Consensus-based recommendations on priority activities to address acute kidney injury in children: A modified Delphi consensus statement

Importance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence Review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and Relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts

Transverse Spin Structure of the Nucleon through Target Single Spin Asymmetry in Semi-Inclusive Deep-Inelastic (e,e′π±)(e,e^\prime \pi^\pm) Reaction at Jefferson Lab

Jefferson Lab (JLab) 12 GeV energy upgrade provides a golden opportunity to perform precision studies of the transverse spin and transverse-momentum-dependent structure in the valence quark region for both the proton and the neutron. In this paper, we focus our discussion on a recently approved experiment on the neutron as an example of the precision studies planned at JLab. The new experiment will perform precision measurements of target Single Spin Asymmetries (SSA) from semi-inclusive electro-production of charged pions from a 40-cm long transversely polarized $^3$He target in Deep-Inelastic-Scattering kinematics using 11 and 8.8 GeV electron beams. This new coincidence experiment in Hall A will employ a newly proposed solenoid spectrometer (SoLID). The large acceptance spectrometer and the high polarized luminosity will provide precise 4-D ($x$, $z$, $P_T$ and $Q^2$) data on the Collins, Sivers, and pretzelocity asymmetries for the neutron through the azimuthal angular dependence. The full 2$\pi$ azimuthal angular coverage in the lab is essential in controlling the systematic uncertainties. The results from this experiment, when combined with the proton Collins asymmetry measurement and the Collins fragmentation function determined from the e$^+$e$^-$ collision data, will allow for a quark flavor separation in order to achieve a determination of the tensor charge of the d quark to a 10% accuracy. The extracted Sivers and pretzelocity asymmetries will provide important information to understand the correlations between the quark orbital angular momentum and the nucleon spin and between the quark spin and nucleon spin.Comment: 23 pages, 13 figures, minor corrections, matches published versio

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: A report from the COVID-19 and Cancer Consortium

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701

Void Growth in BCC Metals Simulated with Molecular Dynamics using the Finnis-Sinclair Potential

The process of fracture in ductile metals involves the nucleation, growth, and linking of voids. This process takes place both at the low rates involved in typical engineering applications and at the high rates associated with dynamic fracture processes such as spallation. Here we study the growth of a void in a single crystal at high rates using molecular dynamics (MD) based on Finnis-Sinclair interatomic potentials for the body-centred cubic (bcc) metals V, Nb, Mo, Ta, and W. The use of the Finnis-Sinclair potential enables the study of plasticity associated with void growth at the atomic level at room temperature and strain rates from 10^9/s down to 10^6/s and systems as large as 128 million atoms. The atomistic systems are observed to undergo a transition from twinning at the higher end of this range to dislocation flow at the lower end. We analyze the simulations for the specific mechanisms of plasticity associated with void growth as dislocation loops are punched out to accommodate the growing void. We also analyse the process of nucleation and growth of voids in simulations of nanocrystalline Ta expanding at different strain rates. We comment on differences in the plasticity associated with void growth in the bcc metals compared to earlier studies in face-centred cubic (fcc) metals.Comment: 24 pages, 12 figure

Coherent states for the hydrogen atom

We construct wave packets for the hydrogen atom labelled by the classical action-angle variables with the following properties. i) The time evolution is exactly given by classical evolution of the angle variables. (The angle variable corresponding to the position on the orbit is now non-compact and we do not get exactly the same state after one period. However the gross features do not change. In particular the wave packet remains peaked around the labels.) ii) Resolution of identity using this overcomplete set involves exactly the classical phase space measure. iii) Semi-classical limit is related to Bohr-Sommerfield quantization. iv) They are almost minimum uncertainty wave packets in position and momentum.Comment: 9 pages, 2 figures, minor change in language and journal reference adde

Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics

Analytical method for perturbed frozen orbit around an Asteroid in highly inhomogeneous gravitational fields : A first approach

This article provides a method for nding initial conditions for perturbed frozen orbits around inhomogeneous fast rotating asteroids. These orbits can be used as reference trajectories in missions that require close inspection of any rigid body. The generalized perturbative procedure followed exploits the analytical methods of relegation of the argument of node and Delaunay normalisation to arbitrary order. These analytical methods are extremely powerful but highly computational. The gravitational potential of the heterogeneous body is rstly stated, in polar-nodal coordinates, which takes into account the coecients of the spherical harmonics up to an arbitrary order. Through the relegation of the argument of node and the Delaunay normalization, a series of canonical transformations of coordinates is found, which reduces the Hamiltonian describing the system to a integrable, two degrees of freedom Hamiltonian plus a truncated reminder of higher order. Setting eccentricity, argument of pericenter and inclination of the orbit of the truncated system to be constant, initial conditions are found, which evolve into frozen orbits for the truncated system. Using the same initial conditions yields perturbed frozen orbits for the full system, whose perturbation decreases with the consideration of arbitrary homologic equations in the relegation and normalization procedures. Such procedure can be automated for the first homologic equation up to the consideration of any arbitrary number of spherical harmonics coefficients. The project has been developed in collaboration with the European Space Agency (ESA)