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Protecting and promoting editorial independence
- Kamaldeep Bhui, Aileen O'Brien, Rachel Upthegrove, Alexander C. Tsai, Mustafa Soomro, Giles Newton-Howes, Matthew R. Broome, Andrew Forrester, Patricia Casey, Anne M. Doherty, William Lee, Kenneth R. Kaufman
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- The British Journal of Psychiatry , FirstView
- Published online by Cambridge University Press:
- 15 February 2024, pp. 1-3
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We argue that editorial independence, through robust practice of publication ethics and research integrity, promotes good science and prevents bad science. We elucidate the concept of research integrity, and then discuss the dimensions of editorial independence. Best practice guidelines exist, but compliance with these guidelines varies. Therefore, we make recommendations for protecting and strengthening editorial independence.
Impact of primary care triage using the Head and Neck Cancer Risk Calculator version 2 on tertiary head and neck services in the post-coronavirus disease 2019 period
- Jiak-Ying Tan, Christopher John Callaghan, Alexander William Lewthwaite, Claudia Ching Hei Chan, Colette Teng Wee, Emily Yeg Hei To, Isabel Summers, James William Nelson, Mathew Benjamin Smith, Lucy Qian Li, Catriona Morton, Lorna Porteous, Andrew Stewart Evans, Iain James Nixon
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- The Journal of Laryngology & Otology , First View
- Published online by Cambridge University Press:
- 22 January 2024, pp. 1-6
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Objective
This study investigates the impact of primary care utilisation of a symptom-based head and neck cancer risk calculator (Head and Neck Cancer Risk Calculator version 2) in the post-coronavirus disease 2019 period on the number of primary care referrals and cancer diagnoses.
MethodsThe number of referrals from April 2019 to August 2019 and from April 2020 to July 2020 (pre-calculator) was compared with the number from the period January 2021 to August 2022 (post-calculator) using the chi-square test. The patients’ characteristics, referral urgency, triage outcome, Head and Neck Cancer Risk Calculator version 2 score and cancer diagnosis were recorded.
ResultsIn total, 1110 referrals from the pre-calculator period were compared with 1559 from the post-calculator period. Patient characteristics were comparable for both cohorts. More patients were referred on the cancer pathway in the post-calculator cohort (pre-calculator patients 51.1 per cent vs post-calculator 64.0 per cent). The cancer diagnosis rate increased from 2.7 per cent in the pre-calculator cohort to 3.3 per cent in the post-calculator cohort. A lower rate of cancer diagnosis in the non-cancer pathway occurred in the cohort managed using the Head and Neck Cancer Risk Calculator version 2 (10 per cent vs 23 per cent, p = 0.10).
ConclusionHead and Neck Cancer Risk Calculator version 2 demonstrated high sensitivity in cancer diagnosis. Further studies are required to improve the predictive strength of the calculator.
Searching for spots: a comprehensive survey for the Arabian leopard Panthera pardus nimr in Saudi Arabia – CORRIGENDUM
- Carolyn E. Dunford, J. Philip B. Faure, Michael D. Ross, J. Andrew Spalton, Marine Drouilly, Kai J.P. Pryce-Fitchen, Ross De Bruin, Alexander E. Botha, Abdullah Alshehri, Nikki Le Roex, Guy Balme, Ahmed Almalki, Emma Gallacher, Mesfer Alhlafi, Saleh Alaamri, David R. Mills, Gareth Mann
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- Oryx , First View
- Published online by Cambridge University Press:
- 10 January 2024, p. 1
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Bentonite/Magnetite Composite for Removal of Nitrofurazone
- Olga V. Alekseeva, Anna N. Rodionova, Andrew V. Noskov, Alexander V. Agafonov
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- Clays and Clay Minerals / Volume 67 / Issue 6 / December 2019
- Published online by Cambridge University Press:
- 01 January 2024, pp. 471-480
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The presence of pharmaceutical pollutants in the environment is one of the most pressing environmental problems. Adsorption from solution is an effective way to remove pharmaceuticals from liquid media, but the problem then is to separate the adsorbent from the liquids. The objective of the present study was to remove nitrofurazone from aqueous solutions using a bentonite/magnetite composite, prepared by co-precipitation of magnetite with bentonite, which could then be collected by magnetic separation. The bentonite/magnetite composite was characterized using diverse techniques, such as X-ray diffraction, scanning electron microscopy, low-temperature N2 adsorption/desorption, laser diffraction, and magnetization measurements. The particle size of the composite material did not exceed 50 μm and the particle size distribution was mono-modal with a maximum at 3.2 μm. The strong hysteresis in the magnetization curve revealed that the bentonite/magnetite particles were ferromagnetic. Adsorption of nitrofurazone by the bentonite/magnetite composite from aqueous solutions was measured and the amount of nitrofurazone adsorbed was 3.2×10–2 mmol/g. The adsorption kinetics of nitrofurazone to the bentonite/magnetite composite followed a pseudo-second-order kinetics equation. Upon adsorption, hydrogen bonds were formed between the amide groups of nitrofurazone and oxygen groups in bentonite.
53 2-Back Performance Does Not Differ Between Cognitive Training Groups in Older Adults Without Dementia
- Nicole D Evangelista, Jessica N Kraft, Hanna K Hausman, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Cheshire Hardcastle, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric Porges, Adam J Woods
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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. 360-361
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Objective:
Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.
Participants and Methods:48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.
Results:Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).
Conclusions:After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.
77 The Shell Game Task: Pilot Data Using a Simulator-Design Study to Evaluate a Novel Attentional Performance Validity Test
- Andrew M. Bryant, Kendra Pizzonia, Claire Alexander, Grace Lee, Olivia Revels-Strother, Sarah Weekman, Brianna Hart, Julie Suhr
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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. 751-752
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Objective:
We developed the Shell Game Task (SGT) as a novel Performance Validity Test (PVT). While most PVTs use a forced-choice paradigm with “memory” as the primary domain being assessed, the SGT is a face-valid measure of attention and working memory. We explored the accuracy of the SGT to detect noncredible performance using a simulatordesign study.
Participants and Methods:Ninety-four university students were randomly assigned to either best effort (CON) (n=49) or simulating traumatic brain injury (TBI) (SIM) (n=45) conditions. Participants completed a full battery of neuropsychological tests to simulate an actual evaluation, including the Test of Memory Malingering (TOMM) and the SGT. The SGT involves three cups and a red ball shown on the screen. Participants watch as the ball is placed under one of the three cups. Cups are then shuffled. Participants are asked to track the cup that contains the ball and correctly identify its location. We created two difficulty levels (easy vs hard, 20 trials each) by changing the number of times the cups were shuffled. Participants were given feedback (correct vs incorrect) after each trial. At the conclusion of the study, participants were asked about adherence to study directions they were given.
Results:Participants with missing data (CON=1; SIM=2) or who reported non-adherence to study directions (CON=2; SIM=1) were removed from analyses. Twenty-five percent in SIM and 0% in CON failed TOMM
Trial 2 (<45) suggesting adequate manipulation of groups. Groups were not different in age, gender, ethnicity, or education (all p’s>.05). There were 9 participants in each group with concussion/TBI history. TBI history was not significantly related to performance on the SGT in either group, although participants with TBI history tended to do better. Average performances on TOMM Trial 1 (36.62 vs 47.91, p<.001) and TOMM Trial 2 (37.50 vs 49.71, p<.001) were significantly lower in the SIM group. Performance on SGT was also significantly lower in the SIM group across SGT Total Correct (20.17 vs 24.65 of 40, p=.008), SGT Easy (10.60 vs 13.52 of 20, p=.002), and SGT Hard (9.57 vs 11.13 of 20, p=.068). Mixed ANOVA showed a trend towards significant group by SGT difficulty interaction (F(1,86)=3.41, p=.052, np2=.043). There was steeper decline in performance on SGT Hard compared to SGT Easy for CON. ROC analyses suggested adequate but not ideal sensitivity/specificity: scores <8 on SGT Easy (sensitivity=26%; false positive=11%), <7 on SGT Hard (sensitivity=26%; false positive=7%), and <15 on SGT Total (sensitivity=24%; false positive=9%).
Conclusions:These preliminary data indicate the SGT may be able to detect malingered TBI. However, additional development of this measure is necessary. Further refinement of difficulty level may improve sensitivity/specificity (e.g., CON mean performance for SGT Easy trails was 13.52, suggesting the items may be too difficult). This study was limited to an online administration due to COVID, which could have affected results; future studies should test inperson administration of the SGT. In addition, performance in clinical control groups (larger samples of individuals with mild TBI, ADHD) should be tested to better determine specificity for these preliminary cutoffs.
2 Higher White Matter Hyperintensity Load Adversely Affects Pre-Post Proximal Cognitive Training Performance in Healthy Older Adults
- Emanuel M Boutzoukas, Andrew O’Shea, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Hanna K Hausman, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Samantha G Smith, Hyun Song, Eric C Porges, Alex Hishaw, Steven T DeKosky, Samuel S Wu, Michael Marsiske, Gene E Alexander, Ronald Cohen, Adam J Woods
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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. 671-672
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Objective:
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
78 BVMT-R Learning Ratio Moderates Cognitive Training Gains in Useful Field of View Task in Healthy Older Adults
- Cheshire Hardcastle, Jessica N. Kraft, Hanna K. Hausman, Andrew O’Shea, Alejandro Albizu, Nicole D. Evangelista, Emanuel Boutzoukas, Emily J. Van Etten, Pradyumna K. Bharadwaj, Hyun Song, Samantha G. Smith, Eric Porges, Steven DeKosky, Georg A. Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E. Alexander, Adam J. Woods
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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. 180-181
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Objective:
Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there is variability in the level of cognitive gains after cognitive training across studies. One potential explanation for this variability could be moderating factors. Prior studies suggest variables moderating cognitive training gains share features of the training task. Learning trials of the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) recruit similar cognitive abilities and have overlapping neural correlates with the UFOV task and speed-ofprocessing/working memory tasks and therefore could serve as potential moderators. Exploring moderating factors of cognitive training gains may boost the efficacy of interventions, improve rigor in the cognitive training literature, and eventually help provide tailored treatment recommendations. This study explored the association between the HVLT-R and BVMT-R learning and the UFOV task, and assessed the moderation of HVLT-R and BVMT-R learning on UFOV improvement after a 3-month speed-ofprocessing/attention and working memory cognitive training intervention in cognitively healthy older adults.
Participants and Methods:75 healthy older adults (M age = 71.11, SD = 4.61) were recruited as part of a larger clinical trial through the Universities of Florida and Arizona. Participants were randomized into a cognitive training (n=36) or education control (n=39) group and underwent a 40-hour, 12-week intervention. Cognitive training intervention consisted of practicing 4 attention/speed-of-processing (including the UFOV task) and 4 working memory tasks. Education control intervention consisted of watching 40-minute educational videos. The HVLT-R and BVMT-R were administered at the pre-intervention timepoint as part of a larger neurocognitive battery. The learning ratio was calculated as: trial 3 total - trial 1 total/12 - trial 1 total. UFOV performance was measured at pre- and post-intervention time points via the POSIT Brain HQ Double Decision Assessment. Multiple linear regressions predicted baseline Double Decision performance from HVLT-R and BVMT-R learning ratios controlling for study site, age, sex, and education. A repeated measures moderation analysis assessed the moderation of HVLT-R and BVMT-R learning ratio on Double Decision change from pre- to post-intervention for cognitive training and education control groups.
Results:Baseline Double Decision performance significantly associated with BVMT-R learning ratio (β=-.303, p=.008), but not HVLT-R learning ratio (β=-.142, p=.238). BVMT-R learning ratio moderated gains in Double Decision performance (p<.01); for each unit increase in BVMT-R learning ratio, there was a .6173 unit decrease in training gains. The HVLT-R learning ratio did not moderate gains in Double Decision performance (p>.05). There were no significant moderations in the education control group.
Conclusions:Better visuospatial learning was associated with faster Double Decision performance at baseline. Those with poorer visuospatial learning improved most on the Double Decision task after training, suggesting that healthy older adults who perform below expectations may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes.
6 Adjunctive Transcranial Direct Current Stimulation and Cognitive Training Alters Default Mode and Frontoparietal Control Network Connectivity in Older Adults
- Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Emanuel M Boutzoukas, Andrew O’Shea, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Eric S Porges, Georg A Hishaw, Samuel Wu, Steven DeKosky, Gene E Alexander, Michael Marsiske, Ronald A Cohen, Adam J Woods
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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. 675-676
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Objective:
Aging is associated with disruptions in functional connectivity within the default mode (DMN), frontoparietal control (FPCN), and cingulo-opercular (CON) resting-state networks. Greater within-network connectivity predicts better cognitive performance in older adults. Therefore, strengthening network connectivity, through targeted intervention strategies, may help prevent age-related cognitive decline or progression to dementia. Small studies have demonstrated synergistic effects of combining transcranial direct current stimulation (tDCS) and cognitive training (CT) on strengthening network connectivity; however, this association has yet to be rigorously tested on a large scale. The current study leverages longitudinal data from the first-ever Phase III clinical trial for tDCS to examine the efficacy of an adjunctive tDCS and CT intervention on modulating network connectivity in older adults.
Participants and Methods:This sample included 209 older adults (mean age = 71.6) from the Augmenting Cognitive Training in Older Adults multisite trial. Participants completed 40 hours of CT over 12 weeks, which included 8 attention, processing speed, and working memory tasks. Participants were randomized into active or sham stimulation groups, and tDCS was administered during CT daily for two weeks then weekly for 10 weeks. For both stimulation groups, two electrodes in saline-soaked 5x7 cm2 sponges were placed at F3 (cathode) and F4 (anode) using the 10-20 measurement system. The active group received 2mA of current for 20 minutes. The sham group received 2mA for 30 seconds, then no current for the remaining 20 minutes.
Participants underwent resting-state fMRI at baseline and post-intervention. CONN toolbox was used to preprocess imaging data and conduct region of interest (ROI-ROI) connectivity analyses. The Artifact Detection Toolbox, using intermediate settings, identified outlier volumes. Two participants were excluded for having greater than 50% of volumes flagged as outliers. ROI-ROI analyses modeled the interaction between tDCS group (active versus sham) and occasion (baseline connectivity versus postintervention connectivity) for the DMN, FPCN, and CON controlling for age, sex, education, site, and adherence.
Results:Compared to sham, the active group demonstrated ROI-ROI increases in functional connectivity within the DMN following intervention (left temporal to right temporal [T(202) = 2.78, pFDR < 0.05] and left temporal to right dorsal medial prefrontal cortex [T(202) = 2.74, pFDR < 0.05]. In contrast, compared to sham, the active group demonstrated ROI-ROI decreases in functional connectivity within the FPCN following intervention (left dorsal prefrontal cortex to left temporal [T(202) = -2.96, pFDR < 0.05] and left dorsal prefrontal cortex to left lateral prefrontal cortex [T(202) = -2.77, pFDR < 0.05]). There were no significant interactions detected for CON regions.
Conclusions:These findings (a) demonstrate the feasibility of modulating network connectivity using tDCS and CT and (b) provide important information regarding the pattern of connectivity changes occurring at these intervention parameters in older adults. Importantly, the active stimulation group showed increases in connectivity within the DMN (a network particularly vulnerable to aging and implicated in Alzheimer’s disease) but decreases in connectivity between left frontal and temporal FPCN regions. Future analyses from this trial will evaluate the association between these changes in connectivity and cognitive performance post-intervention and at a one-year timepoint.
28 Factor Structure of Conventional Neuropsychological Tests and NIH-Toolbox in Healthy Older Adults
- Kailey Langer, Cheshire Hardcastle, Hanna Hausman, Jessica Kraft, Alejandro Albizu, Nicole Evangelista, Emanuel Boutzoukas, Andrew O’Shea, Emily Van Etten, Samantha Smith, Hyun Song, Pradyumna Bharadwaj, Georg Hishaw, Samuel Wu, Steven DeKosky, Gene Alexander, Eric Porges, Michael Marsiske, Ronald Cohen, Adam Woods
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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, p. 710
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Objective:
The National Institutes of Health-Toolbox cognition battery (NIH-TCB) is widely used in cognitive aging studies and includes measures in cognitive domains evaluated for dimensional structure and psychometric properties in prior research. The present study addresses a current literature gap by demonstrating how NIH-TCB integrates into a battery of traditional clinical neuropsychological measures. The dimensional structure of NIH-TCB measures along with conventional neuropsychological tests is assessed in healthy older adults.
Participants and Methods:Baseline cognitive data were obtained from 327 older adults. The following measures were collected: NIH-Toolbox cognitive battery, Controlled Oral Word Association (COWA) letter and animals tests, Wechsler Test of Adult Reading (WTAR), Stroop Color-Word Interference Test, Paced Auditory Serial Addition Test (PASAT), Brief Visuospatial Memory Test (BVMT), Letter-Number Sequencing (LNS), Hopkins Verbal Learning Test (HVLT), Trail Making Test A&B, Digit Span. Hmisc, psych, and GPARotation packages for R were used to conduct exploratory factor analyses (EFA). A 5-factor solution was conducted followed by a 6-factor solution. Promax rotation was used for both EFA models.
Results:The 6-factor EFA solution is reported here. Results indicated the following 6 factors: working memory (Digit Span forward, backward, and sequencing, PASAT trials 1 and 2, NIH-Toolbox List Sorting, LNS), speed/executive function (Stroop color naming, word reading, and color-word interference, NIH-Toolbox Flanker, Dimensional Change, and Pattern Comparison, Trail Making Test A&B), verbal fluency (COWA letters F-A-S), crystallized intelligence (WTAR, NIH-Toolbox Oral Recognition and Picture Vocabulary), visual memory (BVMT immediate and delayed), and verbal memory (HVLT immediate and delayed. COWA animals and NIH-Toolbox Picture Sequencing did not adequately load onto any EFA factor and were excluded from the subsequent CFA.
Conclusions:Findings indicate that in a sample of healthy older adults, these collected measures and those obtained through the NIH-Toolbox battery represent 6 domains of cognitive function. Results suggest that in this sample, picture sequencing and COWA animals did not load adequately onto the factors created from the rest of the measures collected. These findings should assist in interpreting future research using combined NIH-TCB and neuropsychological batteries to assess cognition in healthy older adults.
9 Connecting memory and functional brain networks in older adults: a resting state fMRI study
- Jori L Waner, Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel S Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric C Porges, Adam J Woods
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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. 527-528
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Objective:
Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
18 Regional patterns of mitochondrial function using phosphorus magnetic resonance spectroscopy in older adults at-risk for Alzheimer’s disease.
- Francesca V Lopez, Andrew O’Shea, Stacey Alvarez-Alvarado, Adrianna Ratajska, Lauren Kenney, Rachel Schade, Katie Rodriguez, Alyssa Ray, Rebecca O’Connell, Lauren Santos, Emily Van Etten, Hyun Song, Emma Armstrong, Tiffany Gin, Zhiguang Huo, Gene Alexander, Adam J Woods, Dawn Bowers
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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. 331-332
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Objective:
The brain is reliant on mitochondria to carry out a host of vital cellular functions (e.g., energy metabolism, respiration, apoptosis) to maintain neuronal integrity. Clinically relevant, dysfunctional mitochondria have been implicated as central to the pathogenesis of Alzheimer’s disease (AD). Phosphorous magnetic resonance spectroscopy (31p MRS) is a non-invasive and powerful method for examining in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. At least one prior 31p MRS study found temporal-frontal differences for high energy phosphates in persons with mild AD. The goal of the current study was to examine regional (i.e., frontal, temporal) 31p MRS ratios of mitochondrial function in a sample of older adults at-risk for AD. Given the high energy consumption in temporal lobes (i.e., hippocampus) and preferential age-related changes in frontal structure-function, we predicted 31p MRS ratios of mitochondrial function would be greater in temporal as compared to frontal regions.
Participants and Methods:The current study leveraged baseline neuroimaging data from an ongoing multisite study at the University of Florida and University of Arizona. Participants were older adults with memory complaints and a first-degree family history of AD [N = 70; mean [M] age [years] = 70.9, standard deviation [SD] =5.1; M education [years] = 16.2, SD = 2.2; M MoCA = 26.5, SD = 2.4; 61.4% female; 91.5% non-latinx white]. To achieve optimal sensitivity, we used a single voxel method to examine 31p MRS ratios (bilateral prefrontal and left temporal). Mitochondrial function was estimated by computing 5 ratios for each voxel: summed adenosine triphosphate to total pooled phosphorous (ATP/TP; momentary energy), ATP to inorganic phosphate (ATP/Pi; energy consumption), phosphocreatine to ATP (PCr/ATP; energy reserve), phosphocreatine to inorganic phosphate (PCr/Pi; oxidative phosphorylation), and phosphomonoesters to phosphodiesters (PME/PDE; cellular membrane turnover rate). All ratios were corrected for voxel size and cerebrospinal fluid fraction. Separate repeated measures analyses of variance controlling for scanner site differences (RM ANCOVAs) were performed.
Results:31p MRS ratios were unrelated to demographic characteristics and were not included as additional covariates in analyses. Results of separate RM ANCOVAs revealed all 31p MRS ratios of mitochondrial function were greater in left temporal relative to bilateral prefrontal voxel: ATP/TP (p < .001), ATP/Pi (p = .001), PCr/ATP (p = .004), PCr/Pi (p = .004), and PME/PDE (p = .017). Effect sizes (partial eta squared) ranged from 0.6-.20.
Conclusions:Consistent and extending one prior study, all 31p MRS ratios of mitochondrial function were greater in temporal as compared to frontal regions in older adults at-risk for AD. This may in part be related to the intrinsically high metabolic rate of the temporal region and preferential age-related changes in frontal structure-function. Alternatively, findings may reflect the influence of unaccounted factors (e.g., hemodynamics, auditory stimulation). Longitudinal study designs may inform whether patterns of mitochondrial function across different brain regions are present early in development, occur across the lifespan, or some combination. In turn, this may inform future studies examining differences in mitochondrial function (as measured using 31p MRS) in AD.
Searching for spots: a comprehensive survey for the Arabian leopard Panthera pardus nimr in Saudi Arabia
- Carolyn E. Dunford, J. Philip B. Faure, Michael D. Ross, J. Andrew Spalton, Marine Drouilly, Kai J.P. Pryce-Fitchen, Ross De Bruin, Alexander E. Botha, Abdullah Alshehri, Nikki Le Roex, Guy Balme, Ahmed Almalki, Emma Gallacher, Mesfer Alhlafi, Saleh Alaamri, David R. Mills, Gareth Mann
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- Oryx , First View
- Published online by Cambridge University Press:
- 27 November 2023, pp. 1-12
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The Arabian leopard Panthera pardus nimr is categorized as Critically Endangered, with < 200 individuals estimated to remain in the wild. Historically the species ranged over an extensive area of western Saudi Arabia but, with no confirmed sightings since 2014, investigating potential continued presence and distribution is of critical conservation importance. We present the results of a comprehensive survey designed to detect any remaining Arabian leopard populations in Saudi Arabia. We conducted 14 surveys, deploying 586 camera-trap stations at 13 sites, totalling 82,075 trap-nights. Questionnaire surveys were conducted with 843 members of local communities across the Arabian leopard's historical range to assess the presence of leopards, other predators and prey species. Predator scats were collected ad hoc by field teams and we used mitochondrial DNA analysis to identify the originating species. We obtained 62,948 independent photographs of animals and people, but none were of Arabian leopards. Other carnivores appeared widespread and domestic animals were numerous, but wild prey were comparatively scarce. Three questionnaire respondents reported sightings of leopards within the previous year, but targeted camera-trap surveys in these areas did not yield evidence of leopards. Of the 143 scats sent for analysis, no DNA was conclusively identified as that of the leopard. From this extensive study, we conclude there are probably no surviving, sustainable populations of Arabian leopards in Saudi Arabia. Individual leopards might be present but were not confirmed. Any future Arabian leopard conservation in Saudi Arabia will probably require reintroduction of captive-bred leopards.
New Ediacaran biota from the oldest Nama Group, Namibia (Tsaus Mountains), and re-definition of the Nama Assemblage
- Rachel Wood, Fred. T. Bowyer, Ruaridh Alexander, Mariana Yilales, Collen-Issia Uahengo, Kavevaza Kaputuaza, Junias Ndeunyema, Andrew Curtis
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- Journal:
- Geological Magazine / Volume 160 / Issue 9 / September 2023
- Published online by Cambridge University Press:
- 23 October 2023, pp. 1673-1686
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The Nama Group, Namibia (≥550.5 to <538 million years ago, Ma), preserves one of the most diverse metazoan fossil records of the terminal Ediacaran Period. We report numerous features that may be biological in origin from the shallow marine, siliciclastic, lowermost Mara Member (older than ca. 550.5 Ma) from the Tsaus Mountains. These include forms that potentially represent body fossils, Beltanelliformis and an indeterminate juvenile uniterminal rangeomorph or arboreomorph frond, plug trace fossils, Bergaueria, as well as sedimentary surface textures, which are possibly microbially induced. These are the oldest documented macrofossils in the Nama Group. They represent taxa that persist from the Avalon or White Sea assemblages prior to the later appearance of new biota, including calcified metazoans, calcified and soft-bodied tubular taxa including all cloudinids, as well as more complex trace fossils.
Using a new age model that allows more accurate stratigraphic placement of major Ediacaran macrofossil morphogroups and taxa, we propose a re-definition of the Nama Assemblage following the practice for Phanerozoic evolutionary faunas to include only new morphogroups of soft-bodied tubular, calcified taxa and complex trace fossils, defined by first appearance of Cloudina, which postdates deposition of the Kanies and lower Mara members and first appears ca. 550 Ma and persists until at least 539 Ma.
Finally, the Tsaus Mountain environment is pristine, unspoilt by geologists and naturalists. Following World Heritage Convention, we suggest a pledge of non-destructive excavation that all future scientists should be able to make in publications of work that involve research in this area.
To what extent are depressive or other mood disorders a consequence of earlier traumatic experiences?
- Ian B. Hickie, Alexander C. McFarlane, Laura Ospina-Pinillos, Andrew M. Chanen, Sarah E. Medland, Jacob J. Crouse
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- Research Directions: Depression / Volume 1 / 2024
- Published online by Cambridge University Press:
- 12 October 2023, e7
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The potential relationships between traumatic experiences and the onset and course of major mood disorders have always been controversial. Some experiences, most notably physical or sexual abuse, as well as substantive bullying in childhood, are clearly recognised as major risk factors for a range of mental disorders, as well as a range of linked phenomena including self-harm and suicidal behaviours (McKay et al., 2021; Zatti et al., 2017). There is considerable interest and ongoing research into how these adverse experiences come to be ‘encoded’ via neurobiological or genetic mechanisms that then transmit those effects into later-onset major mental disorders, substance misuse or other self-harming behaviours (Maddox et al., 2019).
Quality Improvement Project: Optimizing Compliance with NICE CG176 Head Injury CT Time Standards at Wexford General Hospital Emergency Department
- Brendan Orsmond, Robin Andrews, Muhammad Bilal, Phillip Jordaan, Alexander Price, Keith Kennedy, Rochelle Kleinhans, Maria Conradie, Michael Molloy, Bryce Wickham, Paul Kelly
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- Journal:
- Prehospital and Disaster Medicine / Volume 38 / Issue S1 / May 2023
- Published online by Cambridge University Press:
- 13 July 2023, pp. s54-s55
- Print publication:
- May 2023
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Introduction:
Head trauma is a high-risk presentation to the emergency department (ED). Preventing secondary brain injury through earlier diagnosis and intervention relies on timely access to head CT. Wexford General Hospital (WGH) ED uses NICE guidelines, which recommend specific timeframes for acquiring CT in head trauma. Following an audit demonstrating low compliance to NICE CG176 time standards in 2020 (34%), a quality improvement project was undertaken to optimize imaging pathways for head trauma.
Method:94 head trauma CT scans were analyzed over a two-month period (June 14, 2022-August 14, 2022) from the NIMIS and IPMS databases to establish current time compliance and median wait times for CT.
Following the implementation of a head injury assessment proforma at triage to prompt earlier evaluation of high-risk head injuries, 108 head trauma CT’s were reviewed over a two-month period (August 15, 2022-October 15, 2022) to determine if these parameters improved.
Unpaired, two-tailed Mann-Whitney’s test was used to compare median wait times from triage to CT. Two-tailed Chi-square test was used to compare overall compliance rates.
Results:Overall ED compliance to NICE time standards improved following implementation of the proforma (43% vs. 36%, p=0.401).
For CT scans that were indicated within one hour, there was a statistically significant decrease in median wait time from triage to CT (134mins vs. 186mins, p=0.046). There was also a decrease in median wait time for scans indicated within 8 hours; however, this did not reach the threshold for statistical significance (216mins vs. 275mins, p=0.230).
Conclusion:Although there was an overall reduction in wait times for CT, this did not translate to a significant improvement in compliance rates to NICE CG176 time standards. This suggests that, despite earlier identification of these high-risk head injuries at triage, other systemic barriers to obtaining head CT are present and warrant further investigation.
Psychosocial Support Interventions for Children During Ongoing War in Ukraine: A Pilot Study
- Amy Nitza, Andrew O'Meara, Gloria Leon, Krystyna Vysotska, Alexander Prokhorov, Cassandre Surinon, Taylor O'Connor
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- Journal:
- Prehospital and Disaster Medicine / Volume 38 / Issue S1 / May 2023
- Published online by Cambridge University Press:
- 13 July 2023, p. s122
- Print publication:
- May 2023
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Introduction:
This presentation describes an initiative to provide psychosocial support to children in Ukraine during the ongoing war using a children’s storybook, coloring book, and activity book. The resources promote emotion identification, self-expression, coping skills, and social support–variables with empirical support in promoting children’s mental health in response to trauma.
Method:The book: “An Unusual Situation” is a bibliotherapy intervention for children struggling with difficult situations. By identifying with the characters, children learn about their own struggles, they learn that other children share similar concerns, and learn important coping skills.
The book was translated into Ukrainian and Russian; supplementary materials including a coloring book, activity book and a guidebook were developed. Following a three-hour training, Ukrainian mental health professionals worked with children on the materials in their respective wartime settings.
Results:Results of the following research questions will be presented:
1) How do mental health professionals working with children in Ukraine utilize the associated book resources measured by a survey and completed by the professionals engaged in the project.
2) What do children who use these resources report about their experiences coping with the ongoing war, measured by:
a) Collecting children’s responses in the activity book.
b) Surveying the mental health professionals about their observations of the children during the intervention process.
3) Does the intervention reduce children’s distress, interpersonal functioning, or problematic behaviors, measured by pre-post scores on the Youth Outcome Questionnaire 2.0.
Conclusion:This pilot study will provide information to guide the implementation of a broad psychosocial support intervention for children living in the setting of the ongoing war in Ukraine. Conclusions to be presented include:
1) Tailoring the intervention to the current needs of Ukrainian children
2) Designing a wide-scale implementation plan tailored to Ukrainian mental health professionals’ recommendations
3) Addressing barriers to implementation.
Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders
- Matthew J. Y. Kang, Dhamidhu Eratne, Hannah Dobson, Charles B. Malpas, Michael Keem, Courtney Lewis, Jasleen Grewal, Vivian Tsoukra, Christa Dang, Ramon Mocellin, Tomas Kalincik, Alexander F. Santillo, Henrik Zetterberg, Kaj Blennow, Christiane Stehmann, Shiji Varghese, Qiao-Xin Li, Colin L. Masters, Steven Collins, Samuel F. Berkovic, Andrew Evans, Wendy Kelso, Sarah Farrand, Samantha M. Loi, Mark Walterfang, Dennis Velakoulis
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- Journal:
- Acta Neuropsychiatrica / Volume 36 / Issue 1 / February 2024
- Published online by Cambridge University Press:
- 28 April 2023, pp. 17-28
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Objective:
People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown.
Methods:We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other.
Results:Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone.
Conclusions:CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.
Recent innovations in adaptive trial designs: A review of design opportunities in translational research
- Alexander M. Kaizer, Hayley M. Belli, Zhongyang Ma, Andrew G. Nicklawsky, Samantha C. Roberts, Jessica Wild, Adane F. Wogu, Mengli Xiao, Roy T. Sabo
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 28 April 2023, e125
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Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of “adaptive” clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint. Emerging topics related to borrowing information from historic or supplemental data sources, sequential multiple assignment randomized trials (SMART), master protocol and seamless designs, and phase I dose-finding studies are also presented. Each design element includes a brief overview with an accompanying case study to illustrate the design method in practice. We close with brief discussions relating to the statistical considerations for these contemporary designs.
266 Decoding the role of polyamine metabolism on anti-tumor immunity in head and neck cancer
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- Richard Alexander Harbison, William Andrews, Michael Mikula, Aleksandra Ogurtsova, Liz Engle, Ogechi Nwankwoala, Reagan Willis, Pritam Sadhukhan, Mark Burns, Drew Pardoll, Tanguy Seiwert, Carole Fakhry, Robert A. Casero, Elana Fertig, Erika Pearce
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 80
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OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.