The role of anion gap normalization time in the management of pediatric diabetic ketoacidosis

IntroductionOur aims were to determine whether anion gap normalization time (AGNT) correlates with risk factors related to the severity of diabetic ketoacidosis (DKA) in children, and to characterize AGNT as a criterion for DKA resolution in children admitted with moderate or severe disease.MethodsA ten-year retrospective cohort study of children admitted to the intensive care unit with DKA. We used a survival analysis approach to determine changes in serum glucose, bicarbonate, pH, and anion gap following admission. Using multivariate analysis, we examined associations between patients' demographic and laboratory characteristics with delayed normalization of the anion gap.ResultsA total of 95 patients were analyzed. The median AGNT was 8 h. Delayed AGNT (>8 h) correlated with pH < 7.1 and serum glucose >500 mg/dL. In multivariate analysis, glucose >500 mg/dL was associated with an increased risk for delayed AGNT, by 3.41 fold. Each 25 mg/dL elevation in glucose was associated with a 10% increment in risk for delayed AGNT. Median AGNT preceded median PICU discharge by 15 h (8 vs. 23 h).DiscussionAGNT represents a return to normal glucose-based physiology and an improvement in dehydration. The correlation observed between delayed AGNT and markers of DKA severity supports the usefulness of AGNT for assessing DKA recovery

Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer

The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric gp160 precursor into three gp120 and three gp41 subunits. Here we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain, and a gp120 trimer association domain composed of the V1/V2 and V3 variable regions. The cage-like architecture, which is unique among characterized viral envelope proteins, restricts antibody access, reflecting requirements imposed by HIV-1 persistence in the host

Hypoparathyroidism-retardation-dysmorphism syndrome—Clinical insights from a large longitudinal cohort in a single medical center

BackgroundHypoparathyroidism, retardation, and dysmorphism (HRD) Syndrome is a rare disease composed of hypoparathyroidism, retardation of both growth and development, and distinctive dysmorphic features. Here, we describe the long-term morbidity and mortality in a large cohort of HRD patients and suggest recommendations for follow up and treatment.MethodsMedical records of 63 HRD syndrome patients who were followed at Soroka Medical Center during 1989–2019 were reviewed retrospectively. Information regarding demographics, medical complications, laboratory findings, and imaging studies was collected.ResultsThe mortality rate was 52%. The main causes of death were infectious diseases including pneumonia, septic shock, and meningitis. Multiple comorbidities were found including brain anomalies in 90% of examined patients (basal ganglia calcifications, tightening of corpus callosum, Chiari malformation, hydrocephalous, and brain atrophy), seizures in 62%, nephrocalcinosis and/or nephrolithiasis in 47%, multiple eye anomalies were recorded in 40%, bowel obstructions in 9.5%, and variable expression of both conductive and senso-neural hearing loss was documented in 9.5%.ConclusionHRD is a severe multisystem disease. Active surveillance is indicated to prevent and treat complications associated with this rare syndrome

Identifying codes and searching with balls in graphs

Given a graph G and a positive integer R we address the following combinatorial search theoretic problem: What is the minimum number of queries of the form "does an unknown vertex v∈V(G) belong to the ball of radius r around u?" with u∈V(G) and r≤R that is needed to determine v. We consider both the adaptive case when the jth query might depend on the answers to the previous queries and the non-adaptive case when all queries must be made at once. We obtain bounds on the minimum number of queries for hypercubes, the Erd\H os-Rényi random graphs and graphs of bounded maximum degree

Measurement of the W+W- production cross section in p(p)over-bar collisions at root s=1.96 TeV using dilepton events

We present a measurement of the W+W- production cross section using 184 pb(-1) of p (p) over bar collisions at a center-of-mass energy of 1.96 TeV collected with the Collider Detector at Fermilab. Using the dilepton decay channel W+W-→ l(+)ν l(-)(ν) over bar, where the charged leptons can be either electrons or muons, we find 17 candidate events compared to an expected background of 5.0(-0.8)(+2.2) events. The resulting W+W- production cross-section measurement of σ(p (p) over bar → W+W-)=14.6(-5.1)(+5.8)(stat)(-3.0)(+1.8)(syst)± 0.9(lum) pb agrees well with the standard model expectation

Apprenticeship Learning via Frank-Wolfe

We consider the applications of the Frank-Wolfe (FW) algorithm for Apprenticeship Learning (AL). In this setting, we are given a Markov Decision Process (MDP) without an explicit reward function. Instead, we observe an expert that acts according to some policy, and the goal is to find a policy whose feature expectations are closest to those of the expert policy. We formulate this problem as finding the projection of the feature expectations of the expert on the feature expectations polytope – the convex hull of the feature expectations of all the deterministic policies in the MDP. We show that this formulation is equivalent to the AL objective and that solving this problem using the FW algorithm is equivalent well-known Projection method of Abbeel and Ng (2004). This insight allows us to analyze AL with tools from convex optimization literature and derive tighter convergence bounds on AL. Specifically, we show that a variation of the FW method that is based on taking “away steps” achieves a linear rate of convergence when applied to AL and that a stochastic version of the FW algorithm can be used to avoid precise estimation of feature expectations. We also experimentally show that this version outperforms the FW baseline. To the best of our knowledge, this is the first work that shows linear convergence rates for AL

Methylenediphosphonotetrathioate: Synthesis, Characterization, and Chemical Properties

Metal chelators are potential therapeutic agents for treating diseases such as Wilson’s and Alzheimer’s where the pathology involves an excess of metal-ions (Cu­(II) and Zn­(II)/Cu­(II)/Fe­(II/III), respectively). In addition to the high affinity of the metal-ion to the chelators, metal selectivity of the chelators is essential to achieve the therapeutic goal, that is, the successful removal of excess of harmful metal-ions in a physiological extracellular medium rich in alkali and alkali earth metal-ions. For this purpose, we synthesized a novel chelator, methylenediphosphonotetrathioate (MDPT) which is the tetrathio analogue of methylenediphosphonic acid (MDP). MDPT was synthesized from bis-methylene­(phosphonicdichloride) in a 3-step synthesis and a 31% overall yield. MDPT formed a stable complex with Zn­(II) (log <i>K</i> = 10.84), which is 10⁷ times more stable than the corresponding Ca­(II) complex. Moreover, the MDPT-Zn­(II) complex was 50-fold more stable than the MDP-Zn­(II) complex. In addition, MDPT was found to inhibit the Cu­(I)-catalyzed Fenton reaction (IC₅₀ 26 μM) 2.5 times more potently than a Fe­(II)-catalyzed Fenton reaction, and 2.5 times more potently than EDTA (IC₅₀ 64 μM) in the Cu­(I)/H₂O₂ system, as monitored by electron spin resonance (ESR). Furthermore, MDPT was found to be relatively stable in both acidic (pD 1.9, <i>t</i>_¹/₂ = 71.5 h) and basic media (pD 12.4, <i>t</i>_¹/₂ = 81 h) as monitored by ³¹P/¹H NMR. However, MDPT was not stable in air because of intramolecular oxidation and disulfide formation (33% oxidation after 27 h). In conclusion, MDPT was found to be a water-soluble chelator showing a clear preference to soft/borderline metal-ions and a remarkable selectivity to those metal-ions vs Ca­(II) ions. The relative sensitivity of MDPT to oxidation may limit its use; however, the application of MDPT in acidic or basic media will increase its lifetime