108 research outputs found
Aeration System Design for Flat Grain Storages with an Expert System
An expert system, Aeration System Design (ASD), was developed for the design of aeration systems for farm-sized flat grain storages. ASD requests information about the storage problem from a user and generates a custom design drawing, component specification list, and management recommendations. The knowledge base was derived from publications and experts. ASD represents the first attempt to consolidate aeration system design guidelines and procedures for flat grain storage into an expert system. ASD uses illustrations to communicate concepts and terminology more clearly with users. A feature of ASD allows an expert to change the design guidelines and factors. For example, alternative methods of determining the layout and length of ducts can be selected. ASD offers the capability of rapidly designing an aeration system and changing design guidelines to study the effects upon the design
Evaluating a Computer Program with a Structured Expert Review Process
A structured expert review process was implemented to evaluate the technical content and usability of a program on aeration system design for grain storages. Technical evaluation was used to determine if the computer program generated solutions similar to expert solutions. Other aspects of the evaluation focused on measures of ease of use, effectiveness of information conveyance and usefulness of solution. The evaluation procedure and questionnaires are described and results from the evaluation of an aeration system design program are summarized. The evaluation process served to validate the aeration system design program, generate suggestions for improving the program, identify areas for further research and advance aeration system design technology by bringing together experts representing the range of practice. The review process was beneficial and could be adapted for use with other decision support programs
Implementable Deep Learning for Multi-sequence Proton MRI Lung Segmentation:A Multi-center, Multi-vendor, and Multi-disease Study
Background: Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton (1H)-MRI lung segmentation. However, previous deep learning studies have utilized single-center data and limited acquisition parameters.Purpose: Develop a generalizable CNN for lung segmentation in 1H-MRI, robust to pathology, acquisition protocol, vendor, and center.Study type: Retrospective.Population: A total of 809 1H-MRI scans from 258 participants with various pulmonary pathologies (median age (range): 57 (6â85); 42% females) and 31 healthy participants (median age (range): 34 (23â76); 34% females) that were split into training (593 scans (74%); 157 participants (55%)), testing (50 scans (6%); 50 participants (17%)) and external validation (164 scans (20%); 82 participants (28%)) sets.Field Strength/Sequence: 1.5-T and 3-T/3D spoiled-gradient recalled and ultrashort echo-time 1H-MRI.Assessment: 2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance.Statistical Tests: KruskalâWallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. BlandâAltman analyses assessed agreement with manually derived lung volumes. A P value of <0.05 was considered statistically significant.Results: The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880â0.987), Average HD of 1.63 mm (0.65â5.45) and XOR of 0.079 (0.025â0.240) on the testing set and a DSC of 0.973 (0.866â0.987), Average HD of 1.11 mm (0.47â8.13) and XOR of 0.054 (0.026â0.255) on external validation data.Data Conclusion: The 3D CNN generated accurate 1H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center.Evidence Level: 4.Technical Efficacy: Stage 1.</p
Implementing the United Kingdom's ten-year teenage pregnancy strategy for England (1999-2010): how was this done and what did it achieve?
In 1999, the UK Labour Government launched a 10-year Teenage Pregnancy Strategy for England to address the country's historically high rates and reduce social exclusion. The goal was to halve the under-18 conception rate. This study explores how the strategy was designed and implemented, and the features that contributed to its success. This study was informed by examination of the detailed documentation of the strategy, published throughout its 10-year implementation. The strategy involved a comprehensive programme of action across four themes: joined up action at national and local level; better prevention through improved sex and relationships education and access to effective contraception; a communications campaign to reach young people and parents; and coordinated support for young parents (The support programme for young parents was an important contribution to the strategy. In the short term by helping young parents prevent further unplanned pregnancies and, in the long term, by breaking intergenerational cycles of disadvantage and lowering the risk of teenage pregnancy.). It was implemented through national, regional and local structures with dedicated funding for the 10-year duration. The under-18 conception rate reduced steadily over the strategy's lifespan. The 2014 under-18 conception rate was 51% lower than the 1998 baseline and there have been significant reductions in areas of high deprivation. One leading social commentator described the strategy as 'The success story of our time' (Toynbee, The drop in teenage pregnancies is the success story of our time, 2013). As rates of teenage pregnancy are influenced by a web of inter-connected factors, the strategy was necessarily multi-faceted in its approach. As such, it is not possible to identify causative pathways or estimate the relative contributions of each constituent part. However, we conclude that six key features contributed to the success: creating an opportunity for action; developing an evidence based strategy; effective implementation; regularly reviewing progress; embedding the strategy in wider government programmes; and providing leadership throughout the programme. The learning remains relevant for the UK as England's teenage birth rate remains higher than in other Western European countries. It also provides important lessons for governments and policy makers in other countries seeking to reduce teenage pregnancy rates. BACKGROUND METHODS RESULTS CONCLUSION
Genetic predisposition to ductal carcinoma in situ of the breast.
BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. RESULTS: Most (67Â %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of Pâ<â5.0x10(-8). CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist
Genetic predisposition to ductal carcinoma in situ of the breast
Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist
Genetic predisposition to in situ and invasive lobular carcinoma of the breast.
Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 Ă 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 Ă 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. Š 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. Š 2018 The Author(s).Peer reviewe
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