Sensing and closed-loop control are critical attributes of a robust 3D printing process, such as Directed Energy Deposition (DED), in which it is necessary to manage geometry, material properties, ...and residual stress and distortion. The present research demonstrates multiple modes of closed-loop melt pool size control in laser-wire based DED, a form of large-scale metal additive manufacturing. First, real-time closed-loop melt pool size control through laser power modulation was demonstrated for intralayer control of bead geometry. Aspects such as controller tuning, response time, interaction with primary process variables, and disturbance rejection are presented. Next, an interlayer trend in laser power during the printing of layered components was documented, which inspired the development of novel modes of control. A controller that modulates print speed and deposition rate on a per-layer basis was developed and demonstrated, enabling the control of either average melt pool size alone or average laser power in coordination with real-time melt pool size control. This work demonstrates that accumulated heat in components under construction can be exploited to maintain process stability as print speed and deposition rate are automatically increased under closed-loop control. This has major implications for overall production efficiency. Control modes are characterized in terms of their effect on local bead geometry, global part geometry, and interlayer effect on energy density, among other factors.
Intra-resuscitation antiarrhythmic drugs may improve resuscitation outcomes, in part by avoiding rearrest, a condition associated with poor out-of-hospital cardiac arrest (OHCA) outcomes. However, ...antiarrhythmics may also alter defibrillation threshold. The objective of this study was to investigate the relationship between rearrest and intra-resuscitation antiarrhythmic drugs in the context of the Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial.
Rearrest rates would be lower in cases treated with amiodarone or lidocaine, versus saline placebo, prior to first return of spontaneous circulation (ROSC). We also hypothesized antiarrhythmic effects would be quantifiable through analysis of the prehospital electrocardiogram.
We conducted a secondary analysis of the ROC ALPS trial. Cases that first achieved prehospital ROSC after randomized administration of study drug were included in the analysis. Rearrest, defined as loss of pulses following ROSC, was ascertained from emergency medical services records. Rearrest rate was calculated overall, as well as by ALPS treatment group. Multivariable logistic regression models were constructed to assess the association between treatment group and rearrest, as well as rearrest and both survival to hospital discharge and survival with neurologic function. Amplitude spectrum area, median slope, and centroid frequency of the ventricular fibrillation (VF) ECG were calculated and compared across treatment groups.
A total of 1144 (40.4%) cases with study drug prior to first ROSC were included. Rearrest rate was 44.0% overall; 42.9% for placebo, 45.7% for lidocaine, and 43.0% for amiodarone. In multivariable logistic regression models, ALPS treatment group was not associated with rearrest, though rearrest was associated with poor survival and neurologic outcomes. AMSA and median slope measures of the first available VF were associated with rearrest case status, while median slope and centroid frequency were associated with ALPS treatment group.
Rearrest rates did not differ between antiarrhythmic and placebo treatment groups. ECG waveform characteristics were correlated with treatment group and rearrest. Rearrest was inversely associated with survival and neurologic outcomes.
Abstract
The present study investigated the effect of urban (traffic noise) vs. natural (birdsongs) soundscapes on mood, state paranoia, and cognitive performance, hypothesizing that birdsongs lead ...to significant improvements in these outcomes. An additional goal was to explore the differential impact of lower vs. higher diversity of the soundscapes by manipulating the number of different typical traffic sounds or songs of different bird species within the respective soundscapes. In a randomized online experiment, N = 295 participants were exposed to one out of four conditions for 6 min: traffic noise low, traffic noise high, birdsong low, and birdsong high diversity soundscapes. Before and after the exposure, participants performed a digit-span and dual n-back task, and filled out depression, anxiety, and paranoia questionnaires. The traffic noise soundscapes were associated with a significant increase in depression (small effect size in low, medium effect size in high diversity condition). Concerning the birdsong conditions, depression exclusively decreased after exposure to the high diversity soundscape (small effect size). Anxiety and paranoia significantly decreased in both birdsong conditions (medium effect sizes). For cognition, no effects were observed. In sum, the present study suggests that listening to birdsongs regardless of diversity improves anxiety, while traffic noise, also regardless of diversity, is related to higher depressiveness. Moreover, for the first time, beneficial, medium-sized effects of birdsong soundscapes were demonstrated, reducing paranoia. Overall, the results bear interesting implications for further research, such as actively manipulating soundscapes in different environments or settings (e.g., psychiatric wards) and testing their effect on subclinical or even clinical manifestations of anxiety and paranoia.
The relationship between depressive symptoms and subsequent cognitive impairment in older adults is controversial. Sex differences and the differences in the method of categorizing depressive ...symptoms may contribute to the inconsistencies. The authors examined the effect of severity of baseline depressive symptoms on risk of incident amnestic mild cognitive impairment (aMCI) separately in men and women.
Community-dwelling and cognitively healthy older adults (aged ≥ 70 years) from the Einstein Aging Study completed the 15-item Geriatric Depression Scale (GDS-15) at their baseline visit. Participants were categorized into "no/low symptoms" (GDS-15 score = 0-2), "mild symptoms" (GDS-15 score = 3-5), and "moderate/severe symptoms" (GDS-15 score > 6) groups. Sex-stratified Cox proportional hazards models, adjusted for age, education, and antidepressant medication, estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident aMCI as a function of depressive symptoms group.
We followed 572 women (mean age: 78) and 345 men (mean age: 77) for 4.2 years on average (range: 1.0-14.6 years). Ninety women and 64 men developed aMCI during follow-up. Cox models revealed that compared with no/low depressive symptoms, mild symptoms were associated with a two times greater risk of developing aMCI in men (HR: 2.22; 95% CI: 1.26-3.89) but not in women (HR: 1.26; 95% CI: 0.77-2.06). Conversely, moderate/severe depressive symptoms were associated with a two times greater risk of developing aMCI in women (HR: 1.99; 95% CI: 1.05-3.77) but not in men (HR: 0.28; 95% CI: 0.04-2.11), possibly because of low statistical power in this subgroup.
Results indicate that mild depressive symptoms in men and moderate/severe symptoms in women may represent a marker for future cognitive impairment.
Given the rising number of older people with HIV (PWH) and the overlap in cognitive dysfunction profiles in HIV-associated neurocognitive disorders (HAND) and Alzheimer's disease and its precursor, ...amnestic mild cognitive impairment (aMCI), methods are needed to distinguish aMCI/Alzheimer's disease from HAND. As an early indicator of Alzheimer's disease, we examined whether olfactory dysfunction could help to distinguish between aMCI/Alzheimer's disease and HAND among PWH.
An observational cohort study.
Eighty-one older (≥50 years) PWH (83% men, 65% white) from the California NeuroAIDS Tissue Consortium completed the University of Pennsylvania Smell Identification Test (UPSIT; higher scores = better smell identification) and a comprehensive seven-domain neuropsychological test battery and neuromedical evaluation. HAND was classified via Frascati criteria. High aMCI risk was defined as impairment (>1.0 SD below normative mean) on two of four delayed recall or recognition outcomes (at least one recognition impairment required) from the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised. We examined UPSIT scores in relation to aMCI risk and HAND status, and continuous memory scores considering adjustments for demographics and relevant clinical or HIV disease characteristics.
Fifty-seven participants were classified with HAND (70%) and 35 participants were classified as high aMCI risk (43%). UPSIT scores were lower (worse) in the high versus low aMCI risk group F (1,76) = 10.04, P = 0.002, but did not differ by HAND status F (1,76) = 0.62, P = 0.43. UPSIT scores positively correlated with all memory outcomes (Ps < 0.05).
Olfactory assessments may help in detecting early aMCI/Alzheimer's disease among PWH and allow for appropriate and early disease intervention.
Studies have shown that women on the Alzheimer's disease (AD) continuum have more pathological tau in the brain and cerebrospinal fluid (CSF), than men. Some studies have found that higher levels of ...tau biomarkers are more strongly associated with clinical AD, cognitive decline and neurodegeneration in women than in men. Despite major developments in the use of plasma tau phosphorylated at threonine 181 (p-tau181) as an AD biomarker, it is unknown whether these sex differences apply to plasma p-tau181. In 1060 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (47% women, 73.8 ± 7.6 years old), we examined sex differences in plasma p-tau181 levels and their association with other biomarkers, cognitive decline and incident AD. Linear regressions tested for an effect of sex on plasma p-tau181 levels and for plasma p-tau181 × sex interactions on CSF p-tau181, as well as entorhinal cortex tau, cortical amyloid-β (Aβ) deposition, and brain glucose metabolism, quantified using PET imaging. Linear mixed effects models tested for a sex × baseline plasma p-tau181 interaction on change in cognition over time. Finally, Cox models tested for a sex × plasma p-tau181 interaction on the risk of AD dementia in participants who were free of dementia at baseline. Despite similar plasma p-tau181 levels between sexes, women had lower brain glucose metabolism, greater brain Aβ and entorhinal cortex tau deposition, higher CSF p-tau181 and faster cognitive decline in relation to higher baseline plasma p-tau181 levels compared with men. Among Aβ positive, dementia-free participants, women had higher rates of incident AD dementia associated with increasing baseline plasma p-tau181 levels, relative to men. Our results suggest that sex may impact the clinical interpretation of plasma p-tau181 concentrations. If replicated, these findings could have important implications for the use of plasma p-tau181 as an accessible AD biomarker and screening tool for preventive and therapeutic clinical trials.
OBJECTIVE:We determined whether there are sex differences in the prevalence and profile of HIV-associated neurocognitive impairment, and whether sex moderates the effect of HIV-serostatus on ...neurocognitive impairment among HIV-positive and HIV-negative individuals. Secondarily, we assessed whether differences were explained by greater biopsychosocial risk factors in HIV-positive women.
DESIGN:An observational cohort study.
METHODS:Analyses included 1361 HIV-positive (204 women) and 702 HIV-negative (214 women) (ages = 18–79 years) participants from the UCSD HIV Neurobehavioral Research Program. Demographically corrected standardized T-scores from 15 neuropsychological tests were used to calculate domain-specific and global deficit scores (GDS). GDS at least 0.5 defined neurocognitive impairment. Biopsychosocial risk factors included low education, low reading level (education quality), lifetime substance use disorders, depressed mood (clinically significant depressive symptoms and/or current major depressive disorder) and a cumulative syndemic count (sum of biopsychosocial risk factors, range = 0–4). Race-stratified analyses were conducted. Analyses were adjusted for relevant demographic and clinical factors.
RESULTS:HIV-associated neurocognitive impairment was more prevalent in women versus men; however, the difference was eliminated after adjustment for reading level. In sex-stratified logistic regressions, the association between HIV-seropositivity and higher likelihood of neurocognitive impairment was stronger in women versus men; however, the association was attenuated in women, but not men, after adjusting for reading level. These results in the overall sample were specific to blacks. Sex differences in the profile of HIV-associated neurocognitive impairment varied by race.
CONCLUSION:Women, particularly black women, were most at-risk for HIV-associated neurocognitive impairment. Higher rates of HIV-associated neurocognitive impairment in women versus men may reflect differences in educational quality.
Women show greater pathological Tau biomarkers than men along the Alzheimer's disease (AD) continuum, particularly among apolipoprotein ε-E4 (APOE4) carriers; however, the reason for this sex ...difference in unknown. Sex differences often indicate an underlying role of sex hormones. We examined whether testosterone levels might influence this sex difference and the modifying role of APOE4 status. Analyses included 172 participants (25 cognitively normal, 97 mild cognitive impairment, 50 AD participants) from the Alzheimer's Disease Neuroimaging Initiative (34% female, 54% APOE4 carriers, aged 55-90). We examined the separate and interactive effects of plasma testosterone levels and APOE4 on cerebrospinal fluid phosphorylated-tau181 (p-Tau) levels in the overall sample and the sex difference in p-Tau levels before and after adjusting for testosterone. A significant APOE4-by-testosterone interaction revealed that lower testosterone levels related to higher p-Tau levels among APOE4 carriers regardless of sex. As expected, women had higher p-Tau levels than men among APOE4 carriers only, yet this difference was eliminated upon adjustment for testosterone. Results suggest that testosterone is protective against p-Tau particularly among APOE4 carriers. The lower testosterone levels that typically characterize women may predispose them to pathological Tau, particularly among female APOE4 carriers.
The advent of effective antiretroviral medications (ARVs) has led to an aging of the HIV population with approximately 50% of people with HIV (PWH) being over the age of 50 years. Neurocognitive ...complications, typically known as HIV-associated neurocognitive disorders (HAND), persist in the era of ARVs and, in addition to risk of HAND, older PWH are also at risk for age-associated, neurodegenerative disorders including Alzheimer’s disease (AD). It has been postulated that risk for AD may be greater among PWH due to potential compounding effects of HIV and aging on mechanisms of neural insult. We are now faced with the challenge of disentangling AD from HAND, which has important prognostic and treatment implications given the more rapidly debilitating trajectory of AD. Herein, we review the evidence to date demonstrating both parallels and differences in the profiles of HAND and AD. We specifically address similarities and difference of AD and HAND as it relates to (1) neuropsychological profiles (cross-sectional/longitudinal), (2) AD-associated neuropathological features as evidenced from neuropathological, cerebrospinal fluid and neuroimaging assessments, (3) biological mechanisms underlying cortical amyloid deposition, (4) parallels in mechanisms of neural insult, and (5) common risk factors. Our current understanding of the similarities and dissimilarities of AD and HAND should be further delineated and leveraged in the development of differential diagnostic methods that will allow for the early identification of AD and more suitable and effective treatment interventions among graying PWH.
INTRODUCTION
We investigated how the associations between tau and cognitive measures differ by sex in the preclinical Alzheimer's disease (AD) stage.
METHODS
A total of 343 cognitively unimpaired, ...amyloid‐positive individuals (205 women, 138 men) who self‐identified as non‐Hispanic White from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study were included. We assessed sex‐stratified associations between 18F‐flortaucipir positron emission tomography (PET) standardized uptake value ratio (SUVR) in the meta‐temporal region and Preclinical Alzheimer's Cognitive Composite (PACC) and Computerized Cognitive Composite (C3) components.
RESULTS
We observed that higher tau level was significantly associated with worse cognitive performance only in women: PACC and its components except for Mini‐Mental State Examination (MMSE) and C3 components: First Letter Name Recall (FNLT) and One‐Card Learning Reaction Time (OCL RT). These associations except for FNLT were apolipoprotein E (APOE) ε4 independent.
DISCUSSION
Women show stronger associations between tau PET and cognitive outcomes in preclinical AD. These findings have important implications for sex‐specific tau‐targeted preventive AD clinical trials.
Highlights
The tau positron emission tomography (PET) signal in the meta‐temporal region was associated with poor cognitive performance in preclinical Alzheimer's disease (AD).
After sex stratification, the associations between regional tau PET and cognitive outcomes were observed only in women.
The associations between tau PET and some cognitive outcomes were independent of apolipoprotein E (APOE) ε4.
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