An Application of Conceptual Design and Multidisciplinary Analysis Transitioning to Detailed Design Stages

This paper presents conceptual design and feasibility analysis for oversized grain harvesting combine headers with dynamic topology. To meet customer harvesting productivity requirements, the harvesting header must increase in width from 40 to 60 feet, yet be usable on current generation combine harvesters. While designing concepts for an oversized harvester head is a complex problem by itself, it also presents a latent challenge with packaging and transporting. Transporting a 60ft harvester header using traditional methods will violate road transport regulations imposed by US state and federal governments. This warrants innovations in both designing an oversized header concepts and viable means to package it for domestic and international shipping. The Advanced Systems Design Suite (ASDS) was used to design, visualize and perform quick assessment of the proposed concept designs. Three preliminary design concepts were generated based on customer requirements and manufacturer’s guidelines, of which one design was chosen for transitioning into detailed design stages. Static engineering analysis showed that the combine harvester’s feederhouse mount can support the additional mass of the larger header. Articulation mechanisms were represented by primitive shapes created in ASDS to visualize the preliminary design solution for packaging the header for transportation. Finite Element Analyses (FEA) was performed to determine the required size, shape, and position of the articulation mechanisms. Harvest productivity analyses were performed to assess business feasibility on the oversized header design. Header performance requirements identified potential time and monetary savings of an articulated header compared to a non articulated head of the same size. Reducing the time required to perform “non-harvesting activities” with currently available combines enables the manufacturer to generate a more feasible detailed design addressing this difficult design challenge. The ASDS, along with supplementary analyses tools can be used to generate viable design concepts and the work presented in this paper shows that the oversized combine header design is feasible and is worthy of transitioning into detailed design stages

DEVELOPMENT OF 1000-TON COMBUSTION DRIVEN COMPACTION PRESS FOR MATERIALS DEVELOPMENT AND PROCESSING

ABSTRACT The following presents the technological development aspects and materials processing efforts of UTRON's 1000 ton Combustion Driven Compaction (CDC) press. The 1000 ton press program has evolved from and earlier program in which a 300 ton press was manufactured and teste

Contraceptive counselling in 3 Canadian bariatric surgery clinics: a multicentre qualitative study of the experiences of patients and health care providers.

BACKGROUND: Evidence suggests an increase in fertility and unintended pregnancy after bariatric surgery; contraceptive counselling, traditionally defined as a discussion of contraception options, is therefore an important facet of surgical planning. Our aim was to investigate patient experiences of contraceptive counselling, the attitudes of health care providers (HCPs) toward contraceptive counselling, and their perceptions of the facilitators and barriers to contraceptive counselling in bariatric surgery clinics. METHODS: We conducted a qualitative study using semistructured interviews with patients and HCPs at publicly funded Canadian bariatric surgery clinics from May 2018 to February 2019. We recruited bariatric HCPs from across Canada using snowball sampling, and recruited patient participants from 3 Canadian bariatric surgery programs. Patient participants had to be at risk of pregnancy in the postoperative period, aged 18-45 years old and have completed all preoperative counselling. We included HCPs who delivered care in a publicly funded, hospital-affiliated bariatric surgery clinic in Canada. Team members analyzed transcripts thematically. RESULTS: We completed 27 interviews (patient n = 16, HCP n = 11). Our analysis identified 3 separate themes: missing information in contraception counselling, making assumptions about who would benefit from counselling and strategies for improving contraception counselling. We found patients and HCPs wanted more resources on the safety and efficacy of contraceptive methods. INTERPRETATION: Our study showed a need for structured contraceptive counselling in bariatric surgery clinics. Information resources that support patients and HCPs who provide counselling are needed

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Evaluating the role of pathogenic dementia variants in posterior cortical atrophy

Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to “posterior Alzheimer's disease (AD)” pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX

Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk.

Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT-CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P = 4.9 × 10(-6) to P = 7.7 × 10(-5)). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERT P = 1.5 × 10(-18), CLPTM1L P = 1.5 × 10(-19)). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.This work was supported by the NHMRC Project Grant (ID#1031333). This work was also supported by Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692)This is the published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00439-014-1515-4