Less is more: Smaller hippocampal subfield volumes predict greater improvements in posttraumatic stress disorder symptoms over 2 years.

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder, and symptom severity varies over time. Neurobiological factors that predict PTSD symptoms and their chronicity remain unclear. This study investigated whether the volume of the hippocampus and its subfields, particularly cornu ammonis (CA) 1, CA3, and dentate gyrus, are associated with current PTSD symptoms and whether they predict PTSD symptom changes over 2 years. We examined clinical and structural magnetic resonance imaging measures from 252 trauma-exposed post-9/11 veterans (159 with Time 1 PTSD diagnosis) during assessments approximately 2 years apart. Automated hippocampal subfield segmentation was performed with FreeSurfer Version 7.1, producing 19 bilateral subfields. PTSD symptoms were measured at each assessment using the Clinician-Administered PTSD Scale-IV (CAPS). All models included total intracranial volume as a covariate. First, similar to previous reports, we showed that smaller overall hippocampal volume was associated with greater PTSD symptom severity at Time 1. Notably, when examining regions of interest (CA1, CA3, dentate gyrus), we found that smaller Time 1 hippocampal volumes in the bilateral CA1-body and CA2/3-body predicted decreased PTSD symptom severity at Time 2. These findings were not accounted for by combat exposure or treatment history. Additionally, both Time 1 CA1-body and CA2/3-body volume showed unique associations with changes in avoidance/numbing, but not with changes in reexperiencing or hyperarousal symptoms. This supports a more complex and nuanced relationship between hippocampal structure and PTSD symptoms, where during the posttrauma years bigger may not always mean better, and suggests that the CA1-body and CA2/3-body are important factors in the maintenance of PTSD symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Indocyanine Green-based Nanoprobe for In Vivo Detection of Cellular Senescence.

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.

Perceptions of gender equity in emergency medicine in Canada.

INTRODUCTION: Women-identifying emergency physicians face gender-based discrimination throughout their careers. The purpose of this study was to explore emergency physician's perceptions and experiences of gender equity in emergency medicine. METHODS: We conducted a secondary analysis of data from a previously conducted survey of Canadian emergency physicians on barriers to gender equity in emergency medicine. Survey responses were analyzed using logistic regression to determine the impact that gender, practice setting, years since graduation, race, equity-seeking status, and parental status had on agreement about gender equity in emergency medicine and five of the problem statements. RESULTS: A total of 710 participants completed the survey. Most identified as women (58.8%), white (77.4%), graduated between 2010 and 2019 (40%), had CCFP (Emergency Medicine) designation (47.9%), an urban practice (84.4%), were parents (62.4%) and did not identify as equity-seeking (79.9%). Women-identifying physicians were less likely to perceive gender equity in emergency medicine, OR 0.52, CI [0.38, 0.73]. Women-identifying physicians were more likely to agree with statements about microaggressions, OR 4.39, CI [2.66, 7.23]; barriers to leadership, OR 3.51, CI [2.25, 5.50]; gender wage gap, OR 13.46, CI [8.27, 21.91]; lack of support for parental leave, OR 2.85, CI [1.82, 4.44]; and education on allyship, OR 2.23 CI [1.44, 3.45] than men-identifying physicians. CONCLUSION: In this study, women-identifying physicians were less likely to perceive that there was gender equity in emergency medicine than men-identifying physicians. Women-identifying physicians agreed that there are greater barriers for career advancement including fewer opportunities for leadership, a gender wage gap, a lack of parental leave policies to support a return to work and a lack of education for men to become allies. Men-identifying physicians were less aware of these inequities. Health systems must work to improve gender equity in emergency medicine and this will require education and allyship from men-identifying physicians.

RéSUMé: INTRODUCTION: Les femmes médecins urgentistes sont confrontées à une discrimination fondée sur le sexe tout au long de leur carrière. L'objectif de cette étude était d'explorer les perceptions et les expériences des médecins urgentistes en matière d'équité entre les sexes en médecine d'urgence. MéTHODES: Nous avons procédé à une analyse secondaire des données d'une enquête menée précédemment auprès des médecins urgentistes canadiens sur les obstacles à l'équité entre les sexes en médecine d'urgence. Les réponses au sondage ont été analysées à l'aide d'une régression logistique pour déterminer l'incidence que le sexe, le milieu de pratique, les années écoulées depuis l'obtention du diplôme, la race, le statut de demandeur d'équité et le statut parental avaient sur l'accord sur l'équité entre les sexes en médecine d'urgence et cinq des énoncés de problème. RéSULTATS: Au total, 710 participants ont répondu à l'enquête. La plupart d'entre eux sont des femmes (58.8 %), de race blanche (77.4 %), ont obtenu leur diplôme entre 2010 et 2019 (40 %), ont le titre de CCMF (médecine d'urgence) (47.9 %), exercent en milieu urbain (84.4 %), sont parents (62.4 %) et ne se déclarent pas en quête d'équité (79.9 %). Les médecins s'identifiant à des femmes étaient moins susceptibles de percevoir l'équité entre les sexes en médecine d'urgence, OR 0.52, IC [0.38,0.73]. Les médecins s'identifiant comme femmes étaient plus susceptibles d'être d'accord avec les déclarations sur les microagressions, OR 4.39, IC [2.66, 7.23] ; obstacles au leadership, OR 3.51, IC [2.25, 5.50] ; écart salarial entre les hommes et les femmes, OR 13.46, IC [8.27, 21.91] ; le manque de soutien pour le congé parental, OR 2.85, IC [1.82, 4.44]; et l'éducation sur l'alliance, OR 2.23 IC [1.44, 3.45] que les médecins s'identifiant comme hommes. CONCLUSION: Dans cette étude, les médecins s'identifiant à des femmes étaient moins susceptibles de percevoir qu'il y avait une équité entre les sexes en médecine d'urgence que les médecins s'identifiant à des hommes. Les femmes médecins s'accordent à dire qu'il existe davantage d'obstacles à l'avancement professionnel, notamment moins d'opportunités de leadership, un écart salarial entre les hommes et les femmes, un manque de politiques de congé parental pour favoriser le retour au travail et un manque d'éducation des hommes pour qu'ils deviennent des alliés. Les médecins s'identifiant à des hommes étaient moins conscients de ces inégalités. Les systèmes de santé doivent s'efforcer d'améliorer l'équité entre les sexes dans la médecine d'urgence, ce qui nécessitera une formation et un allié de la part des médecins qui s'identifient aux hommes.

Inferring transmission routes for foot-and-mouth disease virus within a cattle herd using approximate Bayesian computation.

To control an outbreak of an infectious disease it is essential to understand the different routes of transmission and how they contribute to the overall spread of the pathogen. With this information, policy makers can choose the most efficient methods of detection and control during an outbreak. Here we assess the contributions of direct contact and environmental contamination to the transmission of foot-and-mouth disease virus (FMDV) in a cattle herd using an individual-based model that includes both routes. Model parameters are inferred using approximate Bayesian computation with sequential Monte Carlo sampling (ABC-SMC) applied to data from transmission experiments and the 2007 epidemic in Great Britain. This demonstrates that the parameters derived from transmission experiments are applicable to outbreaks in the field, at least for closely related strains. Under the assumptions made in the model we show that environmental transmission likely contributes a majority of infections within a herd during an outbreak, although there is a lot of variation between simulated outbreaks. The accumulation of environmental contamination not only causes infections within a farm, but also has the potential to spread between farms via fomites. We also demonstrate the importance and effectiveness of rapid detection of infected farms in reducing transmission between farms, whether via direct contact or the environment.

Importance of validity testing in psychiatric assessment: evidence from a sample of multimorbid post-9/11 veterans.

OBJECTIVE: Performance validity (PVTs) and symptom validity tests (SVTs) are necessary components of neuropsychological testing to identify suboptimal performances and response bias that may impact diagnosis and treatment. The current study examined the clinical and functional characteristics of veterans who failed PVTs and the relationship between PVT and SVT failures. METHOD: Five hundred and sixteen post-9/11 veterans participated in clinical interviews, neuropsychological testing, and several validity measures. RESULTS: Veterans who failed 2+ PVTs performed significantly worse than veterans who failed one PVT in verbal memory (Cohen's d = .60-.69), processing speed (Cohen's d = .68), working memory (Cohen's d = .98), and visual memory (Cohen's d = .88-1.10). Individuals with 2+ PVT failures had greater posttraumatic stress (PTS; ß = 0.16; p = .0002), and worse self-reported depression (ß = 0.17; p = .0001), anxiety (ß = 0.15; p = .0007), sleep (ß = 0.10; p = .0233), and functional outcomes (ß = 0.15; p = .0009) compared to veterans who passed PVTs. 7.8% veterans failed the SVT (Validity-10; ≥19 cutoff); Multiple PVT failures were significantly associated with Validity-10 failure at the ≥19 and ≥23 cutoffs (p's < .0012). The Validity-10 had moderate correspondence in predicting 2+ PVTs failures (AUC = 0.83; 95% CI = 0.76, 0.91). CONCLUSION: PVT failures are associated with psychiatric factors, but not traumatic brain injury (TBI). PVT failures predict SVT failure and vice versa. Standard care should include SVTs and PVTs in all clinical assessments, not just neuropsychological assessments, particularly in clinically complex populations.

Routine, molecular point-of-care testing for SARS-CoV-2 and other respiratory viruses within an acute oncology service improves patient care.

OBJECTIVES: COVID-19 has caused significant challenges for infection prevention measures and patient flow in hospital admission pathways. We aimed to assess the impact of replacing laboratory PCR with molecular point-of-care testing (mPOCT) for respiratory viruses including SARS-CoV-2, within an Acute Oncology Service (AOS). METHODS: This pre- and post-implementation study took place in the AOS of a large teaching hospital, in Southampton, UK. We collected data from two periods: November 25th, 2019 to November 24th, 2020, when respiratory virus testing utilised laboratory PCR, and December 1st, 2020 to May 31st, 2021 following the introduction of mPOCT. The primary outcome was the time to results. RESULTS: 2189 patients were tested in the pre-implementation period and 1540 in the post implementation period. Median (IQR) time to results was 5.8 h (4.2-10.6) pre-implementation and 1.9 h (1.5-3.0) post-implementation (difference -3.6 h [95%CI to -3.8 to -3.5]; p < 0.0001). Median time spent in assessment areas was 6.0 h (4.1-7.9) pre-implementation and 5.5 h (3.8-7.4) post-implementation (p < 0.0001). 20 (0.9%) patients admitted via AOS assessment unit developed hospital-acquired respiratory virus infection pre-implementation versus 0 (0%) post-implementation (p = 0.031). CONCLUSIONS: Routine mPOCT for respiratory viruses, including SARS-CoV-2, was associated with a reduced time to results, reduced time in assessment areas, and a reduction in the rates of hospital-acquired respiratory virus infection in an acute oncology assessment unit.

Risks & Protective Factors for Depression & Suicide Among Hawai'i Agricultural Producers.

Studies have consistently shown that agricultural producers in the continental United States have disproportionately high rates of depression and suicide as compared to other occupations. It is not known whether this is true in Hawai'i, which is both geographically distinct and ethnically diverse. To examine rates of depression and suicide as well as potential risk and protective factors, a state-wide mental health needs assessment was conducted from November 2021 to September 2022. We conducted a survey with a nonprobability-based convenience sample targeting agricultural producers across Hawai'i, and performed descriptive statistics and logistic regression analyses. In a sample of 408 respondents, 35% (n = 143) had clinical depression symptomatology, and 8% (n = 33) had suicidal ideation based on the Patient Health Questionnaire-9. Older age was slightly protective in that every year of increase in age was associated with 0.98 times (95% CI: 0.96, 0.99) reduced odds of depression symptomatology, and 0.96 times (95% CI:0.94, 0.98) reduced odds of suicidal ideation. Identifying as East Asian had 2.04 times (95% CI: 1.16, 3.61) higher odds of depression symptomatology, and Southeast Asian had 3.04 times odds (95% CI:1.15, 8.00) of suicidal ideation. However, in the presence of stress and coping variables, the demographic factors became statistically non-significant. Instead, feeling stressed, uncertainty as the stressor, and media-focused coping were significant risk factors in increasing two to eight times the odds of depressive symptoms. For suicidal ideation, depression symptomatology increased odds by 31.95 (95% CI: 5.60-182.32), using media-focused coping increased 5.20 odds (95% CI: 1.66, 16.27), but problem-focused coping decreased 0.32 times odds (0.10, 0.99). Culturally specific prevention and intervention measures should be tailored for Hawai'i agricultural producers with an emphasis toward younger, East, and Southeast Asian producers and attention toward providing skillful coping strategies for effective stress regulation and management.

Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial.

BACKGROUND: PROpel met its primary endpoint showing statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) unselected by homologous recombination repair mutation (HRRm) status, with benefit observed in all prespecified subgroups. Here we report the final prespecified overall survival analysis. METHODS: This was a randomised, double-blind, phase 3 trial done at 126 centres in 17 countries worldwide. Patients with mCRPC aged at least 18 years, Eastern Cooperative Oncology Group performance status 0-1, a life expectancy of at least 6 months, with no previous systemic treatment for mCRPC and unselected by HRRm status were randomly assigned (1:1) centrally by means of an interactive voice response system-interactive web response system to abiraterone acetate (orally, 1000 mg once daily) plus prednisone or prednisolone with either olaparib (orally, 300 mg twice daily) or placebo. The patients, the investigator, and study centre staff were masked to drug allocation. Stratification factors were site of metastases and previous docetaxel at metastatic hormone-sensitive cancer stage. Radiographic progression-free survival was the primary endpoint and overall survival was a key secondary endpoint with alpha-control (alpha-threshold at prespecified final analysis: 0·0377 [two-sided]), evaluated in the intention-to-treat population. Safety was evaluated in all patients who received at least one dose of a study drug. This study is registered with ClinicalTrials.gov, NCT03732820, and is completed and no longer recruiting. FINDINGS: Between Oct 31, 2018 and March 11, 2020, 1103 patients were screened, of whom 399 were randomly assigned to olaparib plus abiraterone and 397 to placebo plus abiraterone. Median follow-up for overall survival in patients with censored data was 36·6 months (IQR 34·1-40·3) for olaparib plus abiraterone and 36·5 months (33·8-40·3) for placebo plus abiraterone. Median overall survival was 42·1 months (95% CI 38·4-not reached) with olaparib plus abiraterone and 34·7 months (31·0-39·3) with placebo plus abiraterone (hazard ratio 0·81, 95% CI 0·67-1·00; p=0·054). The most common grade 3-4 adverse event was anaemia reported in 64 (16%) of 398 patients in the olaparib plus abiraterone and 13 (3%) of 396 patients in the placebo plus abiraterone group. Serious adverse events were reported in 161 (40%) in the olaparib plus abiraterone group and 126 (32%) in the placebo plus abiraterone group. One death in the placebo plus abiraterone group, from interstitial lung disease, was considered treatment related. INTERPRETATION: Overall survival was not significantly different between treatment groups at this final prespecified analysis. FUNDING: Supported by AstraZeneca and Merck Sharp & Dohme.

Metformin-Induced Receptor Turnover Alters Antibody Accumulation in HER-Expressing Tumors.

Metformin has effects beyond its antihyperglycemic properties, including altering the localization of membrane receptors in cancer cells. Metformin decreases human epidermal growth factor receptor (HER) membrane density. Depletion of cell-surface HER decreases antibody-tumor binding for imaging and therapeutic approaches. Here, we used HER-targeted PET to annotate antibody-tumor binding in mice treated with metformin. Methods: Small-animal PET annotated antibody binding in HER-expressing xenografts on administration of an acute versus a daily dose schedule of metformin. Analyses at the protein level in the total, membrane, and internalized cell extracts were performed to determine receptor endocytosis, HER surface and internalized protein levels, and HER phosphorylation. Results: At 24 h after injection of radiolabeled anti-HER antibodies, control tumors had higher antibody accumulation than tumors treated with an acute dose of metformin. These differences were temporal, and by 72 h, tumor uptake in acute cohorts was similar to uptake in control. Additional PET imaging revealed a sustained decrease in tumor uptake on daily metformin treatment compared with control and acute metformin cohorts. The effects of metformin on membrane HER were reversible, and after its removal, antibody-tumor binding was restored. The time- and dose-dependent effects of metformin-induced HER depletion observed preclinically were validated with immunofluorescence, fractionation, and protein analysis cell assays. Conclusion: The findings that metformin decreases cell-surface HER receptors and reduces antibody-tumor binding may have significant implications for the use of antibodies targeting these receptors in cancer treatment and molecular imaging.

Immuno-PET Detects Antibody-Drug Potency on Coadministration with Statins.

The human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) are antibody-drug conjugates (ADC) clinically used to treat HER2-positive breast cancer, with the latter receiving clinical approval in 2021 for HER2-positive gastric cancer. Lovastatin, a cholesterol-lowering drug, temporally elevates cell-surface HER2 in ways that enhance HER2-ADC binding and internalization. Methods: In an NCIN87 gastric xenograft model and a gastric patient-derived xenograft model, we used the 89Zr-labeled or 64Cu-labeled anti-HER2 antibody trastuzumab to investigate the dosing regimen of ADC therapy with and without coadministration of lovastatin. We compared the ADC efficacy of a multiple-dose ADC regime, which replicates the clinical dose regimen standard, with a single-dose regime. Results: T-DM1/lovastatin treatment inhibited tumor growth, regardless of multiple- or single-dose T-DM1 administration. Coadministration of lovastatin with T-DM1 or T-DXd as a single dose enhanced tumor growth inhibition, which was accompanied by a decrease in signal on HER2-targeted immuno-PET and a decrease in HER2-mediated signaling at the cellular level. DNA damage signaling was increased on ADC treatment in vitro. Conclusion: Our data from a gastric cancer xenograft show the utility of HER2-targeted immuno-PET to inform the tumor response to ADC therapies in combination with modulators of cell-surface target availability. Our studies also demonstrate that statins enhance ADC efficacy in both a cell-line and a patient-derived xenograft model in ways that enable a single-dose administration of the ADC.

Directional speakers as a tool for animal vocal communication studies.

Audio playbacks are a common experimental tool in vocal communication research. However, low directionality of sound makes it hard to control the audience exposed to the stimuli. Parametric speakers offer a solution for transmitting directional audible signals by using ultrasonic carrier waves. The targeted transmission of vocal signals offers exciting opportunities for testing the diffusion of information in animal groups and mechanisms for resolving informational ambiguities. We have field tested the quality and directionality of a commercial parametric speaker, Soundlazer SL-01. Additionally, we assessed its usability for performing playback experiments by comparing behavioural responses of free-ranging meerkats (Suricata suricatta) with calls transmitted from conventional and parametric speakers. Our results show that the tested parametric speaker is highly directional. However, the acoustic structure of meerkat calls was strongly affected and low frequencies were not reliably reproduced by the parametric speaker. The playback trials elicited weakened behavioural responses probably due to the partial distortion of the signal but also indicating the potential importance of social facilitation for initiating mobbing events in meerkats. We conclude that parametric speakers can be useful tools for directed transmission of animals calls but after a careful assessment of signal fidelity.

Sense of Meaning and Purpose Making Mitigates the Experience of Stress Among Hawai'i Farmers.

Farming is widely acknowledged as being extremely challenging and stressful, yet also potentially very meaningful as farming is an important element of any society and connected to our cultural heritage. Only a few studies have empirically examined the association between sense of purpose in farming and well-being/happiness. This study explored whether a sense of meaning and purpose in being a farmer could mitigate the experience of stress. A cross-sectional survey between November 2021-September 2022 was conducted with a sample of 408 Hawai'i agricultural producers. Descriptive statistics and logistic regressions were conducted to explore factors that predicted farmers' endorsement of high meaning and purpose, and whether meaning and purpose could dampen the impact of stressors on the experience of stress. Results revealed that Hawai'i farmers were highly stressed but also had high sense of meaning and purpose. Predictors of meaning and purpose included operating smaller farms of 1-9 acres and having 51% or greater percentage of income from farming. Meaning and purpose in turn decreased odds of stress, and showed an interaction with stressor intensity such that the stress buffering effect of meaning was more salient for those with lower stressors than those with higher stressors OR = 1.12 (CI = 1.06,1.19). One possible stress management and resilience technique is to highlight and strengthen farmers' sense of meaning and purpose in the farming endeavor.

Performance evaluation of mesoscopic photoacoustic imaging.

Photoacoustic mesoscopy visualises vascular architecture at high-resolution up to ~3 mm depth. Despite promise in preclinical and clinical imaging studies, with applications in oncology and dermatology, the accuracy and precision of photoacoustic mesoscopy is not well established. Here, we evaluate a commercial photoacoustic mesoscopy system for imaging vascular structures. Typical artefact types are first highlighted and limitations due to non-isotropic illumination and detection are evaluated with respect to rotation, angularity, and depth of the target. Then, using tailored phantoms and mouse models, we investigate system precision, showing coefficients of variation (COV) between repeated scans [short term (1 h): COV= 1.2%; long term (25 days): COV= 9.6%], from target repositioning (without: COV=1.2%, with: COV=4.1%), or from varying in vivo user experience (experienced: COV=15.9%, unexperienced: COV=20.2%). Our findings show robustness of the technique, but also underscore general challenges of limited-view photoacoustic systems in accurately imaging vessel-like structures, thereby guiding users when interpreting biologically-relevant information.

Transrectal Absorber Guide Raster-Scanning Optoacoustic Mesoscopy for Label-Free In Vivo Assessment of Colitis.

Optoacoustic imaging (OAI) enables microscale imaging of endogenous chromophores such as hemoglobin at significantly higher penetration depths compared to other optical imaging technologies. Raster-scanning optoacoustic mesoscopy (RSOM) has recently been shown to identify superficial microvascular changes associated with human skin pathologies. In animal models, the imaging depth afforded by RSOM can enable entirely new capabilities for noninvasive imaging of vascular structures in the gastrointestinal tract, but exact localization of intra-abdominal organs is still elusive. Herein the development and application of a novel transrectal absorber guide for RSOM (TAG-RSOM) is presented to enable accurate transabdominal localization and assessment of colonic vascular networks in vivo. The potential of TAG-RSOM is demonstrated through application during mild and severe acute colitis in mice. TAG-RSOM enables visualization of transmural vascular networks, with changes in colon wall thickness, blood volume, and OAI signal intensities corresponding to colitis-associated inflammatory changes. These findings suggest TAG-RSOM can provide a novel monitoring tool in preclinical IBD models, refining animal procedures and underlines the capabilities of such technologies to address inflammatory bowel diseases in humans.

Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.

Approximately 10%-30% of individuals with posttraumatic stress disorder (PTSD) exhibit a dissociative subtype of the condition defined by symptoms of depersonalization and derealization. This study examined the psychometric evidence for the dissociative subtype of PTSD in a sample of young, primarily male post-9/11-era Veterans (n = 374 at baseline and n = 163 at follow-up) and evaluated its biological correlates with respect to resting state functional connectivity (default mode network [DMN]; n = 275), brain morphology (hippocampal subfield volume and cortical thickness; n = 280), neurocognitive functioning (n = 337), and genetic variation (n = 193). Multivariate analyses of PTSD and dissociation items suggested a class structure was superior to dimensional and hybrid ones, with 7.5% of the sample comprising the dissociative class; this group showed stability over 1.5 years. Covarying for age, sex, and PTSD severity, linear regression models revealed that derealization/depersonalization severity was associated with: decreased DMN connectivity between bilateral posterior cingulate cortex and right isthmus (p = .015; adjusted-p [padj] = .097); increased bilateral whole hippocampal, hippocampal head, and molecular layer head volume (p = .010-.034; padj = .032-.053); worse self-monitoring (p = .018; padj = .079); and a candidate genetic variant (rs263232) in the adenylyl cyclase 8 gene (p = .026), previously associated with dissociation. Results converged on biological structures and systems implicated in sensory integration, the neural representation of spatial awareness, and stress-related spatial learning and memory, suggesting possible mechanisms underlying the dissociative subtype of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development and Content Validation of a Questionnaire for Measuring Beliefs About Using Nicotine Replacement Therapy for Smoking Cessation in Pregnancy.

INTRODUCTION: Improving adherence to nicotine replacement therapy (NRT) in pregnancy may result in higher smoking cessation rates. Informed by the Necessities and Concerns Framework, we developed an intervention targeting pregnancy NRT adherence. To evaluate this, we derived the NRT in pregnancy necessities and concerns questionnaire (NiP-NCQ), which measures perceived need for NRT and concerns about potential consequences. AIMS AND METHODS: Here we describe the development and content validation of NiP-NCQ. From qualitative work, we identified potentially modifiable determinants of pregnancy NRT adherence and classed these as necessity beliefs or concerns. We translated these into draft self-report items and piloted items on 39 pregnant women offered NRT and a prototype NRT adherence intervention, assessing distributions and sensitivity to change. After removing poorly performing items, smoking cessation experts (N = 16) completed an online discriminant content validation (DCV) task to determine whether retained items measure a necessity belief, concern, both, or neither construct. RESULTS: Draft NRT concern items encompassed safety for the baby, side effects, too much or insufficient nicotine, and addictiveness. Draft necessity belief items included perceived need for NRT for short- and longer-term abstinence, and desire to minimize or cope without NRT. Of 22 out of 29 items retained after piloting, four were removed following the DCV task: three were judged to measure neither construct and one possibly both. The final NiP-NCQ comprised nine items per construct (18 total). CONCLUSIONS: The NiP-NCQ measures potentially modifiable determinants of pregnancy NRT adherence within two distinct constructs and may have research and clinical utility for evaluating interventions targeting these. IMPLICATIONS: Poor adherence to NRT in pregnancy may result from low perceived need and concerns about consequences; interventions challenging these beliefs may yield higher smoking cessation rates. To evaluate an NRT adherence intervention informed by the Necessities and Concerns Framework, we developed the NiP-NCQ. Through the content development and refinement processes described in this paper, we derived an evidence-based, 18-item questionnaire measuring two distinct constructs within two nine-item subscales. Higher concerns and lower necessity beliefs indicate more negative NRT beliefs; NiP-NCQ may have research and clinical utility for interventions targeting these.

Assessing the effectiveness of environmental sampling for surveillance of foot-and-mouth disease virus in a cattle herd.

The survival of foot-and-mouth disease virus (FMDV) in the environment provides an opportunity for indirect transmission, both within and between farms. However it also presents the possibility of surveillance and detection via environmental sampling. This study assesses the effectiveness of environmental sampling strategies in the event of an outbreak, using a previous model for transmission of FMDV in a cattle herd that had been parameterized using data from transmission experiments and outbreaks. We show that environmental sampling can be an effective means of detecting FMDV in a herd, but it requires multiple samples to be taken on multiple occasions. In addition, environmental sampling can potentially detect FMDV in a herd more quickly than clinical inspection. For example, taking 10 samples every 3 days results in a mean time to detection of 6 days, which is lower than the mean time to detection estimated for the 2001 UK epidemic (8 days). We also show how environmental sampling could be used in a herd considered to be at risk as an alternative to pre-emptive culling. However, because of the time taken for virus to accumulate at the start of an outbreak, a reasonable level of confidence (> 99%) that an at-risk herd is indeed free from infection is unlikely to be achieved in less than 1 week.

Genetic Risk for Alzheimer Disease and Plasma Tau Are Associated With Accelerated Parietal Cortex Thickness Change in Middle-Aged Adults.

Background and Objectives: Neuroimaging and biomarker studies in Alzheimer disease (AD) have shown well-characterized patterns of cortical thinning and altered biomarker concentrations of tau and ß-amyloid (Aß). However, earlier identification of AD has great potential to advance clinical care and determine candidates for drug trials. The extent to which AD risk markers relate to cortical thinning patterns in midlife is unknown. The first objective of this study was to examine cortical thickness change associated with genetic risk for AD among middle-aged military veterans. The second objective was to determine the relationship between plasma tau and Aß and change in brain cortical thickness among veterans stratified by genetic risk for AD. Methods: Participants consisted of post-9/11 veterans (N = 155) who were consecutively enrolled in the Translational Research Center for TBI and Stress Disorders prospective longitudinal cohort and were assessed for mild traumatic brain injury (TBI) and posttraumatic disorder (PTSD). Genome-wide polygenic risk scores (PRSs) for AD were calculated using summary results from the International Genomics of Alzheimer's Disease Project. T-tau and Aß40 and Aß42 plasma assays were run using Simoa technology. Whole-brain MRI cortical thickness change estimates were obtained using the longitudinal stream of FreeSurfer. Follow-up moderation analyses examined the AD PRS × plasma interaction on change in cortical thickness in AD-vulnerable regions. Results: Higher AD PRS, signifying greater genetic risk for AD, was associated with accelerated cortical thickness change in a right hemisphere inferior parietal cortex cluster that included the supramarginal gyrus, angular gyrus, and intraparietal sulcus. Higher tau, but not Aß42/40 ratio, was associated with greater cortical thickness change among those with higher AD PRS. Mild TBI and PTSD were not associated with cortical thickness change. Discussion: Plasma tau, particularly when combined with genetic stratification for AD risk, can be a useful indicator of brain change in midlife. Accelerated inferior parietal cortex changes in midlife may be an important factor to consider as a marker of AD-related brain alterations.