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Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study
- Stephanie Haering, Antonia V. Seligowski, Sarah D. Linnstaedt, Vasiliki Michopoulos, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Jr., Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Nina T. Gentile, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Samuel A. McLean, Ronald C. Kessler, Karestan C. Koenen, Jennifer S. Stevens, Abigail Powers
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-11
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Background
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
MethodsAs part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
ResultsWomen reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
ConclusionsOur findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis
- Kuan-Yu Pan, Lonneke van Tuijl, Maartje Basten, Judith J. M. Rijnhart, Alexander de Graeff, Joost Dekker, Mirjam I. Geerlings, Adriaan Hoogendoorn, Adelita V. Ranchor, Roel Vermeulen, Lützen Portengen, Adri C. Voogd, Jessica Abell, Philip Awadalla, Aartjan T. F. Beekman, Ottar Bjerkeset, Andy Boyd, Yunsong Cui, Philipp Frank, Henrike Galenkamp, Bert Garssen, Sean Hellingman, Monika Hollander, Martijn Huisman, Anke Huss, Melanie R. Keats, Almar A. L. Kok, Steinar Krokstad, Flora E. van Leeuwen, Annemarie I. Luik, Nolwenn Noisel, Yves Payette, Brenda W. J. H. Penninx, Susan Picavet, Ina Rissanen, Annelieke M. Roest, Judith G. M. Rosmalen, Rikje Ruiter, Robert A. Schoevers, David Soave, Mandy Spaan, Andrew Steptoe, Karien Stronks, Erik R. Sund, Ellen Sweeney, Alison Teyhan, Emma L. Twait, Kimberly D. van der Willik, Femke Lamers
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- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 29 April 2024, pp. 1-14
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Background
Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).
MethodsTwo-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).
ResultsSmoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).
ConclusionsSmoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.
Implementation of point-of-care molecular testing for respiratory viruses in congregate living settings
- Charlie Tan, Christina K. Chan, Marianna Ofner, Jaclyn O’Brien, Neethu R. Thomas, James Callahan, Brigitte Pascual, Shawn J. Palmer, Victoria Serapion, Hannah Fabro, Robert A. Kozak, Heather Candon, Adrienne K. Chan, Jeff E. Powis, Jerome A. Leis
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- Journal:
- Infection Control & Hospital Epidemiology , First View
- Published online by Cambridge University Press:
- 25 April 2024, pp. 1-5
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Objective:
To implement and evaluate a point-of-care (POC) molecular testing platform for respiratory viruses in congregate living settings (CLS).
Design:Prospective quality improvement study.
Setting:Seven CLS, including three nursing homes and four independent-living facilities.
Participants:Residents of CLS.
Methods:A POC platform for COVID-19, influenza A and B, and respiratory syncytial virus was implemented at participating CLS from December 1, 2022 to April 15, 2023. Residents with respiratory symptoms underwent paired testing, with respiratory specimens tested first with the POC platform and then delivered to an off-site laboratory for multiplex respiratory virus panel (MRVP) polymerase chain reaction (PCR) as per standard protocol. Turn-around time and diagnostic accuracy of the POC platform were compared against MRVP PCR. In an exploratory analysis, time to outbreak declaration among participating CLS was compared against a convenience sample of 19 CLS that did not use the POC platform.
Results:A total of 290 specimens that underwent paired testing were included. Turn-around time to result was significantly shorter with the POC platform compared to MRVP PCR, with median difference of 36.2 hours (interquartile range 21.8–46.4 hours). The POC platform had excellent diagnostic accuracy compared to MRVP PCR, with area under the curve statistic of .96. Time to outbreak declaration was shorter in CLS that used the POC platform compared to CLS that did not.
Conclusion:Rapid POC testing platforms for respiratory viruses can be implemented in CLS, with high diagnostic accuracy, expedited turn-around times, and shorter time to outbreak declaration.
VaTEST III: Validation of eight potential super-earths from TESS data
- Priyashkumar Mistry, Aniket Prasad, Mousam Maity, Kamlesh Pathak, Sarvesh Gharat, Georgios Lekkas, Surendra Bhattarai, Dhruv Kumar, Jack J. Lissauer, Joseph D. Twicken, Abderahmane Soubkiou, Francisco J. Pozuelos, Jon Jenkins, Keith Horne, Steven Giacalone, Khalid Barkaoui, Mathilde Timmermans, Cristilyn N. Watkins, Ramotholo Sefako, Karen A. Collins, David R. Ciardi, Catherine A. Clark, Boris S. Safonov, Avi Shporer, Joshua E. Schlieder, Zouhair Benkhaldoun, Chris Stockdale, Carl Ziegler, Emily A. Gilbert, Jehin Emmanuël, Felipe Murgas, Ian J. M. Crossfield, Martin Paegert, Michael B. Lund, Norio Narita, Richard P. Schwarz, Robert F. Goeke, Sergio B. Fajardo-Acosta, Steve B. Howell, Thiam-Guan Tan, Thomas Barclay, Yugo Kawai
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 41 / 2024
- Published online by Cambridge University Press:
- 11 April 2024, e030
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NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
Investigation of management practices to optimize cereal rye cover crop-based weed mitigation in Canadian sweet corn production
- Hayley L. Brackenridge, Jichul Bae, Marie-Josée Simard, François J. Tardif, Kerry Bosveld, Robert E. Nurse
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- Journal:
- Weed Technology / Volume 38 / 2024
- Published online by Cambridge University Press:
- 02 April 2024, e35
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Fall-sown cereal rye has gained popularity as a cover crop in vegetable production due to its weed-suppressive capabilities. However, previous research has shown that replacing preemergence and/or postemergence herbicide applications with roller-crimped rye has variable success at controlling weeds and maintaining vegetable cash crop yields. The objective of this research was to determine whether roller-crimped rye can provide season-long weed control and maintain sweet corn yield. Two rye cultivars (early vs. standard maturity) were compared at three seeding rates (150, 300, and 600 seeds m−2) for their effect on weed control and sweet corn yield. The trial was conducted at three locations: Harrow, ON, and St. Jean-sur-Richelieu, QC, from 2019 to 2021; and Agassiz, BC, in 2019 and 2021. Results suggest that although the early-maturing cultivar allowed for earlier roller crimping in some locations, it was inferior at weed control and resulted in lower sweet corn yield than local standard cultivars. The average rye biomass was lower than the current literature recommendations, and the resulting level of weed control was not high enough to prevent sweet corn yield loss in cover crop treatments. Weed control provided by roller-crimped rye peaked between crimping and 8 wk after crimping and was highest in the standard cultivars sown at 300 and 600 seeds m−2. Preliminary testing of supplemental postemergence weed control showed evidence for sweet corn yields comparable to the weed-free no-cover crop check. However, more research is needed. Overall, with the cultivars and seeding rates tested, roller-crimped rye is not a suitable stand-alone weed control option in sweet corn production. Given the benefits of cover crops, further research should evaluate its potential as a component of an integrated weed management program.
Healthcare personnel with laboratory-confirmed mpox in California during the 2022 outbreak
- Allison E. Bailey, Shua J. Chai, Robert E. Snyder, David P. Bui, Linda S. Lewis, Kayla Saadeh, J. Bradford Bertumen, Erin Epson, Jane D. Siegel
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- Infection Control & Hospital Epidemiology , First View
- Published online by Cambridge University Press:
- 27 March 2024, pp. 1-3
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The California Department of Public Health (CDPH) reviewed 109 cases of healthcare personnel (HCP) with laboratory-confirmed mpox to understand transmission risk in healthcare settings. Overall, 90% of HCP with mpox had nonoccupational exposure risk factors. One occupationally acquired case was associated with sharps injury while unroofing a patient’s lesion for diagnostic testing.
Mechanisms and Crystal Chemistry of Oxidation in Annite: Resolving the Hydrogen-Loss and Vacancy Reactions
- D. G. Rancourt, P. H. J. Mercier, D. J. Cherniak, S. Desgreniers, H. Kodama, J.-L. Robert, E. Murad
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- Journal:
- Clays and Clay Minerals / Volume 49 / Issue 6 / December 2001
- Published online by Cambridge University Press:
- 28 February 2024, pp. 455-491
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A synthetic octahedral-site-vacancy-free annite sample and its progressive oxidation, induced by heating in air, were studied by powder X-ray diffraction (pXRD), Mössbauer spectroscopy, nuclear reaction analysis (NRA), Raman spectroscopy, X-ray fluorescence (XRF) spectroscopy, gas chromatography (GC), thermogravimetric analysis (TGA), differential thermal analysis (DTA), scanning electron microscopy (SEM), and size-fraction separation methods. For a set heating time and as temperature is increased, the sample first evolves along an annite-oxyannite join, until all H is lost via the oxybiotite reaction (Fe2+ + OH− ⇌ Fe3+ + O2− + H↑). It then evolves along an oxyannite-ferrioxyannite join, where ideal ferrioxyannite, KFe3+8/3□1/3AlSi3O12, is defined as the product resulting from complete oxidation of ideal oxyannite, KFe3+2Fe2+AlSi3O12, via the vacancy mechanism (3 Fe2+ ⇌ 2 Fe3+ + [6]□ + Fe↑). A pillaring collapse transition is observed as a collapse of c near the point where and all OH groups are predicted and observed to be lost. Quantitative analyses of H, using NRA, GC, and Raman spectroscopy, corroborate this interpretation and, in combination with accurate ferric/ferrous ratios from Mössbauer spectroscopy and lattice parameter determinations, allow a clear distinction to be made between vacancy-free and vacancy-bearing annite. The amount of Fe in ancillary Fe oxide phases produced by the vacancy mechanism is measured by Mössbauer spectroscopy to be 11.3(5)% of total Fe, in agreement with both the theoretical prediction of 1/9 = 11.1% and the observed TGA weight gain. The initiation of Fe oxide formation near the point of completion of the oxybiotite reaction () is corroborated by pXRD, TGA, Raman spectroscopy, and appearance of an Fe oxide hyperfine field sextet in the Mössbauer spectra. The region of Fe oxide formation is shown to coincide with a region of octahedral site vacancy formation, using a new Mössbauer spectral signature of vacancies that consists of a component at 2.2 mm/s in the [6]Fe3+ quadrupole splitting distribution (QSD). The crystal chemical behaviors of annite-oxyannite and of oxyannite-ferrioxyannite are best contrasted and compared to the behaviors of other layer-silicate series in terms of b vs. [D] (average octahedral cation to O bond length). This also leads to a diagnostic test for the presence of octahedral site vacancies in hydrothermally synthesized annite, based on a graph of b vs. Fe2+/Fe. The implications of the observed sequence of thermal oxidation reactions for the thermodynamic relevance of the oxybiotite and vacancy reactions in hydrothermal syntheses are examined and it is concluded that the oxybiotite reaction is the relevant reaction in the single-phase stability field of annite, at high hydrogen fugacity and using ideal starting cation stoichiometry. The vacancy reaction is only relevant in a multi-phase field, at lower hydrogen fugacity, that includes an Fe oxide equilibrium phase (magnetite) that can effectively compete for Fe, or when using non-ideal starting cation stoichiometries.
The Al Pillaring of Clays. Part I. Pillaring with Dilute and Concentrated Al Solutions
- Robert A. Schoonheydt, J. van den Eynde, H. Tubbax, H. Leeman, M. Stuyckens, I. Lenotte, W. E. E. Stone
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- Clays and Clay Minerals / Volume 41 / Issue 5 / October 1993
- Published online by Cambridge University Press:
- 28 February 2024, pp. 598-607
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Saponite, hectorite, and laponite have been pillared with cationic Al clusters, and special attention has been given to the solution chemistry or Al. Pillared saponite is obtained after exchange with refluxed Al solutions; while for hectorite, Al solutions treated with ammonium acetate give a pillared product with 1.8–1.9 nm spacing and thermal stability up to 873 K. In both types of solutions, the Keggin ion Al cluster is a minority species or totally absent. The typical 1.8–1.9 nm spacing is only obtained after washing. The quality of the pillared material can be judged from its thermal stability, its surface area, and the width of the d001 line before and after pillaring. The width should not exceed 0.3 nm before calcination and 0.5 nm after calcination. The latter criterion reflects the importance of the crystallinity of the parent clay for successful pillaring. Pillaring in concentrated conditions occurs by a combination of ion exchange and precipitation of Al and gives materials that exhibit poor thermal stability.
Phosphates in Some Missouri Refractory Clays
- Robert B. Hall, Eugene E. Foord, David J. Keller, Walter D. Keller
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- Clays and Clay Minerals / Volume 45 / Issue 3 / June 1997
- Published online by Cambridge University Press:
- 28 February 2024, pp. 353-364
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This paper describes in detail phosphate minerals occurring in refractory clays of Missouri and their effect on the refractory degree of the clays. The minerals identified include carbonate-fluorapatite (francolite), crandallite, goyazite, wavellite, variscite and strengite. It is emphasized that these phosphates occur only in local isolated concentrations, and not generally in Missouri refractory clays.
The Missouri fireclay region comprises 2 districts, northern and southern, separated by the Missouri River. In this region, clay constitutes a major part of the Lower Pennsylvanian Cheltenham Formation. The original Cheltenham mud was an argillic residue derived from leaching and dissolution of pre-Pennsylvanian carbonates. The mud accumulated on a karstic erosion surface truncating the pre-Cheltenham rocks. Fireclays of the northern district consist mainly of poorly ordered kaolinite, with variable but minor amounts of illite, chlorite and fine-grained detrital quartz. Clays of the southern district were subjected to extreme leaching that produced well-ordered kaolinite flint clays. Local desilication formed pockets of diaspore, or more commonly, kaolinite, with oolite-like nubs or burls of diaspore (“burley” clay).
The phosphate-bearing materials have been studied by X-ray diffraction (XRD), scanning electron microscopy-energy dispersive spectral analysis (SEM-EDS) and chemical analysis. Calcian goyazite was identified in a sample of diaspore, and francolite in a sample of flint clay. A veinlet of wavellite occurs in flint clay at one locality, and a veinlet of variscite-strengite at another locality.
The Missouri flint-clay-hosted francolite could not have formed in the same manner as marine francolite. The evidence suggests that the Cheltenham francolite precipitated from ion complexes in pore water, nearly simultaneously with crystallization of kaolinite flint clay from an alumina-silica gel. Calcian goyazite is an early diagenetic addition to its diaspore host. The wavellite and variscite-strengite veinlets are secondary, precipitated from ion complexes in ground water percolating along cracks in the flint clay. The flint clay host of the variscite-strengite veinlet contains strontian crandallite. All of the phosphates contain significant amounts of strontium. The source of P, Ca and Sr was the marine carbonates. Dissolution of these carbonates produced the argillic residue that became the primordial Cheltenham paludal mud, which ultimately altered to fireclay.
Preliminary firing tests show that the presence of phosphates lowers fusion temperature. However, it is not clear whether poor refractoriness is due to the presence of phosphates, per se, or to Ca, Sr and other alkaline elements present in the phosphates.
How best can we name the channels seen in the setting of deficient ventricular septation? – CORRIGENDUM
- Robert H. Anderson, Diane E. Spicer, Colin J. McMahon, R. Krishna Kumar, Justin T. Tretter
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- Cardiology in the Young / Volume 34 / Issue 2 / February 2024
- Published online by Cambridge University Press:
- 19 January 2024, p. 468
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Peer review of clinical and translational research manuscripts: Perspectives from statistical collaborators
- Phillip J. Schulte, Judith D. Goldberg, Robert A. Oster, Walter T. Ambrosius, Lauren Balmert Bonner, Howard Cabral, Rickey E. Carter, Ye Chen, Manisha Desai, Dongmei Li, Christopher J. Lindsell, Gina-Maria Pomann, Emily Slade, Tor D. Tosteson, Fang Yu, Heidi Spratt
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 04 January 2024, e20
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Research articles in the clinical and translational science literature commonly use quantitative data to inform evaluation of interventions, learn about the etiology of disease, or develop methods for diagnostic testing or risk prediction of future events. The peer review process must evaluate the methodology used therein, including use of quantitative statistical methods. In this manuscript, we provide guidance for peer reviewers tasked with assessing quantitative methodology, intended to complement guidelines and recommendations that exist for manuscript authors. We describe components of clinical and translational science research manuscripts that require assessment including study design and hypothesis evaluation, sampling and data acquisition, interventions (for studies that include an intervention), measurement of data, statistical analysis methods, presentation of the study results, and interpretation of the study results. For each component, we describe what reviewers should look for and assess; how reviewers should provide helpful comments for fixable errors or omissions; and how reviewers should communicate uncorrectable and irreparable errors. We then discuss the critical concepts of transparency and acceptance/revision guidelines when communicating with responsible journal editors.
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.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, 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. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
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.
4 Methamphetamine, cannabis, HIV, and their combined effects on neurocognition
- Jeffrey M Rogers, Igor Grant, Maria Cecilia Marcondes, Erin E Morgan, Mariana Cherner, Ronald J Ellis, Scott L Letendre, Robert K Heaton, Jennifer E Iudicello
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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. 797-798
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Objective:
Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.
Participants and Methods:HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.
Results:Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.
Conclusions:In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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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. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
How best can we name the channels seen in the setting of deficient ventricular septation?
- Robert H. Anderson, Diane E. Spicer, Colin J. McMahon, R. Krishna Kumar, Justin T. Tretter
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- Cardiology in the Young / Volume 34 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 01 December 2023, pp. 1-10
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Surgical repair of channels between the ventricles is enhanced when the surgeon knows precisely where to place a patch, or baffle, so as to restore septal integrity. The paediatric cardiologist should provide the necessary information. Communication will be enhanced if the same words are used to account for the structures in question. Currently, however, the same term, namely “ventricular septal defect,” is used to account for markedly different areas within the heart. Closure of perimembranous defects found in hearts with concordant or discordant ventriculo-arterial connections restores the integrity of the ventricular septum, at the same time separating the systemic and pulmonary blood streams. When both arterial trunks arise from the right ventricle, in contrast, the surgeon when placing a baffle so as to separate the blood streams, does not close the channel most frequently described as the “ventricular septal defect.” In this review, we show that the perimembranous lesions as found in hearts with concordant or discordant ventriculo-arterial connections are the right ventricular entrances to the areas subtended beneath the hinges of the leaflets of the aortic or pulmonary valves. When both arterial trunks arise from the right ventricle, and the channel between the ventricles is directly subaortic, then the channel termed the “ventricular septal defect” is the left ventricular entrance to the comparable space subtended beneath the aortic root. We argue that recognition of these fundamental anatomical differences enhances the appreciation of the underlying morphology of the various lesions that reflect transfer, during cardiac development, of the aortic root from the morphologically right to the morphologically left ventricle.
Developing a framework to improve global estimates of conservation area coverage
- Rachel E. Sykes, Helen M.K. O'Neill, Diego Juffe-Bignoli, Kristian Metcalfe, P.J. Stephenson, Matthew J. Struebig, Piero Visconti, Neil D. Burgess, Naomi Kingston, Zoe G. Davies, Robert J. Smith
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Area-based conservation is a widely used approach for maintaining biodiversity, and there are ongoing discussions over what is an appropriate global conservation area coverage target. To inform such debates, it is necessary to know the extent and ecological representativeness of the current conservation area network, but this is hampered by gaps in existing global datasets. In particular, although data on privately and community-governed protected areas and other effective area-based conservation measures are often available at the national level, it can take many years to incorporate these into official datasets. This suggests a complementary approach is needed based on selecting a sample of countries and using their national-scale datasets to produce more accurate metrics. However, every country added to the sample increases the costs of data collection, collation and analysis. To address this, here we present a data collection framework underpinned by a spatial prioritization algorithm, which identifies a minimum set of countries that are also representative of 10 factors that influence conservation area establishment and biodiversity patterns. We then illustrate this approach by identifying a representative set of sampling units that cover 10% of the terrestrial realm, which included areas in only 25 countries. In contrast, selecting 10% of the terrestrial realm at random included areas across a mean of 162 countries. These sampling units could be the focus of future data collation on different types of conservation area. Analysing these data could produce more rapid and accurate estimates of global conservation area coverage and ecological representativeness, complementing existing international reporting systems.
Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery
- Bistra Zheleva, Amy Verstappen, David M. Overman, Farhan Ahmad, Sulafa K.M. Ali, Zohair Y. Al Halees, Joumana Ghandour Atallah, Isabella E. Badhwar, Carissa Baker-Smith, Maria Balestrini, Amy Basken, Jonah S. Bassuk, Lee Benson, Horacio Capelli, Santo Carollo, Devyani Chowdhury, M. Sertaç Çiçek, Mitchell I. Cohen, David S. Cooper, John E. Deanfield, Joseph Dearani, Blanca del Valle, Kathryn M. Dodds, Junbao Du, Frank Edwin, Ekanem Ekure, Nurun Nahar Fatema, Anu Gomanju, Babar Hasan, Lewis Henry, Christopher Hugo-Hamman, Krishna S. Iyer, Marcelo B. Jatene, Kathy J. Jenkins, Tara Karamlou, Tom R. Karl, James K. Kirklin, Christián Kreutzer, Raman Krishna Kumar, Keila N. Lopez, Alexis Palacios Macedo, Bradley S. Marino, Eva M. Marwali, Folkert J. Meijboom, Sandra S. Mattos, Hani Najm, Dan Newlin, William M. Novick, Sir Shakeel A. Qureshi, Budi Rahmat, Robert Raylman, Irfan Levent Saltik, Craig Sable, Nestor Sandoval, Anita Saxena, Emma Scanlan, Gary F. Sholler, Jodi Smith, James D. St Louis, Christo I. Tchervenkov, Koh Ghee Tiong, Vladimiro Vida, Susan Vosloo, Douglas J. “DJ” Weinstein, James L. Wilkinson, Liesl Zuhlke, Jeffrey P. Jacobs
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- Journal:
- Cardiology in the Young / Volume 33 / Issue 8 / August 2023
- Published online by Cambridge University Press:
- 24 August 2023, pp. 1277-1287
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The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
Folic acid prescription and suicide attempt prevention: effect of past suicidal behaviour, psychiatric diagnosis and psychotropic medication
- J. John Mann, Kwan Hur, Jill E. Lavigne, Robert D. Gibbons
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- BJPsych Open / Volume 9 / Issue 5 / September 2023
- Published online by Cambridge University Press:
- 22 August 2023, e159
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We previously showed that folic acid prescriptions for any indication were associated with lower rates of suicidal behaviour. Given that future randomised clinical trials are likely to focus on psychiatric disorders carrying elevated risk for suicide, we now report on the moderating effects of prior suicidal behaviour, psychiatric diagnoses and psychotropic medications on potential antisuicidal effects of folic acid. Data were obtained from the MarketScan Commercial Claims and Encounters databases that cover 164 million insured persons from 2005–2017, from which a cohort of 866 586 patients was derived. Analysis revealed no significant moderation effects on the antisuicidal effect of folic acid. These findings indicate that the potential benefit of folic acid for preventing suicidal behaviour is comparable in psychiatric populations at higher risk of suicide and that it may be additive to any benefit from psychotropic medications.