Thermally Stable Red-Emitting Oxide Ceramics for Laser Lighting.

Laser-driven phosphor-converted white light sources are highly desirable for their unprecedented energy efficiency and lighting quality. However, important challenges remain due to a lack of efficient and stable red-emitting materials. Here Eu2+ -activated oxide-based double perovskites are explored as red emitters with thermally stable photoluminescence. Sr3 TaO5.5 :Eu2+ ceramics exhibit a red emission band peaking at 620 nm upon blue laser pumping owing to the Eu2+ occupation at highly ordered substitutional lattice sites. A constructed laser-driven white light wheel under an incident power density of 19.2 W mm-2 presents a record luminous flux of 1115 lm with an excellent color rendering index of 90. This study invigorates the development of Eu2+ -activated oxide-based ceramics with thermally stable luminescence for laser-pumped lighting and display applications.

Total TauProtein as Investigated by Cerebral Microdialysis Increases in Hypothermic Cardiac Arrest: A Pig Study.

The understanding and neurological prognostication of hypoxic ischemic encephalopathy (HIE) after hypothermic cardiac arrest (CA) is limited. Recent data suggest that the protein tau (total tau) might be a useful marker for outcome in patients with HIE. This translational porcine study aimed to analyze brain physiology in relation to total tau protein release during hypothermic CA. Eight domestic pigs were studied as part of a prospective porcine study using cerebral microdialysis (CMD). CMD samples for tau analysis were collected at baseline, after reaching the targeted core temperature of 28°C (hypothermia), after hypoxic hypercapnia (partial asphyxia), and finally 20 minutes after cardiopulmonary resuscitation. CMD-total tau-protein was analyzed using enzyme-linked immunosorbent essay. Cerebral tau protein was slightly elevated at baseline most likely due to an insertion trauma, remained stable during hypercapnic hypoxia, and significantly (p = 0.009) increased in 8/8 pigs during resuscitation to 1335 pg/mL (interquartile range: 705-2100). CMD-tau release was associated with lower levels of brain tissue oxygen tension (p = 0.011), higher CMD-lactate/pyruvate ratio, higher CMD-lactate, CMD-glutamate, and CMD-glycerol levels (p < 0.001, respectively), but not with cerebral perfusion pressure, intracranial pressure, or CMD-glucose levels. This study demonstrates an immediate tau protein release accompanied by deranged cerebral metabolism and decreased brain tissue oxygen tension during mechanical resuscitation in hypothermic CA. Understanding tau physiology and release kinetics is important for the design and interpretation of studies investigating tau as a biomarker of HIE.

Effects of hypothermia, hypoxia, and hypercapnia on brain oxygenation and hemodynamic parameters during simulated avalanche burial: a porcine study.

Avalanche patients who are completely buried but still able to breathe are exposed to hypothermia, hypoxia, and hypercapnia (triple H syndrome). Little is known about how these pathological changes affect brain physiology. The study aim was to investigate the effect of hypothermia, hypoxia, and hypercapnia on brain oxygenation and systemic and cerebral hemodynamics. Anesthetized pigs were surface cooled to 28°C. Fraction of inspiratory oxygen ([Formula: see text]) was reduced to 17% and hypercapnia induced. Hemodynamic parameters and blood gas values were monitored. Cerebral measurements included cerebral perfusion pressure (CPP), brain tissue oxygen tension ([Formula: see text]), cerebral venous oxygen saturation ([Formula: see text]), and regional cerebral oxygen saturation (rSo2). Tests were interrupted when hemodynamic instability occurred or 60 min after hypercapnia induction. ANOVA for repeated measures was used to compare values across phases. There was no clinically relevant reduction in cerebral oxygenation ([Formula: see text], [Formula: see text], rSo2) during hypothermia and initial [Formula: see text] reduction. Hypercapnia was associated with an increase in pulmonary resistance followed by a decrease in cardiac output and CPP, resulting in hemodynamic instability and cerebral desaturation (decrease in [Formula: see text], [Formula: see text], rSo2). Hypercapnia may be the main cause of cardiovascular instability, which seems to be the major trigger for a decrease in cerebral oxygenation in triple H syndrome despite severe hypothermia.NEW & NOTEWORTHY Avalanche patients who are completely buried but still able to breathe are exposed to hypothermia, hypoxia, and hypercapnia (triple H syndrome). In a porcine model, there was no clinically relevant reduction in cerebral oxygenation during hypothermia and initial reduction of fraction of inspiratory oxygen ([Formula: see text]), as observed during hypercapnia. Hypercapnia may be the main cause of cardiovascular instability, which seems to be the major trigger for a decrease in cerebral oxygenation in triple H syndrome despite severe hypothermia.

Multicenter clinical evaluation of alinity m HBV assay performance.

BACKGROUND: Accurate molecular methods to detect and quantify hepatitis B virus (HBV) DNA are essential to diagnose chronic infections, guide treatment decisions, assess response to treatment, and determine risk of HBV-related complications. New generations of real-time HBV DNA assay platforms provide results in less than 2-3 h, with continuous loading of specimens and true random-access capability. OBJECTIVES: We examined the clinical performance of the new Alinity m HBV assay, run on the fully automated, continuous, random-access Alinity m platform, to accurately detect and quantify HBV DNA in a large series of patient samples infected with different HBV genotypes frequently encountered in clinical practice. STUDY DESIGN: This international, multisite study assessed the precision and reproducibility of the Alinity m HBV assay and compared its performance to four HBV assays currently in clinical use. RESULTS: The Alinity m HBV assay demonstrated linear quantitation of HBV DNA in plasma samples, with high precision (coefficient of variation 4.1 %-8.8 %) and reproducibility. The Alinity m HBV assay showed excellent correlation (correlation coefficients ≥0.947) with comparator HBV assays, with an overall observed bias ranging from -0.07 to 0.17 Log10 IU/mL. 97 % of quantifiable patient results were <1 Log10 IU/mL different than the respective comparator assays, with comparable results across HBV genotypes. CONCLUSIONS: The newly developed real-time PCR-based Alinity m HBV assay is sensitive, reproducible, and accurately quantifies HBV DNA levels from HBsAg-positive patients across the full dynamic range of quantification.

Multicenter clinical evaluation of alinity m HCV assay performance.

BACKGROUND: Nucleic acid testing is essential for the detection and quantification of HCV RNA in the diagnosis of HCV infection and treatment monitoring. The Alinity m HCV assay was recently developed by Abbott Molecular for rapid detection and quantification of HCV RNA on the fully automated, continuous, random-access Alinity m analyzer. OBJECTIVES: Our study assessed the performance of the new Alinity m HCV assay for detection and quantification of HCV RNA in a large series of patient samples of various genotypes. This international, multicentric study evaluated the linearity, precision, and reproducibility of the Alinity m HCV assay and its performance in comparison to three other HCV assays currently used in clinical practice. RESULTS: The Alinity m HCV assay demonstrated high linearity (correlation coefficient r = 1.00), precision (coefficients of variation [CV] 6.6-13.5 %) and reproducibility (CV 1.7-4.3 % across three control lots). At a concentration near the lower limit of detection, the Alinity m HCV assay exhibited >98 % detectability. The Alinity m HCV assay showed excellent correlation with comparator HCV assays in serum (n = 406) and plasma (n = 1401) samples (correlation coefficients ≥0.96, bias 0.01 to 0.14 Log10 IU/mL). More than 95 % of the quantified results with the Alinity m HCV assay were less than mean bias ± 1.96 SD different from those of the comparator assays. CONCLUSIONS: The newly developed Alinity m HCV assay is sensitive, reproducible, and accurately quantifies HCV RNA levels in serum and plasma samples from patients with chronic HCV infection, with no impact of HCV genotype on assay performance.

Multicenter clinical comparative evaluation of Alinity m HIV-1 assay performance.

BACKGROUND: Accurate, rapid detection of HIV-1 RNA is critical for early diagnosis, treatment decision making, and long-term management of HIV-1 infection. OBJECTIVE: We evaluated the diagnostic performance of the Alinity m HIV-1 assay, which uses a dual target/dual probe design against highly conserved target regions of the HIV-1 genome and is run on the fully automated Alinity m platform. STUDY DESIGN: This was an international, multisite study that compared the diagnostic performance of the Alinity m HIV-1 assay to four commercially available HIV-1 assays routinely used in nine independent clinical laboratories. Alinity m HIV-1 assay precision, detectability, and reproducibility was compared across four study sites. RESULTS: The Alinity m HIV-1 assay produced comparable results to currently available HIV-1 assays (correlation coefficient >0.995), with an overall bias of -0.1 to 0.10 Log10 copies/mL. The Alinity m HIV-1 assay and its predecessor m2000 HIV-1 assay demonstrated comparable detection of 16 different HIV-1 subtypes (R2 = 0.956). A high level of agreement (>88 %) between all HIV-1 assays was seen near clinical decision points of 1.7 Log10 copies/mL (50 copies/mL) and 2.0 Log10 copies/mL (200 copies/mL). Alinity m HIV-1 assay precision was 0.08 and 0.21 Log10 copies/mL at VLs of 1000 and 50 copies/mL, respectively, with a high level of detectability (≥97 % hit rate) and reproducibility across sites. CONCLUSIONS: The Alinity m HIV-1 assay provides comparable diagnostic accuracy to current HIV-1 assays, and when run on the Alinity m system, has the capacity to shorten the time between diagnosis and treatment.

Multicenter Evaluation of Two Next-Generation HIV-1 Quantitation Assays, Aptima Quant Dx and Cobas 6800, in Comparison to the RealTime HIV-1 Reference Assay.

High accuracy and precision at the lower end of quantification are crucial requirements of a modern HIV viral load (VL) assay, since some clinically relevant thresholds are located at 50 and 200 copies/ml. In this study, we compared the performance of two new fully automated HIV-1 VL assays, Aptima HIV-1 Quant Dx and Cobas HIV-1 (Cobas 6800), with the established RealTime m2000 assay. Assay precision and accuracy were evaluated in a retrospective evaluation out of excess plasma material from four HIV-1+ individuals (subtypes B, C, CRF01_AE, and CRF02_AG). Native plasma samples were diluted to nominal concentrations at 50 and 200 copies/ml (according to the RealTime m2000 assay). All dilutions were tested in triplicate in five independent runs over 5 days and in three labs per system. Assay concordance was determined using 1,011 surplus clinical routine samples, as well as selected retrospective longitudinal samples from 7 patients on treatment. The three assays yielded highly concordant results for individual clinical samples (R2 > 0.98; average difference, ≤0.2 log copies/ml) and retrospective longitudinal samples from patients on treatment. The Aptima and RealTime assays showed similar high precision, meeting the 5σ criterion for the majority of samples across all labs and subtypes. The Cobas assay was less precise, missing the 5σ criterion for the majority of samples at low concentrations. In this analysis, results from the Cobas assay appeared less reliable near the clinically relevant cutoff and should be interpreted with more caution in this context. Due to high precision, full automation, and high concordance with the RealTime assay, the Aptima assay represents a good alternative in routine VL monitoring.

Effects of head-up vs. supine CPR on cerebral oxygenation and cerebral metabolism - a prospective, randomized porcine study.

BACKGROUND: Recent studies have shown that during cardiopulmonary resuscitation (CPR) head-up position (HUP) as compared to standard supine position (SUP) decreases intracranial pressure (ICP) and increases cerebral perfusion pressure (CPP). The impact of this manoeuvre on brain oxygenation and metabolism is not clear. We therefore investigated HUP as compared to SUP during basic life support (BLS) CPR for their effect on brain oxygenation and metabolism. METHODS: Twenty pigs were anaesthetized and instrumented. After 8 min of cardiac arrest (CA) pigs were randomized to either HUP or SUP and resuscitated mechanically for 20 min. Mean arterial pressure (MAP), ICP, CPP, cerebral regional oxygen saturation (rSO2) and brain tissue oxygen tension (PbtO2) were measured at baseline, after CA and every 5 min during CPR. Cerebral venous oxygen saturation (ScvO2) was measured at baseline, after CA and after 20 min of CPR. Cerebral microdialysis parameters, e.g. lactate/pyruvate ratio (L/P ratio) were taken at baseline and the end of the experiment. RESULTS: ICP was significantly lower in HUP compared to SUP animals after 5 min (18.0 ±â€¯4.5 vs. 24.1 ±â€¯5.2 mmHg; p = 0.033) and 20 min (12.0 ±â€¯3.4 vs. 17.8 ±â€¯4.3 mmHg; p = 0.023) of CPR. Accordingly, CPP was significantly higher in the HUP group after 5 min (11.2 ±â€¯9.5 vs. 1.0 ±â€¯9.2 mmHg; p = 0.045) and 20 min (3.4 ±â€¯6.4 vs. -3.8 ±â€¯2.8 mmHg; p = 0.023) of CPR. However, no difference was found in rSO2, PbtO2, ScvO2 and L/P ratio between groups after 20 min of CPR. CONCLUSION: In this animal model of BLS CPR, HUP as compared to SUP did not improve cerebral oxygenation or metabolism.

A European multicenter study on the analytical performance of the VERIS HBV assay.

BACKGROUND: Hepatitis B viral load monitoring is an essential part of managing patients with chronic Hepatits B infection. Beckman Coulter has developed the VERIS HBV Assay for use on the fully automated Beckman Coulter DxN VERIS Molecular Diagnostics System.1 OBJECTIVES: To evaluate the analytical performance of the VERIS HBV Assay at multiple European virology laboratories. STUDY DESIGN: Precision, analytical sensitivity, negative sample performance, linearity and performance with major HBV genotypes/subtypes for the VERIS HBV Assay was evaluated. RESULTS: Precision showed an SD of 0.15 log10 IU/mL or less for each level tested. Analytical sensitivity determined by probit analysis was between 6.8-8.0 IU/mL. Clinical specificity on 90 unique patient samples was 100.0%. Performance with 754 negative samples demonstrated 100.0% not detected results, and a carryover study showed no cross contamination. Linearity using clinical samples was shown from 1.23-8.23 log10 IU/mL and the assay detected and showed linearity with major HBV genotypes/subtypes. CONCLUSIONS: The VERIS HBV Assay demonstrated comparable analytical performance to other currently marketed assays for HBV DNA monitoring.

A European multicientre study on the comparison of HBV viral loads between VERIS HBV assay and Roche COBAS® TAQMAN® HBV test, Abbott RealTime HBV assay, Siemens VERSANT HBV assay, and Qiagen artus HBV RG kit.

BACKGROUND: Hepatitis B viral load testing is essential to treatment and monitoring decisions in patients with chronic Hepatitis B. Beckman Coulter has developed the VERIS HBV Assay (Veris) for use on the fully automated DxN VERIS Molecular Diagnostics System.1 OBJECTIVES: To evaluate the clinical performance of the Veris HBV Assay at multiple EU laboratories STUDY DESIGN: Method comparison was performed with a total of 344 plasma specimens from HBV infected patients tested with Veris and COBAS® TaqMan® HBV Test (Cobas), 207 specimens tested with Veris and RealTime HBV Assay (RealTime), 86 specimens tested with Veris and VERSANT® HBV Assay (Versant), and 74 specimens tested with Veris and artus® HBV RG PCR kit (artus). RESULTS: Bland-Altman analysis showed average bias of -0.46 log10 IU/mL between Veris and Cobas, -0.46 log10IU/mL between Veris and RealTime, -0.36 log10IU/mL between Veris and Versant, and -0.12 log10IU/mL between Veris and artus. Bias was consistent across the assay range. Patient monitoring results using Veris demonstrated similar viral load trends over time to Cobas, RealTime, and artus. CONCLUSIONS: The VERIS HBV Assay demonstrated comparable clinical performance, with varying degrees of negative bias, compared to other currently marketed assays for HBV DNA monitoring. This negative bias should be taken into consideration if switching monitoring methods to Veris.

A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay.

BACKGROUND: Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System.¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. STUDY DESIGN: Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. RESULTS: Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be <0.3 log10 cp/mL for VERIS HIV-1 Assay versus COBAS HIV-1 Test and RealTime HIV-1 Assay, and <0.5 log10cp/mL versus VERSANT HIV-1 Assay. Analysis on 174 specimens tested with the 0.175mL volume VERIS HIV-1 Assay and COBAS HIV-1 Test showed average bias of 0.39 log10cp/mL. Patient monitoring results using VERIS HIV-1 Assay demonstrated similar viral load trends over time to all comparators. CONCLUSIONS: The VERIS HIV-1 Assay for use on the DxN VERIS System demonstrated comparable clinical performance to COBAS® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay.

European Multicenter Study on Analytical Performance of Veris HIV-1 Assay.

The analytical performance of the Veris HIV-1 assay for use on the new, fully automated Beckman Coulter DxN Veris molecular diagnostics system was evaluated at 10 European virology laboratories. The precision, analytical sensitivity, performance with negative samples, linearity, and performance with HIV-1 groups/subtypes were evaluated. The precision for the 1-ml assay showed a standard deviation (SD) of 0.14 log10 copies/ml or less and a coefficient of variation (CV) of ≤6.1% for each level tested. The 0.175-ml assay showed an SD of 0.17 log10 copies/ml or less and a CV of ≤5.2% for each level tested. The analytical sensitivities determined by probit analysis were 19.3 copies/ml for the 1-ml assay and 126 copies/ml for the 0.175-ml assay. The performance with 1,357 negative samples demonstrated 99.2% with not detected results. Linearity using patient samples was shown from 1.54 to 6.93 log10 copies/ml. The assay performed well, detecting and showing linearity with all HIV-1 genotypes tested. The Veris HIV-1 assay demonstrated analytical performance comparable to that of currently marketed HIV-1 assays. (DxN Veris products are Conformité Européenne [CE]-marked in vitro diagnostic products. The DxN Veris product line has not been submitted to the U.S. FDA and is not available in the U.S. market. The DxN Veris molecular diagnostics system is also known as the Veris MDx molecular diagnostics system and the Veris MDx system.).

A European multicentre study on the comparison of HCV viral loads between VERIS HCV assay and COBAS® TaqMan® HCV Test and RealTime HCV Assay.

BACKGROUND: Beckman Coulter has developed the VERIS HCV Assay for use on the new fully automated DxN VERIS Molecular Diagnostic System¥ for HCV viral load monitoring. OBJECTIVES: Evaluate the clinical performance of the new quantitative VERIS HCV Assay. STUDY DESIGN: Comparison was performed on 279 plasma specimens from HCV infected patients tested with the VERIS HCV Assay and COBAS® Ampliprep/COBAS® Taqman® HCV Test and 369 specimens tested with the VERIS HCV Assay and RealTime HCV Assay. Patient monitoring sample results from four time points were also compared. RESULTS: The average bias between the VERIS HCV Assay and the COBAS® Ampliprep/COBAS® Taqman® HCV Test was 0.04 log10IU/mL, while between the VERIS HCV Assay and the RealTime HCV Assay average bias was 0.21 log10IU/mL. Bias, however, was not consistent across the measuring range. Analysis at the lower end of quantification levels 50, 100, and 1000IU/mL showed a predicted bias for VERIS HCV Assay versus COBAS® Ampliprep/COBAS® Taqman® HCV Test between -0.42 and -0.22 log10IU/mL and for VERIS HCV Assay versus RealTime HCV Assay between 0.00 and 0.13 log10IU/mL. Patient monitoring of HCV viral load over time demonstrated similar levels between VERIS HCV Assay results and COBAS® Ampliprep/COBAS® Taqman® HCV Test (52 samples from 13 patients) and RealTime HCV Assay (112 samples from 28 patients). CONCLUSIONS: VERIS HCV Assay for use on the DxN VERIS Molecular Diagnostic System represents a reliable new tool for easy sample to result HCV RNA viral load monitoring.

European Multicenter Study on Analytical Performance of DxN Veris System HCV Assay.

The analytical performance of the Veris HCV Assay for use on the new and fully automated Beckman Coulter DxN Veris Molecular Diagnostics System (DxN Veris System) was evaluated at 10 European virology laboratories. Precision, analytical sensitivity, specificity, and performance with negative samples, linearity, and performance with hepatitis C virus (HCV) genotypes were evaluated. Precision for all sites showed a standard deviation (SD) of 0.22 log10 IU/ml or lower for each level tested. Analytical sensitivity determined by probit analysis was between 6.2 and 9.0 IU/ml. Specificity on 94 unique patient samples was 100%, and performance with 1,089 negative samples demonstrated 100% not-detected results. Linearity using patient samples was shown from 1.34 to 6.94 log10 IU/ml. The assay demonstrated linearity upon dilution with all HCV genotypes. The Veris HCV Assay demonstrated an analytical performance comparable to that of currently marketed HCV assays when tested across multiple European sites.

Monitoring of brain oxygenation during hypothermic CPR - A prospective porcine study.

BACKGROUND AND AIM: Limited data are available concerning the impact of CPR interventions on cerebral oxygenation during hypothermic cardiac arrest. We therefore studied cerebral perfusion pressure (CPP), brain tissue oxygen tension (PbtO2), cerebral venous oxygen saturation (ScvO2) and regional cerebral oxygen saturation (rSO2) in an animal model of hypothermic CPR. We also assessed the correlation between rSO2 and CPP, PbtO2 and ScvO2 to clarify whether near-infrared spectroscopy (NIRS) may be used to non-invasively monitor changes in cerebral oxygenation during hypothermic CPR. METHODS: Nine pigs were surface-cooled to a core temperature of 28°C and underwent a period of asphyxia before cardiac arrest was induced. After 2min of untreated cardiac arrest they were resuscitated for 45min. CPP, PbtO2, ScvO2 and rSO2 were monitored after periods of stable external chest compression, a short interruption of CPR and after epinephrine administration. RESULTS: During external chest-compressions before adrenalin administration CPP, PbtO2, ScvO2 and rSO2 increased in parallel and changes in rSO2 closely correlated with changes in CPP (r=.844; p<.001) and ScvO2 (r=.868; p<.001). After adrenaline administration CPP and PbtO2 increased, ScvO2 decreased and rSO2 values did not change and there was no significant correlation between rSO2 and CPP, PbtO2, or ScvO2. CONCLUSION: In this animal model of hypothermic cardiac arrest adrenaline was associated with an increase in global cerebral oxygen extraction despite an increase in CPP. Discrepancies in the time course of PbtO2 and ScvO2 suggest differences in regional oxygen metabolism after adrenalin. rSO2 values correlated closely with CPP and ScvO2 only during periods of external chest compression without adrenaline administration.

Effects of Stomach Inflation on Cardiopulmonary Function and Survival During Hemorrhagic Shock: A Randomized, Controlled, Porcine Study.

BACKGROUND: Ventilation of an unprotected airway may result in stomach inflation. The purpose of this study was to evaluate the effect of clinically realistic stomach inflation on cardiopulmonary function during hemorrhagic shock in a porcine model. METHODS: Pigs were randomized to a sham control group (n = 9), hemorrhagic shock (35 mL kg over 15 min [n = 9]), and hemorrhagic shock combined with stomach inflation (35 mL kg over 15 min and 5 L stomach inflation [n = 10]). RESULTS: When compared with the control group, hemorrhagic shock (n = 9) increased heart rate (103 ±â€Š11 vs. 146 ±â€Š37 beats min; P = 0.002) and lactate (1.4 ±â€Š0.5 vs. 4.0 ±â€Š1.9 mmol L; P < 0.001), and decreased mean arterial blood pressure (81.3 ±â€Š12.8 vs. 35.4 ±â€Š8.1 mmHg; P < 0.001) and stroke-volume index (38.1 ±â€Š6.4 vs. 13.6 ±â€Š4.8 mL min m; P < 0.001). Hemorrhagic shock combined with stomach inflation (n = 10) versus hemorrhagic shock only (n = 9) increased intra-abdominal pressure (27.0 ±â€Š9.3 vs. 1.1 ±â€Š1.0 mmHg; P < 0.001), and decreased stroke-volume index (9.9 ±â€Š6.0 vs. 20.8 ±â€Š8.5 mL min m; P = 0.007), and dynamic respiratory system compliance (10.8 ±â€Š4.5 vs. 38.1 ±â€Š6.1 mL cmH2O; P < 0.001). Before versus after stomach evacuation during hemorrhagic shock, intra-abdominal pressure decreased (27.0 ±â€Š9.3 vs. 9.8 ±â€Š5.4 mmHg; P = 0.042). Survival in the sham control and hemorrhagic shock group was 9 of 9, respectively, and 3 of 10 after hemorrhagic shock and stomach inflation (P < 0.001). CONCLUSIONS: During hemorrhagic shock stomach inflation caused an abdominal compartment syndrome and thereby impaired cardiopulmonary function and aerobic metabolism, and increased mortality. Subsequent stomach evacuation partly reversed adverse stomach-inflation triggered effects.

Manual versus Mechanical Chest Compressions on Surfaces of Varying Softness with or without Backboards: A Randomized, Crossover Manikin Study.

BACKGROUND: Chest compression quality is decisive for overall outcome after cardiac arrest. Chest compression depth may decrease when cardiopulmonary resuscitation (CPR) is performed on a mattress, and the use of a backboard does not necessarily improve compression depth. Mechanical chest compression devices may overcome this problem. OBJECTIVES: We sought to investigate the effectiveness of manual chest compressions both with and without a backboard compared to mechanical CPR performed on surfaces of different softness. METHODS: Twenty-four advanced life support (ALS)-certified rescuers were enrolled. LUCAS2 (Physio-Control, Redmond, WA) delivers 52 ± 2 mm deep chest compressions and active decompressions back to the neutral position (frequency 102 min(-1); duty cycle, 50%). This simulated CPR scenario was performed on a Resusci-Anne manikin (Laerdal, Stavanger, Norway) that was lying on 3 different surfaces: 1) a concrete floor, 2) a firm standard mattress, and 3) a pressure-relieving mattress. Data were recorded by the Laerdal Skill Reporting System. RESULTS: Manual chest compression with or without a backboard were performed correctly less often than mechanical chest compressions (floor: 33% [interquartile range {IQR}, 27-48%] vs. 90% [IQR, 86-94%], p < 0.001; standard mattress: 32% [IQR, 20-45%] vs. 27% [IQR, 14-46%] vs. 91% [IQR, 51-94%], p < 0.001; and pressure-relieving mattress 29% [IQR, 17-49%] vs. 30% [IQR, 17-52%] vs. 91% [IQR, 87-95%], p < 0.001). The mean compression depth on both mattresses was deeper with mechanical chest compressions (floor: 53 mm [range, 47-57 mm] vs. 56 mm [range, 54-57 mm], p = 0.003; standard mattress: 50 mm [range, 44-55 mm] vs. 51 mm [range, 47-55 mm] vs. 55 mm [range, 54-58 mm], p < 0.001; and pressure-relieving mattress: 49 mm [range, 44-55 mm] vs. 50 mm [range, 44-53 mm] vs. 55 mm [range, 55-56 mm], p < 0.001). In this ∼6-min scenario, the mean hands-off time was ∼15 to 20 s shorter in the manual CPR scenarios. CONCLUSIONS: In this experimental study, only ∼30% of manual chest compressions were performed correctly compared to ∼90% of mechanical chest compressions, regardless of the underlying surface. Backboard use did not influence the mean compression depth during manual CPR. Chest compressions were deeper with mechanical CPR. The mean hands-off time was shorter with manual CPR.

A dual-use laryngoscope to facilitate apneic oxygenation.

BACKGROUND: In preoxygenated patients, time until oxygen saturation drops can be extended by insufflating oxygen into their airways, thus oxygenating them apneically. OBJECTIVES: To compare different methods of apneic oxygenation. METHODS: A noncommercial dual-use laryngoscope with an internal lumen in its blade was used to provide oxygen insufflation into a simulated laryngeal space during intubation. In this experimental study, oxygen insufflation via the dual-use laryngoscope was compared with no oxygen insufflation, with nasal oxygen insufflation, and with direct intratracheal oxygen insufflation. In a preoxygenated test lung of a manikin, oxygen percentage decrease was measured over a 20-min observation period for each method of oxygen application. RESULTS: Oxygen percentage in the test lung dropped from 97% to 37 ± 1% in the control group (p < 0.001 compared to all other groups) and to 68 ± 1% in the nasal insufflation group (p < 0.001 compared to all other groups). Oxygen percentage remained over 90% in both the direct intratracheal insufflation group (96 ± 0%) and the laryngoscope blade insufflation group (94 ± 1%) (p < 0.01 between the latter two groups). CONCLUSIONS: Simulating apneic oxygenation in a preoxygenated manikin, deep laryngeal oxygen insufflation via the dual-use laryngoscope kept oxygen percentage in the test lung above 90%, and was more effective than oxygen insufflation via nasal prongs.

The TLQP-21 peptide activates the G-protein-coupled receptor C3aR1 via a folding-upon-binding mechanism.

TLQP-21, a VGF-encoded peptide is emerging as a novel target for obesity-associated disorders. TLQP-21 is found in the sympathetic nerve terminals in the adipose tissue and targets the G-protein-coupled receptor complement-3a receptor1 (C3aR1). The mechanisms of TLQP-21-induced receptor activation remain unexplored. Here, we report that TLQP-21 is intrinsically disordered and undergoes a disorder-to-order transition, adopting an α-helical conformation upon targeting cells expressing the C3aR1. We determined that the hot spots for TLQP-21 are located at the C terminus, with mutations in the last four amino acids progressively reducing the bioactivity and, a single site mutation (R21A) or C-terminal amidation abolishing its function completely. Additionally, the human TLQP-21 sequence carrying a S20A substitution activates the human C3aR1 receptor with lower potency compared to the rodent sequence. These studies reveal the mechanism of action of TLQP-21 and provide molecular templates for designing agonists and antagonists to modulate C3aR1 functions.

Low level HIV viremia is more frequent under protease-inhibitor containing firstline therapy than under NNRTI-regimens.

INTRODUCTION: An association of persistent low level viremia (LLV) below 500 copies/mL and a higher risk of therapy failure is still point of controversial discussion. Furthermore, it seems that LLV occurs more frequently in patients with protease-inhibitor regimens than in NNRTI- / or integrase-inhibitor containing therapies. The focus of this work was to assess the prevalence of LLV (50-200 copies/mL) and weak viremia (201-500 copies/mL) in firstline-treated patients according to their therapy regimen. METHODS: A total of 832 and 944 patients from 23 German centres were under firstline therapy in 2012 and 2013, respectively. All patients received their therapy for more than 24 weeks. VL data was related to clinical data retrospectively including ART-composition, subdivided into NNRTIs (Efavirenz, Nevirapine), PIs (Atazanavir, Darunavir, Lopinavir) and INIs (Raltegravir). Low viremic patients were classified into two arms of 50-200 copies/mL (group A) and 201-500 copies/mL (group B). RESULTS: Success of therapy was defined as <50 copies/mL and was observed in 90.0% and 91.1% (2012/2013), respectively. An additional 2.0% and 2.3% had LLV. The amount of viremic patients with VLs <500 copies/mL differed significantly between NNRTI-based firstline regimens 1.7% and 2.5% and PI-based regimens 4.8% and 5.7% (2012/2013), respectively. LLV was clearly less often observed in EFV-based- (1.6% and 1.1% [group A] / 0.4% and 0.4% [group B]) or NVP-based firstline therapies (1.0% and 3.6% [group A] + 0% and 0% [group B]) than in ATV-based- (7.5% and 3.8% [group A] + 1.5% and 2.5% [group B]), DRV-based- (2.9% and 3.0% [group A] + 2.2% and 0% [group B]) or LPV-based firstline therapies (1.6% and 3.3% [group A] + 0.8% and 2.5% [group B]) and also in parts for RAL-based regimens (0% and 3.7% [group A] + 0% and 1.9% [group B]). CONCLUSIONS: LLV is more often observed under PI-based firstline than under NNRTI-regimens. Only one NNRTI-patient of group B remained on therapy. A possible explanation for this discrepancy might be the fact that physicians seem to tolerate LLV more often in PI-regimens than in NNRTI-regimens due to a higher genetic barrier against resistance and it remains a point of discussion if constant LLV does affect immune recovery and risk of therapy failure.