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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Individuals with schizophrenia experience significantly higher rates of chronic physical health conditions, driving a 20-year reduction in life expectancy. Poor diet quality is a key modifiable risk factor; however, owing to side-effects of antipsychotic medication, cognitive challenges and food insecurity, standard dietary counselling may not be sufficient for this population group.
Aim
To evaluate the feasibility, acceptability and preliminary effectiveness of two dietary interventions – pre-prepared meals and meal kits – for individuals with schizophrenia.
Method
The Schizophrenia, Nutrition and Choices in Kilojoules (SNaCK) study is a 12-week, three-arm, cross-over, randomised controlled trial. Eighteen participants aged 18–64 years diagnosed with schizophrenia or schizoaffective disorder will be recruited from community mental health services in Australia. Participants will be randomised to receive pre-prepared meals, meal kits or a supermarket voucher as a control, crossing-over at the end of weeks 4 and 8, so that all participants experience all three study arms. Primary outcomes include feasibility (recruitment rate and retention, number of days participants use pre-prepared meals or meal kits, adherence to meals as prescribed, difficulty in meal preparation and meal wastage) and acceptability (meal provision preference ranking and implementation) of the nutrition interventions. Secondary outcomes include the effects of the intervention on metabolic syndrome components, dietary intake, quality of life and food security measures.
Conclusions
Feasible, acceptable and effective dietary interventions for people with schizophrenia are urgently needed. Findings from this trial will inform future larger randomised controlled trials that have the potential to influence policy and improve health outcomes for this vulnerable population.
Background: Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder, characterized by gradual loss of motor, verbal and social skills. This study describes the epidemiology and healthcare resource utilization (HCRU) of RTT in Ontario, Canada. Methods: RTT patients (≥ one ICD-10-CA code F84.2) were identified using data held at the Institute for Clinical Evaluative Sciences (ICES), between September 2018-August 2023. Incidence and prevalence rates from Ontario were extrapolated nationally using the Stats Can population estimates. Results: A total of 246 patients were indexed; 95% female, median age 21 years and 40% from central Ontario. There were 57 incident and 257 prevalent RTT cases identified in Ontario. National extrapolations estimated 175 incident and 613 prevalent RTT cases. Common comorbidities included developmental disability (85.4%) and epilepsy (49.6%). Patients frequently had outpatient visits (primary care 96.7%, specialists 86.6%), emergency department visits (76.8%) and inpatient hospitalizations (54.5%). Most patients (95.1%) had at least one public claim for all-cause medication. Disease-specific medication claims were for anti-infectives (69.1%) and anti-seizure medications associated with mood effects (65.0%). Conclusions: This study provides population-based estimates of RTT in Canada. Findings highlight the high burden of illness and HCRU of RTT and the opportunities to improve healthcare outcomes in this population.
Nearly half of all Australians (42.9%) will experience a mental health disorder during their lifetime(1). Preliminary research suggests an association between dietary and tissue advanced glycation end-products (AGEs) and mental health conditions, such as depression(2,3). However, more research is needed to determine the extent to which poor mental health is linked with AGEs(4). This study examined whether dietary consumption of the AGE carboxymethyl-lysine (CML), tissue accumulation of AGEs, or levels of circulating glycated haemoglobin (HbA1c) were associated with depression or anxiety. Fifty adults participated in a cross-sectional study. Depression and anxiety were assessed using the Centre for Epidemiologic Studies Depression Scale (CES-D) and Spielberger’s State-Trait Anxiety Inventory (STAI). Dietary CML intake was assessed from 3-day food records by matching food items to those in published, validated food AGE databases and adjusting for energy intake (CML/MJ). Tissue accumulation of AGEs was measured as skin autofluorescence (SAF) using an AGE Reader. HbA1c was measured in whole blood using a Capillary 3 HbA1c kit. Spearman’s rank correlations were performed to explore relationships between variables. Participants included 14 males and 36 females, aged (median (range)) 30.6 (18–72) years. Participants were predominantly healthy, with a BMI of 23.3 (18.5–31.1) kg/m2 and energy intake of 7889 (5452–12568) kJ/day. Depression scores were 8 (0–40) out of 60. State anxiety scores were 26 (20–53) and trait anxiety scores were 33.5 (20–66) out of 80, where higher scores indicated greater symptom severity. Daily intake of CML was 0.6 (0.2–1.9) mg/MJ/day. SAF was 1.8 (1.2–3.3) arbitrary units (AU), similar to previously reported normal reference values(5). Circulating HbA1c was 5.1% (4.4–6.2%), all within the healthy range(6). Spearman’s correlation tests indicated no significant associations between any of the independent variables (CML/MJ, SAF, HbA1c) and any of the dependent variables (CES-D, STAI) (all p > 0.05). In this population of predominantly of healthy individuals, there was no association between dietary CML intake, tissue AGE accumulation or circulating HbA1c and increased symptom severity for depression or anxiety. The next step of this research is to investigate metabolomic markers in this population and their association with depression and anxiety. In relatively healthy people, dietary metabolites may be more sensitive to uncover whether a relationship exists between AGEs and depression and anxiety.
Despite advances in antiretroviral treatment (ART), human immunodeficiency virus (HIV) can detrimentally affect everyday functioning. Neurocognitive impairment (NCI) and current depression are common in people with HIV (PWH) and can contribute to poor functional outcomes, but potential synergies between the two conditions are less understood. Thus, the present study aimed to compare the independent and combined effects of NCI and depression on everyday functioning in PWH. We predicted worse functional outcomes with comorbid NCI and depression than either condition alone.
Methods:
PWH enrolled at the UCSD HIV Neurobehavioral Research Program were assessed for neuropsychological performance, depression severity (≤minimal, mild, moderate, or severe; Beck Depression Inventory-II), and self-reported everyday functioning.
Results:
Participants were 1,973 PWH (79% male; 66% racial/ethnic minority; Age: M = 48.6; Education: M = 13.0, 66% AIDS; 82% on ART; 42% with NCI; 35% BDI>13). ANCOVA models found effects of NCI and depression symptom severity on all functional outcomes (ps < .0001). With NCI and depression severity included in the same model, both remained significant (ps < .0001), although the effects of each were attenuated, and yielded better model fit parameters (i.e., lower AIC values) than models with only NCI or only depression.
Conclusions:
Consistent with prior literature, NCI and depression had independent effects on everyday functioning in PWH. There was also evidence for combined effects of NCI and depression, such that their comorbidity had a greater impact on functioning than either alone. Our results have implications for informing future interventions to target common, comorbid NCI and depressed mood in PWH and thus reduce HIV-related health disparities.
Norm-based accounts of social behavior in economics typically reflect tradeoffs between maximization of own consumption utility and conformity to social norms. Theories of norm-following tend to assume that there exists a single, stable, commonly known injunctive social norm for a given choice setting and that each person has a stable propensity to follow social norms. We collect panel data on 1468 participants aged 11–15 years in Belfast, Northern Ireland and Bogotá, Colombia in which we measure norms for the dictator game and norm-following propensity twice at 10 weeks apart. We test these basic assumptions and find that norm-following propensity is stable, on average, but reported norms show evidence of change. We find that individual-level variation in reported norms between people and within people across time has interpretable structure using a series of latent transition analyses (LTA) which extend latent class models to a panel setting. The best fitting model includes five latent classes corresponding to five sets of normative beliefs that can be interpreted in terms of what respondents view as “appropriate” (e.g. equality vs. generosity) and how they view deviations (e.g. deontological vs. consequentialist). We also show that a major predictor of changing latent classes over time comes from dissimilarity to others in one’s network. Our application of LTA demonstrates how researchers can engage with heterogeneity in normative perceptions by identifying latent classes of beliefs and deepening understanding of the extent to which norms are shared, stable, and can be predicted to change. Finally, we contribute to the nascent experimental literature on the economic behavior of children and adolescents.
Clozapine-induced gastrointestinal hypomotility and constipation can result in severe and sometimes fatal gastrointestinal complications. Laxatives should be prophylactically prescribed with clozapine, but this is inconsistently achieved. Digital clinical decision support (CDS) alerts can promote safer prescribing.
Aims
To evaluate whether a CDS alert could promote timely laxative use with clozapine in hospital.
Method
Retrospective in-patient prescribing data was used to compare co-prescribing of laxatives for first clozapine prescriptions pre-alert (January 2017–September 2019) and post-alert (September 2019–December 2023) implementation across 1194 hospital admissions where clozapine was prescribed. Regular non-bulking laxative and any laxative co-prescribing for first clozapine prescriptions within 24 h were assessed. Multivariable logistic regression was performed to determine the impact of alert implementation on laxative co-prescribing.
Results
Of the 1194 admissions included, 449 admissions had clozapine prescribed pre-alert implementation and 745 admissions had post-alert implementation. Regular non-bulking laxative co-prescription occurred for 67.0% of first clozapine prescriptions pre-alert and 76.1% post-alert (P < 0.001). Any laxative co-prescription occurred for 87.3% of first clozapine prescriptions pre-alert and 96.5% post-alert (P < 0.001). Alert implementation was associated with increased likelihoods of regular non-bulking laxative co-prescribing (odds ratio, 1.341; 95% CI, 1.021–1.756; P = 0.035) and any laxative co-prescribing (odds ratio, 3.487; 95% CI, 2.135–5.838; P < 0.001) for first clozapine prescriptions within 24 h.
Conclusions
CDS alert implementation was associated with increased and earlier laxative co-prescribing for clozapine. Our findings suggest that a CDS alert is an effective tool for promoting timely laxative use with clozapine in hospital.
Epidemiological evidence shows a concerning rise in youth mental health difficulties over the past three decades. Most evidence, however, comes from countries in Europe or North America, with far less known about changes in other global regions. This study aimed to compare adolescent mental health across two population-based cohorts in the UK, and two population-based cohorts in Pelotas, Brazil.
Methods
Four population-based cohorts with identical mental health measures were compared. In Brazil, these included the 1993 Pelotas Birth Cohort and the 2004 Pelotas Birth Cohort. In the UK, cohorts included the Avon Longitudinal Study of Parents and Children, and the Millennium Cohort Study. Mental health was measured in all cohorts using identical, parent-rated scores from the Strengths and Difficulties Questionnaire (SDQ). This was assessed in both countries over approximately the same time periods, when adolescents were aged 11 (2004 vs 2015 in Brazil, and 2003 vs 2012 in the UK), with follow-up analyses focused on outcomes in later adolescence.
Results
Mental health problems were higher in the UK for adolescents born in the early 2000s compared to those born in the early 1990s. In Pelotas, the opposite was found, whereby problems were lower for adolescents born in the early 2000s compared to those born in the early 1990s. Despite these promising reductions in mental health problems in Pelotas over time, SDQ scores remained higher in Pelotas compared to the UK.
Conclusions
Our study represents the first to compare two population-based cohorts in the UK, and two population-based cohorts in Pelotas, Brazil, to understand how mental health problems have changed over time across the two settings. Our findings provide the most up-to-date insight into population-level rates of youth mental health problems in Pelotas, and shed novel insight into how these have changed over the last two decades in comparison to the UK. In doing so, our study provides a tentative first step towards understanding youth mental health over time at a more global scale, and presents a valuable opportunity to examine putative contributors to differences across time.
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.
Methods
We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.
Results
FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.
Conclusions
Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.
The depression, obstructive sleep apnea and cognitive impairment (DOC) screen assesses three post-stroke comorbidities, but additional information may be gained from the time to complete the screen. Cognitive screening completion time is rarely used as an outcome measure.
Objective:
To assess DOC screen completion time as a predictor of cognitive impairment in stroke/transient ischemic attack clinics.
Methods:
Consecutive English-speaking stroke prevention clinic patients consented to undergo screening and neuropsychological testing (n = 437). DOC screen scores and times were compared to scores on the NINDS-CSC battery using multiple linear regression (controlling for age, sex, education and stroke severity) and receiver operating characteristic (ROC) curve analysis.
Results:
Completion time for the DOC screen was 3.8 ± 1.3 minutes. After accounting for covariates, the completion time was a significant predictor of the speed of processing (p = 0.002, 95% CI: −0.016 to −0.004), verbal fluency (p < 0.001, CI: −0.012 to −0.006) and executive function (p = 0.004, CI: −0.006 to −0.001), but not memory. Completion time above 5.5 minutes was associated with a high likelihood of impairment on executive and speed of processing tasks (likelihood ratios 3.9–5.2).
Conclusions:
DOC screen completion time is easy to collect in routine care. People needing over 5.5 minutes to be screened likely have deficits in executive functioning and speed of processing – areas commonly impaired, but challenging to screen for, after stroke. DOC screen time provides a simple, feasible approach to assess these under-identified cognitive impairments.
As evidence has converged on the feasibility and effectiveness of focused, non-specialized, manualized interventions for treating mental distress in humanitarian settings, challenges persist in how to promote implementation fidelity and rigorously evaluate interventions designed to be more preventive or promotive in addressing risk and protective factors for poor mental health. One such intervention, Baby Friendly Spaces (BFS), is a psychosocial support program implemented for Rohingya mothers and their malnourished children living in refugee camps of Cox’s Bazar, Bangladesh. That follows a place-based intervention model in which various activities may be offered either individually or in groups with no specified sequence.
Objectives
This presentation describes the process of establishing standards for implementing optimal mental health and psychosocial support (MHPSS) interventions, training BFS workers, and building monitoring and supervision systems to promote implementation fidelity within this flexible support program.
Methods
As BFS services were already being offered as part of Action Against Hunger programming, we first conducted an audit of current services, determining that there was limited current standardization or support for implementation. Therefore, a manualized protocol was designed and covered the program curricula and self-care using didactic and practice-based learning. A series of online training sessions were conducted for 13 psychosocial workers and psychologists at centers delivering the enhanced intervention. Following the training, a baseline evaluation of attitudes, confidence, and knowledge for delivering BFS services was administered. We also collaboratively designed a systematic supervision process to meet the staff’s needs with a focus on capacity building and self-care.
Results
Following the initial training, BFS workers receiving the re-training showed similar levels of knowledge, but greater confidence (p=0.01) than MHPSS workers proceeding as usual. Participants reported that the training was useful for their field of work and for improving the quality of their work, and acknowledged they would be able to integrate the new learnings into their work and daily life. The follow-up with the supervision process confirmed their capacity to deliver the services and highlighted the need for workspace improvements, the lack of continuous motivation, their ability to identify specific issues for which they requested additional trainings.
Conclusions
There is a particular need for careful attention to implementation supports and supervision when offering flexible, place-based mental health and psychosocial support interventions. In that process, ensuring a continuity between the training and the supervision is essential for the quality of both the program and the research project.
We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.
Methods
We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.
Results
The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).
Conclusions
The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
The United Nations’ Agenda 2030 provides a framework of 17 Sustainable Development Goals (SDGs) to achieve peace and prosperity for people and planet, now and into the future(1). The United Nations Decade of Action on Nutrition emphasises that food and nutrition are key levers for optimising both human and planetary health and that individuals working in food, nutrition and health play an essential role in contributing to the SDGs(2,3). This project aimed to (i) map the work being done by staff and higher degree students at Monash University’s Department of Nutrition, Dietetics and Food and its alignment with the SDGs, and (ii) assess the impact of this process on workforce capacity to embed the SDGs in future work activities. Three mapping workshops; one pilot, one in-person and one online, were conducted (n = 28), beginning with a short expert-led seminar about the SDGs before participants engaged in an interactive activity to record their work activities (research, education or engagement) relating to the SDGs. Mapping data were analysed to determine which SDGs were being prioritised and in what type of activities. To determine the impact on workforce capacity, participants completed pre- and post-workshop surveys that assessed their knowledge of and confidence regarding the SDGs. From the three workshops, 129 work activities were described, each linked to one or more of the SDGs. Of those, 41% were education, 36% were research, and 23% were engagement activities. Work activities spanned all 17 of the SDGs, with the most commonly aligned being Goal 3 Good Health and Wellbeing (53% of work activities), Goal 10 Reduced Inequalities (37% of work activities), Goal 4 Quality Education (36% of work activities), Goal 12 Responsible Consumption and Production (34% of work activities), and Goal 17 Partnerships for the Goals (27% of work activities). The pre- and post-workshop surveys indicated increased staff knowledge and confidence related to the SDGs. The percentage of participants that could correctly identify the number of SDGs increased from 43% to 96%, and the percentage of participants that recognised the correct aim of the SDGs increased from 43% to 86%. Regarding confidence in talking about the SDGs, the percentage of staff who indicated that they ‘avoid talking about them’ or are ‘not confident’ decreased from 39% to 4%, and the number of staff who were confident talking about the SDGs ‘in general terms’ increased from 39% to 75%. Nutrition professionals are well-placed to support progress towards each of the SDGs. Workshops such as these provide an opportunity to increase workforce capacity to discuss, share and relate their work to the SDGs and provide a periodic pulse-check to identify opportunities for greater contribution to this urgent, global Agenda.
OBJECTIVES/GOALS: Mayo Clinic (MC) launched the Rapid Activation Trial (RAT) pilot program in 2022 to expedite the activation of high priority and high impact clinical trials. The objective was to develop a process for rapid activation through robust screening, prioritization, and project management (PM) support. METHODS/STUDY POPULATION: The project team developed a robust screening and approval process for the RAT program using a combination of an objective scoring tool (based on strategic priorities) and a diverse selection committee to screen and approve eligible trials. Sponsors had to commit to RAT program timelines. Upon approval, trials were prioritized at the highest level within each business unit involved in the activation process. The number of trials approved annually were limited to 8 to manage volume and facilitate seamless prioritization with an activation timeline goal of 6 weeks. Project management support for RAT program focused on financial, regulatory, logistical, and operational elements to open trials expeditiously. RESULTS/ANTICIPATED RESULTS: In 2022, thirteen (13) applications were received and eight (8) were approved by the RAT selection committee. The approved trials activated with a median open to enrollment time of 6.4 weeks from engaging with business units. They also aligned closely with organization’s strategic priorities, including but not limited to Investigator Initiated Trials, Multi-Site protocols, IND/IDE protocols, Rare Diseases, First in Human and Commercialization potential trials. PI and study team feedback was positive. In 2023, the RAT program was renewed due to the pilot’s significant success in 2022. The goal is to open 10 trials and 5 have been activated by the end of Q3, 2023 with a median timeline of 6 weeks. DISCUSSION/SIGNIFICANCE: Rapid activation of high priority and high impact clinical trials enables an organization to strategically prioritize and open complex clinical trials. This allows the delivery of innovative, timely cures to patients in an expeditious timeline.
To determine whether poorer performance on the Boston Naming Test (BNT) in individuals with transactive response DNA-binding protein 43 pathology (TDP-43+) is due to greater loss of word knowledge compared to retrieval-based deficits.
Methods:
Retrospective clinical-pathologic study of 282 participants with Alzheimer’s disease neuropathologic changes (ADNC) and known TDP-43 status. We evaluated item-level performance on the 60-item BNT for first and last available assessment. We fit cross-sectional negative binomial count models that assessed total number of incorrect items, number correct of responses with phonemic cue (reflecting retrieval difficulties), and number of “I don’t know” (IDK) responses (suggestive of loss of word knowledge) at both assessments. Models included TDP-43 status and adjusted for sex, age, education, years from test to death, and ADNC severity. Models that evaluated the last assessment adjusted for number of prior BNT exposures.
Results:
43% were TDP-43+. The TDP-43+ group had worse performance on BNT total score at first (p = .01) and last assessments (p = .01). At first assessment, TDP-43+ individuals had an estimated 29% (CI: 7%–56%) higher mean number of incorrect items after adjusting for covariates, and a 51% (CI: 15%–98%) higher number of IDK responses compared to TDP-43−. At last assessment, compared to TDP-43−, the TDP-43+ group on average missed 31% (CI: 6%–62%; p = .01) more items and had 33% more IDK responses (CI: 1% fewer to 78% more; p = .06).
Conclusions:
An important component of poorer performance on the BNT in participants who are TDP-43+ is having loss of word knowledge versus retrieval difficulties.
Utilizing high-resolution transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS) and X-raydiffraction (XRD) techniques, we have studied the transition from shallower smectite-rich mudrocks to deeper illite-rich mudrocks in Pliocene-age turbidite sediments from the northern Gulf of Mexico (GOM). Our objective in this work was to better understand how the smectite-illite transition may affect the onset of geopressuring in GOM sediments. The samples studied were sidewall cores from an offshore Louisiana well. In previous studies of GOM sediments, the smectite-to-illite reaction has mainly been documented in considerably older, Miocene-age sediments.
The results of this study elucidate the reaction mechanisms entailed in the transformation of clays in this sediment from smectitic to illitic. We found that illite formed at the expense of smectite in 2 ways: 1) growth of preexisting discrete illite flakes, and 2) creation of new illite layers within mixed-layer illite-smectite. Also, illitization apparently proceeded via a dissolution/precipitation, Al-conserving reaction rather than a solid-state, layer-conserving reaction. Smectite illitization is commonly believed to require input of K from feldspar dissolution. Our XRD results found little correlation between decreases in K-feldsparand increases of illite. However, in 1 instance TEM/EDS analyses indicated the presence of high-charge smectite, which suggests that insufficient K was available for illitization. TEM images also show small packets of authigenic chlorite in illite-rich mudrock. This chlorite may act as a sink for Fe liberated upon smectite illitization.
Low-temperature FTIR spectroscopy was used to characterize the v(OH) region of kaolin-group minerals including well ordered to poorly ordered kaolins from Georgia, Brazil, and England, along with samples of discrete dickite and nacrite. Low-temperature FTIR spectra were useful in resolving dickite- and nacrite-like features present in the spectra of kaolins when cooled to <30 K. These features were not resolved at room temperature and only partially resolved at liquid N2 temperature (77 K). The room-temperature and low-temperature positions of the ν(OH) bands of kaolinite, dickite, and nacrite were linearly correlated with the interatomic OH⋯O distances and this relationship served as the basis for polytype/disorder identification. Dickite or dickite-like disorder was found in high Hinckley-Index kaolinite from Keokuk, Iowa, and from Cornwall, England. Dickite- and nacrite-like features were observed in both high- and low-Hinckley-index kaolinite and the amounts of these stacking sequences generally increased with decreasing Hinckley Index.
The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.