Sun induced chlorophyll fluorescence (SICF) signals could be used to estimate phytoplankton chlorophyll concentration and to investigate algal physiology from space. However, water-leaving SICF is also a product of the ambient light field. In coastal waters both algal and nonalgal materials affect the underwater light field. In this study we examine the independent impacts of varying loads of mineral suspended solids (MSS) and colored dissolved organic materials (CDOM) on water-leaving SICF signals using Hydrolight radiative transfer simulations. We show that SICF signals in coastal waters are strongly influenced by nonalgal materials. Increasing concentrations of CDOM and minerals can reduce the water-leaving SICF per unit chlorophyll by over 50% for the concentration ranges explored here (CDOM = 0 to 1 m(-1) at 440 nm, MSS=0 to 10 g m(-3)). The moderate-resolution imaging spectroradiometer (MODIS) fluorescence line height algorithm is shown to be relatively unaffected by increasing CDOM, but performance is significantly degraded by mineral concentrations greater than 5 g m(-3) owing to increased background radiance levels. The combination of these two effects means that caution is required for the interpretation of SICF signals from coastal waters.

20.
Appl Opt ; 44(1): 126-35, 2005 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-15662894

RESUMEN

More than 90% of stations from the Irish and Celtic Seas are found to have significantly higher back-scattering ratios in the blue (470 nm) than in the red (676 nm) wave band. Attempts to obtain optical closure by use of radiance transfer modeling were least successful for stations at which backscattering ratios are most strongly wavelength dependent. Significantly improved radiance transfer simulation results were obtained with a modified scattering correction algorithm for AC-9 absorption measurements that took wavelength dependency in the scattering phase function into account.

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