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1.
Biopreserv Biobank ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429584

RESUMO

Standardization and sustainability are ideals within the biobanking world, and the demand for high-quality well-annotated specimens is growing just as rapidly as the ever-increasing precision and throughput of today's high-tech scientific methods. In the state of New South Wales (NSW) in Australia, the state government has allocated significant funding toward this requirement in recent years, with the launch of the NSW Health Statewide Biobank in central Sydney in 2017, and the introduction of the voluntary NSW Biobank Certification Program, and Consent Toolkit. For new and established biobanks, the influence of these new resources has been twofold: first they have provided valuable guidance for moving toward standardized practices and raising the bar for biobanking quality standards; second, they have brought to the forefront the challenges of sustainability and transitioning to a certification standard of biobanking. In Westmead, ∼20 km from Sydney's central business district, the Westmead Research Hub has responded to these challenges with a collaborative biobanking project initiated in 2015. As the site of almost 30 individual biobanks, and to inform a pilot project of central biobank services, a questionnaire was developed and administered to all of the biobanks. This article reports on the results from the questionnaire and the rationale for subsequent initiation of a core biobanking facility.

2.
Am J Infect Control ; 46(11): 1284-1289, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29778436

RESUMO

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) cause substantial morbidity and increase antimicrobial use and length of stay among hospitalized children in the United States. CLABSI occurs more frequently among high-risk pediatric patients, such as those with intestinal failure (IF) who are parenteral nutrition (PN) dependent. Following an increase in CLABSI rates, a quality improvement (QI) initiative was implemented. METHODS: Using QI methodology, an enhanced central venous catheter (CVC) maintenance bundle was developed and implemented on 2 units for pediatric PN-dependent patients with IF. CLABSI rates were prospectively monitored pre- and postimplementation, and bundle element adherence was monitored. Enhanced bundle elements included chlorhexidine-impregnated patch, daily bathing, ethanol locks, 2 nurses for CVC care in a distraction-free zone, peripheral laboratory draws, bundling routine laboratory tests, and PN administration set changes every 24 hours. RESULTS: Adherence to enhanced bundle elements increased to >90% over 3 months. CLABSI rates averaged 1.41 per 1,000 central line days preimplementation compared with 0.40 per 1,000 device days postimplementation (P = .003), an 85% absolute reduction in CLABSI rates over 12 months. CONCLUSIONS: Patients with IF are at an increased risk for CLABSI. Enhanced CVC maintenance bundles that specifically target prevention practices in this population may be beneficial.

3.
Biopreserv Biobank ; 16(1): 53-58, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29215912

RESUMO

Biobanks face increasing demands for research materials of consistent quality, which can be used in collaborative studies. Several countries and some international agencies have made formal efforts to standardize biobank operations and outputs. These include the establishment of best practice guidelines for collection management, and certification programs. Such guidelines and programs increase biobanks' opportunities for participation in high impact research and funding. However, they also impose economic and time costs, which may burden biobanks. This study aimed to estimate the costs of gaining certification and maintaining certification (i.e., committing extra resources to continue standards) for three cancer biobanks participating in a biobank certification program in New South Wales, Australia. To gather cost data for a range of cancer biobanks, we recruited three with different full time equivalent (FTE) staff levels (1.0-3.0), recognizing FTE staff level as an indicator of resources and operating scale. In extended interviews with staff, we gathered biobanks' expected costs in obtaining and annually maintaining certification. The biobank with the highest staff level reported the lowest expected costs in gaining certification, due to the strong prealignment of its present operations with certification requirements. The other biobanks expected higher costs as their operations required greater adjustments. Overall, relative costs of gaining certification were between 2% and 6% of current total annual wage costs. To the authors' knowledge, this is the first such costing study of a biobank certification program. Supplementary Data include the interview schedule that other biobanks may use to estimate their own economic certification costs.


Assuntos
Bancos de Espécimes Biológicos/economia , Bancos de Espécimes Biológicos/normas , Certificação/economia , Austrália , Pesquisa Biomédica , Humanos , Guias de Prática Clínica como Assunto
4.
Biopreserv Biobank ; 16(1): 36-41, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29148831

RESUMO

Ongoing quality management is an essential part of biobank operations and the creation of high quality biospecimen resources. Adhering to the standards of a national biobanking network is a way to reduce variability between individual biobank processes, resulting in cross biobank compatibility and more consistent support for health researchers. The Canadian Tissue Repository Network (CTRNet) implemented a set of required operational practices (ROPs) in 2011 and these serve as the standards and basis for the CTRNet biobank certification program. A review of these 13 ROPs covering 314 directives was conducted after 5 years to identify areas for revision and update, leading to changes to 7/314 directives (2.3%). A review of all internal controlled documents (including policies, standard operating procedures and guides, and forms for actions and processes) used by the BC Cancer Agency's Tumor Tissue Repository (BCCA-TTR) to conform to these ROPs was then conducted. Changes were made to 20/106 (19%) of BCCA-TTR documents. We conclude that a substantial fraction of internal controlled documents require updates at regular intervals to accommodate changes in best practices. Reviewing documentation is an essential aspect of keeping up to date with best practices and ensuring the quality of biospecimens and data managed by biobanks.


Assuntos
Certificação/normas , Manejo de Espécimes/normas , Bancos de Tecidos/normas , Canadá , Documentação/normas , Fidelidade a Diretrizes , Humanos
5.
J Pediatric Infect Dis Soc ; 7(4): 317-322, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-29165636

RESUMO

Background: Decreasing the use of redundant anaerobic therapy is a key target for antimicrobial stewardship. Education techniques that optimize knowledge retention could be an important component of reducing these regimens. Methods: We implemented a quality improvement project that incorporated spaced education to reduce the use of redundant anaerobic therapy. The initial interventions (November through December 2015) included education in a hospital-wide newsletter and review of redundant anaerobic regimens by the antimicrobial stewardship program. A spaced education module was then developed with the gastroenterology (GI) service, which had a relatively high rate of redundant anaerobic therapy use. Ten questions with teaching points were delivered to GI physicians at spaced intervals over 2 to 4 weeks (February through March 2016). Knowledge scores were compared at initial and final question presentation using generalized estimating equations. Interrupted time-series analysis was used to compare the rates of redundant-metronidazole-days per 1000 patient-days among patients in the patients admitted to the GI service and those in the non-GI group before and after the intervention. Results: Of 66 GI physicians, 56 (85%) participated in the spaced education activity. After the intervention, their knowledge scores on all the questions improved, and their mean knowledge score increased from 57% to 86% (P < .001). Nearly all (91%) of the participants were very or generally satisfied with the activity. In the GI group, the rate of redundant-metronidazole-days decreased from 26.2 to 13.0 per 1000 patient-days (relative risk [RR], 0.45 [95% confidence interval (CI), 0.27-0.73]; P = .001). This rate in the non-GI group also decreased from 5.47 to 2.18 per 1000 patient-days (RR, 0.47 [95% CI, 0.36-0.60]; P < .001) after our interventions. Conclusions: Spaced education is an effective approach for teaching antimicrobial stewardship topics. Focused provider education was associated with a sustained reduction in the use of redundant anaerobic therapy.

7.
PLoS One ; 11(11): e0166596, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27875546

RESUMO

The objective of this study was to develop a discrete event agent-based stochastic model to explore the likelihood of the occurrence of porcine reproductive and respiratory syndrome (PRRS) outbreaks in swine herds with different PRRS control measures in place. The control measures evaluated included vaccination with a modified-live attenuated vaccine and live-virus inoculation of gilts, and both were compared to a baseline scenario where no control measures were in place. A typical North American 1,000-sow farrow-to-wean swine herd was used as a model, with production and disease parameters estimated from the literature and expert opinion. The model constructed herein was not only able to capture individual animal heterogeneity in immunity to and shedding of the PRRS virus, but also the dynamic animal flow and contact structure typical in such herds under field conditions. The model outcomes included maximum number of females infected per simulation, and time at which that happened and the incidence of infected weaned piglets during the first year of challenge-virus introduction. Results showed that the baseline scenario produced a larger percentage of simulations resulting in outbreaks compared to the control scenarios, and interestingly some of the outbreaks occurred over long periods after virus introduction. The live-virus inoculation scenario showed promising results, with fewer simulations resulting in outbreaks than the other scenarios, but the negative impacts of maintaining a PRRS-positive population should be considered. Finally, under the assumptions of the current model, neither of the control strategies prevented the infection from spreading to the piglet population, which highlights the importance of maintaining internal biosecurity practices at the farrowing room level.


Assuntos
Cruzamento , Surtos de Doenças , Modelos Biológicos , Síndrome Respiratória e Reprodutiva Suína/epidemiologia , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Vírus da Síndrome Respiratória e Reprodutiva Suína , Suínos/virologia , Animais , Feminino , Masculino , América do Norte/epidemiologia
8.
J Med Genet ; 53(12): 800-811, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27595995

RESUMO

BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. METHODS: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. RESULTS: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. CONCLUSIONS: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias da Mama/metabolismo , Quinase do Ponto de Checagem 2/genética , Predisposição Genética para Doença , Mutação , Proteínas Nucleares/genética , Neoplasias da Próstata/metabolismo , Proteínas Supressoras de Tumor/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Estudos de Casos e Controles , Proteína do Grupo de Complementação N da Anemia de Fanconi , Feminino , Estudos de Associação Genética , Humanos , Masculino , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Risco
9.
Breast Cancer Res ; 18(1): 64, 2016 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-27459855

RESUMO

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 12 , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Alelos , Proteína BRCA1/genética , Estudos de Casos e Controles , Biologia Computacional/métodos , Bases de Dados Genéticas , Elementos Facilitadores Genéticos , Epigênese Genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Haplótipos , Heterozigoto , Humanos , Mutação , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , Regiões Promotoras Genéticas , Locos de Características Quantitativas , Risco
10.
Nat Commun ; 7: 11375, 2016 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-27117709

RESUMO

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Receptores Estrogênicos/genética , Proteína BRCA1/genética , Cromossomos Humanos Par 2/genética , Ciclofilinas/genética , Feminino , Genótipo , Heterozigoto , Humanos , Mutação , Polimorfismo de Nucleotídeo Único , Fatores de Risco , tRNA Metiltransferases
11.
Can J Vet Res ; 79(4): 268-78, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26424906

RESUMO

The objectives of this study were to describe demographics, basic biosecurity practices, ownership structure, and prevalence of porcine reproductive and respiratory syndrome (PRRS) in swine sites located in 3 regions in Ontario, and investigate the presence of spatial clustering and clusters of PRRS positive sites in the 3 regions. A total of 370 swine sites were enrolled in Area Regional Control and Elimination projects in Niagara, Watford, and Perth from 2010 to 2013. Demographics, biosecurity, and site ownership data were collected using a standardized questionnaire and site locations were obtained from an industry organization. Status was assigned on the basis of available diagnostic tests and/or assessment by site veterinarians. Spatial dependence was investigated using the D-function, the spatial scan statistic test and the spatial relative risk method. Results showed that the use of strict all-in all-out (AIAO) pig flow and shower before entry are uncommon biosecurity practices in swine sites, but a larger proportion of sites reported having a Danish entry. The prevalence of PRRS in the 3 regions ranged from 17% to 48% and localized high and low risk clusters were detected. Sites enrolled in the PRRS control projects were characterized by membership in multiple and overlapping ownership structures and networks, which complicates the way the results of monitoring and disease management measures are communicated to the target population.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/epidemiologia , Criação de Animais Domésticos , Animais , Coleta de Dados , Feminino , Masculino , Ontário/epidemiologia , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Fatores de Risco , Inquéritos e Questionários , Suínos
13.
Breast Cancer Res Treat ; 150(1): 71-80, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25682074

RESUMO

Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20 % of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0 years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon-intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6 %) triple-negative patients. The mutation prevalence was 9.3 % in Australia and was 9.9 % in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59 % of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.


Assuntos
Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Austrália/epidemiologia , Éxons , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Polimorfismo de Nucleotídeo Único , Prevalência , Fatores de Risco , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia
14.
Biopreserv Biobank ; 12(6): 395-401, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25496151

RESUMO

Sustainability of biorepositories is a key issue globally. This article is a description of the different strategies and mechanisms used by the Australian Breast Cancer Tissue Bank (ABCTB) in developing and operating the resource since its inception in 2005. ABCTB operates according to a hub and spoke model, with a central management hub that is responsible for overall management of the resource including financial, ethical, and legal processes, researcher applications for material, clinical follow-up, information/database activities, and security. A centralized processing laboratory also operates from the hub site where DNA and RNA extractions are performed, digital imaging of stained tumor sections occurs, and specimens are assembled for dispatch for research projects. ABCTB collection sites where donors are identified, consent obtained, and specimens collected and processed for initial storage are located across Australia. Each of the activities of the resource requires financial support and different sources of revenue, some of which are allocated to a specific function of the ABCTB. Different models are in use at different collection centers where local variations may exist and local financial support may sometimes be obtained. There is also significant in-kind support by clinics and diagnostic and research facilities that house the various activities of the resource. However, long-term financial commitment to ensure the survival of the resource is not in place, and forward planning of operations remains challenging under these circumstances.


Assuntos
Bancos de Espécimes Biológicos , Neoplasias da Mama , Bancos de Tecidos , Austrália , Feminino , Humanos , Manejo de Espécimes
15.
Hum Mol Genet ; 23(22): 6034-46, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24927736

RESUMO

Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.


Assuntos
Neoplasias da Mama/genética , Variação Genética , Neoplasias da Mama/patologia , Proteínas de Transporte/genética , Estudos de Casos e Controles , Feminino , Haplótipos , Humanos , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Fatores de Risco , Proteínas Supressoras de Tumor/genética
16.
Biopreserv Biobank ; 12(1): 60-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24620771

RESUMO

Each year funding agencies and academic institutions spend millions of dollars and euros on biobanking. All funding providers assume that after initial investments biobanks should be able to operate sustainably. However the topic of sustainability is challenging for the discipline of biobanking for several major reasons: the diversity in the biobanking landscape, the different purposes of biobanks, the fact that biobanks are dissimilar to other research infrastructures and the absence of universally understood or applicable value metrics for funders and other stakeholders. In this article our aim is to delineate a framework to allow more effective discussion and action around approaches for improving biobank sustainability. The term sustainability is often used to mean fiscally self-sustaining, but this restricted definition is not sufficient for biobanking. Instead we propose that biobank sustainability should be considered within a framework of three dimensions - financial, operational, and social. In each dimension, areas of focus or elements are identified that may allow different types of biobanks to distinguish and evaluate the relevance, likelihood, and impact of each element, as well as the risks to the biobank of failure to address them. Examples of practical solutions, tools and strategies to address biobank sustainability are also discussed.


Assuntos
Bancos de Espécimes Biológicos , Bancos de Espécimes Biológicos/organização & administração , Bancos de Espécimes Biológicos/normas , Bancos de Espécimes Biológicos/tendências , Humanos
17.
Carcinogenesis ; 35(5): 1012-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24325915

RESUMO

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cromossomos Humanos Par 19 , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
18.
Gigascience ; 2(1): 7, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23634721

RESUMO

An increasing portion of biomedical research relies on the use of biobanks and databases. Sharing of such resources is essential for optimizing knowledge production. A major obstacle for sharing bioresources is the lack of recognition for the efforts involved in establishing, maintaining and sharing them, due to, in particular, the absence of adequate tools. Increasing demands on biobanks and databases to improve access should be complemented with efforts of end-users to recognize and acknowledge these resources. An appropriate set of tools must be developed and implemented to measure this impact.To address this issue we propose to measure the use in research of such bioresources as a value of their impact, leading to create an indicator: Bioresource Research Impact Factor (BRIF). Key elements to be assessed are: defining obstacles to sharing samples and data, choosing adequate identifier for bioresources, identifying and weighing parameters to be considered in the metrics, analyzing the role of journal guidelines and policies for resource citing and referencing, assessing policies for resource access and sharing and their influence on bioresource use. This work allows us to propose a framework and foundations for the operational development of BRIF that still requires input from stakeholders within the biomedical community.

19.
Nat Genet ; 45(4): 392-8, 398e1-2, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23535733

RESUMO

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.


Assuntos
Neoplasias da Mama/etiologia , Loci Gênicos/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores Estrogênicos/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Comportamento Cooperativo , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Metanálise como Assunto , Análise de Sequência com Séries de Oligonucleotídeos , Receptores Estrogênicos/genética , Fatores de Risco
20.
Diagn Pathol ; 8: 22, 2013 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-23402499

RESUMO

BACKGROUND: Virtual microscopy includes digitisation of histology slides and the use of computer technologies for complex investigation of diseases such as cancer. However, automated image analysis, or website publishing of such digital images, is hampered by their large file sizes. RESULTS: We have developed two Java based open source tools: Snapshot Creator and NDPI-Splitter. Snapshot Creator converts a portion of a large digital slide into a desired quality JPEG image. The image is linked to the patient's clinical and treatment information in a customised open source cancer data management software (Caisis) in use at the Australian Breast Cancer Tissue Bank (ABCTB) and then published on the ABCTB website (http://www.abctb.org.au) using Deep Zoom open source technology. Using the ABCTB online search engine, digital images can be searched by defining various criteria such as cancer type, or biomarkers expressed. NDPI-Splitter splits a large image file into smaller sections of TIFF images so that they can be easily analysed by image analysis software such as Metamorph or Matlab. NDPI-Splitter also has the capacity to filter out empty images. CONCLUSIONS: Snapshot Creator and NDPI-Splitter are novel open source Java tools. They convert digital slides into files of smaller size for further processing. In conjunction with other open source tools such as Deep Zoom and Caisis, this suite of tools is used for the management and archiving of digital microscopy images, enabling digitised images to be explored and zoomed online. Our online image repository also has the capacity to be used as a teaching resource. These tools also enable large files to be sectioned for image analysis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5330903258483934.


Assuntos
Interpretação de Imagem Assistida por Computador , Sistemas de Informação Administrativa , Registro Médico Coordenado , Sistemas Computadorizados de Registros Médicos , Microscopia/métodos , Patologia Clínica/métodos , Desenho de Programas de Computador , Telepatologia/métodos , Gráficos por Computador , Humanos , Valor Preditivo dos Testes , Resultado do Tratamento , Interface Usuário-Computador
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