Review of CGIAR Research Programs Governance and Management: Final Report

The Review of CGIAR Research Program Governance and Management was requested by the CGIAR Consortium and approved by the Fund Council in November 2012. The Independent Evaluation Arrangement (IEA) is responsible for the review, which was carried out between June 2013 and January 2014. At the time the review was initiated, Consortium Research Programs (CRP) governance and management structures were in place or approved for each CRP. This enabled the review to “take stock of experience so far, identify issues and provide lessons from existing CRPs and elsewhere which can be applicable to other CRPs” (Annex 1, Review Terms of Reference)

Volumetric preload measurement by thermodilution: a comparison with transoesophageal echocardiography

Background. End-diastolic volume indices determined by transpulmonary thermodilution and pulmonary artery thermodilution may give a better estimate of left ventricular preload than pulmonary capillary wedge pressure monitoring. The aim of this study was to compare volume preload monitoring using the two different thermodilution techniques with left ventricular preload assessment by transoesophageal echocardiography (TOE). Methods. Twenty patients undergoing elective cardiac surgery with preserved left-right ventricular function were studied after induction of anaesthesia. Conventional haemodynamic variables, global end-diastolic volume index using the pulse contour cardiac output (PiCCO) system (GEDVIPiCCO), continuous end-diastolic volume index (CEDVIPAC) measured by a modified pulmonary artery catheter (PAC), left ventricular end-diastolic area index (LVEDAI) using TOE and stroke volume indices (SVI) were recorded before and 20 and 40 min after fluid replacement therapy. Analysis of variance (Bonferroni-Dunn), Bland-Altman analysis and linear regression were performed. Results. GEDVIPiCCO, CEDVIPAC, LVEDAI and SVIPiCCO/PAC increased significantly after fluid load (P10% for GEDVIPiCCO and LVEDAI was observed in 85% and 90% of the patients compared with 45% for CEDVIPAC. Mean bias (2 sd) between percentage changes (Δ) in GEDVIPiCCO and ΔLVEDAI was −3.2 (17.6)% and between ΔCEDVIPAC and ΔLVEDAI −8.7 (30.0)%. The correlation coefficient (r2) for ΔGEDVIPiCCO vs ΔLVEDAI was 0.658 and for ΔCEDVIPAC vs ΔLVEDAI 0.161. The relationship between ΔGEDVIPiCCO and ΔSVIPiCCO was stronger (r2=0.576) than that between ΔCEDVIPAC and ΔSVIPAC (r2=0.267). Conclusion. GEDVI assessed by the PiCCO system gives a better reflection of echocardiographic changes in left ventricular preload, in response to fluid replacement therapy, than CEDVI measured by a modified PA

Patient well‐being after general anaesthesia: a prospective, randomized, controlled multi‐centre trial comparing intravenous and inhalation anaesthesia

Background. The aim of this study was to assess postoperative patient well‐being after total i.v. anaesthesia compared with inhalation anaesthesia by means of validated psychometric tests. Methods. With ethics committee approval, 305 patients undergoing minor elective gynaecologic or orthopaedic interventions were assigned randomly to total i.v. anaesthesia using propofol or inhalation anaesthesia using sevoflurane. The primary outcome measurement was the actual mental state 90 min and 24 h after anaesthesia assessed by a blinded observer using the Adjective Mood Scale (AMS) and the State‐Trait‐Anxiety Inventory (STAI). Incidence of postoperative nausea and vomiting (PONV) and postoperative pain level were determined by Visual Analogue Scale (VAS) 90 min and 24 h after anaesthesia (secondary outcome measurements). Patient satisfaction was evaluated using a VAS 24 h after anaesthesia. Results. The AMS and STAI scores were significantly better 90 min after total i.v. anaesthesia compared with inhalation anaesthesia (P=0.02, P=0.05, respectively), but equal 24 h after both anaesthetic techniques (P=0.90, P=0.78, respectively); patient satisfaction was comparable (P=0.26). Postoperative pain was comparable in both groups 90 min and 24 h after anaesthesia (P=0.11, P=0.12, respectively). The incidence of postoperative nausea was reduced after total i.v. compared with inhalation anaesthesia at 90 min (7 vs 35%, P<0.001), and 24 h (33 vs 52%, P=0.001). Conclusion. Total i.v. anaesthesia improves early postoperative patient well‐being and reduces the incidence of PONV. Br J Anaesth 2003; 91: 631-

Laser performance of perylenebis (dicarboximide) dyes with long secondary alkyl chains

The laser performance and related photophysical properties of two very soluble perylene dyes with long chain secondary alkyl groups were investigated in cyclohexane solution. With a dye laser as pump source a tuning range of 555–580 nm was obtained at an optimum concentration of 3×10–4 M. The quantum efficiencies (=0.29 and 0.21) were better than 1/2 that of rhodamine 6G. No photodegradation was observed over an excitation period of several hours

Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome

With a mortality rate of 46% before the onset of COVID-19, acute respiratory distress syndrome (ARDS) affected 200,000 people in the US, causing 75,000 deaths. Mortality rates in COVID-19 ARDS patients are currently at 39%. Extrapulmonary support for ARDS aims to supplement mechanical ventilation by providing life-sustaining oxygen to the patient. A new rapid-onset, human-sized pig ARDS model in a porcine intensive care unit (ICU) was developed. The pigs were nebulized intratracheally with a high dose (4 mg/kg) of the endotoxin lipopolysaccharide (LPS) over a 2 h duration to induce rapid-onset moderate-to- severe ARDS. They were then catheterized to monitor vitals and to evaluate the therapeutic effect of oxygenated microbubble (OMB) therapy delivered by intrathoracic (IT) or intraperitoneal (IP) administration. Post-LPS administration, the PaO2 value dropped below 70 mmHg, the PaO2/FiO2 ratio dropped below 200 mmHg, and the heart rate increased, indicating rapidly developing (within 4 h) moderate-to- severe ARDS with tachycardia. The SpO2 and PaO2 of these LPS-injured pigs did not show significant improvement after OMB administration, as they did in our previous studies of the therapy on small animal models of ARDS injury. Furthermore, pigs receiving OMB or saline infusions had slightly lower survival than their ARDS counterparts. The OMB administration did not induce a statistically significant or clinically relevant therapeutic effect in this model; instead, both saline and OMB infusion appeared to lower survival rates slightly. This result is significant because it contradicts positive results from our previous small animal studies and places a limit on the efficacy of such treatments for larger animals under more severe respiratory distress. While OMB did not prove efficacious in this rapid-onset ARDS pig model, it may retain potential as a novel therapy for the usual presentation of ARDS in humans, which develops and progresses over days to weeks

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base

Biocatalyzed C-C bond formation for the production of alkaloids

Traditional methods of chemical synthesis of alkaloids exhibit various problems such as lack of enantioselectivity, the use of toxic chemical and intermediates, and multiple numbers of synthetic steps. Consequently, various enzymatic methods for the formation of C-C bonds in the alkaloid skeleton have been developed. Herein, we report advances achieved in the enzymatic or chemo-enzymatic synthesis of pharmaceutically important alkaloids that employ three C-C bond forming enzymes: two Pictet-Spenglerases and the oxidative C-C bond forming flavoenzyme Berberine Bridge Enzyme. Protein engineering studies, improving the substrate scope of these enzymes, and thereby leading to the synthesis of non-natural alkaloids possessing higher or newer pharmacological activities, are also discussed. Furthermore, the integration of these biocatalysts with other enzymes, in multi-enzymatic cascades for the enantioselective synthesis of alkaloids, is also reviewed. Current results suggest that these enzymes hold great promise for the generation of C-C bonds in the selective synthesis of alkaloid compounds possessing diverse pharmacological properties

Patient well-being after general anaesthesia: a prospective, randomized, controlled multi-centre trial comparing intravenous and inhalation anaesthesia

Background. The aim of this study was to assess postoperative patient well‐being after total i.v. anaesthesia compared with inhalation anaesthesia by means of validated psychometric tests. Methods. With ethics committee approval, 305 patients undergoing minor elective gynaecologic or orthopaedic interventions were assigned randomly to total i.v. anaesthesia using propofol or inhalation anaesthesia using sevoflurane. The primary outcome measurement was the actual mental state 90 min and 24 h after anaesthesia assessed by a blinded observer using the Adjective Mood Scale (AMS) and the State‐Trait‐Anxiety Inventory (STAI). Incidence of postoperative nausea and vomiting (PONV) and postoperative pain level were determined by Visual Analogue Scale (VAS) 90 min and 24 h after anaesthesia (secondary outcome measurements). Patient satisfaction was evaluated using a VAS 24 h after anaesthesia. Results. The AMS and STAI scores were significantly better 90 min after total i.v. anaesthesia compared with inhalation anaesthesia (P=0.02, P=0.05, respectively), but equal 24 h after both anaesthetic techniques (P=0.90, P=0.78, respectively); patient satisfaction was comparable (P=0.26). Postoperative pain was comparable in both groups 90 min and 24 h after anaesthesia (P=0.11, P=0.12, respectively). The incidence of postoperative nausea was reduced after total i.v. compared with inhalation anaesthesia at 90 min (7 vs 35%, P<0.001), and 24 h (33 vs 52%, P=0.001). Conclusion. Total i.v. anaesthesia improves early postoperative patient well‐being and reduces the incidence of PONV. Br J Anaesth 2003; 91: 631-