Field responsive mechanical metamaterials.

Typically, mechanical metamaterial properties are programmed and set when the architecture is designed and constructed, and do not change in response to shifting environmental conditions or application requirements. We present a new class of architected materials called field responsive mechanical metamaterials (FRMMs) that exhibit dynamic control and on-the-fly tunability enabled by careful design and selection of both material composition and architecture. To demonstrate the FRMM concept, we print complex structures composed of polymeric tubes infilled with magnetorheological fluid suspensions. Modulating remotely applied magnetic fields results in rapid, reversible, and sizable changes of the effective stiffness of our metamaterial motifs

Understanding why EmpaTeach did not reduce teachers' use of violence in Nyarugusu Refugee Camp: A quantitative process evaluation of a school-based violence prevention intervention.

EmpaTeach was the first intervention to address teacher violence to be tested in a humanitarian setting and the first to focus on reducing impulsive use of violence, but a cluster randomised trial found no evidence that the intervention was effective in reducing physical and emotional violence from teachers. We aimed to understand why. We conducted a quantitative process evaluation to describe the intervention implementation process (what was implemented and how); examine teachers' adoption of positive teaching practices (was the content of the intervention taken up by participants), and test mechanisms of impact underlying the program theory (how the intervention was supposed to produce change). Despite participation in the intervention activities and adoption of intervention-recommended strategies (classroom management and positive disciplinary methods), we show that teachers who used more positive discipline did not appear to use less violence; and teachers in intervention schools did not experience gains in intermediate outcomes such as empathy, growth mindset, self-efficacy or social support. Our findings suggest that the intervention did not work due to the failure of some key hypothesised mechanisms, rather than because of implementation challenges

Longitudinal assessment of Allergic Outcomes and Atopic Dermatitis Phenotypes in The Children\u27s Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

Rationale: Atopic dermatitis (AD) is a heterogenous inflammatory skin disease often associated with other allergic diseases. We characterized AD phenotypes and associated allergic outcomes longitudinally across a multi-site consortium. Methods: AD expression in 11 U.S. birth cohorts from the CREW (Children’s Respiratory and Environmental Workgroup) consortium was assessed in each year of life from age 0-7 years (N=7,900). Longitudinal Latent Class Analysis was performed to identify AD phenotypes. Five classes of AD were identified: Persistent AD (15.4%), Early AD with Potential Reoccurrence (2.7%), Late-Onset AD (7.0%), Transient Early AD (3.0%), and Minimal/No AD (72.0%). Serum allergen sensitization patterns and allergic clinical disease were associated with AD phenotype using multinomial logistic regression with a 3-step procedure to account for uncertainty in class membership. Results: Children with Persistent AD, Early AD with Potential Reoccurrence, and Transient Early AD were more likely to have food allergy compared to those with Minimal/No AD (OR[95% CI]=2.73[2.15, 3.45], 2.69[1.63, 4.45], 2.54[1.55, 4.16], respectively). These groups had similarly higher odds of food sensitization. Persistent AD (OR[95% CI]=1.81[1.48, 2.21]) and Early AD with Potential Reoccurrence (OR[95% CI]=3.66[1.90, 7.05]) had significantly higher odds of ever asthma relative to Minimal/No AD. At both 2-4 years and 5-7 years, persistent AD (OR[95% CI]=1.35[1.04, 1.74], 1.25[1.01, 1.53]) and Late-Onset AD (OR[95% CI]=1.68[1.13, 2.50], 2.22[1.33, 3.70]) relative to Minimal/No AD had higher odds of allergic rhinitis. Conclusions: Longitudinal AD phenotypes had varying associations with allergic sensitization, food allergy, asthma and allergic rhinitis, demonstrating the heterogeneity of allergic comorbidity risk associated with AD

Longitudinal Characterization of Atopic Dermatitis Phenotypes in The Children\u27s Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

Rationale: Previously identified longitudinal patterns of atopic dermatitis (AD) may lack generalizability and precision due to small sample size and limited time points. We identify and describe longitudinal AD phenotypes in a large consortium study. Methods: Data from 11 birth cohorts across the United States from the CREW (Children’s Respiratory and Environmental Workgroup) consortium were harmonized to determine physician diagnosis of AD in each year of life from 0-7 years of age (N=7,900). AD phenotypes were identified using Longitudinal Latent Class Analysis, and relationships with demographic variables were determined using multinomial logistic regression with a 3-step procedure to account for uncertainty in class membership. Results: We identified 5 classes of AD expression, selected based on model fit, interpretability, and clinical utility: Persistent AD (15.4%), Early AD with Potential Reoccurrence (2.7%), Late-Onset AD (7.0%), Transient Early AD (3.0%), and Minimal/No AD (72.0%). Males had significantly higher odds of Persistent AD (OR [95% CI]=1.47 [1.22, 1.75]) and Early AD with Potential Reoccurrence (OR [95% CI]=1.89 [1.19, 2.94]). Relative to White children, Black children had higher odds of Persistent AD (OR [95% CI]=2.50 [2.05, 3.05]), Early AD with Potential Reoccurrence (OR [95% CI]=3.07 [1.94, 4.85]), and Transient Early AD (OR [95% CI]=4.12 [2.62, 6.48]). Conclusions: Five AD phenotypes exist in a diverse national sample of children. Black children and males are at increased risk of early and persistent AD. These findings illustrate potential risk factors to target AD prevention

Deep machine learning provides state-of-the art performance in image-based plant phenotyping

Deep learning is an emerging field that promises unparalleled results on many data analysis problems. We show the success offered by such techniques when applied to the challenging problem of image-based plant phenotyping, and demonstrate state-of-the-art results for root and shoot feature identification and localisation. We predict a paradigm shift in image-based phenotyping thanks to deep learning approaches

Therminator DNA Polymerase: Modified Nucleotides and Unnatural Substrates

A variant of 9°N DNA polymerase [Genbank ID (AAA88769.1)] with three mutations (D141A, E143A, A485L) and commercialized under the name “Therminator DNA polymerase” has the ability to incorporate a variety of modified nucleotide classes. This Review focuses on how Therminator DNA Polymerase has enabled new technologies in synthetic biology and DNA sequencing. In addition, we discuss mechanisms for increased modified nucleotide incorporation

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children

Futureproofing [18F]Fludeoxyglucose manufacture at an Academic Medical Center

Abstract Background We recently upgraded our [18F]fludeoxyglucose (FDG) production capabilities with the goal of futureproofing our FDG clinical supply, expanding the number of batches of FDG we can manufacture each day, and improving patient throughput in our nuclear medicine clinic. In this paper we report upgrade of the synthesis modules to the GE FASTLab 2 platform (Phase 1) and cyclotron updates (Phase 2) from both practical and regulatory perspectives. We summarize our experience manufacturing FDG on the FASTLab 2 module with a high-yielding self-shielded niobium (Nb) fluorine-18 target. Results Following installation of Nb targets for production of fluorine-18, a 55 μA beam for 22 min generated 1330 ± 153 mCi of [18F]fluoride. Using these cyclotron beam parameters in combination with the FASTLab 2, activity yields (AY) of FDG were 957 ± 102 mCi at EOS, corresponding to 72% non-corrected AY (n = 235). Our workflow, inventory management and regulatory compliance have been greatly simplified following the synthesis module and cyclotron upgrades, and patient wait times for FDG PET have been cut in half at our nuclear medicine clinic. Conclusions The combination of FASTlab 2 and self-shielded Nb fluorine-18 targets have improved our yield of FDG, and enabled reliable and repeatable manufacture of the radiotracer for clinical use.https://deepblue.lib.umich.edu/bitstream/2027.42/145727/1/41181_2018_Article_48.pd

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

Basal conditions at Engabreen, Norway, inferred from surface measurements and inverse modelling

Engabreen is an outlet glacier of the Svartisen Ice Cap located in Northern Norway. It is a unique glacier due to the Svartisen Subglacial Laboratory which allows direct access to the glacier bed. In this study, we combine both sub- and supraglacial observations with ice-flow modelling in order to investigate conditions at the bed of Engabreen both spatially and temporally. We use the full-Stokes model Elmer/Ice and satellite-based surface-velocity maps from 2010 and 2014 to infer patterns of basal friction. Direct measurements of basal sliding and deformation of lower layers of the ice are used to adjust the ice viscosity and provide essential input to the setup of our model and influence the interpretation of the results. We find a clear seasonal cycle in the subglacial conditions at the higher elevation region of the study area and discuss this in relation to the subglacial hydrological system. Our results also reveal an area with an overdeepening where basal friction is significantly lower than elsewhere on the glacier all year round. We attribute this to either water pooling at the base, or saturated sediments and increased strain heating at this location which softens the ice further