Approach to local thermodynamic equilibrium and the evolution to a glassy core following neutron/ion radiation impact

<p>Using molecular dynamics simulations and statistical-mechanical metrics, we make quantitative predictions on the local thermodynamic and dynamic states following an ion or neutron impact in three materials – copper, silicon and solid argon. Through a two-energy distribution, we first capture the non-equilibrium temperature evolution and the approach to the local thermal equilibrium in three generic stages. By examining the time-resolved van Hove self-correlator, we then demonstrate that the impact core of all the three materials shows the dynamic characteristics of a jammed or glassy state. We delineate a dynamic atom-hopping mechanism that attests to a rapid defect recovery stage in copper; silicon, on the contrary, accommodates only small displacements which resist recovery. The dissimilitude between copper with a close-packed structure and silicon with an open network structure is further drawn out through an isoconfigurational analysis of displacements, which shows a compact dendritic-like condensation front for the mobile atoms in copper through atom hopping. In contrast, silicon portrays larger-scale spatial oscillations of dynamically separated regions, which appear to be a precursor to dynamic lattice instability and eventual amorphisation.</p

Bacterial load and IFN expression during the course of primary infection.

<p><b>A.</b> Course of primary infection in mice with the wild type <i>Lm</i> (EGD-e) and the recombinant <i>L. inn</i>::vgc strain. Mice were infected i.v. with 10³ cfu <i>Lm</i>, 10⁷ cfu <i>L.inn</i>, or 10⁷ cfu <i>L.inn::vgc</i> strains. At different time intervals after the infection, mice were sacrificed and the number of viable bacteria in the organs was enumerated. <b>B.</b> Quantitative measurement of IFNα2 and IFNb1 expression in bone marrow-derived macrophages using RT-PCR at 2 h and 8 h following infection with <i>Lm</i> , <i>L.inn</i>, or the <i>L.inn</i>::<i>vgc</i> strains. *P<0.05 (<i>L.inn</i> vs. <i>Lm</i> and <i>L.inn::vgc</i> strains).</p

Protective immunity and cellular immune response after infection with <i>Lm</i> and the <i>L.inn::vgc</i> strain.

<p><b>A.</b> Induction of protective immunity conferred after infection with the <i>L.inn::vgc strain</i>. Groups of 15 mice were infected i.v. as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035503#pone-0035503-g001" target="_blank">Fig. 1</a>. Two months later all mice were challenged with a lethal dose (20×LD₅₀) of the wild type <i>Lm</i>. As a control, a group of uninfected normal mice was included. Survival of mice after the challenge was monitored up to 8 days. <b>B.</b> Number of antigen-specific IFN-gamma producing CD8+ T cells in spleens of mice infected i.v. with the wild type <i>Lm</i>, <i>L.inn</i> and <i>L.inn::vgc</i> strain determined by ELISPOT. Spleen cells from infected mice were isolated either on day 9 after the primary infection or day 5 after challenge infection and stimulated with the immunodominant MHC class I peptide LLO_91–99 in triplicates in nitrocellulose based 96-well culture plates. Number of specific IFN-gamma producing cells against the dominant H-2K^d restricted LLO_91–99 epitope were determined by counting the number of spots under the microscope. *P<0.05 (<i>L.inn</i> vs. <i>Lm</i> and <i>L.inn::vgc</i> strains).</p

Expression levels of CD62L on CD8⁺ splenocytes following primary and recall infection with <i>Lm</i>, <i>L.inn</i> and the <i>L.inn::vgc</i> strain.

<p>Flow cytometry was performed on spleen cells, isolated from mice on day 60 after the primary infection or day 5 after the challenge. Cells were stained with FITC-labelled anti-Lyt-2 and biotinylated anti-CD62L. The binding of anti-CD62L on the cell surface was detected with PE-conjugated streptavidin. Numbers shown are gated CD8⁺CD62^lo T cells and analyzed with CELLQuest software.</p

Measurement of proinflammatory cytokine levels in serum.

<p>Sera was obtained from mice on days 1, 2, 3, and 4 post-infection after inoculation with 10³ cfu <i>Lm</i>, 10⁷ cfu <i>L.inn</i>, or 10⁷ cfu <i>L.inn::vgc</i>. Levels of IL-1ß, IL-6, IL-12(p70), and TNF-alpha were quantified using a multiplex cytokine assay kit. *P<0.05 (EGD-e vs. <i>L.inn</i> and <i>L.inn::vgc</i> strains).</p

Examination of spleens and DTH response after infection with <i>Lm</i> and the recombinant <i>L.inn::vgc</i> strain.

<p><b>A.</b> Morphological examination of spleens from mice inoculated i.v. with the wild type <i>Lm</i> and the recombinant <i>L.inn::vgc</i> strain. Spleens of mice infected i.v. as mentioned in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035503#pone-0035503-g001" target="_blank">Fig. 1</a> were isolated on day 3 after infection. Shown is a spleen from mice infected with the wild type <i>Lm</i>, the wild type <i>L.inn</i> and its recombinant mutant strain <i>L.inn::vgc</i>. Infiltration of monocytic cells and granulomatous lesions are only detectable in the spleens isolated from mice infected with the wild type <i>Lm</i>. <b>B.</b> Spleen sections were stained with HE and examined. Granulomas with massive leukocyte aggregates can only be detected in spleens of mice infected with <i>Lm</i>. <b>C.</b> DTH response to listerial antigen 9 days after primary infection. Mice were infected with 10³ CFU of <i>Lm</i>, 10⁷ CFU of <i>L.inn</i>, or 10⁷ CFU of <i>L.inn::vgc</i> strain. 9 days after infection, DTH was triggered through injection of soluble somatic listerial antigen. Twenty-four hours later, the specific skin response was determined. The mean value ± S.E. of five animals of a representative experiment is shown.*P<0.05 (EGD-e vs. <i>L.inn::vgc</i> strain).</p

Pharmacological interventions for the prevention of renal injury in surgical patients: a systematic literature review and meta-analysis

BackgroundThe aim of this systematic review was to summarise the results of randomised controlled trials (RCTs) that have evaluated pharmacological interventions for renoprotection in people undergoing surgery.MethodsSearches were conducted to update a previous review using the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to August 23, 2019. RCTs evaluating the use of pharmacological interventions for renal protection in the perioperative period were included. The co-primary outcome measures were 30-day mortality and acute kidney injury (AKI). Pooled effect estimates were expressed as risk ratios (RRs) (95% confidence intervals).ResultsWe included 228 trials enrolling 56 047 patients. Twenty-three trials were considered to be at low risk of bias across all domains. Atrial natriuretic peptides (14 trials; n=2207) reduced 30-day mortality (RR: 0.63 [0.41, 0.97]) and AKI events (RR: 0.43 [0.33, 0.56]) without heterogeneity. These effects were consistent across cardiac surgery and vascular surgery subgroups, and in sensitivity analyses restricted to studies at low risk of bias. Inodilators (13 trials; n=2941) reduced mortality (RR: 0.71 [0.53, 0.94]) and AKI events (RR: 0.65 [0.50, 0.85]) in the primary analysis and in cardiac surgery cohorts. Vasopressors (4 trials; n=1047) reduced AKI (RR: 0.56 [0.36, 0.86]). Nitric oxide donors, alpha-2-agonists, and calcium channel blockers reduced AKI in primary analyses, but not after exclusion of studies at risk of bias. Overall, assessment of the certainty of the effect estimates was low.ConclusionsThere are multiple effective pharmacological renoprotective interventions for people undergoing surgery.</div