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The dry sky: future scenarios for humanity's modification of the atmospheric water cycle
- Patrick W. Keys, Lan Wang-Erlandsson, Michele-Lee Moore, Agnes Pranindita, Fabian Stenzel, Olli Varis, Rekha Warrier, R. Bin Wong, Paolo D'Odorico, Carl Folke
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- Global Sustainability / Volume 7 / 2024
- Published online by Cambridge University Press:
- 20 March 2024, e11
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Non-Technical Summary
Human societies are changing where and how water flows through the atmosphere. However, these changes in the atmospheric water cycle are not being managed, nor is there any real sense of where these changes might be headed in the future. Thus, we develop a new economic theory of atmospheric water management, and explore this theory using creative story-based scenarios. These scenarios reveal surprising possibilities for the future of atmospheric water management, ranging from a stock market for transpiration to on-demand weather. We discuss these story-based futures in the context of research and policy priorities in the present day.
Technical SummaryHumanity is modifying the atmospheric water cycle, via land use, climate change, air pollution, and weather modification. Historically, atmospheric water was implicitly considered a ‘public good’ since it was neither actively consumed nor controlled. However, given anthropogenic changes, atmospheric water can become a ‘common-pool’ good (consumable) or a ‘club’ good (controllable). Moreover, advancements in weather modification presage water becoming a ‘private’ good, meaning both consumable and controllable. Given the implications, we designed a theoretical framing of atmospheric water as an economic good and used a combination of methods in order to explore possible future scenarios based on human modifications of the atmospheric water cycle. First, a systematic literature search of scholarly abstracts was used in a computational text analysis. Second, the output of the text analysis was matched to different parts of an existing economic goods framework. Then, a group of global water experts were trained and developed story-based scenarios. The resultant scenarios serve as creative investigations of the future of human modification of the atmospheric water cycle. We discuss how the scenarios can enhance anticipatory capacity in the context of both future research frontiers and potential policy pathways including transboundary governance, finance, and resource management.
Social Media SummaryStory-based scenarios reveal novel future pathways for the management of the atmospheric water cycle.
Incidence of mental health diagnoses during the COVID-19 pandemic: a multinational network study
- Yi Chai, Kenneth K. C. Man, Hao Luo, Carmen Olga Torre, Yun Kwok Wing, Joseph F. Hayes, David P. J. Osborn, Wing Chung Chang, Xiaoyu Lin, Can Yin, Esther W. Chan, Ivan C. H. Lam, Stephen Fortin, David M. Kern, Dong Yun Lee, Rae Woong Park, Jae-Won Jang, Jing Li, Sarah Seager, Wallis C. Y. Lau, Ian C. K. Wong
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 33 / 2024
- Published online by Cambridge University Press:
- 04 March 2024, e9
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Aims
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
MethodsBy using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
ResultsA total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
ConclusionsHealthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
Associations between food insecurity and diabetes risk factors in US adolescents in the National Health and Nutrition Examination Survey (NHANES) 2007–2016
- Aarohee P Fulay, Joyce M Lee, Ana Baylin, Julia A Wolfson, Cindy W Leung
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- Journal:
- Public Health Nutrition / Volume 27 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 12 February 2024, e68
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Objective:
To evaluate the associations between household food insecurity and diabetes risk factors among lower-income US adolescents.
Design:Cross-sectional analysis. Household food security status was measured using the 18-item Food Security Survey Module. Simple and multivariable linear and logistic regressions were used to assess the association between food security status and fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), HbA1C and homoeostatic model assessment – insulin resistance (HOMA-IR). The analyses were adjusted for household and adolescent demographic and health characteristics.
Setting:USA.
Participants:3412 US adolescents aged 12–19 years with household incomes ≤300 % of the federal poverty line from the National Health and Nutrition Examination Survey cycles 2007–2016.
Results:The weighted prevalence of marginal food security was 15·4 % and of food insecurity was 32·9 %. After multivariate adjustment, adolescents with food insecurity had a 0·04 % higher HbA1C (95 % CI 0·00, 0·09, P-value = 0·04) than adolescents with food security. There was also a significant overall trend between severity of food insecurity and higher HbA1C (Ptrend = 0·045). There were no significant mean differences in adolescents’ FPG, OGTT or HOMA-IR by household food security.
Conclusions:Food insecurity was associated with slightly higher HbA1c in a 10-year sample of lower-income US adolescents aged 12–19 years; however, other associations with diabetes risk factors were not significant. Overall, this suggests slight evidence for an association between food insecurity and diabetes risk in US adolescents. Further investigation is warranted to examine this association over time.
Nation-Wide Variation in Presence of Legislation or Protocols for EMS Care of Operational Canines
- David W. Schoenfeld, Caroline E. Thomas, Lee Palmer, William Justice, Esther Hwang, Kate D. Zimmerman, Jeffrey M. Goodloe, Jonathan D. Shecter, Stephen H. Thomas
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- Journal:
- Prehospital and Disaster Medicine / Volume 39 / Issue 1 / February 2024
- Published online by Cambridge University Press:
- 15 February 2024, pp. 59-64
- Print publication:
- February 2024
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Background & Aims:
Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study’s aim was to assess the current status of states’ OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States.
Methods:Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken. For each state and for the District of Columbia (DC), the presence of OpK9 legislation and/or care protocols was ascertained. Information was obtained through governmental records and from stakeholders (eg, state EMS medical directors and state veterinary boards).
The main endpoints were proportions of states with OpK9 laws and/or treatment protocols. Proportions are reported with 95% confidence intervals (CIs). Fisher’s exact test (P <.05) assessed whether presence of an OpK9 law in a given jurisdiction was associated with presence of an OpK9 care protocol, and whether there was geographic variation (based on United States Census Bureau regions) in presence of OpK9 laws or protocols.
Results:Of 51 jurisdictions, 20 (39.2%) had OpK9 legislation and 23 (45.1%) had state-wide protocols for EMS treatment of OpK9s. There was no association (P = .991) between presence of legislation and presence of protocols. There was no association (P = .144) between presence of legislation and region: Northeast 66.7% (95% CI, 29.9-92.5%), Midwest 50.0% (95% CI, 21.1-78.9%), South 29.4% (95% CI, 10.3-56.0%), and West 23.1% (95% CI, 5.0-53.8%). There was significant (P = .001) regional variation in presence of state-wide OpK9 treatment protocols: Northeast 100.0% (95% CI, 66.4-100.0%), Midwest 16.7% (95% CI, 2.1-48.4%), South 47.1% (95% CI, 23.0-72.2%), and West 30.8% (95% CI, 9.1-61.4%).
Conclusion:There is substantial disparity with regard to presence of OpK9 legal and/or clinical guidance. National collaborative guidelines development is advisable to optimize and standardize care of OpK9s. Additional attention should be paid to educational and training programs to best utilize the limited available training budgets.
Comparisons of Structural Fe Reduction in Smectites by Bacteria and Dithionite: An Infrared Spectroscopic Study
- Kangwon Lee, Joel E. Kostka, Joseph W. Stucki
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- Journal:
- Clays and Clay Minerals / Volume 54 / Issue 2 / April 2006
- Published online by Cambridge University Press:
- 01 January 2024, pp. 195-208
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The reduction of structural Fe in smectite is mediated either abiotically, by reaction with dithionite, or biotically, by Fe-reducing bacteria. The effects of abiotic reduction on clay-surface chemistry are much better known than the effects of biotic reduction. Since bacteria are probably the principal agent for mediating redox processes in natural soils and sediments, further study is needed to ascertain the differences between biotic and abiotic reduction processes. The purpose of the present study was to compare the effects of dithionite (abiotic) and bacteria (biotic) reduction of structural Fe in smectites on the clay structure as observed by infrared spectroscopy. Three reference smectites, namely, Garfield nontronite, ferruginous smectite (SWa-1), and Upton, Wyoming, montmorillonite, were reduced to similar levels by either Shewanella oneidensis or by pH-buffered sodium dithionite. Each sample was then analyzed by Fourier transform infrared spectroscopy (FTIR). Parallel samples were reoxidized by bubbling O2 gas through the reduced suspension at room temperature prior to FTIR analysis. Redox states were quantified by chemical analysis, using 1, 10-phenanthroline. The reduction level achieved by dithionite was controlled to approximate that of the bacterial reduction treatment so that valid comparisons could be made between the two treatments. Bacterial reduction was achieved by incubating the Na-saturated smectites with S. oneidensis strain MR-1 in a minimal medium including 20 mM lactate. After redox treatment, the clay was washed four times with deoxygenated 5 mM NaCl. The sample was then prepared either as a self-supporting film for OH-stretching and deformation bands or as a deposit on ZnSe windows for Si-O stretching bands and placed inside a controlled atmosphere cell also fitted with ZnSe windows. The spectra from bacteria-treated samples were compared with dithionite-treated samples having a similar Fe(II) content. The changes observed in all three spectral regions (OH stretching, M2-O-H deformation, and Si-O stretching) for bacteria-reduced smectite were similar to results obtained at a comparable level of reduction by dithionite. In general, the shift of the structural OH vibration and the Si-O vibration, and the loss of intensity of OH groups, indicate that the bonding and/or symmetry properties in the octahedral and tetrahedral sheets changes as Fe(III) reduces to Fe(II). Upon reoxidation, peak positions and intensities of the reduced smectites were largely restored to the unaltered condition with some minor exceptions. These observations are interpreted to mean that bacterial reduction of Fe modifies the crystal structures of Fe-bearing smectites, but the overall effects are modest and of about the same extent as dithionite at similar levels of reduction. No extensive changes in clay structure were observed under conditions present in our model system.
4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
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Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
93 Impact of Cardiovascular Risk on Cognitive and Brain Aging in Autosomal Dominant Frontotemporal Dementia
- Anna M VandeBunte, Emily W Paolillo, Hyunwoo Lee, Ging-Yuek Robin Hsiung, Adam Staffaroni, Shannon Y Lee, Carmela Tartaglia, Hilary Heur, Joel H Kramer, Brad Boeve, Adam Boxer, Howie Rosen, Kaitlin B Casaletto
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 193-194
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Objective:
Poor cardiovascular health occurs with age and is associated with increased dementia risk, yet its impact on frontotemporal lobar degeneration (FTLD) and autosomal dominant neurodegenerative disease has not been well established. Examining cardiovascular risk in a population with high genetic vulnerability provides an opportunity to assess the impact of lifestyle factors on brain health outcomes. In the current study, we examined whether systemic vascular burden associates with accelerated cognitive and brain aging outcomes in genetic FTLD.
Participants and Methods:166 adults with autosomal dominant FTLD (C9orf72 n= 97; GRN n= 34; MAPT n= 35; 54% female; Mage = 47.9; Meducation = 15.6 years) enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Longitudinal FTD study (ALLFTD) were included. Participants completed neuroimaging and were screened for cardiovascular risk and functional impairment during a comprehensive neurobehavioral and medical interview. A vascular burden score (VBS) was created by summing vascular risk factors (VRS) [diabetes, hypertension, hyperlipidemia, and sleep apnea] and vascular diseases (VDS) [cerebrovascular disease (e.g., TIA, CVA), cardiac arrhythmia (e.g., atrial fibrillation, pacemaker, defibrillator), coronary artery disease (e.g., myocardial infarction, cardiac bypass, stent), and congestive heart failure] following a previously developed composite (range 0 to 8). We examined the interaction between each vascular health metric (VBS, VDS, VRS) and age (vascular health*age) on clinical severity (CDR plus NACC FTLD-SB), and white matter hyperintensity (WMH) volume outcomes, adjusting for age and sex. Vascular risk, disease, and overall burden scores were examined in separate models.
Results:There was a statistically significant interaction between total VBS and age on both clinical severity (ß=0.20, p=0.044) and WMH burden (ß=0.20, p=0.032). Mutation carriers with higher vascular burden evidenced worse clinical and WMH outcomes for their age. When breaking down the vascular burden score into (separate) vascular risk (VRS) and vascular disease (VDS) scores, the interaction between age and VRS remained significant only for WMH (ß=0.26, p=0.009), but not clinical severity (ß=0.04, p=0.685). On the other hand, the interaction between VDS and age remained significant only for clinical severity (ß=0.20, p=0.041) but not WMH (ß=0.17, p=0.066).
Conclusions:Our results demonstrate that systemic vascular burden is associated with an “accelerated aging” pattern on clinical and white matter outcomes in autosomal dominant FTLD. Specifically, mutation carriers with greater vascular burden show poorer neurobehavioral outcomes for their chronological age. When separating vascular risk from disease, risk was associated with higher age-related WMH burden, whereas disease was associated with poorer age-related clinical severity of mutation carriers. This pattern suggests preferential brain-related effects of vascular risk factors, while the functional impact of such factors may be more closely aligned with fulminant vascular disease. Our results suggest cardiovascular health may be an important, potentially modifiable risk factor to help mitigate the cognitive and behavioral disturbances associated with having a pathogenic variant of autosomal dominant FTLD. Future studies should continue to examine the neuropathological processes underlying the impact of cardiovascular risk in FTLD to inform more precise recommendations, particularly as it relates to lifestyle interventions.
24 Associations Between Positive Psychological Factors and Neurocognitive Functioning in Older Adults
- Jacqueline E Maye, Colin A Depp, Ellen E Lee, Ho-Cheol Kim, Dilip V Jeste, Elizabeth W Twamley
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 337
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Objective:
Psychological wellness and strong cognitive skills are both important to successful aging. Although there are well-established relationships between psychiatric illness (e.g., depression, anxiety, PTSD) and cognitive dysfunction, few studies have focused on the relationships between positive psychological factors and neurocognitive function in older adults. Our goal was to explore associations between these two sets of measures in older adults.
Participants and Methods:Participants (n=111) were part of a longitudinal study of biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. Participants were administered a cognitive screening test (Montreal Cognitive Assessment; MoCA), a comprehensive neuropsychological battery, and a set of published self-report scales measuring positive emotional and psychological function. Neuropsychological scores were appropriately normed, and composite scores were calculated for the following domains: language (Boston Naming Test, Delis-Kaplan Executive Function System [D-KEFS] Verbal Fluency), attention/working memory (Wechsler Adult Intelligence Scale-IV [WAIS-IV] Digit Span, DKEFS Visual Scanning), learning and delayed recall (Brief Visuospatial Memory Test-Revised, Hopkins Verbal Learning Test-Revised), processing speed (WAIS-IV Coding, D-KEFS Trails Number and Letter Sequencing, D-KEFS Color-Word Interference Test Color and Word Naming), and executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching, DKEFS Letter/Number Switching). Self-Report scales included the Perceived Stress Scale, Center for Epidemiological Studies in Depression Scale, Emotional Support Scale, Connor-Davidson Resilience Scale, Coping Humor and Self-Efficacy Scales, Personal Mastery Scale, Meaning in Life Scale, Self-Rated Successful Aging, Satisfaction with Life, Cognitive Failures Questionnaire, and Lifetime Orientation Test-Revised. Due to the large number of psychological functioning measures, dimension reduction was undertaken via principal component analysis, resulting in a two-factor solution. Bivariate Pearson correlations were then computed between the two factor scores and each neurocognitive variable.
Results:Factor 1 consisted of variables reflecting Positive Subjective Functioning. A higher score on Factor 1 (indicating higher self-rating of successful aging, fewer perceived cognitive failures, fewer reported depressive symptoms, less perceived stress/anxiety, more perceived emotional support, more satisfaction with life, more meaningfulness in life, and more search for meaning in life) was associated with better attention/working memory (r=0.226, p=0.049) and executive function (r=0.242, p=0.035). Factor 2 consisted of variables that reflected Positive Coping Skills. A higher score on Factor 2 (indicating more happiness, higher optimism, greater resilience, higher sense of personal mastery, more use of humor as a coping strategy, and greater coping self-efficacy) was associated with better performance on tests of language (r=0.325, p=0.004), learning (r=0.313, p=0.006) and delayed recall (r=0.241, p=0.035) of visual and verbal information, and better MoCA performance (r=0.440, p<0.001). Neither factor was associated with processing speed.
Conclusions:Higher levels of subjective functioning and positive outlook/coping skills were associated with better neuropsychological performance. Given that late life is a time of risk for cognitive decline, future research should consider the influence of positive psychological functioning on neurocognitive outcomes and vice versa, as these relationships may have neurobiological and therapeutic implications for overall function in later life.
5 Rejuvenating Blood Factor TIMP2 Relates to Physical Activity and Cognitive Functioning in Older Adults on The Alzheimer’s Disease Continuum
- Emily W Paolillo, Shannon Y Lee, Anna M Vandebunte, Rowan Saloner, Leslie S Gaynor, Joel H Kramer, Kaitlin B Casaletto
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 106-107
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Objective:
Tissue inhibitor of metalloproteinases 2 (TIMP2) is produced peripherally, crosses the blood-brain barrier, and improves synaptic plasticity and hippocampal-dependent cognition in aged mice; however, the role of TIMP2 in human cognitive aging is unclear. We examined associations of circulating TIMP2 levels in blood with a known plasticity-inducing behavior, physical activity, and cognitive functioning among older adults along the Alzheimer’s disease continuum.
Participants and Methods:Participants included 84 community-dwelling older adults (meanage = 78.8; 57% female; 82% cognitively normal; 14% MCI; 4% mild dementia; 35% PET Aß+) enrolled in the UC San Francisco Memory and Aging Center. All participants completed 30 days of observational FitbitTM monitoring to quantify physical activity (average daily steps), as well as a comprehensive in-person visit including blood draw (proteins assayed on SOMAscan platform), [18F]AV-45 positron emission tomography (PET) to quantify brain beta-amyloid (centiloids), and neuropsychological assessment. Composite cognitive z-scores were calculated for memory (California Verbal Learning Test-II [CVLT-II] and Benson Figure Recall), semantic processing (animal fluency and Boston Naming Test), and executive functioning (digits backwards span, Stroop inhibition, modified trail making test, lexical fluency, and design fluency). Multiple linear regression examined TIMP2 as a function of physical activity, covarying for age and PET centiloids. Additional regression models separately examined cognitive z-scores as a function of TIMP2, covarying for age, sex, education, PET centiloids, and body mass index (BMI).
Results:TIMP2 was not significantly correlated with age, sex, education, or PET centiloids (ps > 0.05); however, TIMP2 was negatively correlated with BMI (r = -0.23, p = 0.036). Greater average daily steps related to higher levels of TIMP2 (b = 0.30, 95%CI = 0.04-0.55, p = 0.022). TIMP2 also related to better semantic processing (b = 0.28, 95%CI = 0.04-0.51, p = 0.021) and executive functioning (b = 0.26, 95%CI = 0.03-0.49, p = 0.028). TIMP2 did not significantly relate to memory (p > 0.05).
Conclusions:Greater physical activity was associated with higher concentrations of blood factor TIMP2, which in turn related to better cognitive functioning independent of Alzheimer’s disease pathology burden. These results support previous mouse models by broadly replicating relationships between TIMP2 and cognition in humans, while also uniquely demonstrating an association between TIMP2 and physical activity, a modifiable protective factor in both typical and diseased cognitive aging. Our domain-specific results, however, suggest that benefits of TIMP2 in humans may involve a broader neuroanatomical network than the hippocampal-specific effects previously shown in mice. Although exact mechanisms of TIMP2 need further examination, TIMP2 is known to be enriched in human umbilical cord plasma, has been shown to be involved in cell-growth promoting activities, and may relate to increased neural plasticity in older age. Further examination of TIMP2 and other novel blood-based proteins as potential therapeutic targets for improved cognitive aging, including in the presence of Alzheimer’s disease, is warranted.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
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Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
32 Prediction of Seizure Outcome with Presurgical IAT, MRI, and PET in Patients with Temporal Lobe Epilepsy Undergoing Surgery
- Grant G Moncrief, Stephen L Aita, Jennifer Lee, Bryce Jacobson, George P Thomas, Robert M Roth, Angeline S Andrew, Krzysztof A Bujarski, Vijay M Thadani, Erik J Kobylarz, Stephen J Guerin, David W Roberts, Barbara C Jobst
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 31-32
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Objective:
Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.
Participants and Methods:Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.
Results:Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).
Conclusions:Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.
6 The Moderating Role of Physical Activity on Hippocampal Iron Deposition and Memory Outcomes in Typically Aging Older Adults
- Shannon Y Lee, Emily W Paolillo, Rowan Saloner, Torie Tsuei, Anna VandeBunte, Joel H Kramer, Kaitlin B Casaletto
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 794-795
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Objective:
Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.
Participants and Methods:62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.
Results:Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p > 0.05) or interact with physical activity on verbal memory outcomes (p > 0.05).
Conclusions:Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.
OP87 A Roadmap for Increasing The Usefulness And Impact Of Patient Preference Studies In Health Technology Assessment (HTA)
- Deborah A Marshall, Esther W de Bekker-Grob, Brett Hauber, Sebastian Heidenreich, Ellen Janssen, Alice Bast, Janel Hanmer, Laura Lee Johnson, Andriy Danyliv, Eric Low, Jacoline C Bouvy, John F. P. Bridges
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- Journal:
- International Journal of Technology Assessment in Health Care / Volume 39 / Issue S1 / December 2023
- Published online by Cambridge University Press:
- 14 December 2023, p. S24
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Introduction
The number of patient preference studies in health has increased dramatically. There is growing use of patient preferences in a wide variety of contexts, including health technology assessment. Patient preference studies can help inform decision makers on the needs and priorities of patients and the tradeoffs they are willing to make about health technologies.
MethodsThis International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force included international experts, health preference researchers and others from diverse backgrounds, including regulatory, health technology assessment, medicine, patient advocacy, and the pharmaceutical industry. The report underwent two rounds of written reviews by ISPOR Preferences Special Interest Group members until a final consensus was reached. The Task Force focused on developing a roadmap that would: (i) apply to the wide variety of preference methods, (ii) identify key domains to guide researchers and other stakeholders in making patient preference studies more useful to decision makers, and (iii) detail important questions to guide researchers conducting preference studies and those critically appraising them.
ResultsThis Task Force report provides a novel roadmap that invites patient-preference researchers to work with decision makers, patients and other stakeholders to do even more to ensure that studies are useful and impactful. The ISPOR Roadmap consists of five key elements: (i) Context; (ii) Purpose; (iii) Population; (iv) Method; and (v) Impact. In this report, we define these five elements and provide good practices on how patient-preference researchers can actively contribute to increasing the usefulness and impact of patient preference studies in decision-making. We also present a set of key questions that can support researchers and other stakeholders in assessing efforts that promote preference studies’ intended and unintended impact.
ConclusionsThis roadmap can help increase the usefulness and impact of patient preference studies in decision-making by challenging researchers to engage and partner with decision makers, patients and others, and together consider the intended and unintended impacts of patient preference studies on decision-making while actively fostering positive impact.
The predictive validity of the strange situation procedure: Evidence from registered analyses of two landmark longitudinal studies
- Marissa Nivison, Paul D. Caldo, Sophia W. Magro, K. Lee Raby, Ashley M. Groh, Deborah Lowe Vandell, Cathryn Booth-LaForce, R. Chris Fraley, Elizabeth A. Carlson, Jeffry A. Simpson, Glenn I. Roisman
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- Development and Psychopathology , First View
- Published online by Cambridge University Press:
- 13 December 2023, pp. 1-17
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Meta-analyses demonstrate that the quality of early attachment is modestly associated with peer social competence (r = .19) and externalizing behavior (r = −.15), but weakly associated with internalizing symptoms (r = −.07) across early development (Groh et al., Child Development Perspectives, 11(1), 70–76, 2017). Nonetheless, these reviews suffer from limitations that undermine confidence in reported estimates, including evidence for publication bias and the lack of comprehensive assessments of outcome measures from longitudinal studies in the literature. Moreover, theoretical claims regarding the specificity of the predictive significance of early attachment variation for socioemotional versus academic outcomes had not been evaluated when the analyses for this report were registered (but see Dagan et al., Child Development, 1–20, 2023; Deneault et al., Developmental Review, 70, 101093, 2023). To address these limitations, we conducted a set of registered analyses to evaluate the predictive validity of infant attachment in two landmark studies of the Strange Situation: the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) and the NICHD Study of Early Child Care and Youth Development (SECCYD). Across-time composite assessments reflecting teacher report, mother report, and self-reports of each outcome measure were created. Bivariate associations between infant attachment security and socioemotional outcomes in the MLSRA were comparable to, or slightly weaker than, those reported in the recent meta-analyses, whereas those in the SECCYD were weaker for these outcomes. Controlling for four demographic covariates, partial correlation coefficients between infant attachment and all socioemotional outcomes were r ≤ .10 to .15 in both samples. Compositing Strange Situations at ages 12 and 18 months did not substantively alter the predictive validity of the measure in the MLSRA, though a composite measure of three different early attachment measures in the SECCYD did increase predictive validity coefficients. Associations between infant attachment security and academic skills were unexpectedly comparable to (SECCYD) or larger than (MLSRA) those observed with respect to socioemotional outcomes.
Aircraft fleet availability optimisation: a reinforcement learning approach
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- K. Vos, Z. Peng, E. Lee, W. Wang
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- The Aeronautical Journal / Volume 127 / Issue 1318 / December 2023
- Published online by Cambridge University Press:
- 29 November 2023, pp. 2204-2218
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A fleet of aircraft can be seen as a set of degrading systems that undergo variable loads as they fly missions and require maintenance throughout their lifetime. Optimal fleet management aims to maximise fleet availability while minimising overall maintenance costs. To achieve this goal, individual aircraft, with variable age and degradation paths, need to operate cooperatively to maintain high fleet availability while avoiding mechanical failure by scheduling preventive maintenance actions. In recent years, reinforcement learning (RL) has emerged as an effective method to optimise complex sequential decision-making problems. In this paper, an RL framework to optimise the operation and maintenance of a fleet of aircraft is developed. Three cases studies, with varying number of aircraft in the fleet, are used to demonstrate the ability of the RL policies to outperform traditional operation/maintenance strategies. As more aircraft are added to the fleet, the combinatorial explosion of the number of possible actions is identified as a main computational limitation. We conclude that the RL policy has potential to support fleet management operators and call for greater research on the application of multi-agent RL for fleet availability optimisation.
Excessive fear of clusters of holes, its interaction with stressful life events and the association with anxiety and depressive symptoms: large epidemiological study of young people in Hong Kong
- Stephanie M. Y. Wong, Eric Y. H. Tang, Christy L. M. Hui, Y. N. Suen, Sherry K. W. Chan, Edwin H. M. Lee, K. T. Chan, Michael T. H. Wong, Arnold J. Wilkins, Eric Y. H. Chen
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- Journal:
- BJPsych Open / Volume 9 / Issue 5 / September 2023
- Published online by Cambridge University Press:
- 14 August 2023, e151
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Background
Excessive and persistent fear of clusters of holes, also known as trypophobia, has been suggested to reflect cortical hyperexcitability and may be associated with mental health risks. No study, however, has yet examined these associations in representative epidemiological samples.
AimsTo examine the prevalence of trypophobia in a population-representative youth sample, its association with mental health and functioning, and its interaction with external stress.
MethodA total of 2065 young people were consecutively recruited from a household-based epidemiological youth mental health study in Hong Kong. Trypophobia, symptoms of anxiety, depression and stress, and exposure to personal stressors were assessed. Logistic regression was used to assess the relationships between trypophobia and mental health. Potential additive and interaction effects of trypophobia and high stress exposure on mental health were also tested.
ResultsThe prevalence of trypophobia was 17.6%. Trypophobia was significantly associated with severe symptoms of anxiety (odds ratio (OR) = 1.83, 95% CI = 1.32–2.53), depression (OR = 1.78, 95% CI = 1.24–2.56) and stress (OR = 1.68, 95% CI = 1.11–2.53), even when accounting for sociodemographic factors, personal and family psychiatric history, resilience and stress exposure. Dose–response relationships were observed, and trypophobia significantly potentiated the effects of stress exposure on symptom outcomes, particularly for depressive symptoms. Those with trypophobia also showed significantly poorer functioning across domains and poorer health-related quality of life.
ConclusionsScreening for trypophobia in young people may facilitate early risk detection and intervention, particularly among those with recent stress exposure. Nevertheless, the generally small effect sizes suggest that other factors have more prominent roles in determining recent mental health outcomes in population-based samples; these should be explored in future work.
The evolving role of data & safety monitoring boards for real-world clinical trials
- Bryan J. Bunning, Haley Hedlin, Jonathan H. Chen, Jody D. Ciolino, Johannes Opsahl Ferstad, Emily Fox, Ariadna Garcia, Alan Go, Ramesh Johari, Justin Lee, David M. Maahs, Kenneth W. Mahaffey, Krista Opsahl-Ong, Marco Perez, Kaylin Rochford, David Scheinker, Heidi Spratt, Mintu P. Turakhia, Manisha Desai
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 02 August 2023, e179
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Introduction:
Clinical trials provide the “gold standard” evidence for advancing the practice of medicine, even as they evolve to integrate real-world data sources. Modern clinical trials are increasingly incorporating real-world data sources – data not intended for research and often collected in free-living contexts. We refer to trials that incorporate real-world data sources as real-world trials. Such trials may have the potential to enhance the generalizability of findings, facilitate pragmatic study designs, and evaluate real-world effectiveness. However, key differences in the design, conduct, and implementation of real-world vs traditional trials have ramifications in data management that can threaten their desired rigor.
Methods:Three examples of real-world trials that leverage different types of data sources – wearables, medical devices, and electronic health records are described. Key insights applicable to all three trials in their relationship to Data and Safety Monitoring Boards (DSMBs) are derived.
Results:Insight and recommendations are given on four topic areas: A. Charge of the DSMB; B. Composition of the DSMB; C. Pre-launch Activities; and D. Post-launch Activities. We recommend stronger and additional focus on data integrity.
Conclusions:Clinical trials can benefit from incorporating real-world data sources, potentially increasing the generalizability of findings and overall trial scale and efficiency. The data, however, present a level of informatic complexity that relies heavily on a robust data science infrastructure. The nature of monitoring the data and safety must evolve to adapt to new trial scenarios to protect the rigor of clinical trials.
DIAGNOSTIC CHALLENGES IN DISTINGUISHING AUTISM SPECTRUM DISORDER FROM PSYCHOSIS: A CASE REPORT
- W. W. S. J. Lee, S. Y. L. Lee
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S1092-S1093
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Introduction
Autism spectrum disorders (ASD) and psychotic disorders have historically considered to be related conditions with a long history of diagnostic confusion. Although DSM-III distinguishes ASD and Schizophrenia Spectrum Disorders as distinct clinical entities, they continue to share overlaps in their clinical symptom presentations leading to diagnostic challenges that may consequentially result in delayed treatment. Prompt diagnosis is crucial in the context of psychosis, where early intervention impacts recovery.
ObjectivesTo present the diagnostic challenges encountered in distinguishing ASD from Psychosis.
MethodsWe present a case report demonstrating the challenges of distinguishing ASD from Psychosis.
ResultsThis is a case of a gentleman who initially presented to psychiatric services at 18 years old for conflicts with his mother related to his inflexibility to change. Further psychological evaluation revealed that he had a history of restricted social interaction with his peers, difficulties in non-verbal communications and identifying emotional states, stereotyped interests and obsessions that isolated him from his peers. He was diagnosed with ASD.
In subsequent presentations, there were symptoms of excessive preoccupation of his facial appearance, excessive concern over contracting HIV, obsessions with arranging objects in a particular order and avoiding words starting with the letter “S” out of fears of blasphemy. While these symptoms had qualities of cognitive inflexibility, they could not fully be explained by ASD. Additional diagnoses of Body Dysmorphic Disorder, Borderline Personality Disorder, Obsessive Compulsive Personality Disorder and At-Risk Mental State were considered.
A psychiatric admission was necessitated at 21 years old, when he presented with a 2-year history of repetitive banging of furniture in the middle of the night to communicate his frustrations towards his parents for their perceived acts of blasphemy. He also began to isolate himself, fearing that his parents would be able to look into his soul and reveal his sins. This paranoia towards his parents worsened to the point of urinating and defecating in his room to avoid his parents. His school performance declined as well.
A unifying diagnosis of psychosis was made. His previous diagnosis of ASD was challenged as a misdiagnosis, with the impression that he likely had attenuated psychotic symptoms in his adolescent years, disguised as autistic traits. The diagnosis of psychosis was confirmed when the patient’s symptoms were observed to respond to antipsychotic treatment.
ConclusionsThis case report illustrates the challenges in distinguishing ASD from psychosis. A prior diagnosis of ASD may result in diagnostic overshadowing and subsequent delays in diagnosing psychosis. Further research in diagnostic tools would be helpful for diagnostic precision, thereby enabling prompt treatment for better recovery outcomes.
Disclosure of InterestNone Declared
Systematic Review on the Mechanisms of Action of Psilocybin in the Treatment of Depression
- M. C. Q. Lin, H. Lee, V. W. L. Tsang, B. Chai, A. Howard, C. Uy, J. O. Elefante
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S416-S417
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Introduction
Despite emerging evidence suggesting the efficacy of psilocybin in the treatment of mood disorders such as depression, the exact mechanisms by which psilocybin is able to elicit these antidepressant effects remains unknown.
ObjectivesAs the use of psilocybin as a treatment modality for depression has garnered increasing interest, this study aims to summarize the existing evidence of the mechanism of action with which psilocybin alleviates depressive symptoms, focusing specifically on the neurobiological effects of psilocybin in human subjects.
MethodsFour databases (Ovid MEDLINE, EMBASE, psychINFO, and Web of Science) were searched using a combination of MeSH terms and free text keywords in September 2021. The original search included both human and animal studies and must have included testing of the mechanism of action of psilocybin. Only antidepressant effects were considered, with no other mood disorders or psychiatric diagnoses included. Two independent researchers screened at every stage of the review, with a third researcher resolving any conflicts. Though a full systematic review outlining the current literature on the complete mechanisms of action of psilocybin on depression was conducted, this abstract will focus specifically on the nine papers that included human subjects, disregarding the five animal models. PROSPERO registration number: 282710.
ResultsAfter removing duplicates, the search identified 2193 papers and forty-nine were selected for full text review. Out of nine papers outlining the mechanisms of action of psilocybin use in human subjects, three papers investigated psilocybin’s effect on serotonin or glutamate receptor activity, two found an increase in synaptogenesis in regions such as the medial frontal cortex and hippocampus. Four found variation in blood flow to the amygdala, two found altered blood flow to the prefrontal cortex, and one found a reduction in delta power during sleep. Four papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex.
ConclusionsOverall, the exact mechanism of psilocybin’s potential antidepressant effect remains unclear. Multiple pathways may be involved, including alterations in serotonin and glutamate receptor activity, as well as shifts in amygdala activity, neurogenesis, and functional connectivity in various brain regions. The relative lack of studies, and the variety of neurobiological modalities and endpoints used challenged the consolidation of data into consensus findings. Further studies are needed to better characterize psilocybin’s mechanism of action and to better understand the clinical effects of the use of psilocybin in the treatment of depression.
Disclosure of InterestNone Declared
The host galaxy of FRB 20171020A revisited
- Karen Lee-Waddell, Clancy W. James, Stuart D. Ryder, Elizabeth K. Mahony, Arash Bahramian, Bärbel S. Koribalski, Pravir Kumar, Lachlan Marnoch, Freya O. North-Hickey, Elaine M. Sadler, Ryan Shannon, Nicolas Tejos, Jessica E. Thorne, Jing Wang, Randall Wayth
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- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 11 July 2023, e029
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The putative host galaxy of FRB 20171020A was first identified as ESO 601-G036 in 2018, but as no repeat bursts have been detected, direct confirmation of the host remains elusive. In light of recent developments in the field, we re-examine this host and determine a new association confidence level of 98%. At 37 Mpc, this makes ESO 601-G036 the third closest FRB host galaxy to be identified to date and the closest to host an apparently non-repeating FRB (with an estimated repetition rate limit of $<$$0.011$ bursts per day above $10^{39}$ erg). Due to its close distance, we are able to perform detailed multi-wavelength analysis on the ESO 601-G036 system. Follow-up observations confirm ESO 601-G036 to be a typical star-forming galaxy with H i and stellar masses of $\log_{10}\!(M_{\rm{H\,{\small I}}} / M_\odot) \sim 9.2$ and $\log_{10}\!(M_\star / M_\odot) = 8.64^{+0.03}_{-0.15}$, and a star formation rate of $\text{SFR} = 0.09 \pm 0.01\,{\rm M}_\odot\,\text{yr}^{-1}$. We detect, for the first time, a diffuse gaseous tail ($\log_{10}\!(M_{\rm{H\,{\small I}}} / M_\odot) \sim 8.3$) extending to the south-west that suggests recent interactions, likely with the confirmed nearby companion ESO 601-G037. ESO 601-G037 is a stellar shred located to the south of ESO 601-G036 that has an arc-like morphology, is about an order of magnitude less massive, and has a lower gas metallicity that is indicative of a younger stellar population. The properties of the ESO 601-G036 system indicate an ongoing minor merger event, which is affecting the overall gaseous component of the system and the stars within ESO 601-G037. Such activity is consistent with current FRB progenitor models involving magnetars and the signs of recent interactions in other nearby FRB host galaxies.