Nonstationary Collisional Dynamics in Determining Nitric Oxide Laser-Induced Flourescence Spectra

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77237/1/AIAA-8783-947.pd

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, setting, and participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main outcomes and measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR Conclusions and relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial registration: ClinicalTrials.gov Identifier: NCT04364737

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database

AbstractBackgroundMixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC).MethodsRetrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994–2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared.ResultsWe identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002).DiscussionPatients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively

Citizens and Condemnation: Strategic Uses of International Human Rights Pressure in Authoritarian States

Governments with strict control over the information that their citizens hear from foreign sources are regular targets of human rights pressure, but we know little about how this information matters in the domestic realm. I argue that authoritarian regimes strategically pass on certain types of external pressure to their public to “internationalize” human rights violations, making citizens view human rights in terms of defending their nation internationally rather than in terms of individual violations, and making them more likely to be satisfied with their government’s behavior. I find strong support for this model through statistical analysis of Chinese state media reports of external human rights pressure and a survey experiment on Chinese citizens’ responses to pressure on women’s rights. This analysis demonstrates that authoritarian regimes may be able to manipulate international human rights diplomacy to help them retain the support of their population while suppressing their human rights

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society

Foundational stigma: place‐based stigma in the age before advanced marginality.

This paper joins the debate on the formation of territorial stigma by uncovering the existence of a form of “foundational stigma” that preceded place-based stigma of the era of advanced marginality. I show that not only were the traces of stigma present prior to the era of advanced marginality but that these early traces facilitate later forms of stigma by providing the necessary foundations upon which adhesive and detrimental stigma was operationalized. Following a critical discourse analysis approach, this paper examines coverage in the British press of Toxteth, Liverpool between 1900 and 1981 as a paradigmatic case study to show that this primitive stigma existed in three key ways: relating to inter-community strife, to crime, and to substandard housing conditions. These traces of stigma laid the foundations for later forms of stigma based on the presence of the poor, violent, deviant other that would be operationalized by dominant voices during the era of advanced marginality

An extension of the momentum transfer model to time-dependent pipe turbulence

We analyze a possible extension of Gioia and Chakraborty's momentum transfer model of friction in steady turbulent pipe flows (Phys. Rev. Lett. 96, 044502 (2006)) to the case of time and/or space dependent turbulent flows. The end result is an expression for the stress at the wall as the sum of an steady and a dynamic component. The steady part is obtained by using the instantaneous velocity in the expression for the stress at the wall of a stationary flow. The unsteady part is a weighted average over the history of the flow acceleration, with a weighting function similar to that proposed by Vardy and Brown (Journal of Sound and Vibration 259, 1011 (2003); ibid. 270, 233 (2004)), but naturally including the effect of spatial derivatives of the mean flow, as in the Brunone model (B. Brunone et al., J. of Water Resources Planning and Management 236 (2000)).Comment: 15 pages. 2 figures (included) arXiv admin note: text overlap with arXiv:1005.040