Association of Stages of Objective Memory Impairment With Incident Symptomatic Cognitive Impairment in Cognitively Normal Individuals

Background and objectivesIncreasing evidence indicates that a subset of cognitively normal individuals has subtle cognitive impairment at baseline. We sought to identify them using the Stages of Objective Memory Impairment (SOMI) system. Symptomatic cognitive impairment was operationalized by a Clinical Dementia Rating (CDR) ≥0.5. We hypothesized that incident impairment would be higher for participants with subtle retrieval impairment (SOMI-1), higher still for those with moderate retrieval impairment (SOMI-2), and highest for those with storage impairment (SOMI-3/4) after adjusting for demographics and APOE ε4 status. A secondary objective was to determine whether including biomarkers of β-amyloid, tau pathology, and neurodegeneration in the models affect prediction. We hypothesized that even after adjusting for in vivo biomarkers, SOMI would remain a significant predictor of time to incident symptomatic cognitive impairment.MethodsAmong 969 cognitively normal participants, defined by a CDR = 0, from the Knight Alzheimer Disease Research Center, SOMI stage was determined from their baseline Free and Cued Selective Reminding Test scores, 555 had CSF and structural MRI measures and comprised the biomarker subgroup, and 144 of them were amyloid positive. Cox proportional hazards models tested associations of SOMI stages at baseline and biomarkers with time to incident cognitive impairment defined as the transition to CDR ≥0.5.ResultsAmong all participants, the mean age was 69.35 years, 59.6% were female, and mean follow-up was 6.36 years. Participants in SOMI-1-4 had elevated hazard ratios for the transition from normal to impaired cognition in comparison with those who were SOMI-0 (no memory impairment). Individuals in SOMI-1 (mildly impaired retrieval) and SOMI-2 (moderately impaired retrieval) were at nearly double the risk of clinical progression compared with persons with no memory problems. When memory storage impairment emerges (SOMI-3/4), the hazard ratio for clinical progression increased approximately 3 times. SOMI stage remained an independent predictor of incident cognitive impairment after adjusting for all biomarkers.DiscussionSOMI predicts the transition from normal cognition to incident symptomatic cognitive impairment (CDR ≥0.5). The results support the use of SOMI to identify those cognitively normal participants most likely to develop incident cognitive impairment who can then be referred for biomarker screening

Numerical Studies of Droplets on Superhydrophobic Surfaces

The work presented here explores and utilizes numerical methods to study the phenomenon of superhydrophobic surfaces. Interest in superhydrophobic surfaces has been the source of much research over the past decade due to new applications and better techniques for theoretical and computational research. Numerical simulations have been very helpful in elucidating and understanding roughness-induced superhydrophobicity and droplet behavior. In this thesis, we first explore superhydrophobic surfaces using a Gibbs free energy model. Advancing work that has been done on the metastable Cassie and Wenzel states identified by this approach, we apply the string method to identify saddle point states and associated energy barriers. Furthermore, this model is extended to include surfaces with a hierarchical microstructure that can further increase the superhydrophobicity of the surface. Next, we present and discuss a phase field model that has been used to study wetting. We then present an analysis of the shifting parameters in the model when numerically implemented and find that a near uniform shift in the phase field results in a change in the droplet size and contact angle. We also present an analysis of spontaneous droplet shrinkage and derive values for the critical droplet size in two and three dimensions such that larger droplets will not shrink. We then present results obtained using this model to study droplets on topographically and chemically patterned surfaces. We study the associated energy landscape of a pillared surface. Additionally, we discuss the different modes of transition for each surface and examine energy barrier dependence on different problem parameters. Finally, we propose a novel, proof-of-concept surface optimization problem that evolves towards an optimal surface geometry such that droplet rolling is more energetically probable than collapsing. This is achieved by minimizing an objective functional that is constructed to minimize favorable energy barriers and increase unfavorable barriers. We present a thorough development of the numerical implementation of this method and present the results from several test cases. This work introduces a new approach to the search for optimized superhydrophobic surfaces

The Impact of Oxidative Stress on Postmortem Meat Quality

This study was conducted to evaluate the relationship between animal oxidative status, using lipopolysaccharide (LPS) as a promoter for oxidation. This was used as a model to evaluate tenderization and meat quality factors early postmortem. Lambs were administered an intravenous injection of either saline, 50 ng/kg bodyweight (LPS50), or 100 ng/kg bodyweight (LPS100) every 72 hours for a 9- day period to stimulate physiological oxidative stress. After a day of rest, lambs were harvested, and pre- rigor Longissimus dorsi-muscles were obtained for transcriptomic analysis. Loins, aged for 1 and 14 days, were analyzed for attributes relating to oxidative potential, meat tenderness, color, and lipid stability. Results show lambs administered lipopolysaccharide treatments exhibited greater oxidative potential, as indicated by increased rectal temperatures, and upregulated expression of mRNA protein pathways essential for cellular differentiation, proliferation, and apoptotic events. Lambs administered LPS50 tended to be more tender early postmortem, with significantly increased proteolysis (Troponin T). Interestingly, LPS treatment was not detrimental to meat quality, as indicated by more ideal color values and no significant changes in lipid oxidation. These data indicate that oxidative potential via oxidative stress can potentially increase tenderization early postmortem, which may provide more tender meat with no detriment to other meat quality factors

The Impact of COVID-19 and Racial Injustices on Resilience of Incoming Medical Students

Medical students (MS) are at higher risk for depression than their peers. Incoming U.S. MS completed a survey that included the validated RS-14, which measures resilience and its two subcomponents: self-assuredness and drive. Surveys were administered before classes started in 2019 (pre-pandemic-cohort; n = 178) and 2020 (pandemic-cohort; n = 181). Resiliency, self-assuredness, and drive were not different between cohorts. Demographic subgroup analyses revealed that underrepresented in medicine (URiM) MS in the pre-pandemic-cohort scored higher on drive (p = 0.007) than non-URiM MS (6.07 ± 1.00 vs. 5.59 ± 0.97); however, this difference was not significant in the pandemic-cohort. Additionally, students in the pandemic-cohort were more likely to agree that peer discussions about emotional challenges would be beneficial (p = 0.014). Qualitative analysis revealed that 45.9% of pandemic-cohort respondents felt more motivated to pursue medicine. This is the first study to report differences in drive between URiM MS cohorts matriculating before and during a pandemic, a positive correlation between multiple-mini-interview (MMI) scores and drive, and a negative correlation between MCAT scores and drive. Collectively, these results suggest that the circumstances of 2020 may have negatively influenced the drive of URiM students, positively impacted the receptivity of MS to peer discussions, and motivated students to pursue medicine

Predicting Amyloid Positivity in Cognitively Unimpaired Older Adults: A Machine Learning Approach Using A4 Data.

BACKGROUND AND OBJECTIVES: To develop and test the performance of the Positive Aβ Risk Score (PARS) for prediction of β-amyloid (Aβ) positivity in cognitively unimpaired individuals for use in clinical research. Detecting Aβ positivity is essential for identifying at-risk individuals who are candidates for early intervention with amyloid targeted treatments. METHODS: We used data from 4,134 cognitively normal individuals from the Anti-Amyloid Treatment in Asymptomatic Alzheimers (A4) Study. The sample was divided into training and test sets. A modified version of AutoScore, a machine learning-based software tool, was used to develop a scoring system using the training set. Three risk scores were developed using candidate predictors in various combinations from the following categories: demographics (age, sex, education, race, family history, body mass index, marital status, and ethnicity), subjective measures (Alzheimers Disease Cooperative Study Activities of Daily Living-Prevention Instrument, Geriatric Depression Scale, and Memory Complaint Questionnaire), objective measures (free recall, Mini-Mental State Examination, immediate recall, digit symbol substitution, and delayed logical memory scores), and APOE4 status. Performance of the risk scores was evaluated in the independent test set. RESULTS: PARS model 1 included age, body mass index (BMI), and family history and had an area under the curve (AUC) of 0.60 (95% CI 0.57-0.64). PARS model 2 included free recall in addition to the PARS model 1 variables and had an AUC of 0.61 (0.58-0.64). PARS model 3, which consisted of age, BMI, and APOE4 information, had an AUC of 0.73 (0.70-0.76). PARS model 3 showed the highest, but still moderate, performance metrics in comparison with other models with sensitivity of 72.0% (67.6%-76.4%), specificity of 62.1% (58.8%-65.4%), accuracy of 65.3% (62.7%-68.0%), and positive predictive value of 48.1% (44.1%-52.1%). DISCUSSION: PARS models are a set of simple and practical risk scores that may improve our ability to identify individuals more likely to be amyloid positive. The models can potentially be used to enrich trials and serve as a screening step in research settings. This approach can be followed by the use of additional variables for the development of improved risk scores. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in cognitively unimpaired individuals PARS models predict Aβ positivity with moderate accuracy

Processing and microstructure of a Cu-Al-Fe-Mn alloy via droplet-on-demand additive manufacturing

Control over the microstructure and properties of alloys produced via additive manufacturing (AM) is a key barrier that limits widespread industrial adoption. Herein we demonstrate that liquid metal jetting (LMJ), an emerging metal-AM technique, can address this need by controlling the microstructure evolution during printing of bronze alloy C95400 (Cu-Al-Fe-Mn). We probed several solid-state phase transformations upon cooling by printing single-tracks onto a heated baseplate ranging from 50 °C to 600 °C surface temperature, which led to significant variation in the α-Cu and δ-Fe phase distribution, grain morphology, and chemical distribution within the deposited single-tracks. The printed microstructures exhibited as much as 80% difference in α-Cu grain size and nearly 30 % difference in α-Cu phase fraction due to baseplate temperature variation, indicating a wide range of available microstructures and properties achievable. Greater than 92% dense multi-layer samples were fabricated with fine grain structure and 27–34% higher hardness values compared to the barstock in the as-printed condition, demonstrating the applicability of this printing approach for multi-layer part fabrication. Our results highlight a unique microstructure tailoring capability for metal-AM parts that can be leveraged by manufacturers and end-users of AM technologies

APOE and immunity: Research highlights

INTRODUCTION: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry. RESULTS: During the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor α [TNFα]). DISCUSSION: This manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development