Intravital Microscopic Evidence that Polylactide-Polyglycolide (PLGA) Delays Neo-Osteogenesis and Neo-Angiogenesis in Healing Bone

The bone chamber implant (BCI) has allowed monitoring a healing bone defect as well as the effect of an eroding implant on the healing process. The BCI is a useful tool and intravital microscopy a valuable technique for obtaining quantitative data chronicling osseous wound healing. The physiological parameters that form the initial data base documenting healing are neo-osteogenesis and neo-angiogenesis. This review compares and characterizes osseous wound healing in a BCI loaded with an erodible copolymer, PLGA (polylactide-polyglycolide). To determine if a statistically significant deviation from normal healing had occurred, the results were compared with present and historical controls. In the BCI PLGA erosion was accompanied by a delay in the onset of neo-osteogenesis, as measured by trabecular apposition. Concurrently, neo-angiogenesis was both detained and retarded. The neo-angiogenesis delay was interpreted as a direct consequence of the neo-osteogenesis delay since the major part of the vasculature was carried by the apposing trabeculae. Angiogenesis inhibition is more difficult to interpret until data are further analyzed to determine if apposing trabeculae in the presence of eroding PLGA carry less vasculature

Influence of the Soret effect on convection of binary fluids

Convection in horizontal layers of binary fluids heated from below and in particular the influence of the Soret effect on the bifurcation properties of extended stationary and traveling patterns that occur for negative Soret coupling is investigated theoretically. The fixed points corresponding to these two convection structures are determined for realistic boundary conditions with a many mode Galerkin scheme for temperature and concentration and an accurate one mode truncation of the velocity field. This solution procedure yields the stable and unstable solutions for all stationary and traveling patterns so that complete phase diagrams for the different convection types in typical binary liquid mixtures can easily be computed. Also the transition from weakly to strongly nonlinear states can be analyzed in detail. An investigation of the concentration current and of the relevance of its constituents shows the way for a simplification of the mode representation of temperature and concentration field as well as for an analytically manageable few mode description.Comment: 30 pages, 12 figure

Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study

Introduction: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock. Methods: The Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality. Results: Median age was 66 years (interquartile range 55–75), and 28-day mortality was 22% (95% confidence interval [CI] 19%−25%). Of the patients, 293 (50.3%) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95% CI = 1.8–6.0], 3.9 [95% CI = 2.1–7.2], and 3.4 [95% CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery. Conclusion: Admission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients

Growth of GaInTlAs layers on InP by molecular beam epitaxy

International audienceGrowth of GaInTlAs alloys on InP001 has been attempted by solid source molecular beam epitaxy. Thallium incorporation into Ga 1x In x As matrices was studied as a function of substrate temperature, arsenic overpressure, matrix composition, and growth rate. At high temperatures 350 °C thallium evaporates, whereas at intermediary temperatures 270-350 °C thallium segregates into droplets on the surface. Only in the low temperature range 180-260 °C can thallium be incorporated in some conditions, leading to mirror-like surfaces. Up to 18% Tl content was incorporated into a Ga 0.70 In 0.30 As matrix and up to 40% Tl into a GaAs matrix. For these high Tl concentrations, Tl droplets are avoided and Tl incorporation is achieved only when using high arsenic pressures. However, this limits surface adatom diffusion and leads to amorphous, polycrystalline, or twinned materials. Finally, a narrow window for single-crystal growth has been found for low Tl contents 4% using optimized growth conditions with low V/III pressure ratios and high growth rates

Influence of the Dufour effect on convection in binary gas mixtures

Linear and nonlinear properties of convection in binary fluid layers heated from below are investigated, in particular for gas parameters. A Galerkin approximation for realistic boundary conditions that describes stationary and oscillatory convection in the form of straight parallel rolls is used to determine the influence of the Dufour effect on the bifurcation behaviour of convective flow intensity, vertical heat current, and concentration mixing. The Dufour--induced changes in the bifurcation topology and the existence regimes of stationary and traveling wave convection are elucidated. To check the validity of the Galerkin results we compare with finite--difference numerical simulations of the full hydrodynamical field equations. Furthermore, we report on the scaling behaviour of linear properties of the stationary instability.Comment: 14 pages and 10 figures as uuencoded Postscript file (using uufiles

Universal Crossover between Efros-Shklovskii and Mott Variable-Range-Hopping Regimes

A universal scaling function, describing the crossover between the Mott and the Efros-Shklovskii hopping regimes, is derived, using the percolation picture of transport in strongly localized systems. This function is agrees very well with experimental data. Quantitative comparison with experiment allows for the possible determination of the role played by polarons in the transport.Comment: 7 pages + 1 figure, Revte

Influence of through-flow on linear pattern formation properties in binary mixture convection

We investigate how a horizontal plane Poiseuille shear flow changes linear convection properties in binary fluid layers heated from below. The full linear field equations are solved with a shooting method for realistic top and bottom boundary conditions. Through-flow induced changes of the bifurcation thresholds (stability boundaries) for different types of convective solutions are deter- mined in the control parameter space spanned by Rayleigh number, Soret coupling (positive as well as negative), and through-flow Reynolds number. We elucidate the through-flow induced lifting of the Hopf symmetry degeneracy of left and right traveling waves in mixtures with negative Soret coupling. Finally we determine with a saddle point analysis of the complex dispersion relation of the field equations over the complex wave number plane the borders between absolute and convective instabilities for different types of perturbations in comparison with the appropriate Ginzburg-Landau amplitude equation approximation. PACS:47.20.-k,47.20.Bp, 47.15.-x,47.54.+rComment: 19 pages, 15 Postscript figure

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015