E-Manufacturing for product improvement at Red Bull technology

In Formula 1 racing, there is a strong motive for reducing component weight and thereby improving efficiency. This paper demonstrates the advantages e-Manufacturing brings to the production of hydraulic components. The DMLS production technique would enable weight reductions to be attained by its geometric design freedom coupled with this material’s attributes. The use of EOS Titanium Ti64 material for hydraulic components has been assessed by a hydraulic soak test at 25 MPa and no significant losses or failure occurred. The benefits to the efficiency of hydraulic flow have been measured using Particle Image Velocimetry (PIV) and the use of DMLS designed geometry has improved flow characteristics by 250% over that of the currently used techniques of manufacturing channels and bores

Tobacco Smoking and Dementia in a Kentucky Cohort: A Competing Risk Analysis

Tobacco smoking was examined as a risk for dementia and neuropathological burden in 531 initially cognitively normal older adults followed longitudinally at the University of Kentucky’s Alzheimer’s Disease Center. The cohort was followed for an average of 11.5 years; 111 (20.9%) participants were diagnosed with dementia, while 242 (45.6%) died without dementia. At baseline, 49 (9.2%) participants reported current smoking (median pack-years = 47.3) and 231 (43.5%) former smoking (median pack-years = 24.5). The hazard ratio (HR) for dementia for former smokers versus never smokers based on the Cox model was 1.64 (95% CI: 1.09, 2.46), while the HR for current smokers versus never smokers was 1.20 (0.50, 2.87). However, the Fine-Gray model, which accounts for the competing risk of death without dementia, yielded a subdistribution hazard ratio (sHR) = 1.21 (0.81, 1.80) for former and 0.70 (0.30, 1.64) for current smokers. In contrast, current smoking increased incidence of death without dementia (sHR = 2.38; 1.52, 3.72). All analyses were adjusted for baseline age, education, sex, diabetes, head injury, hypertension, overweight, APOE ɛ4, family history of dementia, and use of hormone replacement therapy. Once adjusted for the competing risk of death without dementia, smoking was not associated with incident dementia. This finding was supported by neuropathology on 302 of the participants

Design & manufacture of a high-performance bicycle crank by additive manufacturing

A new practical workflow for the laser Powder Bed Fusion (PBF) process, incorporating topological design, mechanical simulation, manufacture, and validation by computed tomography is presented, uniquely applied to a consumer product (crank for a high-performance racing bicycle), an approach that is tangible and adoptable by industry. The lightweight crank design was realised using topology optimisation software, developing an optimal design iteratively from a simple primitive within a design space and with the addition of load boundary conditions (obtained from prior biomechanical crank force–angle models) and constraints. Parametric design modification was necessary to meet the Design for Additive Manufacturing (DfAM)considerations for PBF to reduce build time, material usage, and post-processing labour. Static testing proved performance close to current market leaders with the PBF manufactured crank found to be stiffer than the benchmark design (static load deflection of 7.0±0.5 mm c.f. 7.67mm for a Shimano crank at a competitive mass (155g vs. 175g). Dynamic mechanical performance proved inadequate, with failure at 2495±125cycles; the failure mechanism was consistent in both its form and location. This research is valuable and novel as it demonstrates a complete work flow from design, manufacture, post-treatment, and validation of a highly loaded PBF manufactured consumer component, offering practitioners a validated approach to the application of PBF for components with application outside of the accepted sectors (aerospace, biomedical, autosports, space, and power generation)

Self-Reported Sleep Apnea and Dementia Risk: Findings from the Prevention of Alzheimer\u27s Disease with Vitamin E and Selenium Trial

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer\u27s Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status. DESIGN: Secondary analysis based on data collected during PREADViSE. SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location. PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = 7,547). MEASUREMENTS: Participants were interviewed at baseline for sleep apnea. The Memory Impairment Screen (MIS) was administered to each participant annually. Subjects who failed this initial screen were tested with secondary screening tests. Medical history and medication use were determined, and the AD8 dementia screening instrument was used. RESULTS: The effect of self-reported sleep apnea on dementia risk depended on APOE ɛ4 status. When the allele was absent, baseline self-reported sleep apnea was associated with a 66% higher risk of developing dementia (95% confidence interval = 2-170%), whereas self-reported sleep apnea conferred no additional risk for participants with an ɛ4 allele. CONCLUSION: Sleep apnea may increase risk of dementia in the absence of APOE ɛ4. This may help inform prevention strategies for dementia or AD in older men with sleep apnea. Registration: PREADViSE is registered at ClinicalTrials.gov: NCT00040378

Fabrication of large-area CCD detectors on high-purity, float-zone silicon

In this report on the fabrication of a 1024 x 1024 charge coupled device (CCD) imager to be used as a soft x-ray sensor onboard the Advanced X-ray Astronomical Facility (AXAF), the following conclusions were found: the dislocations that limited the performance of the high resistivity imager were characterized; the sources of stress were identified and the dislocations found were eliminated; and a charge transfer inefficiency (CTI) of 10(exp -6) and read noise as low as 1.3/e was demonstrated. This sensor must have low noise and a low CTI and must be radiation hardened to withstand any radiation damage from a space environment

Targeting Gene Expression to Cones With Human Cone Opsin Promoters in Recombinant AAV

Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and specific expression of GFP in the long- and medium-wavelength-absorbing cones (L/M cones) of normal and diseased retinas. The PR0.5 promoter was not effective. Adding three copies of the 35-bp LCR in front of PR0.5 lead to weak GFP expression in L/M cones. The HB569 promoter was not specific, and GFP was expressed in a few L/M cones, some rods and the retinal pigment epithelium. These results suggest that L/M cones, the predominant class of cone photoreceptors in the retinas of dogs and most mammalian species can be successfully targeted using the human red cone opsin promoter

Mild Cognitive Impairment: Statistical Models of Transition Using Longitudinal Clinical Data

Mild cognitive impairment (MCI) refers to the clinical state between normal cognition and probable Alzheimer's disease (AD), but persons diagnosed with MCI may progress to non-AD forms of dementia, remain MCI until death, or recover to normal cognition. Risk factors for these various clinical changes, which we term “transitions,” may provide targets for therapeutic interventions. Therefore, it is useful to develop new approaches to assess risk factors for these transitions. Markov models have been used to investigate the transient nature of MCI represented by amnestic single-domain and mixed MCI states, where mixed MCI comprised all other MCI subtypes based on cognitive assessments. The purpose of this study is to expand this risk model by including a clinically determined MCI state as an outcome. Analyses show that several common risk factors play different roles in affecting transitions to MCI and dementia. Notably, APOE-4 increases the risk of transition to clinical MCI but does not affect the risk for a final transition to dementia, and baseline hypertension decreases the risk of transition to dementia from clinical MCI

The Cosmic Ultraviolet Baryon Survey (CUBS) I. Overview and the diverse environments of Lyman limit systems at z<1

We present initial results from the Cosmic Ultraviolet Baryon Survey (CUBS). CUBS is designed to map diffuse baryonic structures at redshift z<~1 using absorption-line spectroscopy of 15 UV-bright QSOs with matching deep galaxy survey data. CUBS QSOs are selected based on their NUV brightness to avoid biases against the presence of intervening Lyman Limit Systems (LLSs) at zabs~ 17.2 over a total redshift survey pathlength of dz=9.3, and a number density of n(z)=0.43 (-0.18, +0.26). Considering all absorbers with log N(HI)/cm^-2 > 16.5 leads to n(z)=1.08 (-0.25, +0.31) at z<1. All LLSs exhibit a multi-component structure and associated metal transitions from multiple ionization states such as CII, CIII, MgII, SiII, SiIII, and OVI absorption. Differential chemical enrichment levels as well as ionization states are directly observed across individual components in three LLSs. We present deep galaxy survey data obtained using the VLT-MUSE integral field spectrograph and the Magellan Telescopes, reaching sensitivities necessary for detecting galaxies fainter than 0.1L* at d<~300 physical kpc (pkpc) in all five fields. A diverse range of galaxy properties is seen around these LLSs, from a low-mass dwarf galaxy pair, a co-rotating gaseous halo/disk, a star-forming galaxy, a massive quiescent galaxy, to a galaxy group. The closest galaxies have projected distances ranging from d=15 to 72 pkpc and intrinsic luminosities from ~0.01L* to ~3L*. Our study shows that LLSs originate in a variety of galaxy environments and trace gaseous structures with a broad range of metallicities.Comment: 26 pages, 14 figures, MNRAS in pres

Self-Reported Head Injury and Risk of Late-Life Impairment and AD Pathology in an AD Center Cohort

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer\u27s disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 for the transition from MCI to dementia. Without respect to age, head injury increased the odds of mortality (OR = 1.54). Moreover, it increased the odds of a pathological diagnosis of AD for men (OR = 1.47) but not women (OR = 1.18). Men with a head injury had higher mean amyloid plaque counts in the neocortex and entorhinal cortex than men without. Conclusions: Self-reported head injury is associated with earlier onset, increased risk of cognitive impairment and dementia, increased risk of mortality, and AD-type pathological changes