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Mild traumatic brain injury (mTBI), depression, and posttraumatic stress disorder (PTSD) are a notable triad in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) Veterans. With the comorbidity of depression and PTSD in Veterans with mTBI histories, and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in areas such as prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. Identifying predictors of psychiatric symptom change following CCT would further inform the interventional approach. We sought to examine neuropsychological predictors of PTSD and depressive symptom improvement in Veterans with a history of mTBI who received CCT.
Participants and Methods:
37 OEF/OIF/OND Veterans with mTBI history and cognitive complaints received 10-weekly 120-minute CCT group sessions as part of a clinical trial. Participants completed a baseline neuropsychological assessment including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD Checklist-Military Version; Beck Depression Inventory-II) at baseline, post-treatment, and 5-week follow-up. Paired samples t-tests were used to examine statistically significant change in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores (p^.05) were entered as independent variables in separate multiple linear regression analyses to predict symptom change at post-treatment and follow-up.
Results:
Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (>17.5% score reduction) and over 20% had clinically meaningful improvement in PTSD symptoms (>10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores (re-experiencing, avoidance/numbing, and arousal) revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on D-KEFS Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both D-KEFS Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on D-KEFS Trail Making Test Switching was associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed worse processing speed and worse aspects of executive functioning at baseline significantly predicted depressive symptom improvement at post-treatment and follow-up.
Conclusions:
Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve. Although CCT is not a primary treatment for PTSD or depressive symptoms, our results support consideration of including CCT in hybrid treatment approaches. Further research should examine these relationships in larger samples.
Adolescents with depression need access to culturally relevant psychological treatment. In many low- and middle-income countries treatments are only accessible to a minority. We adapted group interpersonal therapy (IPT) for adolescents to be delivered through schools in Nepal. Here we report IPT's feasibility, acceptability, and cost.
Methods
We recruited 32 boys and 30 girls (aged 13–19) who screened positive for depression. IPT comprised of two individual and 12 group sessions facilitated by nurses or lay workers. Using a pre-post design we assessed adolescents at baseline, post-treatment (0–2 weeks after IPT), and follow-up (8–10 weeks after IPT). We measured depressive symptoms with the Depression Self-Rating Scale (DSRS), and functional impairment with a local tool. To assess intervention fidelity supervisors rated facilitators' IPT skills across 27/90 sessions using a standardised checklist. We conducted qualitative interviews with 16 adolescents and six facilitators post-intervention, and an activity-based cost analysis from the provider perspective.
Results
Adolescents attended 82.3% (standard deviation 18.9) of group sessions. All were followed up. Depression and functional impairment improved between baseline and follow-up: DSRS score decreased by 81% (95% confidence interval 70–95); functional impairment decreased by 288% (249–351). In total, 95.3% of facilitator IPT skills were rated superior/satisfactory. Adolescents found the intervention useful and acceptable, although some had concerns about privacy in schools. The estimate of intervention unit cost was US $96.9 with facilitators operating at capacity.
Conclusions
School-based group IPT is feasible and acceptable in Nepal. Findings support progression to a randomised controlled trial to assess effectiveness and cost-effectiveness.
OBJECTIVES/GOALS: Studies have shown that SARS-CoV-2 specific memory B cells can be maintained at least a year after exposure. However, reports show an altered B cell response during infection in severe COVID-19 cases. This study aims to describe the B cell response during COVID-19 convalescence with a focus on signatures that contribute to durable and robust immunity. METHODS/STUDY POPULATION: Our study cohort consisted of individuals who had recovered from non-severe (hospitalized) or severe (hospitalized and requiring invasive mechanical ventilation) COVID-19. In our comparative analysis, samples from both groups were carefully matched to fall within 4-5 weeks post-symptom onset. We also performed a longitudinal analysis of non-severe patients with sampling ending 5 months post-symptom onset. Using high parameter flow cytometry, we characterized the phenotype of memory B cells using 19 distinct cell markers and fluorescently labeled probes to identify B cells reactive with SARS-CoV-2 spike and receptor-binding domain protein. Additionally, serum collected from individuals was used to quantify antibody titers. RESULTS/ANTICIPATED RESULTS: The frequency of spike-specific B cells and serum antibody titers were similar between severe and non-severe groups. However, we observed that individuals recovered from severe COVID-19 have a significantly reduced frequency of spike specific IgG+ memory B cells expressing Tbet and FcRL5 (markers associated with long lived immunity). In the non-severe patients, we observed IgG+Tbet+ B cells targeting the spike protein peak at 2-3 weeks post-symptom onset, decrease by almost fifty percent 4-5 weeks post-symptom onset, and return to baseline 5 months post-symptom onset. Our study also validated previous findings of a short-lived primary response of IgM+ B cells targeting the spike protein. DISCUSSION/SIGNIFICANCE: Our findings highlight potential implications for long-term immunity against re-infection or severity of the resulting disease in patients with severe COVID-19. Further investigation will be necessary to determine whether the maintenance of immunological protection is hindered in patients who overcame severe COVID-19.
Background: Healthcare exposure results in significant microbiome disruption, particularly in the setting of critical illness, which may contribute to risk for healthcare-associated infections (HAIs). Patients admitted to long-term acute-care hospitals (LTACHs) have extensive prior healthcare exposure and critical illness; significant microbiome disruption has been previously documented among LTACH patients. We compared the predictive value of 3 respiratory tract microbiome disruption indices—bacterial community diversity, dominance, and absolute abundance—as they relate to risk for ventilator-associated pneumonia (VAP) and adverse ventilator-associated events (VAE), which commonly complicate LTACH care. Methods: We enrolled 83 subjects on admission to an academic LTACH for ventilator weaning and performed longitudinal sampling of endotracheal aspirates, followed by 16S rRNA gene sequencing (Illumina HiSeq), bacterial community profiling (QIIME2) for diversity, and 16S rRNA quantitative PCR (qPCR) for total bacterial abundance. Statistical analyses were performed with R and Stan software. Mixed-effects models were fit to relate the admission MDIs to subsequent clinically diagnosed VAP and VAE. Results: Of the 83 patients, 19 had been diagnosed with pneumonia during the 14 days prior to LTACH admission (ie, “recent past VAP”); 23 additional patients were receiving antibiotics consistent with empiric VAP therapy within 48 hours of admission (ie, “empiric VAP therapy”); and 41 patients had no evidence of VAP at admission (ie, “no suspected VAP”). We detected no statistically significant differences in admission Shannon diversity, maximum amplicon sequence variant (ASV)–level proportional abundance, or 16S qPCR across the variables of interest. In isolation, all 3 admission microbiome disruption indices showed poor predictive performance, though Shannon diversity performed better than maximum ASV abundance. Predictive models that combined (1) bacterial diversity or abundance with (2) recent prior VAP diagnosis and (3) concurrent antibiotic exposure best predicted 14-day VAP (type S error < 0.05) and 30-day VAP (type S error < 0.003). In this cohort, VAE risk was paradoxically associated with higher admission Shannon diversity and lower admission maximum ASV abundance. Conclusions: In isolation, respiratory tract microbiome disruption indices obtained at LTACH admission showed poor predictive performance for subsequent VAP and VAE. But diversity and abundance models incorporating recent VAP history and admission antibiotic exposure performed well predicting 14-day and 30-day VAP.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
Methods
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
Results
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
Conclusions
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
This collection of essays pays tribute to Nancy Freeman Regalado, a ground-breaking scholar in the field of medieval French literature whose research has always pushed beyond disciplinary boundaries. The articles in the volume reflect the depth and diversity of her scholarship, as well as her collaborations with literary critics, philologists, historians, art historians, musicologists, and vocalists - in France, England, and the United States. Inspired by her most recent work, these twenty-four essays are tied together by a single question, rich in ramifications: how does performance shape our understanding of medieval and pre-modern literature and culture, whether the nature of that performance is visual, linguistic, theatrical, musical, religious, didactic, socio-political, or editorial? The studies presented here invite us to look afresh at the interrelationship of audience, author, text, and artifact, to imagine new ways of conceptualizing the creation, transmission, and reception of medieval literature, music, and art.
EGLAL DOSS-QUINBY is Professor of French at Smith College; ROBERTA L. KRUEGER is Professor of French at Hamilton College; E. JANE BURNS is Professor of Women's Studies and Adjunct Professor of Comparative Literature at the University of North Carolina, Chapel Hill.
Contributors: ANNE AZÉMA, RENATE BLUMENFELD-KOSINSKI, CYNTHIA J. BROWN, ELIZABETH A. R. BROWN, MATILDA TOMARYN BRUCKNER, E. JANE BURNS, ARDIS BUTTERFIELD, KIMBERLEE CAMPBELL, ROBERT L. A. CLARK, MARK CRUSE, KATHRYN A. DUYS, ELIZABETH EMERY, SYLVIA HUOT, MARILYN LAWRENCE, KATHLEEN A. LOYSEN, LAURIE POSTLEWATE, EDWARD H. ROESNER, SAMUEL N. ROSENBERG, LUCY FREEMAN SANDLER, PAMELA SHEINGORN, HELEN SOLTERER, JANE H. M. TAYLOR, EVELYN BIRGE VITZ, LORI J. WALTERS, AND MICHEL ZINK.
In situ Pleistocene reefs form a gently sloping nearshore terrace around the island of Oahu. TIMS Th–U ages of in situ corals indicate that most of the terrace is composed of reefal limestones correlating to Marine Oxygen Isotope Stage 7 (MIS 7, ~ 190–245 ka). The position of the in situ MIS 7 reef complex indicates that it formed during periods when local sea level was ~ 9 to 20 m below present sea level. Its extensiveness and geomorphic prominence as well as a paucity of emergent in situ MIS 7 reef-framework deposits on Oahu suggest that much of MIS 7 was characterized by regional sea levels below present. Later accretion along the seaward front of the terrace occurred during the latter part of MIS 5 (i.e., MIS 5a–5d, ~ 76–113 ka). The position of the late MIS 5 reefal limestones is consistent with formation during a period when local sea level was below present. The extensiveness of the submerged Pleistocene reefs around Oahu compared to the relative dearth of Holocene accretion is due to the fact that Pleistocene reefs had both more time and more accommodation space available for accretion than their Holocene counterparts.
Environmental influences on the rate of Alzheimer's disease (AD) progression have received little attention. Our objective was to test hypotheses concerning associations between caregiver personality traits and the rate of AD progression.
Methods:
Care receivers (CR) were 161 persons with AD from a population-based dementia progression study; 55 of their caregivers were spouses and 106 were adult children. Cognitive status of the CR was measured with the Mini-Mental State Examination every six months, over an average of 5.6 (range: 1–14) years. Linear mixed models tested rate of cognitive decline as a function of caregiver personality traits from the NEO Five-Factor Inventory.
Results:
Significantly faster cognitive decline was observed with higher caregiver Neuroticism overall; however, in stratified models, effects were significant for adult child but not spouse caregivers. Neuroticism facets of depression, anxiety, and vulnerability to stress were significantly associated with faster decline. Higher caregiver Extraversion was associated with slower decline in the CR when caregivers were adult children but not spouses.
Conclusions:
For adult child caregivers, caregiver personality traits are associated with rate of cognitive decline in CRs with AD regardless of co-residency. Results suggest that dementia caregiver interventions promoting positive care management strategies and ways to react to caregiving challenges may eventually become an important complement to pharmacologic and other approaches aimed at slower rate of decline in dementia.
Adverse early care is associated with attention regulatory problems, but not all so exposed develop attention problems. In a sample of 612 youth (girls = 432, M = 11.82 years, SD = 1.5) adopted from institutions (e.g., orphanages) in 25 countries, we examined whether the Val66Met polymorphism of the brain-derived neurotrophic factor gene moderates attention problems associated with the duration of institutional care. Parent-reported attention problem symptoms were collected using the MacArthur Health and Behavior Questionnaire. DNA was genotyped for the brain-derived neurotrophic factor Val66Met (rs6265) single nucleotide polymorphism. Among youth from Southeast (SE) Asia, the predominant genotype was valine/methionine (Val/Met), whereas among youth from Russia/Europe and Caribbean/South America, the predominant genotype was Val/Val. For analysis, youth were grouped as carrying Val/Val or Met/Met alleles. Being female, being from SE Asia, and being younger when adopted were associated with fewer attention regulatory problem symptoms. Youth carrying at least one copy of the Met allele were more sensitive to the duration of deprivation, yielding an interaction that followed a differential susceptibility pattern. Thus, youth with Val/Met or Met/Met genotypes exhibited fewer symptoms than Val/Val genotypes when adoption was very early and more symptoms when adoption occurred later in development. Similar patterns were observed when SE Asian youth and youth from other parts of the world were analyzed separately.
As with the construction of any secondary mathematics education course, a course on the history of mathematics for teaching can assume many different forms. For example, if the secondary mathematics education major resides in a Department of Mathematics, the course may tend to be more of a pure mathematics course instead of one with explicit attention to pedagogical ideas. Alternatively, if the course is a College of Education offering, it may shed some of its strict mathematical content and concentrate more on biographical, anecdotal, or pedagogical information. In recent years, what constitutes a history of mathematics course has become the subject of discussion for different audiences focused on undergraduate mathematics teaching [6]. Given the professional discussion that takes place about the content of history of mathematics courses in general, I conducted a study to investigate undergraduate mathematics education students' learning in the course, Using History in the Teaching of Mathematics (or, Using History), over four semesters. A natural consequence of the research has been to reflect on subsequent offerings of the course in order to revise topics and assignments for the purpose of fulfilling course objectives. Each of the objectives was designed to create opportunities for pre-service mathematics teachers (PSMTs) to consider using the history of mathematics in their future teaching.
As part of a broader inquiry, I began with the following research questions:
1) In what ways does the study of the history of mathematics impact PSMTs' mathematical, historical, and pedagogical knowledge?
We collected serial blood samples from children in the intensive care unit who underwent daily bathing with 2% Chlorhexidine gluconate (CHG)-impregnated cloths. Low concentrations of CHG were detected in a few blood samples, indicating absorption through intact skin. There was no suggestion that CHG accumulated in the blood with repeated exposures.
Concerns about risks for older people with vitamin B12 deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12 and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n 2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15·8 (sd 14·7) nmol/l in 1995 to 31·1 (sd 26·2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR 1·50 (95 % CI 0·91, 2·46) v. 1·45 (95 % CI 1·19, 1·76)), respectively. The associations of cognitive impairment with low B12 status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2·46; 95 % CI 0·90, 6·71) v. (1·56; 95 % CI 1·30, 1·88)). There was no evidence of modification by high folate status of the associations of low B12 with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.
Mechanical devices implanted in the body present implications for broad themes in religious thought and experience, including the nature and destiny of the human person, the significance of a person's embodied experience, including the experiences of pain and suffering, the person's relationship to ultimate reality, the divine or the sacred, and the vocation of medicine. Community-constituting convictions and narratives inform the method and content of reasoning about such conceptual questions as whether a moral line should be drawn between therapeutic or enhancement interventions and/or between somatic and neural/cognitive interventions. By attending to these broader community-forming concepts, it is possible to identify three general orienting themes in religious perspectives on incorporated mechanical devices, which we shall designate as perspectives of “appropriation,” “ambivalence,” and “resistance.”
