Abeta, oxidative stress in Alzheimer disease: Evidence based on proteomics studies

AbstractThe initiation and progression of Alzheimer disease (AD) is a complex process not yet fully understood. While many hypotheses have been provided as to the cause of the disease, the exact mechanisms remain elusive and difficult to verify. Proteomic applications in disease models of AD have provided valuable insights into the molecular basis of this disorder, demonstrating that on a protein level, disease progression impacts numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and proteasome function. Each of these cellular functions contributes to the overall health of the cell, and the dysregulation of one or more could contribute to the pathology and clinical presentation in AD. In this review, foci reside primarily on the amyloid β-peptide (Aβ) induced oxidative stress hypothesis and the proteomic studies that have been conducted by our laboratory and others that contribute to the overall understanding of this devastating neurodegenerative disease. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction, and Neurodegenerative Diseases

2023 Crummer Truist Portfolio Recommendations: Crummer Investment Management 24th Anniversary

We would like to thank you for your service to the Crummer Truist Portfolio. Without your participation, Crummer students would not benefit from the unique insight you bring to managing an active portfolio. We have been fortunate to listen and learn from some outstanding guest speakers who have been generous with their time and expertise: Phillip Rich, Chief Investment Officer, Seaside Bank; Sarah Passero, Senior Consultant, EY; Shawn Fletcher, Financial Analyst, The Walt Disney Company; Ryan Abronski, Venture Capital Associate, Morgan Creek Digital; Robert Zhang, Senior Research Analyst, DePrince, Race and Zollo; Dr. William Seyfried, Professor, Crummer Graduate School of Business; Marc Miller, Partner, DePrince, Race and Zollo; Rick Ahl, President, Ahl Investment Management; Dr. Rob Roy, Senior VP and Chief Investment Officer, AdventHealth; Jay Menozzi, Principal and Chief Investment Officer, Orange Investment Advisors, LLC; Sean Warrington, Partner & Portfolio Manager, Gresham Partners. SunTrust (now Truist) endowed this portfolio to provide scholarships for future Crummer students and to give current students a practical, hands-on learning opportunity. This year, we are pleased to be able to disburse $55,000 to be used for scholarships. We are extremely grateful for SunTrust’s generosity and investment in higher education. We have all learned a great deal from this experience and the responsibility of managing real money. Our first challenge is to establish a portfolio position that takes advantage of economic opportunities while avoiding unnecessary risk and conforming to the Crummer Truist Investment Policy Statement (IPS). We are also tasked by the IPS to operate at two levels simultaneously – tactical for the near term, and strategic for the long run. Additionally, this portfolio presents some unusual portfolio management challenges by trading only once a year, in early April. Our tactical approach began with a top-down sector analysis. We established an economic forecast based on research and consultation with economists, including Professor William Seyfried of the Crummer School and Philip Rich of Seaside Bank. We based our equity and fixed income split on that forecast with a 20% allocation to bonds, at the highest level allowed by the IPS. That forecast also drove our allocation among the eleven S&P sectors: Communication Services, Consumer Discretionary, Consumer Staples, Energy, Financials, Healthcare, Industrials, Information Technology, Materials, Real Estate, and Utilities. Within the next twelve-month period, we forecast stagnant economic growth that will not quite be a recession. Accordingly, we tilted the allocation towards sectors that should do well in such a macro environment while paying attention to ongoing recovery from inflationary pressures as well as other issues such as the ongoing war in Ukraine. Our asset class allocation embodies the long-run strategy of our portfolio. The IPS sets asset class ranges from low to moderate risk to keep the portfolio from being whipsawed by transitory market cycles. Our equity allocations signify a heightened level of risk, consistent with our view that the stock market will relatively underperform the fixed income market through the end of March 2024. We maintain an allocation to a sector ETF in each sector to ensure diversification. Due to enrollment constraints, we actively manage eight sectors this year with a limit of two individual stocks in each sector. The remaining sectors are invested 100% in their sector ETF. Fixed income is our anchor sector, providing a hedge against the risk of an economic slowdown adversely impacting our equity holdings. Consistent with our non-parallel shifting yield curve projection, we are at the high end of our IPS range for fixed income at 20%, but towards the lower end of the permissible duration level. Furthermore, we have continued to incorporate the theme of Environmental, Social, and Governance (ESG) investing into our portfolio selection process. While ESG investing has become a lightning rod and ESG ratings have been under heavy criticism for lack of consistency, the fund flows into this domain have continued to grow globally. Regardless of a security’s consistency with this theme, all recommendations must be undervalued after rigorous quantitative and qualitative analysis. In other words, our intent is not to maximize the ESG impact of our portfolio but to tilt towards this factor. Specifically, the proposed equity holdings in this year’s portfolio have a weighted average FTSE ESG score of 3.56 out of 5, while S&P 500 holdings have a cap-weighted average score of 3.34. Since the onset of the COVID-19 pandemic, we have witnessed three extraordinary and unpredictable years in many respects. Inflation levels that have not been seen in the past 40 years, supply chain problems, the Russian-Ukrainian war, and interest rate hikes at an unprecedented pace have all contributed to an increased uncertainty. We do not intend to simply follow the crowd. Yet, echoing the philosophy of Warren Buffett, “our opinions and beliefs, grounded in economics and guided by all of those who have counseled us,” lead us to a strategy that is not significantly different from many investors. Even so, we accept responsibility for our investment decisions. We are investing for the long-term and we have been conservative in our forecasts and recommendations. Simultaneously, in the short term, we are mindful of the need to protect the portfolio’s commitment to scholarships. We thank you for your time and participation in this important endeavor. - Sincerely, The Crummer Investment Management Tea

The potential to quantify polypharmacy in older adult hospital inpatients using electronic prescribing software: A feasibility study

Polypharmacy in older adults is a growing problem, as some drugs may be either unnecessary or even harmful. Admission to hospital under a Medicine for the Elderly specialist physicians represents an opportunity to review patients’ medication. The recent introduction of electronic prescribing to some hospitals in the United Kingdom allows the development of tools to measure polypharmacy in in-patients, and subsequently to assess the efficacy of interventions that aim to optimize medication prescribing. We tested the feasibility of developing an Excel-based software code that measured the number of medications a group of patients were taking at admission and how many of these were still prescribed on discharge. Electronic prescribing data was obtained from the Royal Derby Hospital, over a period of 52 weeks from April 2017 to March 2018 for all patients over the age of 65 years who were admitted onto the medicine for the elderly wards and subsequently discharged. On admission, the median number of eligible medications was 11 (interquartile range IQR 8 to 15). At the time of discharge, the median number of eligible medications retained since admission was 9 (IQR 6 to 12). This represents a median number of medications that have been removed from the current medication regimen of 2 (IQR 1 to 3, p [less than] 0.001). Electronic prescribing software in hospitals allows the development of tools to measure the burden of medications, and to examine the efficacy of future interventions that are developed to optimize drug prescribing in older adults

Fit for purpose? Pattern cutting and seams in wearables development

This paper describes how a group of practitioners and researchers are working across disciplines at Nottingham Trent University in the area of Technical Textiles. It introduces strands of ongoing enquiry centred around the development and application of stretch sensors on the body, focusing on how textile and fashion knowledge are being reflexively revealed in the collaborative development of seamful wearable concepts, and on the tensions between design philosophies as revealed by definitions of purpose. We discuss the current research direction of the Aeolia project, which seeks to exploit the literal gaps found in pattern cutting for fitted stretch garments towards experiential forms and potential interactions. Normative goals of fitness for purpose and seamlessness are interrogated and the potential for more integrated design processes, which may at first appear ‘upside down’, is discussed

Prediction of stresses and strains around model tunnels with adjacent embedded walls in overconsolidated clay

This paper presents the results of finite element analyses carried out using different constitutive models for overconsolidated clay: the Modified Cam clay model and the Three-Surface Kinematic Hardening (3-SKH) model. These analyses are evaluated against data from an extensive series of physical model tests examining the influence of an embedded wall placed near a tunnel on ground movements and tunnel stability. It is shown that for heavily overconsolidated soils reasonable predictions of both deformations and failure can be obtained from kinematic hardening models such as the 3-SKH model, which allow plastic deformation inside a Modified Cam clay state boundary surface

The effect of ecological harshness on perceptions of the ideal female body size: an experimental life history approach ☆ , ☆☆

Why do researchers regularly observe a relationship between ecological conditions and the heaviness of female body weight ideals? The current research uses insights from life history theory and female reproductive physiology to examine whether variability in female body ideals might emerge from the different life history strategies typically adopted by individuals living in harsh versus benign ecologies. Across three experiments, we demonstrate that women who were sensitized to faster life history strategies during childhood -as indexed by earlier menarche or lower childhood SES -respond to cues of ecological harshness by shifting away from the thin body weight typically favored by Western women toward a heavier female body ideal. Additionally, although men's perceptions of the ideal male body size did not shift in response to these cues, their perceptions of the ideal female body size did, with developmentally sensitized men also preferring a heavier female body size in the context of harsh ecologies

The Optical Green Valley Versus Mid-infrared Canyon in Compact Groups

Compact groups of galaxies provide conditions similar to those experienced by galaxies in the earlier universe. Recent work on compact groups has led to the discovery of a dearth of mid-infrared transition galaxies (MIRTGs) in Infrared Array Camera (3.6-8.0 micrometers) color space as well as at intermediate specific star formation rates. However, we find that in compact groups these MIRTGs have already transitioned to the optical ([gr]) red sequence. We investigate the optical color-magnitude diagram (CMD) of 99 compact groups containing 348 galaxies and compare the optical CMD with mid-infrared (mid-IR) color space for compact group galaxies. Utilizing redshifts available from Sloan Digital Sky Survey, we identified new galaxy members for four groups. By combining optical and mid-IR data, we obtain information on both the dust and the stellar populations in compact group galaxies. We also compare with more isolated galaxies and galaxies in the Coma Cluster, which reveals that, similar to clusters, compact groups are dominated by optically red galaxies. While we find that compact group transition galaxies lie on the optical red sequence, LVL (Local Volume Legacy) + (plus) SINGS (Spitzer Infrared Nearby Galaxies Survey) mid-IR (infrared) transition galaxies span the range of optical colors. The dearth of mid-IR transition galaxies in compact groups may be due to a lack of moderately star-forming low mass galaxies; the relative lack of these galaxies could be due to their relatively small gravitational potential wells. This makes them more susceptible to this dynamic environment, thus causing them to more easily lose gas or be accreted by larger members

Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014