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Turbulent mixing in a supercritical CO$_2$ shear layer is examined using both experimental and numerical methods. Boundary conditions are selected to focus on the rarely studied near-critical regime, where thermophysical properties vary nonlinearly with respect to temperature and pressure. Experimental results are obtained via Raman spectroscopy and shadowgraphy, while numerical results are obtained via direct numerical simulation. The shear layer growth rate is found to be 0.2. Additionally, density profiles indicate a relaxation of density gradients between the mixed fluid and heavy fluid as the flow evolves downstream, which runs counter to existing supercritical shear layer data in the literature. The computational results identify significant anisotropy in the turbulence in the shear layer, which is discussed in terms of the development of regions of high density gradient magnitude. The Reynolds-averaged enstrophy budget at various streamwise locations indicates no significant dilatational or baroclinic contribution within the shear layer.
OBJECTIVES/GOALS: Total-body symptom surveys among patients with idiopathic orthostatic intolerance (OI) at our referral center suggest that non-conventional OI symptoms, such as pelvic pain, impact quality of life. We seek to identify additional common yet unconventional symptoms reported during clinic visits to improve targeted symptom management. METHODS/STUDY POPULATION: Pelvic pain symptom surveys were completed by 178 patients age 18 and over with a chief complaint of OI. Pelvic pain prevalence was assessed using the International Pelvic Pain Society (IPPS) and Pelvic Congestion Syndrome (PCS) surveys. Expanding on this work, surveys will be distributed to a population with the same inclusion criteria but with a broader symptom scope, chosen based on patient reports during clinical encounters—including presence of migraines, cold digits (Raynaud’s phenomenon), anxiety and depression. The Migraine Disability Assessment Test (MIDAS), modified Assessment of Systemic Sclerosis–Associated Raynaud’s Phenomenon (ASRAP), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) surveys, respectively, will be used to obtain symptom prevalence. RESULTS/ANTICIPATED RESULTS: Of the pelvic pain survey participants, pelvic pain was endorsed by 144/178 (80.9%) of respondents. Prevalence of the additional surveyed symptoms—migraines, cold digits, anxiety, and depression—will similarly be assessed. Given that in our referral clinic we have observed a trend of patients reporting these additional symptoms, we anticipate that at least some of them will be prevalent in a majority of the patient population formally surveyed, similar to the trend observed with pelvic pain prevalence. In particular, we anticipate many patients will report significant migraines, as migraine pain severity on a scale of 0-10 with 0 being no migraine pain and 10 being the most severe migraine pain imaginable is one of the elements of the IPSS survey, and 106/178 (59.6%) reported migraine pain of 5 or higher. DISCUSSION/SIGNIFICANCE: Novel treatment approaches for OI are needed, as lifestyle management is the current treatment paradigm. Several patients reporting pelvic pain have undergone targeted workup and subsequent symptomatic treatment that has improved their quality of life. Other targeted symptom approaches to prevalent symptoms could have the same effect.
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:
This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:
The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:
Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:
This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:
Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:
The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
Research on proactive and reactive aggression has identified covariates unique to each function of aggression, but hypothesized correlates have often not been tested with consideration of developmental changes in or the overlap between the types of aggression. The present study examines the unique developmental trajectories of proactive and reactive aggression over adolescence and young adulthood and tests these trajectories’ associations with key covariates: callous–unemotional (CU) traits, impulsivity, and internalizing emotions. In a sample of 1,211 justice-involved males (ages 15–22), quadratic growth models (i.e., intercepts, linear slopes, and quadratic slopes) of each type of aggression were regressed onto quadratic growth models of the covariates while controlling for the other type of aggression. After accounting for the level of reactive aggression, the level of proactive aggression was predicted by the level of CU traits. However, change in proactive aggression over time was not related to the change in any covariates. After accounting for proactive aggression, reactive aggression was predicted by impulsivity, both at the initial level and in change over time. Results support that proactive and reactive aggression are unique constructs with separate developmental trajectories and distinct covariates.
To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.
Design:
Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.
Setting:
Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.
Participants:
HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic.
Methods:
Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection.
Results:
Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3–14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient’s bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs).
Conclusions:
In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.
Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.
Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
‘Discourses of climate delay’ pervade current debates on climate action. These discourses accept the existence of climate change, but justify inaction or inadequate efforts. In contemporary discussions on what actions should be taken, by whom and how fast, proponents of climate delay would argue for minimal action or action taken by others. They focus attention on the negative social effects of climate policies and raise doubt that mitigation is possible. Here, we outline the common features of climate delay discourses and provide a guide to identifying them.
Disturbed prefrontal cortex (PEC) functions as consequent upon a hyperresponsive amygdala (bottom-up) or/and a lack of PFC-amygdala top-down control are discussed as main reasons for affective disorders. Here we aimed to investigate the specific function of the dorsolateral-PFC (DLPFC) on emotional processing by a temporary deactivation of this region by means of 1-Hz rTMS.
Methods
Before and after rTMS (1 Hz, 1800 stimuli, N = 15) or sham (N = 15) treatment of the right DLPFC, subjects viewed pictures of fearful (40) or neutral (40) emotional faces, while visual evoked magnetic fields were acquired with a 275 sensor whole head MEG system.
Results
There was a clear increase of neural processing within bilateral parietal areas as consequence of rTMS but not sham treatment starting around 90ms after stimulus onset. While this parietal treatment effect occurred for both affective conditions, an area at the right temporo-parietal junction (TPJ) showed an increases sensory processing specifically for fearful faces.
Conclusions
RTMS associated decrease of DLPFC function diminished the known inhibitory impact of this region on limbic and paralimbic structures such as the orbitofrontal cortex, leading to a valence independent modulation of parietal top-down attention areas and an eventually amplified sensory processing of emotional material at right TPJ.
The current study advanced research on the link between community violence exposure and aggression by comparing the effects of violence exposure on different functions of aggression and by testing four potential (i.e., callous–unemotional traits, consideration of others, impulse control, and anxiety) mediators of this relationship. Analyses were conducted in an ethnically/racially diverse sample of 1,216 male first-time juvenile offenders (M = 15.30 years, SD = 1.29). Our results indicated that violence exposure had direct effects on both proactive and reactive aggression 18 months later. The predictive link of violence exposure to proactive aggression was no longer significant after controlling for proactive aggression at baseline and the overlap with reactive aggression. In contrast, violence exposure predicted later reactive aggression even after controlling for baseline reactive aggression and the overlap with proactive aggression. Mediation analyses of the association between violence exposure and reactive aggression indicated indirect effects through all potential mediators, but the strongest indirect effect was through impulse control. The findings help to advance knowledge on the consequences of community violence exposure on justice-involved youth.
Healthcare workers (HCWs) reporting no history of varicella frequently receive varicella vaccination (vOka) if they test varicella-zoster virus (VZV) immunoglobulin G (IgG) negative. In this study, the utilities of VZV-IgG time-resolved fluorescence immunoassay (VZV-TRFIA) and a commercial VZV-IgG purified glycoprotein enzyme immunoassay (gpEIA) currently used in England for confirming VZV immunity have been compared to the fluorescent-antibody-to-membrane-antigen assay (FAMA). A total of 110 HCWs received two doses of vOka vaccine spaced 6 weeks apart and sera collected pre-vaccination (n = 100), at 6 weeks post-completion of vaccination (n = 86) and at 12–18 months follow-up (n = 73) were analysed. Pre-vaccination, by FAMA, 61·0% sera were VZV IgG negative, and compared to FAMA the sensitivities of VZV-TRFIA and gpEIA were 74·4% [95% confidence interval (CI) 57·9–87·0] and 46·2% (95% CI 30·1–62·8), respectively. Post-completion of vaccination the seroconversion rate by FAMA was 93·7% compared to rates of 95·8% and 70·8% determined by VZV-TRFIA and gpEIA, respectively. At 12–18 months follow-up seropositivity rates by FAMA, VZV-TRFIA and gpEIA were 78·1%, 74·0% and 47·9%, respectively. Compared to FAMA the sensitivities of VZV-TRFIA and gpEIA for measuring VZV IgG following vaccination were 96·4% (95% CI 91·7–98·8) and 74·6% (95% CI 66·5–81·6), respectively. Using both FAMA and VZV-TRFIA to identify healthy adult VZV susceptibles and measure seroconversion showed that vOka vaccination of HCWs is highly immunogenic.
This study prospectively assesses the mental health outcomes among women seeking abortions, by comparing women having later abortions with women denied abortions, up to 2 years post-abortion seeking.
Method
We present the first 2 years of a 5-year telephone interview study that is following 956 women who sought an abortion from 30 facilities throughout the USA. We use adjusted linear mixed-effects regression analyses to assess whether symptoms of depression and anxiety, as measured by the Brief Symptom Inventory-short form and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, differ over time among women denied an abortion due to advanced gestational age, compared with women who received abortions.
Results
Baseline predicted mean depressive symptom scores for women denied abortion (3.07) were similar to women receiving an abortion just below the gestational limit (2.86). Depressive symptoms declined over time, with no difference between groups. Initial predicted mean anxiety symptoms were higher among women denied care (2.59) than among women who had an abortion just below the gestational limit (1.91). Anxiety levels in the two groups declined and converged after 1 year.
Conclusions
Women who received an abortion had similar or lower levels of depression and anxiety than women denied an abortion. Our findings do not support the notion that abortion is a cause of mental health problems.
In the psychological tradition, desistance from antisocial behavior is viewed as the product of psychosocial maturation, including increases in the ability to control impulses, consider the implications of one's actions on others, delay gratification in the service of longer term goals, and resist the influences of peers. The present study investigates how individual variability in the development of psychosocial maturity is associated with desistance from antisocial behavior in a sample of 1,088 serious juvenile offenders followed from adolescence to early adulthood (ages 14–25). We find that psychosocial maturity continues to develop to the midtwenties and that different developmental patterns of maturation are found among those who desist and those who persist in antisocial behavior. Compared to individuals who desisted from antisocial behavior, youths who persisted exhibited diminished development of psychosocial maturity. Moreover, earlier desistance compared to later desistance is linked to greater psychosocial maturity, suggesting that there is an association between desistance from antisocial behavior and normative increases in psychosocial maturity.
Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD) control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent (BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development. (JINS, 2013, 19, 1–14)
Improvements in temperance, perspective, and responsibility are a part of typical development of psychosocial maturity during adolescence. The existing literature suggests that the developmental course of psychosocial maturity is influenced by normative variations in social context, but little is known about how atypical contexts, such as incarceration, influence its development. The study investigates how the development of psychosocial maturity is affected by incarceration, using data from a 7-year longitudinal study of 1,171 adolescent males. We compared the effects of confinement in juvenile facilities with varying degrees of focus on incarceration versus rehabilitation (i.e., secure vs. residential treatment facilities) and tested whether facility quality and age at incarceration moderate the effect of incarceration on psychosocial maturity. The results indicate that incarceration in a secure setting, but not a residential treatment facility, is associated with a short-term decline in temperance and responsibility. The total amount of time incarcerated in a residential treatment facility, but not a secure setting, had a negative effect on the developmental trajectory of psychosocial maturity. Age at incarceration, but not the facility quality, moderated the effect of recent incarceration: older youths were more susceptible to short-term negative effects of recent incarceration in a secure setting, but they also benefited more than younger participants from short-term positive effects of incarceration in a residential treatment setting. Furthermore, youths who perceived their incarceration setting as unsafe evinced a decline in temperance. Future research and policy implications are discussed.