Effect of Elevated Intra-Abdominal Pressure on Portal Vein and Superior Mesenteric Artery Blood Flow in a Rat

Abstract Aim: Recent clinical experience suggests that minimal access portoenterostomy (the Kasai procedure) for biliary atresia leads to transplantation sooner, compared to the traditional open approach. It should be emphasized that elevated intra-abdominal pressure (IAP) may reduce hepatic and portal blood flow and thus may cause histologic liver damage. The aim of the present study was to evaluate the effects of IAP on blood flow in the portal vein (PV), compared to the superior mesenteric artery (SMA), and on the systemic mean arterial blood pressure (MABP). Materials and Methods: Male Sprague-Dawley rats were anesthetized with intraperitoneal ketamine (90 mg per kg) and xylasine (13 mg per kg). Polyethylene catheters (PE-50) were introduced into the right carotid artery for the measurement of MABP. After a midline laparotomy, the SMA and PV were isolated. Ultrasonic blood-flow probes were placed on the vessels for the continuous measurement of regional blood flow. Two large-caliber percutaneous peripheral intravenous catheters were introduced into the peritoneal cavity for inflation of air and for the measurement of IAP. The time course of MABP and SMA and PV flow as well as the relationship between IAP and SMA and PV flow were determined. Results: Although all three hemodynamic parameters decreased with the increase in the IAP, the most significant changes were observed in PV blood flow. IAP at 3 mm Hg resulted in a 26% decrease in PV flow (P < 0.05), a 19% decrease in SMA flow (P < 0.05), and an 11% decrease in MABP (P < 0.05). IAP at 6 mm Hg caused a two-fold decrease in PV flow (P < 0.05), a 30% decrease in SMA flow (P < 0.05), and a 19% decrease in MABP (P < 0.05). There were no changes in the time course of MABP and PV and SMA flow. PV and SMA flow returned to normal values immediately after abdominal deflation. Conclusions: Persistent IAP decreased MABP, SMA, and, especially, PV flow by 50%. We speculate that in biliary atresia patients with already present liver dysfunction, decrease in SMA flow and even a greater decrease in PV flow from increased IAP, which occurs during a laparoscopic Kasai procedure, may further compromise liver function. This may be one of the explanations for the progression to earlier transplantation in infants undergoing a laparoscopic Kasai procedure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78156/1/lap.2008.0145.supp.pd

Local Behavior of Sparse Analysis Regularization: Applications to Risk Estimation

In this paper, we aim at recovering an unknown signal x0 from noisy L1measurements y=Phi*x0+w, where Phi is an ill-conditioned or singular linear operator and w accounts for some noise. To regularize such an ill-posed inverse problem, we impose an analysis sparsity prior. More precisely, the recovery is cast as a convex optimization program where the objective is the sum of a quadratic data fidelity term and a regularization term formed of the L1-norm of the correlations between the sought after signal and atoms in a given (generally overcomplete) dictionary. The L1-sparsity analysis prior is weighted by a regularization parameter lambda>0. In this paper, we prove that any minimizers of this problem is a piecewise-affine function of the observations y and the regularization parameter lambda. As a byproduct, we exploit these properties to get an objectively guided choice of lambda. In particular, we develop an extension of the Generalized Stein Unbiased Risk Estimator (GSURE) and show that it is an unbiased and reliable estimator of an appropriately defined risk. The latter encompasses special cases such as the prediction risk, the projection risk and the estimation risk. We apply these risk estimators to the special case of L1-sparsity analysis regularization. We also discuss implementation issues and propose fast algorithms to solve the L1 analysis minimization problem and to compute the associated GSURE. We finally illustrate the applicability of our framework to parameter(s) selection on several imaging problems

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Domain bias in web search

This paper uncovers a new phenomenon in web search that we call domain bias — a user’s propensity to believe that a page is more relevant just because it comes from a par-ticular domain. We provide evidence of the existence of domain bias in click activity as well as in human judgments via a comprehensive collection of experiments. We begin by studying the difference between domains that a search engine surfaces and that users click. Surprisingly, we find that despite changes in the overall distribution of surfaced domains, there has not been a comparable shift in the dis-tribution of clicked domains. Users seem to have learned the landscape of the internet and their click behavior has thus become more predictable over time. Next, we run a blind domain test, akin to a Pepsi/Coke taste test, to determine whether domains can shift a user’s opinion of which page is more relevant. We find that domains can actually flip a user’s preference about 25 % of the time. Finally, we demon-strate the existence of systematic domain preferences, even after factoring out confounding issues such as position bias and relevance, two factors that have been used extensively in past work to explain user behavior. The existence of domain bias has numerous consequences including, for example, the importance of discounting click activity from reputable do-mains

Amino acid substitutions in human growth hormone affect secondary structure and receptor binding

The interaction between human Growth Hormone (hGH) and hGH Receptor (hGHR) has basic relevance to cancer and growth disorders, and hGH is the scaffold for Pegvisomant, an anti-acromegaly therapeutic. For the latter reason, hGH has been extensively engineered by early workers to improve binding and other properties. We are particularly interested in E174 which belongs to the hGH zinc-binding triad; the substitution E174A is known to significantly increase binding, but to now no explanation has been offered. We generated this and several computationally-selected single-residue substitutions at the hGHR-binding site of hGH. We find that, while many successfully slow down dissociation of the hGH-hGHR complex once bound, they also slow down the association of hGH to hGHR. The E174A substitution induces a change in the Circular Dichroism spectrum that suggests the appearance of coiled-coiling. Here we show that E174A increases affinity of hGH against hGHR because the off-rate is slowed down more than the on-rate. For E174Y (and certain mutations at other sites) the slowdown in on-rate was greater than that of the off-rate, leading to decreased affinity. The results point to a link between structure, zinc binding, and hGHR-binding affinity in hGH

Amino acid substitutions in human growth hormone affect secondary structure and receptor binding.

The interaction between human Growth Hormone (hGH) and hGH Receptor (hGHR) has basic relevance to cancer and growth disorders, and hGH is the scaffold for Pegvisomant, an anti-acromegaly therapeutic. For the latter reason, hGH has been extensively engineered by early workers to improve binding and other properties. We are particularly interested in E174 which belongs to the hGH zinc-binding triad; the substitution E174A is known to significantly increase binding, but to now no explanation has been offered. We generated this and several computationally-selected single-residue substitutions at the hGHR-binding site of hGH. We find that, while many successfully slow down dissociation of the hGH-hGHR complex once bound, they also slow down the association of hGH to hGHR. The E174A substitution induces a change in the Circular Dichroism spectrum that suggests the appearance of coiled-coiling. Here we show that E174A increases affinity of hGH against hGHR because the off-rate is slowed down more than the on-rate. For E174Y (and certain mutations at other sites) the slowdown in on-rate was greater than that of the off-rate, leading to decreased affinity. The results point to a link between structure, zinc binding, and hGHR-binding affinity in hGH