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At least 307 records · Page 17

MABAL: a Novel Deep-Learning Architecture for Machine-Assisted Bone Age Labeling

Bone age assessment (BAA) is a commonly performed diagnostic study in pediatric radiology to assess skeletal maturity. The most commonly utilized method for assessment of BAA is the Greulich and Pyle method (Pediatr Radiol 46.9:1269–1274, 2016; Arch Dis Child 81.2:172–173, 1999) atlas. The evaluation of BAA can be a tedious and time-consuming process for the radiologist. As such, several computer-assisted detection/diagnosis (CAD) methods have been proposed for automation of BAA. Classical CAD tools have traditionally relied on hard-coded algorithmic features for BAA which suffer from a variety of drawbacks. Recently, the advent and proliferation of convolutional neural networks (CNNs) has shown promise in a variety of medical imaging applications. There have been at least two published applications of using deep learning for evaluation of bone age (Med Image Anal 36:41–51, 2017; JDI 1–5, 2017). However, current implementations are limited by a combination of both architecture design and relatively small datasets. The purpose of this study is to demonstrate the benefits of a customized neural network algorithm carefully calibrated to the evaluation of bone age utilizing a relatively large institutional dataset. In doing so, this study will aim to show that advanced architectures can be successfully trained from scratch in the medical imaging domain and can generate results that outperform any existing proposed algorithm. The training data consisted of 10,289 images of different skeletal age examinations, 8909 from the hospital Picture Archiving and Communication System at our institution and 1383 from the public Digital Hand Atlas Database. The data was separated into four cohorts, one each for male and female children above the age of 8, and one each for male and female children below the age of 10. The testing set consisted of 20 radiographs of each 1-year-age cohort from 0 to 1 years to 14–15+ years, half male and half female. The testing set included left-hand radiographs done for bone age assessment, trauma evaluation without significant findings, and skeletal surveys. A 14 hidden layer-customized neural network was designed for this study. The network included several state of the art techniques including residual-style connections, inception layers, and spatial transformer layers. Data augmentation was applied to the network inputs to prevent overfitting. A linear regression output was utilized. Mean square error was used as the network loss function and mean absolute error (MAE) was utilized as the primary performance metric. MAE accuracies on the validation and test sets for young females were 0.654 and 0.561 respectively. For older females, validation and test accuracies were 0.662 and 0.497 respectively. For young males, validation and test accuracies were 0.649 and 0.585 respectively. Finally, for older males, validation and test set accuracies were 0.581 and 0.501 respectively. The female cohorts were trained for 900 epochs each and the male cohorts were trained for 600 epochs. An eightfold cross-validation set was employed for hyperparameter tuning. Test error was obtained after training on a full data set with the selected hyperparameters. Using our proposed customized neural network architecture on our large available data, we achieved an aggregate validation and test set mean absolute errors of 0.637 and 0.536 respectively. To date, this is the best published performance on utilizing deep learning for bone age assessment. Our results support our initial hypothesis that customized, purpose-built neural networks provide improved performance over networks derived from pre-trained imaging data sets. We build on that initial work by showing that the addition of state-of-the-art techniques such as residual connections and inception architecture further improves prediction accuracy. This is important because the current assumption for use of residual and/or inception architectures is that a large pre-trained network is required for successful implementation given the relatively small datasets in medical imaging. Instead we show that a small, customized architecture incorporating advanced CNN strategies can indeed be trained from scratch, yielding significant improvements in algorithm accuracy. It should be noted that for all four cohorts, testing error outperformed validation error. One reason for this is that our ground truth for our test set was obtained by averaging two pediatric radiologist reads compared to our training data for which only a single read was used. This suggests that despite relatively noisy training data, the algorithm could successfully model the variation between observers and generate estimates that are close to the expected ground truth.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Microstructural Coarsening Kinetics and Mechanical Property Changes in Long-Term Aged Sn–Pb–Sb Solder Joints

Tin-lead-antimony (50Sn–47Pb–3Sb wt.%) soldered assemblies were mechanically tested approximately 30 years after initial production and found to have solder joints of reduced strength. The microstructure of this solder alloy exhibits a ternary eutectic structure with Sn-rich, Pb-rich, and SnSb phases. Accelerated aging was performed to evaluate solder microstructural coarsening and associated strength of laboratory solder joints to correlate these properties to the “naturally aged” solder joints. Isothermal aging was conducted at room temperature, 55, 70, 100, and 135 °C and aging times that ranged from 0.1 to 365 days. The coarsening kinetics of the Pb-rich phase were determined through optical microscopy and image analysis methods established in previous studies on binary Sn–Pb solder. A kinetic equation was developed with time exponent n of 0.43 and activation energy of 24000 J/mol, suggesting grain boundary diffusion or other fast diffusion pathways controlling the microstructural evolution. Compression testing and Vickers microhardness showed significant strength loss within the first 20–30 days after soldering; then, the microstructure and mechanical properties changed more slowly over long periods of time. Further, by combining accelerated aging data and the microstructure-based kinetics, strength predictions were made that match well with the properties of the actual soldered assemblies naturally aged for 30 years. However, aging at the highest temperature of 135 °C produced anomalous behavior suggesting that extraneous aging mechanisms are active. Therefore, data obtained at this temperature or higher should not be used. Overall, the combined microstructural and mechanical property methods used in this study confirmed that the observed reduction in strength of ~ 30-year-old solder joints can be accounted for by the microstructural coarsening that takes place during long-term solid-state aging.

36 MATERIALS SCIENCE↗

The combined effects of hydrogen and aging condition on the deformation and fracture behavior of a precipitation-hardened nickel-base superalloy

The effect of hydrogen (H) on the deformation behavior of Monel K-500 in various isothermal heat treatment conditions (non-aged, under-aged, peak-aged, and over-aged) was assessed via uniaxial mechanical testing. H-charged and non-charged specimens were strained to failure to facilitate a comparison of ductility, fracture surface morphology, strength, and work hardening behavior. For all examined heat treatment conditions, H charging leads to a significant reduction in ductility, which is accompanied by a consistent change in fracture surface morphology from ductile microvoid coalescence to brittle intergranular fracture. While H charging led to a systematic enhancement in the yield strength of all heat treatments, the three age-hardened conditions exhibited a more than 2-fold increase relative to the non-aged heat treatment. This suggests that H modifies the dislocation–precipitate interactions, which also manifest themselves through changes in work hardening metrics related to the dislocation storage and recovery rates. In particular, the H-charged peak-aged specimen exhibited a significant increase in initial hardening (dislocation storage) rate relative to the H-charged under-aged specimen. Transmission electron microscopy of these samples revealed the onset of widespread dislocation looping in the H-charged peak-aged sample, in addition to the planar slip bands characteristic of the non-charged condition. This result suggests that hydrogen induces the particle shearing-to-looping transition at smaller particle sizes. Possible mechanistic explanations for this observed behavior are presented.

36 MATERIALS SCIENCE↗

Nuclear AMPK regulated CARM1 stabilization impacts autophagy in aged heart

Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart. We found that fasting could promote autophagy in young hearts but not in aged hearts. The CARM1 stabilization is markedly decrease in aged hearts, which impaired nucleus TFEB-CARM1 complex and autophagy flux. Further, S-phase kinase-associated protein 2(SKP2), responsible for CARM1 degradation, was increased in aged hearts. We further validated that AMPK dependent FoxO3 phosphorylation was markedly reduced in nucleus, the decreased nuclear AMPK-FoxO3 activity fails to suppress SKP2-E3 ubiquitin ligase. This loss of repression leads to The CARM1 level and autophagy in aged hearts could be restored through AMPK activation. Taken together, AMPK deficiency results in nuclear CARM1 decrease mediated in part by SKP2, contributing to autophagy dysfunction in aged hearts. Our results identified nuclear AMPK controlled CARM1 stabilization as a new actor that regulates cardiac autophagy. - Highlights: • AMPK-dependent CARM1 stabilization is an important nuclear mechanism in cardiac autophagy. • AMPK deficiency lead to SKP2-mediated decrease in CARM1. • AMPK–SKP2–CARM1 in the regulation of autophagy dysfunction in aged heart.

60 APPLIED LIFE SCIENCES↗

Downregulation of FOXP1 correlates with tendon stem/progenitor cells aging

Aging is known as a major risk factor for tendon disorders whereas the molecular mechanisms of age-related tendon disorders still remains unclear. Since tendon-derived stem/progenitor cells (TSPCs) play a vital role in tendon maintenance and healing, in this study we aimed to investigate the role of Forkhead box P1 (FOXP1) in aged TSPCs, we found that FOXP1 mRNA and protein levels were markedly decreased in the aged TSPCs. Moreover, overexpression of FOXP1 attenuates TSPCs aging, as confirmed by decreased of senescence-associated β-gal staining, as well as the senescence marker, p16{sup INK4A}. Conversely, FOXP1 depletion by siRNA promoted senescence in young TSPCs. Meanwhile, FOXP1 overexpression also restores the age-associated reduction of self-renewal, migration and differentiation of TSPCs. In addition, FOXP1 overexpression rescued decreased levels of E2F1, pRb and cyclin D1 in aged TSPCs, which suggested that FOXP1 regulates TSPCs aging through cellular senescence. These results indicate that FOXP1 plays a crucial role in TSPCs aging.

60 APPLIED LIFE SCIENCES↗

High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia

Aging is associated with tissue-level changesin cellular composition that are correlated withincreased susceptibility to disease. Aging humanmammary tissue shows skewed progenitor cell po-tency, resulting in diminished tumor-suppressivecelltypes and the accumulation ofdefective epithelialprogenitors. Quantitative characterization of theseage-emergent human cell subpopulations is lacking,impeding our understanding of the relationship be-tween age and cancer susceptibility. We conductedsingle-cell resolution proteomic phenotyping ofhealthy breast epithelia from 57 women, aged 16–91years, using mass cytometry. Remarkable hetero-geneity was quantified within the two mammaryepithelial lineages. Population partitioning identifiedasubsetofaberrantbasal-likeluminalcellsthataccu-mulate with age and originate from age-alteredprogenitors. Quantification of age-emergent pheno-types enabled robust classification of breast tissuesby age in healthy women. This high-resolution map-ping highlighted specific epithelial subpopulationsthat change with age in a manner consistent withincreased susceptibility to breast cancer.

60 APPLIED LIFE SCIENCES↗

Calendar-life versus cycle-life aging of lithium-ion cells with silicon-graphite composite electrodes

The use of blended silicon-graphite (Si-Gr) negative electrodes increases the energy density of lithium-ion cells over those containing only graphite (Gr) electrodes. However, volume changes in the Si particles that occur during cycling causes deterioration of the solid-electrolyte interphase (SEI) layer on the particles resulting in further electrolyte reduction that immobilizes Li+ ions and, therefore, capacity fade. Because the volume changes are not expected to occur during a potentiostatic hold (referred to as calendar-life aging), by comparison of cycle-life and calendar-life aged cells one can expect to assess the role of volume changes in the deterioration of cell performance. To this end, cells with Si-Gr and Gr negative electrodes (and Li 1.03 (Ni 0.5 Co 0.2 Mn 0.3 ) 0.97 O 2 containing positive electrodes) were assembled, tested, and compared using cycle-life and calendar-life aging protocols. As expected, the capacity loss of the cycle-life aged cells was higher than that of the calendar-life aged cells. However, the measurable capacity loss for the calendar-life aged cells indicated continued immobilization of Li + ions. Furthermore, electrolytes extracted from the calendar-life aged cells showed more LiPF 6 hydrolysis products than those extracted from the cycle-life aged cells. In conclusion, we discuss possible mechanistic causes for the observed aging behaviors in this article.

25 ENERGY STORAGE↗

Microstructural evolution and the variation of tensile behavior after aging heat treatment of precipitation hardened martensitic steel

The effects of aging temperature on the microstructural evolution and the tensile behavior of precipitation hardened martensitic steel were investigated. Microscopic analysis using transmission electron microscope (TEM) was combined with the microstructural analysis using the synchrotron X-ray diffraction (XRD) to characterize the microstructural evolution with aging temperature. Peak hardness was obtained by precipitation of the Ni{sub 3}Al ordered phase. After aging at temperature range from 420 to 590 °C, spherical Ni{sub 3}Al precipitates and ellipsoidal M{sub 23}C{sub 6} carbides were observed within laths and at lath boundaries, respectively. Strain hardening behavior was analyzed with Ludwik equation. It is observed that the plastic strain regimes can be divided into two different stages by a rapid increase in strain hardening followed by a comparatively lower increase. At the first strain hardening stage, the aged specimen exhibited higher strain hardening exponent than the as-quenched specimen, and the exponent in the aged specimen was not changed considerably with increasing aging temperature. It is revealed that the strain hardening exponents at the first and the second stages were associated with the Ni{sub 3}Al precipitates and the domain size representing the coherent scattering area, respectively. - Highlights: • All of aged specimen exhibited higher strain hardening exponent than the as-quenched specimen at the first stage. • The value of strain hardening exponent in the aged specimen was nearly constant with aging temperature. • Ni{sub 3}Al precipitation dominantly influenced to the increase of strain hardening exponent at the first strain hardening stage. • Domain size was associated with strain hardening exponent at the second strain hardening stage.

36 MATERIALS SCIENCE↗

Effect of in-situ (TiC-TiB2) reinforcement on aging and mechanical behavior of AZ91 magnesium matrix composite

Highlights: • Effect of TiC-TiB{sub 2} particles on precipitation behavior of in-situ composite was studied. • The age-hardening rate of in-situ composites is faster than that of alloy. • Faster age hardening rate is due to the presence of high dislocation density in composite. • Post aging treatment improved the mechanical properties of both base and composite. - Abstract: In the present work, influence of in-situ TiC-TiB{sub 2} reinforcement on age hardening behavior and mechanical properties of TiC-TiB{sub 2}/AZ91 composite was investigated. The base and in-situ composite materials were solution treated at 400 °C for 24 h and then aged at different temperatures up to 100 h. The kinetics of age hardening results revealed that the addition of in-situ TiC-TiB{sub 2} reinforcement increase the age hardening kinetics of the composite as compared to AZ91 magnesium alloy. The improvement in age hardening kinetics is attributed to the presence of high dislocation density resulted from the mismatch of coefficients of thermal expansion between in-situ TiC-TiB{sub 2} reinforcement and magnesium matrix. The precipitation behavior of Mg{sub 17}Al{sub 12} phase in both AZ91 alloy and TiC-TiB{sub 2}/AZ91 composites were established. After age hardening, base and in-situ composite materials show significant improvement in ultimate tensile strength by 47.72% and 66.49% respectively as compared with the base monolithic alloy. The enhancement of mechanical properties in the base and in-situ composites is explained in detail by analyzing their fractographs and microstructures.

36 MATERIALS SCIENCE↗

Effect of Extended Aging and Oxidation on Linear Poly(propylenimine)-Mesoporous Silica Composites for CO 2 Capture from Simulated Air and Flue Gas Streams

Physical aging or degradation of amine-containing polymers and supported amine adsorbents is a critical issue that could limit practical application of such materials for CO 2 capture. However, to date, there is a scarcity of studies that evaluate the long-term stability of amine-based sorbents without the exclusive use of accelerated aging tests. Here, we demonstrate that extended aging (~2 years) of linear poly(propylenimine) (LPPI) confined in mesoporous silica (SBA-15) supports does not drastically impact the CO 2 adsorption performance under simulated flue gas (10% CO 2 ) and direct air capture (DAC, 400 ppm CO 2 ) conditions, although the behavior of the aged sorbents and polymers in the two CO 2 concentration regimes differs. Sorbents made with aged LPPI had modestly decreased CO 2 uptake performance (<~20% lower) compared to the fresh polymers, with overall good CO 2 cycling performance. The data indicate that only slow degradation occurs under the deployed ambient storage conditions. Even after extended aging, the LPPI-based sorbents preserved their ability to display stable temperature-swing cycling performance. In parallel, the impact of blending LPPI polymers of different number-average molecular weights, M n , is evaluated, seeking to understand its impact on adsorbent performance. We find that the results demonstrate that blends of two M n aged LPPI give similar CO 2 adsorption performance to adsorbents made from a single M n LPPI, suggesting that molecular weight will not negatively impact adsorbent performance in the studied M n range. After an accelerated oxidation experiment, the aged LPPI sorbents retained a larger portion of the samples’ original performance when cycling under simulated flue gas conditions than under DAC conditions. However, in each case, the oxidized sorbents could be cycled repeatedly with consistent uptake performance. Overall, these first of their kind extended aging tests suggest that LPPI-based amine adsorbents offer promise for long term, stable use in carbon capture applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

The Role of Topography in Controlling Evapotranspiration Age

Abstract Evapotranspiration (ET) age is a key metric of water sustainability but a major unknown partly due to the extreme difficulty in modeling it. Groundwater is found to be important in ET age variations in small‐scale studies, yet our understanding is insufficient because groundwater systems are nested across scales. Here, we conducted GPU‐accelerated particle tracking with integrated hydrologic modeling to quantify the variations in ET age at a regional scale of ∼0.4 M km 2 . Simulation results reveal topography‐driven flow paths shaping the spatial and temporal patterns of ET age variations. On ridges, where root zone decoupling with deep subsurface storage, ET age is generally young, with seasonal variations dominated by meteorological conditions. In the valley bottom, ET age is generally old, with significant subseasonal variations caused by the convergence of subsurface flow paths. On hillslopes with water table depths ranging from 1 to 10 m, ET age shows strong seasonal variations caused by the connections with lateral groundwater regulated by ET demand. Our modeling approach provides insights into the basic linkages between ET age and topography at large scale. Our work highlights the perspective of multiscale studies of ET age, suggesting new field experiments to test these process connections and to determine if such linkages warrant inclusion in Earth System Models.

54 ENVIRONMENTAL SCIENCES↗

A transcriptomic atlas of aged human microglia

With a rapidly aging global human population, finding a cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding of what constitutes the phenotype of aged human microglia—the cell type that has been strongly implicated by genetic studies in the pathogenesis of age-related neurodegenerative disease. Here, we establish the set of genes that is preferentially expressed by microglia in the aged human brain. This HuMi_Aged gene set captures a unique phenotype, which we confirm at the protein level. Furthermore, we find this gene set to be enriched in susceptibility genes for Alzheimer’s disease and multiple sclerosis, to be increased with advancing age, and to be reduced by the protective APOEe2 haplotype. APOEe4 has no effect. These findings confirm the existence of an aging-related microglial phenotype in the aged human brain and its involvement in the pathological processes associated with brain aging.

60 APPLIED LIFE SCIENCES↗

Gray matter volume drives the brain age gap in schizophrenia: a SHAP study

Neuroimaging-based brain age is a biomarker that is generated by machine learning (ML) predictions. The brain age gap (BAG) is typically defined as the difference between the predicted brain age and chronological age. Studies have consistently reported a positive BAG in individuals with schizophrenia (SCZ). However, there is little understanding of which specific factors drive the ML-based brain age predictions, leading to limited biological interpretations of the BAG. We gathered data from three publicly available databases - COBRE, MCIC, and UCLA - and an additional dataset (TOPSY) of early-stage schizophrenia (82.5% untreated first-episode sample) and calculated brain age with pre-trained gradient-boosted trees. Then, we applied SHapley Additive Explanations (SHAP) to identify which brain features influence brain age predictions. We investigated the interaction between the SHAP score for each feature and group as a function of the BAG. These analyses identified total gray matter volume (group × SHAP interaction term β = 1.71 [0.53; 3.23]; p corr < 0.03) as the feature that influences the BAG observed in SCZ among the brain features that are most predictive of brain age. Other brain features also presented differences in SHAP values between SCZ and HC, but they were not significantly associated with the BAG. We compared the findings with a non-psychotic depression dataset (CAN-BIND), where the interaction was not significant. This study has important implications for the understanding of brain age prediction models and the BAG in SCZ and, potentially, in other psychiatric disorders.

60 APPLIED LIFE SCIENCES↗

The Milky Way’s middle-aged inner ring

Aims. We investigate the metallicity, age, and orbital anatomy of the inner Milky Way, specifically focussing on the outer bar region. Methods. We integrated a sample of APOGEE DR16 inner Galaxy stars in a state of the art bar-bulge potential with a slow pattern speed and investigated the link between the resulting orbits and their [Fe/H] and ages. By superimposing the orbits, we built density, [Fe/H], and age maps of the inner Milky Way, which we divided further using the orbital parameters eccentricity, |Xmax|, and |Zmax|. Results. We find that at low heights from the Galactic plane, the Galactic bar gradually transitions into a radially thick, vertically thin, elongated inner ring with average solar [Fe/H]. This inner ring is mainly composed of stars with AstroNN ages between 4 and 9 Gyr with a peak in age between 6 and 8 Gyr, making the average age of the ring ~6 Gyr. The vertical thickness of the ring decreases markedly towards younger ages. We also find very large L4 Lagrange orbits that have average solar to super-solar metallicities and intermediate ages. Lastly, we confirm a clear X-shape in the [Fe/H] and density distributions at large Galactic heights. Conclusions. The orbital structure obtained for the APOGEE stars reveals that the Milky Way hosts an inner ring-like structure between the planar bar and corotation. This structure is on average metal rich, intermediately aged, and enhances the horizontal metallicity gradient along the bar’s major axis.

79 ASTRONOMY AND ASTROPHYSICS↗

THE RELATIONSHIP BETWEEN {nu}{sub max} AND AGE t FROM ZAMS TO RGB-TIP FOR LOW-MASS STARS

Stellar age is an important quantity in astrophysics, which is useful for many fields both in the universe and galaxies. It cannot be determined by direct measurements, but can only be estimated or inferred. We attempt to find a useful indicator of stellar age, which is accurate from the zero-age main sequence to the tip of red giant branch for low-mass stars. Using the Yale Rotation and Evolution Code (YREC), a grid of stellar models has been constructed. Meanwhile, the frequency of maximum oscillations' power {nu}{sub max} and the large frequency separation {Delta}{nu} are calculated using the scaling relations. For the stars, the masses of which are from 0.8 M{sub Sun} to 2.8 M{sub Sun }, we can obtain the {nu}{sub max} and stellar age by combing the scaling relations with the four sets of grid models (YREC, Dotter et al., Marigo et al., and YY isochrones). We find that {nu}{sub max} is tightly correlated and decreases monotonically with the age of the star from the main sequence to the red giant evolutionary stages. Moreover, we find that the line shapes of the curves in the Age versus {nu}{sub max} diagram, which is plotted by the four sets of grid models, are consistent for red giants with masses from 1.1 M{sub Sun} to 2.8 M{sub Sun }. For red giants, the differences of correlation coefficients between Age and {nu}{sub max} for different grid models are minor and can be ignored. Interestingly, we find two peaks that correspond to the subgiants and bump of red giants in the Age versus {nu}{sub max} diagram. By general linear least-squares, we make the polynomial fitting and deduce the relationship between log(Age) and log({nu}{sub max}) in red giants' evolutionary state.

79 ASTRONOMY AND ASTROPHYSICS↗

FUNDAMENTAL PARAMETERS AND SPECTRAL ENERGY DISTRIBUTIONS OF YOUNG AND FIELD AGE OBJECTS WITH MASSES SPANNING THE STELLAR TO PLANETARY REGIME

We combine optical, near-infrared, and mid-infrared spectra and photometry to construct expanded spectral energy distributions for 145 field age (>500 Myr) and 53 young (lower age estimate <500 Myr) ultracool dwarfs (M6-T9). This range of spectral types includes very low mass stars, brown dwarfs, and planetary mass objects, providing fundamental parameters across both the hydrogen and deuterium burning minimum masses for the largest sample assembled to date. A subsample of 29 objects have well constrained ages as probable members of a nearby young moving group. We use 182 parallaxes and 16 kinematic distances to determine precise bolometric luminosities (L{sub bol}) and radius estimates from evolutionary models give semi-empirical effective temperatures (T{sub eff}) for the full range of young and field age late-M, L, and T dwarfs. We construct age-sensitive relationships of luminosity, temperature, and absolute magnitude as functions of spectral type and absolute magnitude to disentangle the effects of degenerate physical parameters such as T{sub eff}, surface gravity, and clouds on spectral morphology. We report bolometric corrections in J for both field age and young objects and find differences of up to a magnitude for late-L dwarfs. Our correction in Ks shows a larger dispersion but not necessarily a different relationship for young and field age sequences. We also characterize the NIR–MIR reddening of low gravity L dwarfs and identify a systematically cooler T{sub eff} of up to 300 K from field age objects of the same spectral type and 400 K cooler from field age objects of the same M{sub H} magnitude.

79 ASTRONOMY AND ASTROPHYSICS↗

Disentangling Alzheimer’s disease neurodegeneration from typical brain ageing using machine learning

Abstract Neuroimaging biomarkers that distinguish between changes due to typical brain ageing and Alzheimer’s disease are valuable for determining how much each contributes to cognitive decline. Supervised machine learning models can derive multivariate patterns of brain change related to the two processes, including the Spatial Patterns of Atrophy for Recognition of Alzheimer’s Disease (SPARE-AD) and of Brain Aging (SPARE-BA) scores investigated herein. However, the substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology, and associated results, towards disentangling the two. T1-weighted MRI scans of 4054 participants (48–95 years) with Alzheimer’s disease, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the Imaging-based coordinate SysTem for AGIng and NeurodeGenerative diseases (iSTAGING) consortium were analysed. Multiple sets of SPARE scores were investigated, in order to probe imaging signatures of certain clinically or molecularly defined sub-cohorts. First, a subset of clinical Alzheimer’s disease patients (n = 718) and age- and sex-matched CN adults (n = 718) were selected based purely on clinical diagnoses to train SPARE-BA1 (regression of age using CN individuals) and SPARE-AD1 (classification of CN versus Alzheimer’s disease) models. Second, analogous groups were selected based on clinical and molecular markers to train SPARE-BA2 and SPARE-AD2 models: amyloid-positive Alzheimer’s disease continuum group (n = 718; consisting of amyloid-positive Alzheimer’s disease, amyloid-positive MCI, amyloid- and tau-positive CN individuals) and amyloid-negative CN group (n = 718). Finally, the combined group of the Alzheimer’s disease continuum and amyloid-negative CN individuals was used to train SPARE-BA3 model, with the intention to estimate brain age regardless of Alzheimer’s disease-related brain changes. The disentangled SPARE models, SPARE-AD2 and SPARE-BA3, derived brain patterns that were more specific to the two types of brain changes. The correlation between the SPARE-BA Gap (SPARE-BA minus chronological age) and SPARE-AD was significantly reduced after the decoupling (r = 0.56–0.06). The correlation of disentangled SPARE-AD was non-inferior to amyloid- and tau-related measurements and to the number of APOE ε4 alleles but was lower to Alzheimer’s disease-related psychometric test scores, suggesting the contribution of advanced brain ageing to the latter. The disentangled SPARE-BA was consistently less correlated with Alzheimer’s disease-related clinical, molecular and genetic variables. By employing conservative molecular diagnoses and introducing Alzheimer’s disease continuum cases to the SPARE-BA model training, we achieved more dissociable neuroanatomical biomarkers of typical brain ageing and Alzheimer’s disease.

Hwang, Gyujoon↗

Systemic clearance of p16 INK4a -positive senescent cells mitigates age-associated intervertebral disc degeneration

RATIONALE:Age-related changes in the intervertebral discs are the predominant contributors to back pain, a common physical and functional impairment experienced by older persons. Cellular senescence, a process wherein cells undergo growth arrest and chronically secrete numerous inflammatory molecules and proteases, has been reported to cause decline in the health and function of multiple tissues with age. Although senescent cells have been reported to increase in intervertebral degeneration (IDD), it is not known whether they are causative in age-related IDD. OBJECTIVE:The study aimed to elucidate whether a causal relationship exists between cellular senescence and age-related IDD. METHODS AND RESULTS:To examine the impact of senescent cells on age-associated IDD, we used p16-3MR transgenic mice, which enables the selective removal of p16 INK4a -positive senescent cells by the drug ganciclovir. Disc cellularity, aggrecan content and fragmentation alongside expression of inflammatory cytokine (IL-6) and matrix proteases (ADAMTS4 and MMP13) in discs of p16-3MR mice treated with GCV and untreated controls were assessed. In aged mice, reducing the per cent of senescent cells decreased disc aggrecan proteolytic degradation and increased overall proteoglycan matrix content along with improved histological disc features. Additionally, reduction of senescent cells lowered the levels of MMP13, which is purported to promote disc degenerative changes during aging. CONCLUSIONS:The findings of this study suggest that systemic reduction in the number of senescent cells ameliorates multiple age-associated changes within the disc tissue. Cellular senescence could therefore serve as a therapeutic target to restore the health of disc tissue that deteriorates with age.

60 APPLIED LIFE SCIENCES↗