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•Describes the ABCD study aims and design.•Covers issues surrounding estimation of meaningful associations, including population inferences, effect sizes, and control of covariates.•Outlines best practices for reproducible research and reporting of results.•Provides worked examples that illustrate the main points of the paper. The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children's health in the United States. A cohort of n = 11,880 children aged 9–10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

Children that experience a mild traumatic brain injury (mTBI) are at an increased risk of neural alterations that can deteriorate mental health. We test the hypothesis that mTBI is associated with psychopathology and that structural brain metrics (e.g., volume, area) meaningfully mediate the relation in an adolescent population. We analyzed behavioral and brain MRI data from 11,876 children who participated in the Adolescent Brain Cognitive Development (ABCD) Study. Mixed-effects models were used to examine the longitudinal association between mTBI and mental health outcomes. Bayesian methods were used to investigate brain regions that are intermediate between mTBI and symptoms of poor mental health. There were 199 children with mTBI and 527 with possible mTBI across the three ABCD Study visits. There was a 7% (IRR = 1.07, 95% CI: 1.01, 1.13) and 15% (IRR = 1.16, 95% CI: 1.05, 1.26) increased risk of emotional or behavioral problems in children that experienced possible mTBI or mTBI, respectively. Possible mTBI was associated with a 17% (IRR: 1.17, 95% CI: 0.99, 1.40) increased risk of experiencing distress following a psychotic-like experience. We did not find any brain regions that meaningfully mediated the relationship between mTBI and mental health outcomes. Analysis of volumetric measures found that approximately 2% to 5% of the total effect of mTBI on mental health outcomes operated through total cortical volume. Image intensity measure analyses determined that approximately 2% to 5% of the total effect was mediated through the left-hemisphere of the dorsolateral prefrontal cortex. Results indicate an increased risk of emotional and behavioral problems in children that experienced possible mTBI or mTBI. Mediation analyses did not elucidate the mechanisms underlying the association between mTBI and mental health outcomes.

Stem cell derived insulin producing cells or islets have shown promise in reversing Type 1 Diabetes (T1D), yet successful transplantation currently necessitates long‐term modulation with immunosuppressant drugs. An alternative approach to avoiding this immune response is to utilize an islet macroencapsulation device, where islets are incorporated into a selectively permeable membrane that can protect the transplanted cells from acute host response, whilst enabling delivery of insulin. These macroencapsulation systems have to meet a number of stringent and challenging design criteria in order to achieve the ultimate goal of reversing T1D. In this progress report, the design considerations and functional requirements of macroencapsulation systems are reviewed, specifically for stem‐cell derived islets (SC‐islets), highlighting distinct design parameters. Additionally, a perspective on the future for macroencapsulation systems is given, and how incorporating continuous sensing and closed‐loop feedback can be transformative in advancing toward an autonomous biohybrid artificial pancreas. Transplantation of stem‐cell‐derived islets (SC‐islets) is a promising treatment option for the reversal of Type 1 diabetes. This progress report reviews the design considerations and functional requirements for macroencapsulation systems, specifically for SC‐islets, highlighting distinct design parameters. Incorporating continuous sensing and closed‐loop feedback in future macroencapsulation systems could be transformative in advancing toward an autonomous biohybrid artificial pancreas.

Fibrous capsule (FC) formation, secondary to the foreign body response (FBR), impedes molecular transport and is detrimental to the long-term efficacy of implantable drug delivery devices, especially when tunable, temporal control is necessary. We report the development of an implantable mechanotherapeutic drug delivery platform to mitigate and overcome this host immune response using two distinct, yet synergistic soft robotic strategies. Firstly, daily intermittent actuation (cycling at 1 Hz for 5 minutes every 12 hours) preserves long-term, rapid delivery of a model drug (insulin) over 8 weeks of implantation, by mediating local immunomodulation of the cellular FBR and inducing multiphasic temporal FC changes. Secondly, actuation-mediated rapid release of therapy can enhance mass transport and therapeutic effect with tunable, temporal control. In a step towards clinical translation, we utilise a minimally invasive percutaneous approach to implant a scaled-up device in a human cadaveric model. Our soft actuatable platform has potential clinical utility for a variety of indications where transport is affected by fibrosis, such as the management of type 1 diabetes. Drug delivery implants suffer from diminished release profiles due to fibrous capsule formation over time. Here, the authors use soft robotic actuation to modulate the immune response of the host to maintain drug delivery over the longer-term and to perform controlled release in vivo.

Background The complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study. We examined the role of DNA methylation on the association between PA and CVD. Results The Multi-Ethnic Study of Atherosclerosis (MESA) cohort Exam 5 data with 1065 participants free of CVD were used for final analysis. The quartile categorical total PA variable was created by activity intensity (METs/week). During a median follow-up of 4.0 years, 69 participants developed CVD. Illumina HumanMethylation450 BeadChip was used to provide genome-wide DNA methylation profiles in purified human monocytes (CD14+). We identified 23 candidate DNA methylation loci to be associated with both PA and CVD. We used the structural equation modeling (SEM) approach to test the complex relationships among multiple variables and the roles of mediators. Three of the 23 identified loci (corresponding to genes VPS13D , PIK3CD and VPS45 ) remained as significant mediators in the final SEM model along with other covariates. Bridged by the three genes, the 2nd PA quartile (β = − 0.959; 95%CI: − 1.554 to − 0.449) and the 3rd PA quartile (β = − 0.944; 95%CI: − 1.628 to − 0.413) showed the greatest inverse associations with CVD development, while the 4th PA quartile had a relatively weaker inverse association (β = − 0.355; 95%CI: − 0.713 to − 0.124). Conclusions The current study is among the first to simultaneously examine the relationships among PA, DNA methylation, and CVD in a large cohort with long-term exposure. We identified three DNA methylation loci bridged the association between PA and CVD. The function of the identified genes warrants further investigation in the pathogenesis of CVD.

Recent experimental studies have demonstrated the possibility of utilizing strong terahertz pulses to manipulate individual ferroic orders on pico- and femtosecond timescales. Here, we extend these findings and showcase the simultaneous manipulation of multiple ferroic orders in BiFeO 3 , a material that is both ferroelectric and antiferromagnetic at room temperature. We find a concurrent enhancement of ferroelectric and antiferromagnetic second-harmonic generation (SHG) following the resonant excitation of a high-frequency fully-symmetric phonon mode. Based on first-principles calculations and phenomenological modeling, we ascribe this observation to the inherent coupling of the two ferroic orders to the nonequilibrium distortions induced in the crystal lattice by nonlinearly driven phonons. Our finding highlights the potential of nonlinear phononics as a technique for manipulating multiple ferroic order parameters at once. In addition, this approach provides a promising avenue to studying the dynamical magnetic and polarization behavior, as well as their intrinsic coupling, on ultrashort timescales.

A bstract We apply the effective field theory formalism that was used to study CP violation induced by heavy new physics in the τ → K S πν τ decays to the other two-meson tau decay channels. We focus on the rate and the forward-backward asymmetries, that are predicted using current bounds on the complex Wilson coefficients of the effective Lagrangian. We discuss our outcomes for the modes with ( K / π ) π 0 and KK S , that can be studied at Belle-II and a super-tau-charm facility. Our main finding is that current and forthcoming experiments would be sensitive to the maximum allowed CP rate asymmetry in the K ± K S modes if a precision of 5% is reached on this observable, that can check as well the BaBar anomaly in K S π . For the π ± π 0 channels, new physics would be difficult to probe at present. Disentangling new sources of CP violation would be most challenging in K ± π 0 and the other modes.

A new crocodyliform, Sebecus ayrampu, sp. nov., is described based on the rostral region of the skull, mandibular rami, and a distal portion of the femur collected in Paleocene rocks of northwestern Argentina. The new taxon is diagnosed (among other characters) by the presence of a sharp sagittal torus on the palatal surface of the premaxilla and maxilla, the surface of the alveolar region of the premaxilla descending vertically with respect to the palatal surface of the maxilla and the rest of the premaxilla, deep premaxillary fossa for the hypertrophied mandibular tooth with a ridge along its anterior margin, a differential pattern of ornamentation of the rostrum external surface, and a V-shaped anterior margin of the choana (with the vertex pointing anteriorly). This specimen is recovered as a new member of Sebecidae in a phylogenetic analysis, increasing the taxonomic diversity of the group in the Paleogene of northwestern Argentina. A sensitivity parsimony analysis using equal and implied weights (with different K values) retrieves two distinct lineages within Sebecidae: the Ayllusuchus + Bretesuchus clade and the Sebecus clade (in which the new taxon is included). Sebecidae is also recovered as a sister group to Baurusuchidae, forming together the monophyletic Sebecosuchia within Notosuchia.

A new species of Toxodontia (Mammalia, Notoungulata), Pampahippus secundus sp. nov., is described based on remains recovered from outcrops of the Lumbrera Formation exposed in Salta Province, northwest Argentina. The material studied consists of mandibular, maxillary, and premaxillary fragments with complete and incomplete teeth representing at least three individuals. It differs from the type species P. arenalesi by its smaller size and the presence of several dental features: I2 smaller than the I1 and I3, paraconule absent on the P3, upper molars wider than long and subquadrangular, with a single crista projecting from the ectoloph, strong mesiolingual cingulum surrounding the protocone on the M1, conspicuous metacone fold on the ectoloph of M1 and M2, and absence of labial cingulids on lower molars. In order to determine the phylogenetic position of P. secundus as well as different Paleogene notoungulates of northwestern Argentina, we performed a cladistic analysis. This analysis supports the paraphyly of Notohippidae proposed by previous authors and validates the monophyly of the genus Pampahippus, which ranks as a relatively basal taxon within Toxodontia. This contribution illustrates the significant and yet poorly known diversity of Paleogene toxodontians from northwestern Argentina and the importance of their study in the reconstruction of the evolutionary history of Notoungulata.

Plant-based beverages are one of the foods that currently arouse a lot of interest in the population due to their composition with compounds beneficial to health in addition to their being used as milk substitutes for people who suffer from food disorders. Also, their fortification with different nutrients or healthy ingredients with the aim of improving plant-based health potential is actually gaining importance in the food industry. For this reason, the aim of the present investigation was the preparation of a healthy Brazil nut beverage enriched with Opuntia stricta var. dillenii pulp green extracts (ODPs), in order to produce a healthy plant-based beverage with improved nutritional characteristics. The microstructural characterization of the Brazil nut beverage, its stability during cold storage for up to 24 days at 5 °C, the composition of bioactive compounds provided via ODP extract (betalains and phenolic compounds), and their antioxidant activity were evaluated in this study. Green ODP extracts (0.5 and 1 g/100 g beverage) were added to a standardized Brazil nut beverage (reduced fat beverage). The characterization of the bioactive composition (betalains and phenolic compounds) of the elaborated beverage was achieved via HPLC (UV-vis and MS-QT of detection), and the antioxidant activity measurements via ORAC were also carried out. Optical microscopy, particle size, and Z potential analysis was conducted to characterize the structure of the Brazil nut beverages as food emulsions in which ODP extract was added. Most of the bioactive compounds from the green ODP extract added to the beverages showed good retention and remained stable throughout the 24 days of storage at 7 °C, with encapsulation efficiencies ranging from 98.34% to 92.35% for betalains and from 93.67% and 81.20% for phenolic compounds. According to the results of this study, Brazil nut beverage seems to be a healthy and efficient food emulsion system to encapsulate ODP extract rich in betalains and phenolic compounds, with high antioxidant activity, making possible the development of a Brazil nut beverage with improved health potential.