Maintenance intravenous fluids (IVFs) are used to provide critical supportive care for children who are acutely ill. IVFs are required if sufficient fluids cannot be provided by using enteral ...administration for reasons such as gastrointestinal illness, respiratory compromise, neurologic impairment, a perioperative state, or being moribund from an acute or chronic illness. Despite the common use of maintenance IVFs, there is high variability in fluid prescribing practices and a lack of guidelines for fluid composition administration and electrolyte monitoring. The administration of hypotonic IVFs has been the standard in pediatrics. Concerns have been raised that this approach results in a high incidence of hyponatremia and that isotonic IVFs could prevent the development of hyponatremia. Our goal in this guideline is to provide an evidence-based approach for choosing the tonicity of maintenance IVFs in most patients from 28 days to 18 years of age who require maintenance IVFs. This guideline applies to children in surgical (postoperative) and medical acute-care settings, including critical care and the general inpatient ward. Patients with neurosurgical disorders, congenital or acquired cardiac disease, hepatic disease, cancer, renal dysfunction, diabetes insipidus, voluminous watery diarrhea, or severe burns; neonates who are younger than 28 days old or in the NICU; and adolescents older than 18 years old are excluded. We specifically address the tonicity of maintenance IVFs in children.The Key Action Statement of the subcommittee is as follows:
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Mutations that alter chromosomal structure play critical roles in evolution and disease, including in the origin of new lifestyles and pathogenic traits in microbes. Large-scale rearrangements in ...genomes are often mediated by recombination events involving new or existing copies of mobile genetic elements, recently duplicated genes, or other repetitive sequences. Most current software programs for predicting structural variation from short-read DNA resequencing data are intended primarily for use on human genomes. They typically disregard information in reads mapping to repeat sequences, and significant post-processing and manual examination of their output is often required to rule out false-positive predictions and precisely describe mutational events.
We have implemented an algorithm for identifying structural variation from DNA resequencing data as part of the breseq computational pipeline for predicting mutations in haploid microbial genomes. Our method evaluates the support for new sequence junctions present in a clonal sample from split-read alignments to a reference genome, including matches to repeat sequences. Then, it uses a statistical model of read coverage evenness to accept or reject these predictions. Finally, breseq combines predictions of new junctions and deleted chromosomal regions to output biologically relevant descriptions of mutations and their effects on genes. We demonstrate the performance of breseq on simulated Escherichia coli genomes with deletions generating unique breakpoint sequences, new insertions of mobile genetic elements, and deletions mediated by mobile elements. Then, we reanalyze data from an E. coli K-12 mutation accumulation evolution experiment in which structural variation was not previously identified. Transposon insertions and large-scale chromosomal changes detected by breseq account for ~25% of spontaneous mutations in this strain. In all cases, we find that breseq is able to reliably predict structural variation with modest read-depth coverage of the reference genome (>40-fold).
Using breseq to predict structural variation should be useful for studies of microbial epidemiology, experimental evolution, synthetic biology, and genetics when a reference genome for a closely related strain is available. In these cases, breseq can discover mutations that may be responsible for important or unintended changes in genomes that might otherwise go undetected.
Information scrambling in quantum circuits Mi, Xiao; Roushan, Pedram; Quintana, Chris ...
Science (American Association for the Advancement of Science),
2021-Dec-17, 2021-12-17, 20211217, Volume:
374, Issue:
6574
Journal Article
Peer reviewed
Open access
Interactions in quantum systems can spread initially localized quantum information into the exponentially many degrees of freedom of the entire system. Understanding this process, known as quantum ...scrambling, is key to resolving several open questions in physics. Here, by measuring the time-dependent evolution and fluctuation of out-of-time-order correlators, we experimentally investigate the dynamics of quantum scrambling on a 53-qubit quantum processor. We engineer quantum circuits that distinguish operator spreading and operator entanglement and experimentally observe their respective signatures. We show that whereas operator spreading is captured by an efficient classical model, operator entanglement in idealized circuits requires exponentially scaled computational resources to simulate. These results open the path to studying complex and practically relevant physical observables with near-term quantum processors.
Quantum many-body systems display rich phase structure in their low-temperature equilibrium states
. However, much of nature is not in thermal equilibrium. Remarkably, it was recently predicted that ...out-of-equilibrium systems can exhibit novel dynamical phases
that may otherwise be forbidden by equilibrium thermodynamics, a paradigmatic example being the discrete time crystal (DTC)
. Concretely, dynamical phases can be defined in periodically driven many-body-localized (MBL) systems via the concept of eigenstate order
. In eigenstate-ordered MBL phases, the entire many-body spectrum exhibits quantum correlations and long-range order, with characteristic signatures in late-time dynamics from all initial states. It is, however, challenging to experimentally distinguish such stable phases from transient phenomena, or from regimes in which the dynamics of a few select states can mask typical behaviour. Here we implement tunable controlled-phase (CPHASE) gates on an array of superconducting qubits to experimentally observe an MBL-DTC and demonstrate its characteristic spatiotemporal response for generic initial states
. Our work employs a time-reversal protocol to quantify the impact of external decoherence, and leverages quantum typicality to circumvent the exponential cost of densely sampling the eigenspectrum. Furthermore, we locate the phase transition out of the DTC with an experimental finite-size analysis. These results establish a scalable approach to studying non-equilibrium phases of matter on quantum processors.
The biogeochemical cycles of carbon (C), nitrogen (N), and phosphorus (P) are fundamental to life on Earth. Because organisms require these elements in strict proportions, the cycles of C, N, and P ...are coupled at molecular to global scales through their effects on the biochemical reactions controlling primary production, respiration, and decomposition. The coupling of the C, N, and P cycles constrains organismal responses to climatic and atmospheric change, suggesting that present-day estimates of climate warming through the year 2100 are conservative. N and P supplies constrain C uptake in the terrestrial biosphere, yet these constraints are often not incorporated into global-scale analyses of Earth's climate. The inclusion of coupled biogeochemical cycles is critical to the development of next-generation, global-scale climate models.
Biliary cancers (BCs) carry a poor prognosis, but targeting the RAS/RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is of significance. Selumetinib ...is an inhibitor of MEK1/2, so this trial was designed to determine the safety and efficacy of selumetinib in BC.
This was a multi-institutional phase II study of selumetinib at 100 mg given orally twice per day to patients with advanced BC. The primary end point was response rate. All patients were required to provide tissue before enrolling. The levels of phosphorylated ERK (pERK) and AKT (pAKT) were assessed by immunohistochemistry. Tumors were genotyped for the presence of BRAF- and/or RAS-activating mutations.
Twenty-eight eligible patients with a median age of 55.6 years were enrolled. Thirty-nine percent of patients had received one prior systemic therapy. Three patients (12%) had a confirmed objective response. Another 17 patients (68%) experienced stable disease (SD), 14 of whom (56%) experienced prolonged SD (> 16 weeks). Patients gained an average nonfluid weight of 8.6 pounds. Median progression-free survival was 3.7 months (95% CI, 3.5 to 4.9) and median overall survival was 9.8 months (95% CI, 5.97 to not available). Toxicities were mild, with rash (90%) and xerostomia (54%) being most frequent. Only one patient experienced grade 4 toxicity (fatigue). All patients had tissue available for analysis. No BRAF V600E mutations were found. Two patients with short-lived SD had KRAS mutations. Absence of pERK staining was associated with lack of response.
Selumetinib displays interesting activity and acceptable tolerability in patients with metastatic BC. Our results warrant further evaluation of selumetinib in patients with metastatic BC.
Understanding structural stability and phase transformation of nanoparticles under high pressure is of great scientific interest, as it is one of the crucial factors for design, synthesis, and ...application of materials. Even though high-pressure research on nanomaterials has been widely conducted, their shape-dependent phase transition behavior still remains unclear. Examples of phase transitions of CdS nanoparticles are very limited, despite the fact that it is one of the most studied wide band gap semiconductors. Here we have employed in situ synchrotron wide-angle X-ray scattering and transmission electron microscopy (TEM) to investigate the high-pressure behaviors of CdS nanoparticles as a function of particle shapes. We observed that CdS nanoparticles transform from wurtzite to rocksalt phase at elevated pressure in comparison to their bulk counterpart. Phase transitions also vary with particle shape: rod-shaped particles show a partially reversible phase transition and the onset of the structural phase transition pressure decreases with decreasing surface-to-volume ratios, while spherical particles undergo irreversible phase transition with relatively low phase transition pressure. Additionally, TEM images of spherical particles exhibited sintering-induced morphology change after high-pressure compression. Calculations of the bulk modulus reveal that spheres are more compressible than rods in the wurtzite phase. These results indicate that the shape of the particle plays an important role in determining their high-pressure properties. Our study provides important insights into understanding the phase–structure–property relationship, guiding future design and synthesis of nanoparticles for promising applications.
SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of ...this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of primary human lung non-small cell lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes.
B cell development is a highly regulated process involving multiple differentiation steps, yet many details regarding this pathway remain unknown. Sequencing of patients with B cell-restricted ...immunodeficiency reveals autosomal dominant mutations in TOP2B. TOP2B encodes a type II topoisomerase, an essential gene required to alleviate topological stress during DNA replication and gene transcription, with no previously known role in B cell development. We use Saccharomyces cerevisiae, and knockin and knockout murine models, to demonstrate that patient mutations in TOP2B have a dominant negative effect on enzyme function, resulting in defective proliferation, survival of B-2 cells, causing a block in B cell development, and impair humoral function in response to immunization.
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