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BACKGROUND: Highly variable insulin sensitivity, susceptibility to hypoglycemia and inability to effectively communicate hypoglycemic symptoms pose significant challenges for young children with type 1 diabetes (T1D). Herein, outcomes during clinical MiniMed™ 670G system use were evaluated in children aged 2-6 years with T1D. METHODS: Participants (N = 46, aged 4.6 ± 1.4 years) at seven investigational centers used the MiniMed™ 670G system in Manual Mode during a two-week run-in period followed by Auto Mode during a three-month study phase. Safety events, mean A1C, sensor glucose (SG), and percentage of time spent in (TIR, 70-180 mg/dl), below (TBR, 180 mg/dl) range were assessed for the run-in and study phase and compared using a paired t-test or Wilcoxon signed-rank test. RESULTS: From run-in to end of study (median 87.1% time in auto mode), mean A1C and SG changed from 8.0 ± 0.9% to 7.5 ± 0.6% (p

BACKGROUND: Optimized symptom-based COVID-19 case definitions that guide public health surveillance and individual patient management in the community may assist pandemic control. METHODS: We assessed diagnostic performance of existing cases definitions (e.g. influenza-like illness, COVID-like illness) using symptoms reported from 185 household contacts to a PCR-confirmed case of COVID-19 in Wisconsin and Utah, United States. We stratified analyses between adults and children. We also constructed novel case definitions for comparison. RESULTS: Existing COVID-19 case definitions generally showed high sensitivity (86-96%) but low positive predictive value (PPV) (36-49%; F-1 score 52-63) in this community cohort. Top performing novel symptom combinations included taste or smell dysfunction and improved the balance of sensitivity and PPV (F-1 score 78-80). Performance indicators were generally lower for children (

Our understanding of polyploid genome evolution is constrained because we cannot know the exact founders of a particular polyploid. To differentiate between founder effects and post polyploidization evolution, we use a pan-genomic approach to study the allotetraploid Brachypodium hybridum and its diploid progenitors. Comparative analysis suggests that most B. hybridum whole gene presence/absence variation is part of the standing variation in its diploid progenitors. Analysis of nuclear single nucleotide variants, plastomes and k-mers associated with retrotransposons reveals two independent origins for B. hybridum, ~1.4 and ~0.14 million years ago. Examination of gene expression in the younger B. hybridum lineage reveals no bias in overall subgenome expression. Our results are consistent with a gradual accumulation of genomic changes after polyploidization and a lack of subgenome expression dominance. Significantly, if we did not use a pan-genomic approach, we would grossly overestimate the number of genomic changes attributable to post polyploidization evolution.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

Exciting examples of physics principles illuminate the power and scope of our discipline. In this paper, we discuss a conservation of energy example for an introductory course. Energy conservation is applied to bird and dinosaur eggs to derive a method to predict the incubation period and the embryonic metabolism solely from the egg geometry. The power of this fundamental principle to yield insights into a biological example helps to demonstrate the utility of conservation of energy.

The article explores the metabolic rates of non-avian dinosaurs, crocodiles, and birds during embryonic development by calculating the activation energy of their metabolic reactions. The study uses conservation of energy principles and the Boltzmann factor to determine how metabolism changes with temperature. Results show that birds had the highest metabolism in the egg, with Troodon dinosaurs having the highest metabolism among the three dinosaur species studied. The findings suggest a link between metabolic rate and incubation temperature, with implications for sex determination in crocodilians. [Extracted from the article]

To be a stakeholder/validator/token holder is not so difficult in the Proof of Stake (POS)-based blockchain networks; that is why the number of validators is large in these networks. These validators play an essential part in the block creation process in the PoS-based blockchain network. Due to the large validators, the block creation time and communication message broadcasting overhead get increased in the network. Many consensus algorithms use different techniques to reduce the number of validators, such as Delegated Proof of Stake (DPoS) consensus algorithms, which select the set of delegators via stake transactions for the block creation process. In this paper, we propose S&SEM, a secure and speed-up election process to select the 'z' number of validators/delegators. The presented election process is based on a traditional voting style with multiple numbers of rounds. The presented election mechanism reduces the possibility of malicious activity in the voting process by introducing a special vote message and a round that checks duplicate votes. We did horizontal scaling in the network to speed up the election process. We designed an improved incentive mechanism for the fairness of the election process. The designed reward and penalty procedure controls the nodes' behaviors in the network. We simulate the S&SEM, and the result shows that the presented election process is faster and more secure to select delegators than the existing process used by DPOS. [ABSTRACT FROM AUTHOR]

Most physics courses begin with one-dimensional kinematics, which is usually restricted to the case of constant acceleration. Here we report a unique exercise for an introductory algebra-based physics course involving the running and non-constant acceleration of the theropod dinosaur "Dilophosaurus wetherilli" and the world-famous Jamaican sprinter Usain Bolt. Given the interest that most students have about dinosaurs (as well as Usain Bolt), students are excited to examine a hypothetical 100-meter race between "Dilophosaurus" and Usain Bolt. Since these students have not yet taken calculus, and as part of our effort to build computational skills in our students, numerical methods are used via a spreadsheet to calculate displacements and accelerations numerically from velocity data. This work includes a discussion of uncertainties.

BackgroundCountries across sub-Saharan Africa are scaling up Community Health Worker (CHW) programmes, yet there remains little high-quality research assessing strategies for CHW supervision and performance improvement. This randomised controlled trial aimed to determine the effect of a personalised performance dashboard used as a supervision tool on the quantity, speed, and quality of CHW care.MethodsWe conducted a randomised controlled trial in a large health catchment area in peri-urban Mali. One hundred forty-eight CHWs conducting proactive case-finding home visits were randomly allocated to receive individual monthly supervision with or without the CHW Performance Dashboard from January to June 2016. Randomisation was stratified by CHW supervisor, level of CHW experience, and CHW baseline performance for monthly quantity of care (number of household visits). With regression analysis, we used a difference-in-difference model to estimate the effect of the intervention on monthly quantity, timeliness (percentage of children under five treated within 24 hours of symptom onset), and quality (percentage of children under five treated without protocol error) of care over a six-month post-intervention period relative to a three-month pre-intervention period.ResultsUse of the Dashboard during monthly supervision significantly increased the mean number of home visits by 39.94 visits per month (95% CI = 3.56-76.3; P = 0.031). Estimated effects on secondary outcomes of timeliness and quality were positive but not statistically significant. Across both study arms, CHW quantity, timeliness, and quality of care significantly improved over the study period, during which time all CHWs received dedicated monthly supervision, although effects plateaued over time.ConclusionsOur findings suggest that dedicated monthly supervision and personalised feedback using performance dashboards can increase CHW productivity. Further operational research is needed to understand how to sustain the performance improvements over time.Trial registrationClinicalTrials.gov (NCT03684551).

Résumé : Cet article traite de la question de l’agir des populations et des institutions en période de crise à partir d’un corpus littéraire : Entrez dans la danse de Jean Teulé (2019). Il engage le texte de l’auteur français comme allégorie du temps présent ; temps dominé par la crise sanitaire de la Covid-19. Une lecture allégorique de Entrez dans la danse permet de mettre en lumière, après décryptage, la dimension satirique sous-jacente découlant du propos de l’œuvre : l’origine du mal en période de crise sanitaire n’est pas toujours viral.

Abstract Background Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance. Results In reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5–100× more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels. Conclusion These new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.

Acute myeloid leukemia (AML) has a poor survival rate for both pediatric and adult patients due to its frequent relapse. To elucidate the bioenergetic principle underlying AML relapse, we investigated the transcriptional regulation of mitochondrial–nuclear dual genomes responsible for metabolic plasticity in treatment-resistant blasts. Both the gain and loss of function results demonstrated that NFκB2, a noncanonical transcription factor (TF) of the NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) family, can control the expression of TFAM (mitochondrial transcription factor A), which is known to be essential for metabolic biogenesis. Furthermore, genetic tracking and promoter assays revealed that NFκB2 is in the mitochondria and can bind the specific "TTGGGGGGTG" region of the regulatory D-loop domain to activate the light-strand promoter (LSP) and heavy-strand promoter 1 (HSP1), promoters of the mitochondrial genome. Based on our discovery of NFκB2′s novel function of regulating mitochondrial–nuclear dual genomes, we explored a novel triplet therapy including inhibitors of NFκB2, tyrosine kinase, and mitochondrial ATP synthase that effectively eliminated primary AML blasts with mutations of the FMS-related receptor tyrosine kinase 3 (FLT3) and displayed minimum toxicity to control cells ex vivo. As such, effective treatments for AML must include strong inhibitory actions on the dual genomes mediating metabolic plasticity to improve leukemia prognosis. [ABSTRACT FROM AUTHOR]

The outbreak of clade 2.3.4.4b H5 highly pathogenic avian influenza (HPAI) in North America that started in 2021 has increased interest in applying vaccination as a strategy to help control and prevent the disease in poultry. Two commercially available vaccines based on the recombinant herpes virus of turkeys (rHVT) vector were tested against a recent North American clade 2.3.4.4b H5 HPAI virus isolate: A/turkey/Indiana/22-003707-003/2022 H5N1 in specific pathogen free white leghorn (WL) chickens and commercial broiler chickens. One rHVT-H5 vaccine encodes a hemagglutinin (HA) gene designed by the computationally optimized broadly reactive antigen method (COBRA-HVT vaccine). The other encodes an HA gene of a clade 2.2 virus (2.2-HVT vaccine). There was 100% survival of both chicken types COBRA-HVT vaccinated groups and in the 2.2-HVT vaccinated groups there was 94.8% and 90% survival of the WL and broilers respectively. Compared to the 2.2-HVT vaccinated groups, WL in the COBRA-HVT vaccinated group shed significantly lower mean viral titers by the cloacal route and broilers shed significantly lower titers by the oropharyngeal route than broilers. Virus titers detected in oral and cloacal swabs were otherwise similar among both vaccine groups and chicken types. To assess antibody-based tests to identify birds that have been infected after vaccination (DIVA-VI), sera collected after the challenge were tested with enzyme-linked lectin assay-neuraminidase inhibition (ELLA-NI) for N1 neuraminidase antibody detection and by commercial ELISA for detection of antibodies to the NP protein. As early as 7 days post challenge (DPC) 100% of the chickens were positive by ELLA-NI. ELISA was less sensitive with a maximum of 75% positive at 10DPC in broilers vaccinated with 2.2-HVT. Both vaccines provided protection from challenge to both types of chickens and ELLA-NI was sensitive at identifying antibodies to the challenge virus therefore should be evaluated further for DIVA-VI. [ABSTRACT FROM AUTHOR]