The Ice, Cloud, and land Elevation Satellite – 2 (ICESat-2) observatory was launched on 15 September 2018 to measure ice sheet and glacier elevation change, sea ice freeboard, and enable the ...determination of the heights of Earth's forests. ICESat-2's laser altimeter, the Advanced Topographic Laser Altimeter System (ATLAS) uses green (532 nm) laser light and single-photon sensitive detection to measure time of flight and subsequently surface height along each of its six beams. In this paper, we describe the major components of ATLAS, including the transmitter, the receiver and the components of the timing system. We present the major components of the ICESat-2 observatory, including the Global Positioning System, star trackers and inertial measurement unit. The ICESat-2 Level 1B data product (ATL02) provides the precise photon round-trip time of flight, among other data. The ICESat-2 Level 2A data product (ATL03) combines the photon times of flight with the observatory position and attitude to determine the geodetic location (i.e. the latitude, longitude and height) of the ground bounce point of photons detected by ATLAS. The ATL03 data product is used by higher-level (Level 3A) surface-specific data products to determine glacier and ice sheet height, sea ice freeboard, vegetation canopy height, ocean surface topography, and inland water body height.
•Describes the ICESat-2 Observatory and its sole instrument: the Advanced Topographic Laser Altimeter System (ATLAS)•Presents the structure and major contents of the ICESat-2 Level 1B data product (ATL02; photon times of flight)•Presents the structure and major contents of the ICESat-2 Level 2A data product (ATL03; Global Geolocated Photons)
Abstract Objective To investigate the short-term efficacy of a multicomponent intervention to reduce office workers' sitting time. Methods Allocation for this non-randomized controlled trial (n = 43 ...participants; 56% women; 26–62 years; Melbourne, Australia) was by office floor, with data collected during July–September 2011. The 4-week intervention emphasized three key messages: “Stand Up, Sit Less, Move More” and comprised organizational, environmental, and individual elements. Changes in minutes/day at the workplace spent sitting (primary outcome), in prolonged sitting (sitting time accumulated in bouts ≥ 30 min), standing, and moving were objectively measured (activPAL3). Results Relative to the controls, the intervention group significantly reduced workplace sitting time (mean change 95%CI: − 125 − 161, − 89 min/8-h workday), with changes primarily driven by a reduction in prolonged sitting time (− 73 − 108, − 40 min/8-h workday). Workplace sitting was almost exclusively replaced by standing (+ 127 + 92, + 162 min/8-h workday) with non-significant changes to stepping time (− 2 − 7, + 4 min/8-h workday) and number of steps (− 70 − 350, 210). Conclusions This multicomponent workplace intervention demonstrated that substantial reductions in sitting time are achievable in an office setting. Larger studies with longer timeframes are needed to assess sustainability of these changes, as well as their potential longer-term impacts on health and work-related outcomes.
Display omitted
Recent developments in 3D printing (3DP) research have led to a variety of scaffold designs and techniques for osteochondral tissue engineering; however, the simultaneous ...incorporation of multiple types of gradients within the same construct remains a challenge. Herein, we describe the fabrication and mechanical characterization of porous poly(ε-caprolactone) (PCL) and PCL-hydroxyapatite (HA) scaffolds with incorporated vertical porosity and ceramic content gradients via a multimaterial extrusion 3DP system. Scaffolds of 0 wt% HA (PCL), 15 wt% HA (HA15), or 30 wt% HA (HA30) were fabricated with uniform composition and porosity (using 0.2 mm, 0.5 mm, or 0.9 mm on-center fiber spacing), uniform composition and gradient porosity, and gradient composition (PCL-HA15-HA30) and porosity. Micro-CT imaging and porosity analysis demonstrated the ability to incorporate both vertical porosity and pore size gradients and a ceramic gradient, which collectively recapitulate gradients found in native osteochondral tissues. Uniaxial compression testing demonstrated an inverse relationship between porosity, ϕ, and compressive modulus, E, and yield stress, σy, for uniform porosity scaffolds, however, no differences were observed as a result of ceramic incorporation. All scaffolds demonstrated compressive moduli within the appropriate range for trabecular bone, with average moduli between 86 ± 14–220 ± 26 MPa. Uniform porosity and pore size scaffolds for all ceramic levels had compressive moduli between 205 ± 37–220 ± 26 MPa, 112 ± 13–118 ± 23 MPa, and 86 ± 14–97 ± 8 MPa respectively for porosities ranging between 14 ± 4–20 ± 6%, 36 ± 3–43 ± 4%, and 54 ± 2–57 ± 2%, with the moduli and yield stresses of low porosity scaffolds being significantly greater (p < 0.05) than those of all other groups. Single (porosity) gradient and dual (composition/porosity) gradient scaffolds demonstrated compressive properties similar (p > 0.05) to those of the highest porosity uniform scaffolds (porosity gradient scaffolds 98 ± 23–107 ± 6 MPa, and 102 ± 7 MPa for dual composition/porosity gradient scaffolds), indicating that these properties are more heavily influenced by the weakest section of the gradient. The compression data for uniform scaffolds were also readily modeled, yielding scaling laws of the form E ∼ (1 − ϕ)1.27 and σy ∼ (1 − ϕ)1.37, which demonstrated that the compressive properties evaluated in this study were well-aligned with expectations from previous literature and were readily modeled with good fidelity independent of polymer scaffold geometry and ceramic content. All uniform scaffolds were similarly deformed and recovered despite different porosities, while the large-pore sections of porosity gradient scaffolds were significantly more deformed than all other groups, indicating that porosity may not be an independent factor in determining strain recovery. Moving forward, the technique described here will serve as the template for more complex multimaterial constructs with bioactive cues that better match native tissue physiology and promote tissue regeneration.
This manuscript describes the fabrication and mechanical characterization of “dual” porosity/ceramic content gradient scaffolds produced via a multimaterial extrusion 3D printing system for osteochondral tissue engineering. Such scaffolds are designed to better address the simultaneous gradients in architecture and mineralization found in native osteochondral tissue. The results of this study demonstrate that this technique may serve as a template for future advances in 3D printing technology that may better address the inherent complexity in such heterogeneous tissues.
Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) ...cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.
Display omitted
•Biomarkers for response monitoring are lacking in medulloblastoma•CSF-derived cfDNA profiling captures chromosomal landscapes of primary tumors•Detectability of CNVs in cfDNA carries clinical utility as an MRD biomarker•Liquid biopsy analyses should be incorporated into future medulloblastoma trials
Liu et al. describe the utility of profiling CSF-derived cfDNA from 123 children with medulloblastoma. Use of low-coverage whole-genome sequencing captures tumor-associated CNVs as MRD surrogate, allowing correlation with tumor burden and prediction of disease progression. Serial analysis of cfDNA reflects evolution of the medulloblastoma genome in response to therapy.
The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+, is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice ...without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD+ nor NADP+ was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects.
Display omitted
•Nicotinamide (NAM) supplementation does not extend lifespan in mice•NAM prevents hepatosteatosis in obese mice while improving glucose metabolism•NAM reduces oxidative stress and inflammation•NAM depresses NAM salvage and does not produce a net boost in tissue NAD levels
Interventions that increase NAD+ bioavailability are of therapeutic interest for the improvement of healthspan and lifespan. Mitchell and Bernier et al. show that chronic treatment with nicotinamide, an NAD+ precursor, is associated with health improvements and lower inflammation in the absence of lifespan extension in high-fat-diet-fed mice.
Serum perfluoroalkyl acids (PFAAs) have been linked to disruption of maternal thyroid hormone homeostasis, but results have varied between studies which we hypothesized was due to timing of the ...thyroid hormone measurements, variability in PFAA isomer patterns, or presence of other stressors. In a longitudinal study design, we investigated the time-dependency of associations between PFAA isomers and thyroid hormones during pregnancy and post-partum while considering thyroid peroxidase antibody (TPOAb) status and mercury (Hg) co-exposure. In participants of a prospective Canadian birth cohort (n = 494), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH) and TPOAb were quantified in maternal plasma collected in each trimester and 3-months postpartum, and 25 PFAAs (15 linear and 10 branched) and Hg were quantified in samples collected during the second trimester. Perfluorohexane sulfonate (PFHxS) and total branched isomers of perfluorooctane sulfonate (PFOS) were positively associated with TSH in mixed-effect models, with strongest associations early in gestation. Throughout pregnancy and post-partum, PFHxS was inversely associated with FT4, consistent with elevated TSH, while Hg was inversely associated with FT3. In TPOAb-positive women, negative associations were found between PFUnA and FT4, and 1m-PFOS and TSH, supporting previous studies that thyroid disorder could increase susceptibility to PFAA-mediated hormone dysregulation. Hg did not confound associations but was a significant interaction term, revealing further positive associations between PFOS isomers (∑3m+4m-PFOS) and TSH. Higher perfluoroalkyl sulfonate exposures were associated with higher TSH and/or lower FT4, strongly suggestive that PFHxS and branched PFOS isomers are risk factors for subclinical maternal hypothyroidism. Isomer-specific analysis is important in future studies, as crude measures of ‘total-PFOS’ masked the associations of branched isomers. A concerning result was for PFHxS which had consistent negative associations with FT4 at all time points and a positive association with TSH in early pregnancy when fetal development is most sensitive to disruption.
•Perfluoroalkyl acids were associated with thyroid hormones during and after pregnancy.•Associations were strongest in early pregnancy, a sensitive stage of neurodevelopment.•Evidence mounting for cause-effect relationship for perfluorohexane sulfonate•Isomer-specific associations for branched perfluorooctane sulfonate, not linear•Associations influenced by mercury co-exposure and thyroid peroxidase antibodies.
Perfluoroalkyl acids (PFAAs) within the broader class of per- and polyfluoroalkyl substances (PFAS) are present in human serum as isomer mixtures, but epidemiological studies have yet to address ...isomer-specific associations with child development and behavior.
To examine associations between prenatal exposure to 25 PFAAs, including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) isomers, and child neurodevelopment among 490 mother–child pairs in a prospective Canadian birth cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. To consider the influence of a classic neurotoxicant, total mercury (THg), based on its likelihood of co-exposure with PFAAs from common dietary sources.
Maternal blood samples were collected in the second trimester and child neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III). Linear or curvilinear multiple regression models were used to examine associations between exposures and neurodevelopment outcomes.
Select PFAAs were associated with lower Cognitive composite scores, including perfluoroheptanoate (PFHpA) (β = −0.88, 95% confidence interval (CI): −1.7, −0.06) and perfluorododecanoate (PFDoA) (β = −2.0, 95% CI: −3.9, −0.01). Non-linear relationships revealed associations of total PFOS (β = −4.4, 95% CI: −8.3, −0.43), and linear-PFOS (β = −4.0, 95% CI: −7.5, −0.57) and 1m-PFOS (β = −1.8, 95% CI: −3.3, −0.24) isomers with lower Language composite scores. Although there was no effect modification, including THg interaction terms in PFAA models revealed negative associations between perfluorononanoate (PFNA) and Motor (β = −3.3, 95% CI: −6.2, −0.33) and Social-Emotional (β = −3.0, 95% CI: −5.6, −0.40) composite scores.
These findings reinforce previous reports of adverse effects of maternal PFAA exposure during pregnancy on child neurodevelopment. The unique hazards posed from isomers of PFOS justify isomer-specific analysis in future studies. To control for possible confounding, mercury co-exposure may be considered in studies of PFAAs.
Interpreting and modelling astronomical catalogues requires an understanding of the catalogues’ completeness or selection function: what properties determine an object’s probability of being ...including in the catalogue? Here we set out to empirically quantify the completeness of the overall catalogue of
Gaia
’s third data release (DR3). This task is not straightforward because
Gaia
is the all-sky optical survey with the highest angular resolution to date and no consistent ground truth exists to allow direct comparisons. However, well-characterised deeper imaging enables an empirical assessment of
Gaia
’s
G
-band completeness across parts of the sky. On this basis, we devised a simple analytical completeness model of
Gaia
as a function of the observed
G
magnitude and position over the sky, which accounts for both the effects of crowding and the complex
Gaia
scanning law. Our model only depends on a single quantity: the median magnitude
M
10
in a patch of the sky of catalogued sources with
astrometric_matched_transits
≤10. We note that
M
10
reflects elementary completeness decisions in the
Gaia
pipeline and is computable from the
Gaia
DR3 catalogue itself and therefore applicable across the whole sky. We calibrated our model using the Dark Energy Camera Plane Survey (DECaPS) and tested its predictions against
Hubble
Space Telescope observations of globular clusters. We found that our model predicts
Gaia
’s completeness values to a few per cent (RMS) across the sky. We make the model available as a part of the
gaiaunlimited
Python package built and maintained by the GaiaUnlimited project.
Coatings offer a means to control nanoparticle (NP) size, regulate dissolution, and mitigate runoff when added to crops through soil. Simultaneously, coatings can enhance particle binding to plants ...and provide an additional source of nutrients, making them a valuable component to existing nanoparticle delivery systems. Here, the surface functionalization of metal and metal-oxide nanoparticles to inhibit aggregation and preserve smaller agglomerate sizes for enhanced transport to the rooting zone and improved uptake in plants is reviewed. Coatings are classified by type and by their efficacy to mitigate agglomeration in soils with variable pH, ionic concentration, and natural organic matter profiles. Varying degrees of success have been reported using a range of different polymers, biomolecules, and inorganic surface coatings. Advances in zwitterionic coatings show the best results for maintaining nanoparticle stability in solutions even under high salinity and temperature conditions, whereas coating by the soil component humic acid may show additional benefits such as promoting dissolution and enhancing bioavailability in soils. Pre-tuning of NP surface properties through exposure to select natural organic matter, microbial products, and other biopolymers may yield more cost-effective nonagglomerating metal/metal-oxide NPs for soil applications in agriculture.
Pineoblastoma is a rare embryonal tumor of childhood that is conventionally treated with high-dose craniospinal irradiation (CSI). Multi-dimensional molecular evaluation of pineoblastoma and ...associated intertumoral heterogeneity is lacking. Herein, we report outcomes and molecular features of children with pineoblastoma from two multi-center, risk-adapted trials (SJMB03 for patients ≥ 3 years; SJYC07 for patients < 3 years) complemented by a non-protocol institutional cohort. The clinical cohort consisted of 58 patients with histologically diagnosed pineoblastoma (SJMB03 = 30, SJYC07 = 12, non-protocol = 16, including 12 managed with SJMB03-like therapy). The SJMB03 protocol comprised risk-adapted CSI (average-risk = 23.4 Gy, high-risk = 36 Gy) with radiation boost to the primary site and adjuvant chemotherapy. The SJYC07 protocol consisted of induction chemotherapy, consolidation with focal radiation (intermediate-risk) or chemotherapy (high-risk), and metronomic maintenance therapy. The molecular cohort comprised 43 pineal parenchymal tumors profiled by DNA methylation array (
n
= 43), whole-exome sequencing (
n
= 26), and RNA-sequencing (
n
= 16). Respective 5-year progression-free survival rates for patients with average-risk or high-risk disease on SJMB03 or SJMB03-like therapy were 100% and 56.5 ± 10.3% (
P
= 0.007); respective 2-year progression-free survival rates for those with intermediate-risk or high-risk disease on SJYC07 were 14.3 ± 13.2% and 0% (
P
= 0.375). Of patients with average-risk disease treated with SJMB03/SJMB03-like therapy, 17/18 survived without progression. DNA-methylation analysis revealed four clinically relevant pineoblastoma subgroups: PB-A, PB-B, PB-B–like, and PB-FOXR2. Pineoblastoma subgroups differed in age at diagnosis, propensity for metastasis, cytogenetics, and clinical outcomes. Alterations in the miRNA-processing pathway genes
DICER1
,
DROSHA
, and
DGCR8
were recurrent and mutually exclusive in PB-B and PB-B–like subgroups; PB-FOXR2 samples universally overexpressed the
FOXR2
proto-oncogene. Our findings suggest superior outcome amongst older children with average-risk pineoblastoma treated with reduced-dose CSI. The identification of biologically and clinically distinct pineoblastoma subgroups warrants consideration of future molecularly-driven treatment protocols for this rare pediatric brain tumor entity.
PDF
