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The presence of an intraluminal thrombus in acutely symptomatic carotid stenosis is thought to represent a high-risk lesion for short-term stroke reccurrence though evidence on natural history and treatment is lacking, leading to equipoise and much variation in practice. The objective of this study was to map these variations in practice (medical management and timing of revascularization), determine the considerations that influence clinician decision-making in this condition and gather opinions that inform the development and design of future trials in the area.
Methods:
This was a mixed-methods study using both quantitative survey methods and qualitative interview-based methods. International perspectives were gathered by distributing a case-based survey via the “Practice Current” section of Neurology: Clinical Practice and interviewing international experts using established qualitative research methods.
Results:
The presence of an intraluminal thrombus significantly increased the likelihood of using a regimen containing anticoagulation agents (p < 0.001) in acutely symptomatic carotid stenosis in the case-based survey. Themes that emerged from qualitative interview analysis were therapeutic uncertainty regarding anticoagulation, decision to reimage, revascularization choices and future trial design and anticipated challenges.
Conclusion:
Results of this study demonstrate a preference for anticoagulation and delayed revascularization after reimaging to examine for clot resolution, though much equipoise remains. While there is interest from international experts in future trials, further study is needed to understand the natural history of this condition in order to inform trial design.
Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.
Design:
We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).
Results:
At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.
Conclusions:
Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.
OBJECTIVES/GOALS: Patients with multiple myeloma (MM) experience significant disease- and treatment-related symptom burden, especially with higher lines of therapy (LOT). We used a remote symptom monitoring app to characterize overall symptom profile, symptom bother, and quality of life (QOL) among patients with MM across LOT and longitudinally. METHODS/STUDY POPULATION: We used Carevive PROmpt, a symptom monitoring app for cancer patients. From 11/10/22 to 9/27/23, we enrolled 84 adult patients with MM of any stage and anywhere in the treatment continuum from Duke Health MM clinics. Participants received weekly symptom surveys while on active treatment. Per prior studies, we defined heavily pretreated patients as those on current LOT ≥4. Our sample had a mean (SD) age of 63.7 (10.8) years and was 56.0% male; 73.8% had a prior bone marrow transplant, 40.5% were on LOT ≥4 (53.6% on LOT <4, 6.0% missing), 58.3% were on triplet therapy or higher. For 14 symptoms, we described the prevalence of moderate to very severe (MOD-VS) symptoms based on LOT overall and over time. We also described responses to “How bothersome are treatment side effects?” and “Overall QOL over the past week” based on LOT. RESULTS/ANTICIPATED RESULTS: Surveys continued for a mean (SD) of 14.9 (9.6) weeks (range: 44). The top 5 MOD-VS symptoms ever experienced were fatigue (66.7% of patients), neuropathy (48.8%), muscle pain (44.0%), insomnia (39.3%), and general pain (38.1%). Patients on LOT ≥4 had most of these symptoms more often than LOT <4 (fatigue: 70.6% of patients vs. 60.0%, neuropathy: 71.8% vs. 40.0%, muscle pain: 47.1% vs. 42.2%, insomnia: 35.3% vs. 40.0%, general pain: 47.1% vs. 33.3%). For those on LOT ≥4, 42.9% of survey responses endorsed “somewhat”, “quite a bit”, or “very much” symptom bother compared to 32.7% for LOT <4. QOL was similar between groups. Over many months, patients on LOT ≥4 had several persistent symptoms (neuropathy, sadness, insomnia), but even those on LOT <4 had unmet symptom needs (fatigue, general pain, constipation). DISCUSSION/SIGNIFICANCE: Evidence shows that treatment selection at higher LOT in MM often underrates the impact of cumulative symptom burden. Our study reveals significant longitudinal unmet needs regarding symptom and distress management in MM; understanding this can help guide treatment decisions and palliative care for MM patients with escalating treatment demands.
We review successes and challenges from five recent subglacial bedrock drilling campaigns intended to find evidence for Antarctic Ice Sheet retreat during warm periods in the geologic past. Insights into times when the polar ice sheets were smaller than present serve as guiding information for modeling efforts that aim to predict the rate and magnitude of future sea level rise that would accompany major retreat of the Antarctic Ice Sheet. One method to provide direct evidence for the timing of deglaciations and minimum extent of prior ice sheets is to extract subglacial bedrock cores for cosmogenic nuclide analysis from beneath the modern ice sheet surface. Here we summarize the lessons learned from five field seasons tasked with obtaining bedrock cores from shallow depths (<120 m beneath ice surface) across West Antarctica since 2016. We focus our findings on drilling efforts and technology and geophysical surveys with ground-penetrating radar. Shallow subglacial drilling provides a high risk, high reward means to test for past instabilities of the Antarctic Ice Sheet, and we highlight key challenges and solutions to increase the likelihood of success for future subglacial drilling efforts in polar regions.
FoodRx is a 12-month healthy food prescription incentive program for people with type 2 diabetes (T2DM) and experiences of household food insecurity. In this study, we aimed to explore potential users’ prospective acceptability (acceptability prior to program use) of the design and delivery of the FoodRx incentive and identify factors influencing prospective acceptability.
Design:
We used a qualitative descriptive approach and purposive sampling to recruit individuals who were interested or uninterested in using the FoodRx incentive. Semi-structured interviews were guided by the theoretical framework of acceptability, and corresponding interview transcripts were analysed using differential qualitative analysis guided by the socioecological model.
Setting:
Individuals living in Alberta, Canada.
Participants:
In total, fifteen adults with T2DM and experiences of household food insecurity.
Results:
People who were interested in using the FoodRx incentive (n 10) perceived it to be more acceptable than those who were uninterested (n 5). We identified four themes that captured factors that influenced users’ prospective acceptability: (i) participants’ confidence, views and beliefs of FoodRx design and delivery and its future use (intrapersonal), (ii) the shopping routines and roles of individuals in participants’ social networks (interpersonal), (iii) access to and experience with food retail outlets (community), and (iv) income and food access support to cope with the cost of living (policy).
Conclusion:
Future healthy food prescription programs should consider how factors at all levels of the socioecological model influence program acceptability and use these data to inform program design and delivery.
Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levels
Participants and Methods:
Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (<1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.
Results:
58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.
Conclusions:
Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.
Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.
Participants and Methods:
283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.
Results:
Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).
Conclusions:
PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:
The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:
APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:
Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
We show that many graphs with bounded treewidth can be described as subgraphs of the strong product of a graph with smaller treewidth and a bounded-size complete graph. To this end, define the underlying treewidth of a graph class $\mathcal{G}$ to be the minimum non-negative integer $c$ such that, for some function $f$, for every graph $G \in \mathcal{G}$ there is a graph $H$ with $\textrm{tw}(H) \leqslant c$ such that $G$ is isomorphic to a subgraph of $H \boxtimes K_{f(\textrm{tw}(G))}$. We introduce disjointed coverings of graphs and show they determine the underlying treewidth of any graph class. Using this result, we prove that the class of planar graphs has underlying treewidth $3$; the class of $K_{s,t}$-minor-free graphs has underlying treewidth $s$ (for $t \geqslant \max \{s,3\}$); and the class of $K_t$-minor-free graphs has underlying treewidth $t-2$. In general, we prove that a monotone class has bounded underlying treewidth if and only if it excludes some fixed topological minor. We also study the underlying treewidth of graph classes defined by an excluded subgraph or excluded induced subgraph. We show that the class of graphs with no $H$ subgraph has bounded underlying treewidth if and only if every component of $H$ is a subdivided star, and that the class of graphs with no induced $H$ subgraph has bounded underlying treewidth if and only if every component of $H$ is a star.
This study aimed to assess degree of audiovestibular handicap in patients with vestibular schwannoma.
Methods
Audiovestibular handicap was assessed using the Hearing Handicap Inventory, Tinnitus Handicap Inventory and Dizziness Handicap Inventory. Patients completed questionnaires at presentation and at least one year following treatment with microsurgery, stereotactic radiosurgery or observation. Changes in audiovestibular handicap and factors affecting audiovestibular handicap were assessed.
Results
All handicap scores increased at follow up, but not significantly. The Tinnitus Handicap Inventory and Dizziness Handicap Inventory scores predicted tinnitus and dizziness respectively. The Hearing Handicap Inventory was not predictive of hearing loss. Age predicted Tinnitus Handicap Inventory score and microsurgery was associated with a deterioration in Dizziness Handicap Inventory score.
Conclusion
Audiovestibular handicap is common in patients with vestibular schwannoma, with 75 per cent having some degree of handicap in at least one inventory. The overall burden of handicap was, however, low. The increased audiovestibular handicap over time was not statistically significant, irrespective of treatment modality.
This study explored programme recipients’ and deliverers’ experiences and perceived outcomes of accessing or facilitating a grocery gift card (GGC) programme from I Can for Kids (iCAN), a community-based programme that provides GGC to low-income families with children.
Design:
This qualitative descriptive study used Freedman et al’s framework of nutritious food access to guide data generation and analysis. Semi-structured interviews were conducted between August and November 2020. Data were analysed using directed content analysis with a deductive–inductive approach.
Participants:
Fifty-four participants were purposively recruited, including thirty-seven programme recipients who accessed iCAN’s GGC programme and seventeen programme deliverers who facilitated it.
Setting:
Calgary, Alberta, Canada.
Results:
Three themes were generated from the data. First, iCAN’s GGC programme promoted a sense of autonomy and dignity among programme recipients as they appreciated receiving financial support, the flexibility and convenience of using GGC, and the freedom to select foods they desired. Recipients perceived these benefits improved their social and emotional well-being. Second, recipients reported that the use of GGC improved their households’ dietary patterns and food skills. Third, both participant groups identified programmatic strengths and limitations.
Conclusion:
Programme recipients reported that iCAN’s GGC programme provided them with dignified access to nutritious food and improved their households’ finances, dietary patterns, and social and emotional well-being. Increasing the number of GGC provided to households on each occasion, establishing clear and consistent criteria for distributing GGC to recipients, and increasing potential donors’ awareness of iCAN’s GGC programme may augment the amount of support iCAN could provide to households.
Children need to be repeatedly and consistently exposed to a variety of vegetables from an early age to achieve an increase in vegetable intake. A focus on enjoyment and learning to like eating vegetables at an early age is critical to forming favourable lifelong eating habits. Coordinated work is needed to ensure vegetables are available and promoted in a range of settings, using evidence-based initiatives, to create an environment that will support children’s acceptance of vegetables. This will help to facilitate increased intake and ultimately realise the associated health benefits. The challenges and evidence base for a new approach are described.
The Amazon River dolphin Inia geoffrensis occurs throughout the basins of the Amazon and Orinoco Rivers and is categorized as Endangered on the IUCN Red List. Using satellite tracking data from eight dolphins (one female and seven males) in the Peruvian Amazon, we demonstrate that these dolphins inhabit a variety of habitat types and have core areas and home range areas of variable magnitudes. To gain a better understanding of how threats affect these dolphins, we examined the distance of dolphin records to locations of current and potential future anthropogenic threats. On average, dolphin home ranges overlapped with fisheries by 89%. Dolphins were found at an average distance of 252 km from the nearest proposed dam and 125 km from the nearest proposed dredging site. Given that many of these threats are still in the planning stage, we advise the government to consider the negative effects these activities have already had on other riverine species before proceeding. Additionally, efforts should be made to expand river dolphin tracking programmes to span multiple seasons, to track more females at our study sites and to increase the numbers tracked overall in other areas to improve our knowledge of the species' movement patterns.
It has been argued in previous work that Hedley Byrne v Heller addressed no actual mischief. In the case itself, the defendant's credit reference about Easipower Ltd. was neither a misstatement nor negligently given, and in general the indemnification of reliance on negligent statements is far better regulated by contract than it can possibly be by negligent misstatement. This paper expands on the significance of contract relative to tort in Hedley Byrne, but mainly argues that the mischief perceived by the claimant was caused by the operation of the statutory regime regulating Easipower's insolvency. This makes regarding Hedley Byrne as a necessary response to “the privity of contract fallacy” even more implausible.
Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis.
Methods:
We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts.
Results:
Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT.
Conclusion:
Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.
Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.
Methods
The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.
Results
Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.
Discussion
Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.
Major depressive disorder (MDD) was previously associated with negative affective biases. Evidence from larger population-based studies, however, is lacking, including whether biases normalise with remission. We investigated associations between affective bias measures and depressive symptom severity across a large community-based sample, followed by examining differences between remitted individuals and controls.
Methods
Participants from Generation Scotland (N = 1109) completed the: (i) Bristol Emotion Recognition Task (BERT), (ii) Face Affective Go/No-go (FAGN), and (iii) Cambridge Gambling Task (CGT). Individuals were classified as MDD-current (n = 43), MDD-remitted (n = 282), or controls (n = 784). Analyses included using affective bias summary measures (primary analyses), followed by detailed emotion/condition analyses of BERT and FAGN (secondary analyses).
Results
For summary measures, the only significant finding was an association between greater symptoms and lower risk adjustment for CGT across the sample (individuals with greater symptoms were less likely to bet more, despite increasingly favourable conditions). This was no longer significant when controlling for non-affective cognition. No differences were found for remitted-MDD v. controls. Detailed analysis of BERT and FAGN indicated subtle negative biases across multiple measures of affective cognition with increasing symptom severity, that were independent of non-effective cognition [e.g. greater tendency to rate faces as angry (BERT), and lower accuracy for happy/neutral conditions (FAGN)]. Results for remitted-MDD were inconsistent.
Conclusions
This suggests the presence of subtle negative affective biases at the level of emotion/condition in association with depressive symptoms across the sample, over and above those accounted for by non-affective cognition, with no evidence for affective biases in remitted individuals.
Ecotoxicology offers a comprehensive overview of the science underpinning the recognition and management of environmental contamination. It describes the toxicology of environmental contaminants, the methods used for assessing their toxicity and ecological impacts, and approaches employed to mitigate pollution and ecological health risks globally. Chapters cover the latest advances in research, including genomics, natural toxins, endocrine disruption and the toxicology of radioactive substances. The second half of the book focuses on applications, such as cradle-to-grave effects of selected industries, legal and economic approaches to environmental regulation, ecological risk assessment, and contaminated site remediation. With short capsules written by invited experts, numerous case studies from around the world and further reading lists, this textbook is designed for advanced undergraduate and graduate one-semester courses. It is also a valuable reference for graduate students and professionals. Online resources for instructors and students are also available.