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Synthetic Aperture Radar Interferometry (InSAR) is an active remote sensing method that uses repeated radar scans of the Earth's solid surface to measure relative deformation at centimeter precision over a wide swath. It has revolutionized our understanding of the earthquake cycle, volcanic eruptions, landslides, glacier flow, ice grounding lines, ground fluid injection/withdrawal, underground nuclear tests, and other applications requiring high spatial resolution measurements of ground deformation. This book examines the theory behind and the applications of InSAR for measuring surface deformation. The most recent generation of InSAR satellites have transformed the method from investigating 10's to 100's of SAR images to processing 1000's and 10,000's of images using a wide range of computer facilities. This book is intended for students and researchers in the physical sciences, particularly for those working in geophysics, natural hazards, space geodesy, and remote sensing. This title is also available as Open Access on Cambridge Core.
Aircraft tyres play a critical role in ensuring the safety of aircraft landings. This paper introduces a novel multi-scale analytical method for evaluating tyre impact performance, explicitly studying the effect of damage defects in the manufacturing and service process on tyre landing dynamic performance. Building on this approach, a numerical simulation of aircraft tyre static and impact load scenarios was conducted, followed by experimental validation. The study systematically compares and analyses the effects of void volume fraction, cord volume fraction and material scale factor on the maximum impact force experienced by aircraft tyre. The variations in maximum impact force arising from changes in tyre structural strength, and deformation can be explained by specific parameters. The findings of this research have significant implications for tyre design and engineering, as well as for enhancing the understanding of the factors that influence tyre performance and safety.
Objectives/Goals: Imaging neuromas, benign tumors of nerve tissue, can be difficult in amputees with osseointegrated (OI) prostheses, in which a metal rod is implanted into the residual limb. Magnetic resonance imaging can be inadequate due to the implanted metal. The aim of this study is to assess the use of ultrasound to detect neuromas in patients with OI prostheses. Methods/Study Population: This is a single-institutional observational study of 7 patients undergoing lower limb OI prostheses. Lower extremity nerve ultrasounds with 2-D grayscale and Doppler were completed at postoperative follow-up visits following OI prosthesis implantation. Specifically, the sciatic nerve, tibial nerve, common peroneal nerve, and sural nerve were targeted for imaging. Neuromas found on ultrasound were measured by maximal length in three planes. Results/Anticipated Results: Our study to date includes two patients with OI prostheses. The remaining patients will be accrued by the end of December. The first patient with a left below-the-knee amputation completed imaging 3 years after OI prosthesis implantation. The common peroneal nerve showed preserved fascicular architecture and morphology, with no distinct neuroma formation. However, the sural nerve demonstrated a 6 × 5 × 4 mm neuroma with minimal pain with deep palpation. The tibial nerve demonstrated a 14 × 11 × 8 mm neuroma within the medial calf musculature, with mild pain with deep palpation. The second patient with a right above-the-knee amputation was imaged 10 months after OI prosthesis implantation. The sciatic nerve demonstrated preserved fascicular morphology and terminated in a smooth taper. There was no defined neuroma. Discussion/Significance of Impact: In conclusion, we have preliminarily shown in the first two patients that ultrasound can successfully image neuromas in patients with OI prostheses in the postoperative period. Furthermore, despite a patient that was 3 years postoperative with two neuromas, the neuromas produced minimal to mild pain with targeted palpation.
Objectives/Goals: This proposal outlines the successful deployment of a research training initiative to support the formation of a Learning Healthcare System. Mayo Clinic Health System (MCHS) rural providers were offered the opportunity to the fundamentals of clinical research via Clinical and Translational Science Awards core curriculum, mentorship, and an online seminar series. Methods/Study Population: MCHS funded 4 key introductory research courses: 1) Manuscript Writing, 2) Grant Writing, 3) Basic Biostatistics, and 4) Essentials of Clinical and Translations Science Program. In addition to course offerings, a Research Interest Group was formed to guide novice rural researchers on topic selection and study design. This cultivated interest to create a 16-month clinical research webinar series offering CME credits. Subsequently, an internal MCHS RFA was launched seeking early-stage investigator pilot proposals focused on rural health. Results/Anticipated Results: In 2023, over 140 MCHS providers enrolled in 324 CCaTS research courses. This training led to the submission of 53 proposals to the inaugural MCHS 2023 RFA, of which 15 were awarded. Additionally, 14 MCHS extramural grants were submitted in 2023. Training efforts expanded in 2024 to include an online research seminar series covering various study topics and providing CME credit, with an approximate attendance up to 196 attendees per session. The second annual MCHS RFA resulted in 4 internal awards, with an additional 22 extramural grant submissions. These collective efforts have increased the number of MCHS first and last author publications and the number of MCHS providers with academic rank. Discussion/Significance of Impact: Leadership’s commitment of resources to educate, mentor, and engage clinicians was crucial to our success and demonstrated a strong return on investment. To maximize impact in community-based practice, continued commitment is needed in the form of protected research time, funding, and research administration support of projects of interest
Access to information via social media is one of the biggest differentiators of public health crises today. During the early stages of the Covid-19 outbreak in January 2020, we conducted an experiment in Wuhan, China to assess the impact of viral social media content on pro-social and trust behaviours and preferences towards risk taking with known and unknown probabilities. Prior to the experiment, participants viewed one of two videos that had been widely and anonymously shared on Chinese social media: a central government leader visiting a local hospital and supermarket, or health care volunteers transiting to Wuhan. In a control condition, participants watched a Neutral video, unrelated to the crisis. Viewing one of the leadership or volunteer videos leads to higher levels of pro-sociality and lesser willingness to take risks in an ambiguous situation relative to the control condition. The leadership video, however, induces lower levels of trust. We provide evidence from two post-experiment surveys that the video’s impact on pro-sociality is modulated by influencing the viewer’s affective emotional state.
Early adversity increases risk for child mental health difficulties. Stressors in the home environment (e.g., parental mental illness, household socioeconomic challenges) may be particularly impactful. Attending out-of-home childcare may buffer or magnify negative effects of such exposures. Using a longitudinal observational design, we leveraged data from the NIH Environmental influences on Child Health Outcomes Program to test whether number of hours in childcare, defined as 1) any type of nonparental care and 2) center-based care specifically, was associated with child mental health, including via buffering or magnifying associations between early exposure to psychosocial and socioeconomic risks (age 0–3 years) and later internalizing and externalizing symptoms (age 3–5.5 years), in a diverse sample of N = 2,024 parent–child dyads. In linear regression models, childcare participation was not associated with mental health outcomes, nor did we observe an impact of childcare attendance on associations between risk exposures and symptoms. Psychosocial and socioeconomic risks had interactive effects on internalizing and externalizing symptoms. Overall, the findings did not indicate that childcare attendance positively or negatively influenced child mental health and suggested that psychosocial and socioeconomic adversity may need to be considered as separate exposures to understand child mental health risk in early life.
The unsteady flow physics of wind-turbine wakes under dynamic forcing conditions are critical to the modelling and control of wind farms for optimal power density. Unsteady forcing in the streamwise direction may be generated by unsteady inflow conditions in the atmospheric boundary layer, dynamic induction control of the turbine or streamwise surge motions of a floating offshore wind turbine due to floating-platform oscillations. This study seeks to identify the dominant flow mechanisms in unsteady wakes forced by a periodic upstream inflow condition. A theoretical framework for the problem is derived, which describes travelling-wave undulations in the wake radius and streamwise velocity. These dynamics encourage the aggregation of tip vortices into large structures that are advected along in the wake. Flow measurements in the wake of a periodically surging turbine were obtained in an optically accessible towing-tank facility, with an average diameter-based Reynolds number of 300 000 and with surge-velocity amplitudes of up to 40 % of the mean inflow velocity. Qualitative agreement between trends in the measurements and model predictions is observed, supporting the validity of the theoretical analyses. The experiments also demonstrate large enhancements in the recovery of the wake relative to the steady-flow case, with wake-length reductions of up to 46.5 % and improvements in the available power at 10 diameters downstream of up to 15.7 %. These results provide fundamental insights into the dynamics of unsteady wakes and serve as additional evidence that unsteady fluid mechanics can be leveraged to increase the power density of wind farms.
We aimed to describe the incidence, pathogens, and antimicrobial susceptibility of central line-associated bloodstream infections (CLABSI) in adult intensive care units (ICU).
Design:
State surveillance data from 2011 to 2022 were analyzed to identify patient and device days and CLABSI events. Pathogen data were analyzed to determine the most common organisms and patterns of antimicrobial resistance grouped into 3-year time epochs.
Setting:
Adult ICU in Victoria, Australia.
Participants:
Healthcare organizations participating in CLABSI state surveillance.
Results:
608 events were reported over 751,350 device days. Overall, CLABSI incidence was 0.81 per 1,000 central-line days, with a 49.3% rate reduction from 2011 to 2022 (1.39 to 0.70 per 1,000 central-line days). Overall device utilization ratio was 0.57, with a 15.4% reduction from 2011 to 2022 (0.67 vs 0.56). Of 690 pathogens, the most common by rank order were coagulase-negative Staphylococci (CNS), Candida species, Staphylococcus aureus, and Enterococcus faecalis. The proportion of CNS-causing events increased by 69.0% from 2011 to 2022; this trend was not observed for other organisms. For every increase in epoch, a 33% decrease in methicillin-resistant S. aureus (MRSA), 4% increase in vancomycin-resistant Enterococcus faecium, and 12% increase in ceftriaxone-resistant Escherichia coli pathogens were observed.
Conclusions:
We demonstrate a decreasing incidence of CLABSI in Victorian adult ICU and an increasing burden of infections due to CNS. No significant time trend increases in antimicrobial-resistant organisms, including MRSA, vancomycin-resistant E. faecium, and ceftriaxone-resistant E. coli were observed. These findings are relevant for identifying priorities for CLABSI prevention in Victorian adult ICU.
Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.
Methods
Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.
Results
Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.
Conclusions
While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.
Identification of sugarcane hybrids is difficult when selections are based solely on morphological traits. Our objective was to combine morphological traits and molecular marker analysis to select F1 hybrids from two separate crosses between Djatiroto, a clone of Saccharum spontaneum, and elite sugarcane clones, LCP 85-384 (Cross 97-3144) and CP 62-258 (Cross 97-3146). The maternal inflorescences of Djatiroto were emasculated by submersion in a circulating 45°C hot-water tank for 10 min to minimize self-fertilization. Cross 97-3144 produced 4.7 g of seeds with 338 viable seeds per gram and Cross 97-3146 produced 2.4 g of seeds with 166 viable seeds per gram. After greenhouse germination, 96 progeny from each cross were evaluated in a field plot. Evaluations were conducted on the ratoon crops for stalk diameter (mm), juice Brix (percentage soluble solids), and a randomly amplified polymorphic DNA (RAPD) marker OPA-11-366 that was reproducibly amplified through PCR from the elite clones, but not the maternal S. spontaneum clone. Fifty progeny (52.1%) from Cross 97-3144 and 36 progeny (37.5%) from Cross 97-3146 inherited the RAPD marker. Five putative F1 progeny were selected from each cross, namely US 99-43, US 99-44, US 99-45, US 99-46 and US 99-47 from Cross 97-3144, and US 99-48, US 99-49, US 99-50, US 99-51 and US 99-52 from Cross 97-3146, based on their relatively larger stalk diameter, higher Brix and inheritance of the RAPD marker. The hybrid nature of these selected progeny was verified with sugarcane microsatellite markers. This is the first report of the development of Saccharum hybrids with the cytoplasm of S. spontaneum for breeding purpose through a combination of conventional and molecular breeding approaches. Availability of these F1 hybrids could enhance the genetic diversity of Saccharum germplasm and has enabled sugarcane geneticists and breeders to explore the possible contribution of S. spontaneum cytoplasm in the development of new sugarcane cultivars.
Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.
Methods
Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.
Results
The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).
Conclusions
Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.
Although food insecurity affects a significant proportion of young children in New Zealand (NZ)(1), evidence of its association with dietary intake and sociodemographic characteristics in this population is lacking. This study aims to assess the household food security status of young NZ children and its association with energy and nutrient intake and sociodemographic factors. This study included 289 caregiver and child (1-3 years old) dyads from the same household in either Auckland, Wellington, or Dunedin, NZ. Household food security status was determined using a validated and NZ-specific eight-item questionnaire(2). Usual dietary intake was determined from two 24-hour food recalls, using the multiple source method(3). The prevalence of inadequate nutrient intake was assessed using the Estimated Average Requirement (EAR) cut-point method and full probability approach. Sociodemographic factors (i.e., socioeconomic status, ethnicity, caregiver education, employment status, household size and structure) were collected from questionnaires. Linear regression models were used to estimate associations with statistical significance set at p <0.05. Over 30% of participants had experienced food insecurity in the past 12 months. Of all eight indicator statements, “the variety of foods we are able to eat is limited by a lack of money,” had the highest proportion of participants responding “often” or “sometimes” (35.8%). Moderately food insecure children exhibited higher fat and saturated fat intakes, consuming 3.0 (0.2, 5.8) g/day more fat, and 2.0 (0.6, 3.5) g/day more saturated fat compared to food secure children (p<0.05). Severely food insecure children had lower g/kg/day protein intake compared to food secure children (p<0.05). In comparison to food secure children, moderately and severely food insecure children had lower fibre intake, consuming 1.6 (2.8, 0.3) g/day and 2.6 (4.0, 1.2) g/day less fibre, respectively. Severely food insecure children had the highest prevalence of inadequate calcium (7.0%) and vitamin C (9.3%) intakes, compared with food secure children [prevalence of inadequate intakes: calcium (2.3%) and vitamin C (2.8%)]. Household food insecurity was more common in those of Māori or Pacific ethnicity; living in areas of high deprivation; having a caregiver who was younger, not in paid employment, or had low educational attainment; living with ≥2 other children in the household; and living in a sole-parent household. Food insecure young NZ children consume a diet that exhibits lower nutritional quality in certain measures compared to their food-secure counterparts. Food insecurity was associated with various sociodemographic factors that are closely linked with poverty or low income. As such, there is an urgent need for poverty mitigation initiatives to safeguard vulnerable young children from the adverse consequences of food insecurity.
Transmission electron microscopy has been used to characterize coexisting pyrophyllite and muscovite in low-grade metamorphosed pelites from Witwatersrand and northeastern Pennsylvania. The Witwatersrand sample consisted largely of porphyroblasts of interlayered muscovite and pyrophyllite in a fine-grained matrix of the same phases. In both textures, muscovite and pyrophyllite occurred as interlayered packets (with apparently coherent interfaces) from about 300 Å to a few micrometers in thickness, with no mixed layering. Their compositions were determined with a scanning transmission electron microscope to be
The pyrophyllite and muscovite in the Pennsylvania shale likewise occurred only as coexisting coherent to sub-parallel packets as thin as 200 Å, with compositions of
The textures of both samples were consistent with an equilibrium relationship between pyrophyllite and muscovite. The Pennsylvania sample also contained NH4-rich illite, kaolinite, and an illite-like phase having intermediate Na/K, which collectively imply non-equilibrated low-grade conditions.
The compositions of these coexisting pyrophyllite and muscovite define a solvus with steep limbs and extremely limited solid solution. Illite is a white mica, intermediate in composition between pyrophyllite and muscovite, formed at much lower temperatures than muscovite. These relations show that illite is metastable relative to pyrophyllite + muscovite in all of its diagenetic and low-grade metamorphic occurrences. This further implies that illite precursor phases, such as smectite, are also metastable. The prograde reactions involving smectite, illite, and muscovite are therefore inferred to represent Ostwald-step-rule-like advances through a series of metastable phases toward the equilibrium states attained in the greenschist facies. “Illite crystallinity” can therefore be a measure of reaction progress, for which temperature is only one of several determining factors.
Ordered illite/smectite (I/S) and illite in a pelitic rock from a prograde metamorphic sequence in North Wales were observed by transmission electron microscopy. The dominant phyllosilicate noted was diagenetic-metamorphic illite, occurring as subparallel packets of layers, each about a few hundred Ångstroms thick. It exhibited two-layer polytypism (presumably 2M1) and numerous strain features and had a composition of (K1.21Na0.12)(Al3.36Fe0.31Mg0.33)(Si6.28Al1.72)O20(OH)4.
I/S occurred as thick packets of wavy layers having 10-Å subperiodicity and sharp differences in contrast in successive lattice fringes. All stages in a replacement series were noted, from one or two layers of smectite within illite, through thin packets of I/S, to thick packets that contained inherited deformation textures of diagenetic-metamorphic illite. Deformed illite was replaced by I/S more commonly than was undeformed illite. The I/S replacing undeformed original illite had significantly greater order, primarily of R1 type (ISISIS…), than that replacing deformed illite. R> 1 I/S occurred as small crystallites and contained relatively less smectite than the ordered I/S, Single smectite layers were spaced within several illite layers, forming curved packets of layers. IISIIS… (R2) and IIISIIIS… (R3) ordering were present locally, as was discrete smectite. Analytical electron microscopic analyses indicated that the I/S, (K0.46Na0.43)(Al3.75Fe0.06Mg0.19)(Si6.26Al1.74)O20(OH)4, was rectorite-like in composition and had smaller (Mg + Fe) contents and greater Al/Si ratios than the coexisting illite, which was also anomalous in terms of general crystal-chemical relationships between coexisting illite and I/S in burial diagenesis environments. The I/S appears to have formed by replacement of diagenetic-metamorphic illite, presumably at very low temperatures under hydrous conditions via dissolution and crystallization.
Clay minerals from the MacAdams Sandstone, Kettleman North Dome, California, have been studied by electron microscopy. The clay minerals fill pore space associated with fractured and brecciated clasts of K-feldspar. Curved packets of muscovite and kaolinite are caused by deformation of detrital muscovite that resulted in opening of fissures subsequently filled with dominant kaolinite and minor intergrown mixed-layer illite/smectite (I/S). Regions of authigenic R1 I/S (rectorite) with characteristic ~20 Å periodicity are intergrown with kaolinite in microfissures within K-feldspar or detrital muscovite. Clusters of small grains of muscovite with nearly ideal composition occur as stacks and intergrown with kaolinite and are tentatively inferred to be authigenic. Contrary to previous reports, no illite was found in these samples.
Electron microprobe analyses previously obtained on Kettleman Dome “illite” and subsequently used as a prime example of analyses of illite rich in excess interlayer water (H2O) and hydronium ion (H3O+) are shown to have been obtained on mixtures, and are not representative of the actual clay mineral compositions. Previous conclusions regarding significant H3O+ and H2O contents of illite are invalid because of inaccuracies inherent in bulk and EMPA analyses of illite, and do not affect arguments regarding the metastability of illite. Hydronium substitution should be favored via the reaction H2O + H+ = H3O+ only in highly acidic fluids. Ordinary illite forming in sedimentary environments with carbonates and iron oxides is unlikely to have significant H3O+ substituted for K+.
Helium or neopentane can be used as surrogate gas fill for deuterium (D2) or deuterium-tritium (DT) in laser-plasma interaction studies. Surrogates are convenient to avoid flammability hazards or the integration of cryogenics in an experiment. To test the degree of equivalency between deuterium and helium, experiments were conducted in the Pecos target chamber at Sandia National Laboratories. Observables such as laser propagation and signatures of laser-plasma instabilities (LPI) were recorded for multiple laser and target configurations. It was found that some observables can differ significantly despite the apparent similarity of the gases with respect to molecular charge and weight. While a qualitative behaviour of the interaction may very well be studied by finding a suitable compromise of laser absorption, electron density, and LPI cross sections, a quantitative investigation of expected values for deuterium fills at high laser intensities is not likely to succeed with surrogate gases.
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.
Children who sustain a mild traumatic brain injury (mTBI) are at increased odds of additive injury and continue to show altered motor performance relative to never-injured peers after being medically cleared (MC) to return to normal activities. There is a critical need to determine when children can return to activities without risk of short and long-term adverse effects, with research showing high reinjury rates for 3-12 months after RTP. The Physical and Neurological Examination for Subtle Signs (PANESS) measures subtle signs of motor impairment during gait, balance, and timed motor functions. Recent literature has demonstrated that PANESS timed motor function can distinguish between children medically cleared post-mTBI compared to never-injured controls. The present study examined performance on timed motor tasks in youth medically cleared from mTBI following medical clearance and 3-months later, compared to never-injured peers.
Participants and Methods:
25 children (Mage=14.16, SD=2.46; Male=68%) were enrolled within 6 weeks of medical clearance from mTBI (Mdays post MC=33, SD=13.4, Range=2-59) along with 66 typically developing, never-injured controls (Mage=13.9, SD=2.22; Male=50%). Group differences were evaluated for the Timed Motor section of the PANESS at enrollment and at a 3-month follow-up (Mdays from enrollment to follow-up=95.90, SD=12.69, Range=62-129). This 3-month follow-up occurred on average 4 months after medical clearance (Mdays from MC to follow-up=130.08, SD=17.58, Range=92 - 164). The Timed Motor section includes Repetitive (foot tapping, hand patting, and finger tapping) and Sequential (heel-toe rocking, hand pronate/supinate, finger sequencing) raw time scores, measured in seconds. The Total Timed Motor Speed score is the combination of Repetitive and Sequential Movement and the side-to-side tongue item.
Results:
At 3-month follow-up, mTBI participants (M=67.55, SD=8.26, Range=53.66-83.88) performed worse than controls (M=63.09, SD=10.23, Range=39.86-100.51) on Total Timed Motor Speed, t(89)= 1.95, p<0.05), including when controlling for age and sex, F(1, 87)=4.67, p<0.05. At the same time point, mTBI participants (M=36.54, SD=5.47, Range=28.74-49.17) performed worse on Sequential Speed than controls (M=32.93, SD=6.1, Range=21.49-56.76), t(89)=2.59, p<0.01, including when controlling for age and sex, F(1, 87)=7.687, p<0.01). Although groups performed similarly on Sequential Speed at the initial time point, mTBI participants exhibited a trend of less improvement from initial to follow-up (MmTBI=-1.69, Mcontrol=-3.68, t(90)=1.445, p=0.076).
Conclusions:
Although groups did not significantly differ on Timed Motor Speed items at the initial time point, the mTBI group showed consistently lower scores than controls at both time points and less improvement over time. Results indicate that Total Timed Motor Speed, specifically Sequential Speed, may be a sensitive marker of persisting differences in high-level motor and cognitive learning/control in children who have been medically cleared after mTBI. More data are needed to evaluate these findings over a longer time period, and future studies should examine behavioral markers concurrently with physiologic brain recovery over time.
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.
Internalising disorders are highly prevalent emotional dysregulations during preadolescence but clinical decision-making is hampered by high heterogeneity. During this period impulsivity represents a major risk factor for psychopathological trajectories and may act on this heterogeneity given the controversial anxiety–impulsivity relationships. However, how impulsivity contributes to the heterogeneous symptomatology, neurobiology, neurocognition and clinical trajectories in preadolescent internalising disorders remains unclear.
Aims
The aim was to determine impulsivity-dependent subtypes in preadolescent internalising disorders that demonstrate distinct anxiety–impulsivity relationships, neurobiological, genetic, cognitive and clinical trajectory signatures.
Method
We applied a data-driven strategy to determine impulsivity-related subtypes in 2430 preadolescents with internalising disorders from the Adolescent Brain Cognitive Development study. Cross-sectional and longitudinal analyses were employed to examine subtype-specific signatures of the anxiety–impulsivity relationship, brain morphology, cognition and clinical trajectory from age 10 to 12 years.
Results
We identified two distinct subtypes of patients who internalise with comparably high anxiety yet distinguishable levels of impulsivity, i.e. enhanced (subtype 1) or decreased (subtype 2) compared with control participants. The two subtypes exhibited opposing anxiety–impulsivity relationships: higher anxiety at baseline was associated with higher lack of perseverance in subtype 1 but lower sensation seeking in subtype 2 at baseline/follow-up. Subtype 1 demonstrated thicker prefrontal and temporal cortices, and genes enriched in immune-related diseases and glutamatergic and GABAergic neurons. Subtype 1 exhibited cognitive deficits and a detrimental trajectory characterised by increasing emotional/behavioural dysregulations and suicide risks during follow-up.
Conclusions
Our results indicate impulsivity-dependent subtypes in preadolescent internalising disorders and unify past controversies about the anxiety–impulsivity interaction. Clinically, individuals with a high-impulsivity subtype exhibit a detrimental trajectory, thus early interventions are warranted.