Iterative Learning Control of Single Point Incremental Sheet Forming Process using Digital Image Correlation

Single Point Incremental Sheet Forming (SPIF) is a versatile forming process that has gained significant traction over the past few decades. Its increased formability, quick part adaption, and reduced set-up costs make it an economical choice for small batch and rapid prototype forming applications when compared to traditional stamping processes. However, a common problem with the SPIF process is its tendency to produce high geometric error due to the lack of supporting dies and molds. While geometric error has been a primary focus of recent research, it is still significantly larger for SPIF than traditional forming processes. In this paper, the convergence behavior and the ability to reduce geometric error using a simple Iterative Learning Control (ILC) algorithm is studied with two different forming methods. For both methods a tool path for the desired reference geometry is generated and a part is formed. A Digital Image Correlation (DIC) system takes a measurement and the geometric error along the tool path is calculated. The ILC algorithm then uses the geometric error to alter the tool path for the next forming iteration. The first method, the Single Sheet Forming (SSF) method, performs each iteration on the same sheet. The second method, the Multi Sheet Forming (MSF) method, performs each iteration on a newly replaced sheet. Multiple experiments proved the capability of each method at reducing geometric error. It was concluded that using the MSF method allows for negative corrections to the forming part and, therefore, leads to better final part accuracy. However, this method is less cost effective and more time consuming than using the standard SSF methodology. In addition, it was found that in order to effectively correct a part with an ILC algorithm, steps must be taken to increase the controllability of the part geometry

Analysis of Geometric Accuracy and Thickness Reduction in Multistage Incremental Sheet Forming using Digital Image Correlation

Incremental Sheet Forming (ISF) is a freeform manufacturing method whereby a 3D geometry is created by progressively deforming a metal sheet with a single point tool following a defined trajectory. The thickness distribution of a formed part is a major consideration of the process and is believed to be improved by forming the geometry in multiple stages. This paper describes a series of experiments in which truncated cone geometries were formed using two multistage methods and compared to the same geometry formed using the traditional single stage method. The geometric accuracy and thickness distributions, including 3D thickness distribution plots, of each are examined using digital image correlation (DIC). The data collected indicate that multistage forming, compared to single stage forming, has a significant effect on the geometric accuracy of the processed sheets. Moreover, the results of the experiments conducted in this paper show that sheets processed with multistage forming do not have a uniform sheet thickness reduction, rather they have a parabolic-like thickness distribution in the processed region

Genetic association at the 9p21 glaucoma locus contributes to sex bias in normal-tension glaucoma

Purpose: Many genome-wide association studies have identified common single nucleotide polymorphisms (SNPs) at the 9p21 glaucoma locus (CDKN2B/CDKN2B-AS1) to be significantly associated with primary open-angle glaucoma (POAG), with association being stronger in normal tension glaucoma (NTG) and advanced glaucoma. We aimed to determine whether any observed differences in genetic association at the 9p21 locus are influenced by sex. Methods: Sex was assessed as a risk factor for POAG for 2241 glaucoma participants from the Australian and New Zealand Registry of Advanced Glaucoma, the Glaucoma Inheritance Study in Tasmania, and the Flinders Medical Centre. A total of 3176 controls were drawn from the Blue Mountains Eye Study and South Australia: 1523 advanced POAG and 718 nonadvanced POAG cases were genotyped along with 3176 controls. We selected 13 SNPs at the 9p21 locus, and association results were subanalyszd by sex for high-tension glaucoma (HTG) and NTG. Odds ratios (ORs) between sexes were compared. Results: A sex bias was present within advanced NTG cases (57.1% female versus 42.9% male, P = 0.0026). In all POAG cases, the strongest associated SNP at 9p21 was rs1063192 (OR, 1.43; P = 4 × 10⁻¹⁸). This association was stronger in females (OR, 1.5; P = 5 × 10⁻¹³) than in males (OR, 1.35; P = 7 × 10⁻⁷), with a statistically significant difference in female to male OR comparison (P = 1.0 × 10⁻²). An NTG to HTG subanalysis yielded statistically significant results only in females (OR, 1.63; P = 1.5 × 10⁻⁴) but not in males (OR, 1.15; P = 2.8 × 10⁻¹), with a statistically significant difference in female to male OR comparison (P = 1.4 × 10⁻⁴). Conclusions: This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG.Soo Khai Ng, Kathryn P. Burdon, Jude T. Fitzgerald, Tiger Zhou, Rhys Fogarty, Emmanuelle Souzeau, John Landers, Richard A. Mills, Robert J. Casson, Bronwyn Ridge, Stuart L. Graham, Alex W. Hewitt, David A. Mackey, Paul R. Healey, Jie Jin Wang, Paul Mitchell, Stuart MacGregor, and Jamie E. Crai

Novel mutations support a role for Profilin 1 in the pathogenesis of ALS

AbstractMutations in the gene encoding profilin 1 (PFN1) have recently been shown to cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We sequenced the PFN1 gene in a cohort of ALS patients (n = 485) and detected 2 novel variants (A20T and Q139L), as well as 4 cases with the previously identified E117G rare variant (∼ 1.2%). A case-control meta-analysis of all published E117G ALS+/− frontotemporal dementia cases including those identified in this report was significant p = 0.001, odds ratio = 3.26 (95% confidence interval, 1.6–6.7), demonstrating this variant to be a susceptibility allele. Postmortem tissue from available patients displayed classic TAR DNA-binding protein 43 pathology. In both transient transfections and in fibroblasts from a patient with the A20T change, we showed that this novel PFN1 mutation causes protein aggregation and the formation of insoluble high molecular weight species which is a hallmark of ALS pathology. Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease

The APOE E4 Allele Is Associated with Faster Rates of Neuroretinal Thinning in a Prospective Cohort Study of Suspect and Early Glaucoma

Purpose: To investigate the association between the apolipoprotein E (APOE) E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma. Design: Retrospective analysis of prospective cohort data. Participants: This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which APOE genotypes could be determined. Methods: Apolipoprotein E alleles and genotypes were determined in PROGRESSA, and their distributions were compared with an age-matched and ancestrally matched normative cohort, the Blue Mountains Eye Study. Structural parameters of neuroretinal atrophy measured using spectral-domain OCT were compared within the PROGRESSA cohort on the basis of APOE E4 allele status. Main Outcome Measures: Longitudinal rates of thinning in the macular ganglion cell–inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL). Results: Rates of mGCIPL complex thinning were faster in participants harboring ≥1 copies of the APOE E4 allele (β = –0.13 μm/year; P ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; β = –0.20 μm/year; P = 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up (P = 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 μm vs. 71.9 μm; P = 0.011) and pRNFL (77.6 μm vs. 79.2 μm; P = 0.045) after a minimum of 3 years of monitoring. Conclusions: The APOE E4 allele was associated with faster rates of mCGIPL complex thinning, particularly in eyes with NTG. These results suggest that the APOE E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma

The Relationship between the Physical Activity Environment, Nature Relatedness, Anxiety, and the Psychological Well-being Benefits of Regular Exercisers.

Research from a variety of scientific fields suggests that physical activity in nature and feelings of connection to nature enhance psychological health and well-being. This study investigated the psychological health and well-being impact of the physical activity environment for those already undertaking the recommended weekly amount of physical activity. This topic is important for the design of health and well-being environments and interventions involving physical activity. Participants (N = 262) aged 18-71 years (M = 34.5, SD = 13.1) who met the UK physical activity guidelines completed the Nature Relatedness Scale, the trait section of the State Trait Inventory for Cognitive and Somatic Anxiety and the Psychological Well-Being Scale. Analysis via Multivariate ANOVA indicated that participants who engaged in outdoor physical activity reported significantly lower somatic anxiety levels and higher Nature Relatedness experience (NRexp). Significant results were not evident for wellbeing. Hierarchical regressions revealed that the psychological well-being facet of autonomy, NRexp, and outdoor physical activity predicted lower somatic anxiety, whereas indoor physical activity predicted higher somatic anxiety. Results indicate that somatic anxiety is lower for outdoor physical activity participation, and that outdoor activity, in conjunction with autonomy and NRexp, predicts lower anxiety levels. The findings extend previous work by demonstrating the impact of the physical activity environment on anxiety levels, as well as the contribution of outdoor physical activity and well-being facets to the previously established Nature Relatedness-anxiety relationship

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

DNA methylation at the 9p21 glaucoma susceptibility locus is associated with normal-tension glaucoma

“This is an Accepted Manuscript of an article published by Taylor & Francis in Ophthalmic Genetics on 21 Dec 2017, available online: http://www.tandfonline.com/10.1080/13816810.2017.1413659” This author accepted manuscript is made available following 12 month embargo from date of publication (Dec 2017) in accordance with the publisher’s archiving policyPurpose: Recent genome-wide association studies reported strong association of genetic variation at the CDKN2B/CDKN2B-AS1 locus on 9p21 with normal-tension glaucoma (NTG) in multiple populations. The mechanism by which this locus causes disease remains to be elucidated. We investigated the association of DNA methylation of CpG islands at this locus with NTG. Methods: We conducted a retrospective case–control study of 178 NTG cases and 202 unaffected controls from Australia. CDKN2B and CDKN2B-AS1 promoter methylation was measured quantitatively using the MassCleave assay, and assessed for association with the disease, and the genotype of the associated risk variants using IBM SPSS statistics 22.0 CpG sites at which methylation status was associated with NTG were validated using pyrosequencing. Results: We identified one CpG site (F1:13–14) in the CDKN2B promoter which showed significant association with NTG (p = 0.001). The association was highly significant in female cases (p = 0.006) but not in male cases (p = 0.054). The association was validated using an independent method confirming the likely association of DNA methylation with NTG in females (p = 0.015), but not in males (p = 0.497). In addition, methylation at CpG sites in CDKN2B was also associated with genotype at rs1063192, which is known to confer risk for NTG. Conclusion: This study reveals an association of methylation status in the CDKN2B promoter with NTG, particularly in females. This suggests that the observed genetic association with the disease at this locus could be in part due to epigenetic mechanisms, and is likely to be independent of the association of nonsynonymous coding variation within the gene

Multitrait analysis of glaucoma, intraocular pressure and vertical cup to disc ratio identifies many new loci and enables a polygenic genetic risk score strongly predictive of disease susceptibility in the population, and disease progression and treatment intensity in the clinic

Plenary: Best Paper Presentations #P0404Jamie Craig, Xikun Han, Ayub Qassim, Mark Hassall, Robert Casson, Stuart Graham, John Landers, Colin Willoughby, Andrew Lotery, Janey Wiggs, Owen Siggs, Anna Galanopoulos, Paul Mitchell, Richard Mills, Ashish Agar, Paul Healey, Andrea Vincent, David Mackey, Emmanuelle Souzeau, Alex Hewitt, Stuart MacGrego