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Exposure to traumatic experiences during childhood and adolescence is a significant risk factor for the development of psychiatric disorders in adulthood. An estimated 50% of the worldwide incidence of depression and anxiety can be attributed to childhood maltreatment (Li et al., 2016). In addition, approximately one-third of psychotic experiences are attributable to a history of developmental trauma (McGrath et al., 2017). It is thought that long-lasting, trauma-induced adaptive changes in neurobiological function may lead to a predisposition towards pathophysiology (McCrory and Viding, 2015). However, the precise mechanisms through which developmental trauma exposure alters brain function on cellular and circuit levels remain poorly elucidated.
Methods
A systematic literature search and meta-analysis was performed to establish how dopaminergic functioning in adulthood is affected by developmental stress in rodents. Three databases, Medline®, Embase®, and PsycINFO®, were systematically searched initially on 2nd December 2023. Terms for three superordinate concepts (‘childhood’ terms, ‘trauma’ terms, and ‘dopamine’ terms) were combined. Cohen's d statistic was used for effect sizes. This protocol is pre-registered on PROSPERO® (ID: CRD42018106382).
Results
A total of 104 studies met our inclusion criteria. Meta-analysis indicated that developmental stress exposure leads to complex and long-lasting effects in basal and post-amphetamine extracellular dopamine concentrations in the medial prefrontal cortex, amygdala, and nucleus accumbens. In addition, there is a significant downregulation of D1 receptors and upregulation of D2 receptors in prefrontal and striatal regions involved in threat and reward processing. Effect sizes ranged from 0.36 to 1.55.
Conclusion
These findings strongly suggest that dopaminergic dysfunction is a mechanistic link between developmental trauma and vulnerability towards mental illness in adulthood.
The Biber Figure Learning Test (BFLT) is a serial figure learning assessment previously been shown to be sensitive to various biomarkers of the aging brain. BFLT is an extensive assessment requiring about 30 minutes for administration. In this study, we investigated BFLT’s associations with subjective cognitive decline (SCD), an early marker for preclinical Alzheimer’s Disease (AD), and examined whether alternative BFLT indices could be utilized to considerably shorten the length of assessment without decreasing its sensitivity to SCD.
Participants and Methods:
Participants were 50 cognitively normal older adults (8% Hispanic, 92% Non-Hispanic; 78% White, 16% Black; 64% female; mean age =72.7 (SD =6.2); mean education =17.05 (SD =2.09)). SCD was measured using a 20-item age-anchored dichotomous questionnaire that assessed complaints of cognitive functioning, and the BFLT was administered in full. Pearson correlations were conducted between SCD and BFLT scores including: Trial 1 Learning (T1), Trials 1 to 2 Total Learning (T1T2), Trials 1 to 3 Total Learning (T1T3), Trials 1 to 5 Total Learning (Total Learning), Immediate Recall, Delayed Recall, Proactive Interference (Trial B – Trial 1), Retroactive Interference (Immediate Recall – Trial 5), and Total Discrimination (calculated as [Recognition Total Correct + 0.5]/16) − ([Total False Alarms + 0.5]/31]). A Fishers Exact Test was utilized to compare the correlational strength between SCD and each of the BFLT scores. Lastly, demographically adjusted (age, gender, and education) regression models were conducted to examine SCD as an individual predictor for the various BFLT scores.
Results:
SCD was negatively associated with BFLT T1 (r =-0.406, p =0.003), T1T2 (r =-0.331, p =0.019), T1T3 (r =-0.323, p =0.022), Total Learning (r =-0.283, p =0.046), Immediate Recall (r =-0.322, p =0.023), Delayed Recall (r =-0.318, p =0.025), and Retroactive Interference (r =-0.388, p =0.005) and positively associated with Proactive Interference (r =0.308, p =0.029). There was no significant difference in correlational strength between any of these BFLT scores and SCD. Adjusting for demographics, SCD predicted Immediate Recall (B =-0.273, p =0.029), Total Learning (B =- 0.253, p =0.040), T1 (B =-0.412, p =0.002), T1T2 (B =-0.326, p =0.010), T1T3 (B =-0.299, p =0.017), Proactive Interference (B =0.292, p =0.050), and Retroactive Interference (B =- 0.330, p =0.025).
Conclusions:
Eight of the nine assessed BFLT scores were strongly correlated with age-anchored SCD and age-anchored SCD predicted seven of the nine assessed BFLT indices when adjusted for demographics. Although additional work is needed, these findings suggest SCD’s sensitivity to changes in visuospatial learning and memory, supporting its use as an early marker for preclinical AD. Likewise, our results suggest that an abbreviated version of the BFLT could be utilized that shortens testing time and reduces participant fatigue without a decrease in clinical relevance. Through ongoing longitudinal work, we hope to further disentangle the relationship between SCD and visuospatial learning and memory as measured through the BFTL and to examine how associations between SCD and the BFLT assessment change over time.
Subjective Cognitive Decline (SCD) is the self-reported experience of one’s own declining cognition prior to objective impairment on clinical neuropsychological testing. While SCD is a promising marker of preclinical Alzheimer’s disease (AD), information is needed to determine which cognitive complaints reflect typical aging versus prodromal degenerative disease. The objective of the current study was to examine the extent to which specific cognitive complaints were associated with two clinical outcomes including: 1) lower performance on cognitive tasks sensitive to preclinical AD; and 2) seeking help (i.e., medical attention) for cognitive difficulties.
Participants and Methods:
The current sample consisted of 175 healthy older adults (56 Male, 119 Female), aged 51 to 90 (M=72.67, SD=7.12) with a mean education of 16 years (SD=2.3 years) who performed > -1.5 SD on clinical neuropsychological testing. 26.8% of the sample self-reported as race/ethnic minorities (e.g., Hispanic or Non-Hispanic, Black, Asian, Other.) Participants completed a 20-item SCD questionnaire assessing perceived cognitive difficulties in comparison to same aged peers, and tests shown to be sensitive to preclinical AD including the Face Name Associative Learning Test and the Loewenstein-Acevedo Scales for Semantic Interference and Learning. Participants were coded as having sought help for SCD (39%) if they entered the current study from a clinical referral source, OR if they entered through a non-clinical referral stream but indicated that they had previously seen a doctor specifically for memory concerns or spoken to their doctor about memory concerns. Chi square tests were used to examine relationships between SCD item endorsement and help-seeking; ANOVAs were used to the extent to which item endorsement was associated with performance on cognitive tests. Results were considered significant at p < .05.
Results:
Three SCD items were associated with both lower cognitive test scores and having sought help for SCD (p values ranged from < .001 to .02). Items included difficulty remembering the date or day of the week and remembering a few shopping items without a list. One non-memory item was also associated with both outcomes including difficulty thinking ahead. In contrast, six items were not related to either outcome of interest. Such items included difficulty remembering appointments, remembering where you put things like keys, following a map to a new location, doing two things at once, understanding what you read, or understanding what people say to you. The remaining eleven items explore the extent to which selective associations exist with either help-seeking or cognitive performance.
Conclusions:
Patients and clinicians alike are often unsure about which cognitive difficulties are typical for aging and which may be the cause for further workup. Current results suggest that certain complaints among cognitively healthy older adults may be cause for more thorough evaluation or monitoring. These complaints include specific memory and nonmemory concerns. Future work is needed to determine if these complaints predict future cognitive decline or conversion to Mild Cognitive Impairment.
Subjective Cognitive Decline (SCD), the perception of deteriorating cognition in the absence of apparent impairment on objective testing, has gained momentum in recent literature as a risk marker for AD. Traditional neuropsychological assessments, while typically inclusive of a word list learning task, often do not include a comparable figure learning task. Growing evidence suggests that nonverbal assessments may be particularly sensitive to the earliest cognitive changes associated with Alzheimer’s disease. The Biber Figure Learning Test (BFLT), a visuospatial analogue to verbal list learning tasks, has been shown to associate with brain-based biomarkers of Alzheimer’s disease (AD; hippocampal volume, amyloid load). This study investigates the utility of the BFLT in capturing SCD above and beyond other cognitive measures sensitive to AD progression.
Participants and Methods:
50 community-dwelling, cognitively normal individuals (78% White, 16% Black, 6% Other; 92% Non-Hispanic; 64% Female; Education M=17.1, SD=2.1; Age M=72.7, SD=6.2) participated in a study of SCD. All participants performed >-1.5 SD on clinical neuropsychological testing including a word list learning task. SCD was assessed using a 20-item scale querying individuals’ perception of difficulty across a range of memory and non-memory abilities in relation to others of the same age. Participants completed the BFLT, Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), Short-Term Memory Binding (STMB), and Face-Name Associative Memory Exam (FNAME), previously established as being sensitive to pre-clinical AD, were examined as predictors of SCD. A multiple regression adjusted for demographics (age, gender, education) was used to investigate the extent to which BFLT Trial 1 (T1) predicted SCD above and beyond these other cognitive measures sensitive to AD progression. Trial 1 of the BFLT was used based on a separate abstract examining which BFLT score was most highly associated with SCD (Kann et al., pending acceptance).
Results:
Adjusting for demographics, the present model accounts for 42% of the variance in SCD, while Biber T1 alone accounts for 20% and is the only significant individual predictor of SCD (β=-0.55, p=0.004). In contrast, other variables in the model independently accounted for less than 1% to 4% each (age β=-0.23, p=0.15; gender β=-0.15, p=0.34; education β=0.06, p=0.66; LASSI-L β=-0.11, p=0.55; STMB β=-0.03, p=0.85; FNAME β=-0.10, p=0.64).
Conclusions:
The present study demonstrates the usefulness of the first learning trial of the BFLT as an independent predictor of SCD above and beyond other verbal and nonverbal measures sensitive to AD pathology. It also highlights the value of including even one trial of figure learning (< 5 minutes) in both clinical and research assessments seeking to capture cognitive changes which may be the earliest indicators of a neurodegenerative process. Ongoing longitudinal research is examining the predictive utility of the BFLT for future cognitive decline and transition to Mild Cognitive Impairment. Further research should explore the association between Biber T1, specifically, and neuropathological biomarkers of AD to further establish its utility as a portent of AD.
Research has indicated that racial and ethnic minoritized groups in the United States are disproportionately affected by dementia (e.g., Alzheimer’s disease), and seek help (HS) later in the disease course, if at all. It has also been posited that individuals from different ethno-racial groups have divergent perceptions of the aging process, which may influence HS. These disparities warrant tailored preventive efforts to encourage identification of factors which contribute to HS to enable earlier psychoeducation and enhanced access to resources. The factors which influence HS may differ across ethnoracial groups. Here we examine the relative influence of subjective cognitive decline (SCD), a risk factor for AD, and aging perceptions to HS in these groups.
Participants and Methods:
The current sample consisted of 161 healthy older adults (51 Male, 110 Female), aged 51 to 92 (M=73.43, SD=6.85) with a mean education of 16 years (SD=2.3 years) who performed > -1.5 SD on clinical neuropsychological testing. 26.7% of the sample self-reported as race/ethnic minorities (e.g., Hispanic or Non-Hispanic African American, Asian, Other.) Participants completed a 20-item SCD questionnaire assessing perceived cognitive difficulties in comparison to same aged peers, in addition to measures assessing HS behavior, (e.g., Have you gone to the doctor specifically for memory concerns?), and aging perceptions (e.g., older adulthood group identification, explicit stereotypes, essentialism). Point biserial correlations examined relationships between SCD, HS and aging perceptions, and multinomial logistic regressions examined the contribution of SCD and aging perceptions to HS across majority (White) and minoritized groups (Non-White participants).
Results:
In bivariate analyses of the White participant group, HS was associated with SCD (r=0.43, p<0.001) and age group identification (r=0.27, p<0.01), and the latter were also associated (r=-0.19, p<0.05). The logistic regression model correctly classified 86% of participants (same as null), explaining a relatively small proportion of variance in HS, Snell R2 = 0.09, Nagelkerke’s R2 = 0.16. Age group identification was not associated with HS (b=-0.02, SE=0.26, p=0.94, 95% CI [0.59, 1.63] but SCD was (p=0.04). In the non-White group (n=42), bivariate analyses showed that HS was associated with essentialism (r=-0.41, p<0.01; belief aging as a fixed and inevitable process)) and explicit stereotypes (r=-0.42, p<0.01) but not with SCD (r=0.21, p=0.19). SCD was also associated with essentialism (p=-0.32, p<0.05), stereotypes (p=0.32, p<0.05), and age group identification (r=0.38, p<0.01). The regression model correctly classified 88.9% of participants (same as null); neither SCD (p=0.39), explicit stereotypes (p=0.43), essentialism (p=0.72), nor age group identification (p=0.62) contributed to HS when all were considered.
Conclusions:
When both SCD and age perceptions are examined together as predictors of HS, SCD alone predicts HS in the majority group. Neither construct predicts HS in the minoritized group—despite significant bivariate associations between HS, aging perceptions and SCD that varied across ethno-racial groups. Findings illustrate that SCD and aging perceptions may contribute differently to HS across ethno-racial groups in the US, and as such may indicate different priorities when implementing HS tools (e.g., screeners for detection of cognitive impairment). Ongoing work is addressing illness perceptions, another key barrier in HS in these groups to further inform on tailoring of services.
An individual with dementia suffers from cognitive decline affecting not only memory but at least one of the other domains, such as personality, praxis, abstract thought, language, executive functioning, attention, and social skills. Further, the severity of the decline must be significant enough to interfere with daily functions. It is currently unknown whether any of the causes of dementia can be cured. Many challenges confront patients and their families, including a lack of knowledge about dementia and associated treatments; therefore, it is essential to study illness perception regarding dementia-related symptoms in order to improve psychoeducation and lower barriers to seeking assistance. How individuals perceive and make sense of early dementia symptoms can significantly impact their help-seeking behaviors (HS). Exploring illness-perception regarding dementia-related symptoms may contribute to the development of strategies for increasing HS, early diagnosis, and intervention. The objective of this study is to describe aspects of illness perception in cognitively healthy older adults and examine potential correlations with demographic variables, including age, gender, and education.
Participants and Methods:
The cohort comprised 55 cognitively healthy older adults enrolled in a study examining Subjective Cognitive Decline. All participants performed > -1.5 SD on clinical neuropsychological testing. Participants were 70% female and 30% male; and self-identified as White = 78%, Black = 16%, Asian = 2%, Other = 4% and Non-Hispanic = 98%. Participants read a short vignette describing a person experiencing significant memory issues representative of an individual with mild dementia and answered seven follow-up questions regarding the cause of memory problems, the likely course of memory problems, and potential treatments for memory problems. Chi-square analyses examined the endorsement of items in relation to age, gender, and education.
Results:
When asked about the likely cause of memory problems, 65% of participants endorsed neurologic disease, 53% of participants endorsed normal aging, 26% endorsed stress, 25% endorsed genes, 4% endorsed fate/luck, and 16% endorsed "Don't know" for likely cause of symptoms. 64% of participants responded "will get worse", 18% "will go up and down", 16% "Don't know", and 2% "Other" in response to the progression of memory problems over time. For "Can he do anything to help [memory problems]?", only 2% responded "No" while 76% responded "Yes" and 22% endorsed "Don't know". On a follow-up question regarding ways an individual could improve his cognitive difficulties, 78% "Social Engagement", 73% "Exercise", 64% endorsed "Medication", 48% "Diet", 42% Psychological Treatment", 29% "Rehabilitation", 9%" Don't know" and 15% "Other." Lastly, 58% of participants reported "Independence", 33% "Identity," 4% "Friends," 4% "Respect," and 1% "Don't know" for things he may risk losing due to memory problems. Age, gender, and education were not associated with any of the above responses (p > .05).
Conclusions:
Older adults demonstrate a range of ideas about the cause, course, and potential treatment for memory disorders. Understanding how and what factors impact illness perception is a pivotal step in improving illness perception and ultimately narrowing the gap in health disparities and HS. Further work in a large demographically representative sample is needed on illness perception and how socioeconomic factors, ethnicity, and other mediators interact with its impact on HS for dementia-related symptoms.
The aim of this study was to determine if there was an association between the presence of cytoplasmic strings (CS) and their characteristics, with blastocyst quality, development and clinical outcome in human blastocysts. This two-centre cohort study was performed between July 2017 and September 2018 and involved a total of 1152 blastocysts from 225 patients undergoing in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). All embryos were cultured in Embryoscope+ and were assessed for CS using time-lapse images. A single assessor examined all blastocysts and reviewed videos using the EmbyroViewer® Software. Blastocyst quality was assessed on day 5 of embryo development. The number of CS, location and duration of their activity was recorded on days 5/6. A positive association between the presence of CS in human blastocysts with blastocyst quality was identified. Blastocysts with a higher number of CS present, were of higher quality and were in the more advanced stages of development. Top quality blastocysts had CS activity present for longer, as well as having a higher number of vesicles present travelling along the CS. Blastocysts that had CS present, had a significantly higher live birth rate. This study has confirmed that a higher number of CS and vesicles in human blastocysts is associated with top quality blastocysts and is not a negative predictor of development. They had a higher number of CS present that appeared earlier in development and, although ceased activity sooner, had a longer duration of activity. Blastocysts with CS had a significant increase in live birth rate.
Nerve transfer surgery for patients with nerve and spinal cord injuries can result in dramatic functional improvements. As a result, interdisciplinary complex nerve injury programs (CNIPs) have been established in many Canadian centers, providing electrodiagnostic and surgical consultations in a single encounter. We sought to determine which allied health care services are included in Canadian CNIPs, at the 3rd Annual Canadian Peripheral Nerve Symposium. Twenty CNIPs responded to a brief survey and reported access as follows: occupational therapy = 60%, physiotherapy = 40%, social work = 20%, and mental health = 10%. Access to allied health services is variable in CNIPs across Canada, possibly resulting in heterogeneity in patient care.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
OBJECTIVES/SPECIFIC AIMS: Our primary objective was to understand the relationship between incident or recent stressful events and adherence to HIV care in the context of other person, environment, and HIV-specific stressors in a sample of Black women living with HIV (WLWH). METHODS/STUDY POPULATION: Thirty in-depth interviews were conducted with Black women living with HIV who receive care at an academic HIV primary care clinic in the Southern region of the United States to elicit stressful events influencing adherence to HIV care. Semi-structured interview guides were used to facilitate discussion regarding stressful events and adherence to HIV care. Interviews were audiotaped and transcribed verbatim. Transcripts were independently coded using a theme-based approach by two experienced coders, findings were compared, and discrepancies were resolved by discussion. RESULTS/ANTICIPATED RESULTS: Participants described frequently experiencing incident stressful events including death or serious illness of a close friend or family member, and relationship, financial, and employment difficulties. Furthermore, participants reported experiencing traumatic events such as sexual and physical abuse during childhood and adolescents. While experiencing traumatic events such as sexual and physical abuse during childhood and adolescence may be distressing, these events did not influence adherence to HIV care. However, incident stressful events as defined above did influence adherence to HIV care for some participants, but not for others. For participants who reported that stressful events did not influence adherence to HIV care, factors such as personal motivation, access to social support, and adaptive coping strategies facilitated their engagement in care. DISCUSSION/SIGNIFICANCE OF IMPACT: Experiencing stressful events, incident or traumatic, is common among Black WLWH and have the potential to negatively influence adherence to HIV care. Thus, Interventions aimed at identifying and addressing stress, social support, and coping are essential to improve adherence to HIV care behaviors.
Seed-dispersal ecology in tropical montane forests (TMF) differs in some predictable ways from tropical lowland forests (TLF). Environmental, biogeographic and biotic factors together shape dispersal syndromes which in turn influence forest structure and community composition. Data on diaspore traits along five elevational gradients from forests in Thailand, the Philippines, Tanzania, Malawi and Nigeria showed that diaspore size decreases with increasing altitude, fleshy fruits remain the most common fruit type but the relative proportion of wind-dispersed diaspores increases with altitude. Probably corresponding to diaspore size decreasing with increasing elevation, we also provide evidence that avian body size and gape width decrease with increasing altitude. Among other notable changes in the frugivorous fauna across elevational gradients, we found quantitative evidence illustrating that the proportion of bird versus mammalian frugivores increases with altitude, while TMF primates decrease in diversity and density, and switch diets to include less fruit and more leaf proportionately. A paucity of studies on dispersal distance and seed shadows, the dispersal/predation balance and density-dependent mortality thwart much-needed conclusive comparisons of seed dispersal ecology between TMF and TLF, especially from understudied Asian forests. We examine the available evidence, reveal knowledge gaps and recommend research to enhance our understanding of seed dispersal ecology in tropical forests. This review demonstrates that seed dispersal is a more deterministic and important process in tropical montane forests than has been previously appreciated.
We report on the analysis of virtual powder-diffraction patterns from serial femtosecond crystallography (SFX) data collected at an X-ray free-electron laser. Different approaches to binning and normalizing these patterns are discussed with respect to the microstructural characteristics which each highlights. Analysis of SFX data from a powder of Pr0.5Ca0.5MnO3 in this way finds evidence of other trace phases in its microstructure which was not detectable in a standard powder-diffraction measurement. Furthermore, a comparison between two virtual powder pattern integration strategies is shown to yield different diffraction peak broadening, indicating sensitivity to different types of microstrain. This paper is a first step in developing new data analysis methods for microstructure characterization from serial crystallography data.
Understanding nutrient intakes among women of childbearing age within the USA is important given the accumulating evidence that maternal body weight gain and nutrient intakes prior to pregnancy may influence the health and well-being of the offspring. The objective of the present study was to evaluate nutritional status in women of childbearing age and to ascertain the influence of ethnicity and income on nutrient intakes.
Design
Nutritional status was assessed using data on nutrient intakes through foods and supplements from the National Health and Nutrition Examination Survey. Biomarker data from the Centers for Disease Control and Prevention were used to assess nutritional status for selected nutrients. Poverty–income ratio was used to assess family income.
Subjects
White (n 1560), African-American (n 889) and Mexican-American (n 761) women aged 19–30 and 31–50 years were included.
Setting
A nationally representative sample of non-pregnant women of childbearing age resident in the USA.
Results
African-American women had the lowest intakes of fibre, folate, riboflavin, P, K, Ca and Mg. Women (31–50 years) with a poverty–income ratio of ≤1·85 had significantly lower intakes of almost all nutrients analysed. Irrespective of ethnicity and income, a significant percentage of women were not consuming the estimated recommended amounts (Estimated Average Requirement) of several key nutrients: vitamin A (~80 %), vitamin D (~78 %) and fibre (~92 %). Nutrient biomarker data were generally reflective of nutrient intake patterns among the different ethnic groups.
Conclusions
Women of childbearing age in the USA are not meeting nutrient intake guidelines, with differences between ethnic groups and socio-economic strata. These factors should be considered when establishing nutrition science advocacy and policy.
This paper investigates the radical approach to architectural representation of Bernard Tschumi in the late 1970s and its relationship to the literary and visual practices of Dada and Surrealism. Focussing on Tschumi's Advertisements for Architecture and Manhattan Transcripts, the paper demonstrates how the critique of avant-garde tactics in Peter Bürger and Walter Benjamin applies to a broader understanding of politics in architecture and its efficacy.