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Rey’s Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.
This study advances the Mayo’s Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30–91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided.
From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8–10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex.
Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.
Anthocyanins and bromelain have gained significant attention due to their antioxidative and anti-inflammatory properties. Both have been shown to improve endothelial function, blood pressure (BP) and oxygen utility capacity in humans; however, the combination of these two and the impacts on endothelial function, BP, total antioxidant capacity (TAC) and oxygen utility capacity have not been previously investigated. The purpose of this study was to investigate the impacts of a combined anthocyanins and bromelain supplement (BE) on endothelial function, BP, TAC, oxygen utility capacity and fatigability in healthy adults. Healthy adults (n 18, age 24 (sd 4) years) received BE or placebo in a randomised crossover design. Brachial artery flow-mediated dilation (FMD), BP, TAC, resting heart rate, oxygen utility capacity and fatigability were measured pre- and post-BE and placebo intake. The BE group showed significantly increased FMD, reduced systolic BP and improved oxygen utility capacity compared with the placebo group (P < 0·05). Tissue saturation and oxygenated Hb significantly increased following BE intake, while deoxygenated Hb significantly decreased (P < 0·05) during exercise. Additionally, TAC was significantly increased following BE intake (P < 0·05). There were no significant differences for resting heart rate, diastolic BP or fatigability index. These results suggest that BE intake is an effective nutritional therapy for improving endothelial function, BP, TAC and oxygen utility capacity, which may be beneficial to support vascular health in humans.
− Agency is one of five core analytical problems in the Earth System Governance (ESG) Project’s research framework, which offers a unique approach to the study of environmental governance. − Agency in Earth System Governance draws lessons from ESG–Agency research through a systematic review of 322 peer-reviewed journal articles published between 2008 and 2016 and contained in the ESG–Agency Harvesting Database.− ESG–Agency research draws on diverse disciplinary perspectives with distinct clusters of scholars rooted in the fields of global environmental politics, policy studies, and socio-ecological systems. − Collectively, the chapters in Agency in Earth System Governance provide an accessible synthesis of some of the field’s major questions and debates and a state-of-the-art understanding of how diverse actors engage with and exercise authority in environmental governance.
One of the most important legacies of the Protestant Reformation was the splintering of the western Catholic Church into competing confessions. Protestants introduced permanent schisms into Latin Christendom, both between Protestants and Catholics and amongst Protestants. But even as these divides began to form in the sixteenth century, earnest theologians and rulers, both Protestant and Catholic, sought to reverse and heal them, hoping to recover the unity among Christians for which Christ had prayed (John 17:21). John Calvin participated in a number of these religious colloquies, or formal conversations about contested theological issues. He was present at colloquies in Hagenau (summer 1540), Worms (autumn 1540), and Regensburg (January 1541), although he was more interested in unity among Protestants than between Protestants and Catholics.1 Such colloquies, which were supposed to be cordial in nature, should be distinguished from disputations, where the goal was to prove the truth of one’s position against all claims to the contrary. The English word colloquy comes from the Latin colloquor: to talk together or hold conversation. The goal of Reformation-era religious colloquies was not to arrive at complete uniformity of belief and practice, rather, it was to determine where reconciliation on matters of belief and practice might be possible.
Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.
Retrospective before-and-after study.
A 1,250-bed academic tertiary-care referral center.
Hospitalized adults who had ≥1 urine culture performed during their stay.
The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.
During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).
Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
Although stimulants are commonly used for attention-deficit/hyperactivity disorder (ADHD), 10–30% of patients have an inadequate response, adverse events, or comorbidities preventing use. Thus, there is a need for safe, effective nonstimulant options. Extended-release viloxazine (SPN-812), a nonstimulant, is currently in development for the treatment of ADHD in children and adolescents. SPN-812 is a structurally distinct, bicyclic norepinephrine reuptake inhibitor with selective serotonergic activity. Results of the Phase 2 program demonstrated efficacy (improved mean ADHD Rating Scale-IV total score) and safety of SPN-812 in children (6–12 years), as well as an onset of action within 1–2 weeks.
Four ongoing Phase 3 randomized, double-blind, placebo-controlled, outpatient, US studies are investigating the efficacy and safety of once-daily SPN-812 for ADHD in children (ages 6–11; 100–400mg) and adolescents (ages 12–17; 200–600mg). Two studies are enrolling children and two are enrolling adolescents. Eligible subjects are required to have minimum baseline scores of ≥28 for ADHD-RS-5 and ≥4 for Clinical Global Impression-Severity scale (CGI-S). These studies will randomize ∼1200 subjects, with ∼800 subjects receiving SPN-812 over a 1–3-week titration and 5-week maintenance period. The primary endpoint in all studies is mean change from baseline to end of study (EOS) in ADHD-RS-5 total score for SPN-812 vs. placebo. Secondary endpoints include change from baseline to EOS in 30% responder rate (% change: ADHD RS 5); Hyperactivity/Impulsivity and Inattention ADHD-RS-5 subscale scores; Conners 3 Rating Scale (parent and self-report); CGI-S/CGI-I (Improvement); Weiss Functional Impairment Rating Scale (parent report); Parenting Stress Index (children); and Stress Index for Parents of Adolescents (adolescents) after 6–8 weeks of treatment. Safety is assessed via adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and the Columbia-Suicide Severity Rating Scale. Phase 3 completers are offered the option of enrolling in an open-label extension study (OLE; up to 3 years) with a starting dose of 100/200mg (children/adolescents). Data will be summarized with descriptive statistics and analyzed using appropriate statistical methods.
As of August 2018, enrollment in 1 child study is complete, and the other 3 trials are at ∼89%; rollover into the OLE is ∼90%.
There is an unmet need for nonstimulant ADHD treatment for children and adolescents that is effective, long-acting, and well tolerated. SPN-812 is being investigated in four Phase 3 randomized, placebo-controlled studies for the treatment of children and adolescents with ADHD, based on demonstrated efficacy and safety in the Phase 2 program.
This study is an encore of a poster presentation at the 2018 Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP).
Funding Acknowledgements: Supernus Pharmaceuticals, Inc.
This paper describes a model of electron energization and cyclotron-maser emission applicable to astrophysical magnetized collisionless shocks. It is motivated by the work of Begelman, Ergun and Rees [Astrophys. J. 625, 51 (2005)] who argued that the cyclotron-maser instability occurs in localized magnetized collisionless shocks such as those expected in blazar jets. We report on recent research carried out to investigate electron acceleration at collisionless shocks and maser radiation associated with the accelerated electrons. We describe how electrons accelerated by lower-hybrid waves at collisionless shocks generate cyclotron-maser radiation when the accelerated electrons move into regions of stronger magnetic fields. The electrons are accelerated along the magnetic field and magnetically compressed leading to the formation of an electron velocity distribution having a horseshoe shape due to conservation of the electron magnetic moment. Under certain conditions the horseshoe electron velocity distribution function is unstable to the cyclotron-maser instability [Bingham and Cairns, Phys. Plasmas 7, 3089 (2000); Melrose, Rev. Mod. Plasma Phys. 1, 5 (2017)].
Gray matter (GM) ‘pseudoatrophy’ is well-documented in patients with anorexia nervosa (AN), but changes in white matter (WM) are less well understood. Here we investigated the dynamics of microstructural WM brain changes in AN patients during short-term weight restoration in a combined longitudinal and cross-sectional study design.
Diffusion-weighted images were acquired in young AN patients before (acAN-Tp1, n = 56) and after (acAN-Tp2, n = 44) short-term weight restoration as well as in age-matched healthy controls (HC, n = 60). Images were processed using Tract-Based-Spatial-Statistics to compare fractional anisotropy (FA) across groups and timepoints.
In the cross-sectional comparison, FA was significantly reduced in the callosal body in acAN-Tp1 compared with HC, while no differences were found between acAN-Tp2 and HC. In the longitudinal arm, FA increased with weight gain in acAN-Tp2 relative to acAN-Tp1 in large parts of the callosal body and the fornix, while it decreased in the right corticospinal tract.
Our findings reveal that dynamic, bidirectional changes in WM microstructure in young underweight patients with AN can be reversed with brief weight restoration therapy. These results parallel those previously observed in GM and suggest that alterations in WM in non-chronic AN are also state-dependent and rapidly reversible with successful intervention.
OBJECTIVES/SPECIFIC AIMS: Reducing radiologic exams has been a focus of cost reduction in healthcare systems. The utility and justification of obtaining cross-sectional imaging (PPCSI) before surgical intervention continues to be evaluated. For peripheral artery disease (PAD) consensus guidelines regarding PPCSI do not exist and may be influenced by patient complexity, variation of disease presentation, and physician preference. The objective of this study was to determine the utility of PPCSI before percutaneous PAD intervention. METHODS/STUDY POPULATION: Patients receiving first-time endovascular revascularization procedure for PAD from 2013 to 2015 were evaluated for PPCSI done within 180 days prior to revascularization. Patient and physician demographics, perioperative characteristics, and disease distribution/severity were evaluated. The primary outcome was technical success defined as improving inflow and/or revascularization of the target outflow vessels to <50% stenosis. RESULTS/ANTICIPATED RESULTS: Of the 348 patients who underwent an attempted revascularization procedure 159 (45.7%) patients underwent PPCSI, including 151 CTA and 8 MRA. Of these, 48% were ordered by the referring provider (84% at an outside institution), and 52% were ordered by the treating physician. PPCSI was performed a median of 26 days (IQR 9-53) prior to procedure. Individual vascular surgeon practice identified PPCSI rates ranging from 31% to 70%. On multivariate analysis chronic kidney disease (OR=0.35; CI 0.17–0.73) had the strongest effect against of PPCSI, and Inpatient/ED evaluation (OR=3.20; CI 1.58–6.50), aorto-iliac (OR=2.78; CI 1.46–5.29) and femoral-popliteal occlusions (OR=2.51; CI 1.38–4.55) most strongly predicted PPCSI. After excluding 31 diagnostic procedures, technical success did not differ between endovascular procedures with PPSCI (91.3%) or without PPCSI (85.6%), p=0.11. When analyzing 89 femoral-popliteal occlusions, technical success was higher with PPCSI (88%) compared to procedures without PPSCI (69%), p=0.026. DISCUSSION/SIGNIFICANCE OF IMPACT: PPCSI use is influenced by inpatient status, chronic kidney disease, and anatomic consideration. PPCSI was not associated with overall technical success although it appeared beneficial for femoral-popliteal occlusions. Routine practices of ordering of PPCSI may not be warranted when considering technical success but may be important in treatment planning. Further studies are warranted to determine if radiation, cost, and contrast load justify PPCSI.