Malolactic Fermentation Sensor Development Project

Malolactic fermentation (MLF) is commonly carried out in winemaking as a tool for deacidification, altering the sensory profile and increasing the microbial stability of a wine. MLF must be monitored and sometimes stopped so as to prevent unwanted microbial spoilage. Current methods for monitoring MLF are both expensive and labor intensive and a low cost automated sensor could be of practical relevance for the wine industry. Due to the different densities of malic acid and lactic acid, density measurements could be used to monitor MLF. This multifaceted project involved two key studies, a study of density during MLF in a Zinfandel wine and a study of the pressure tube density meter during MLF. The goal of the study of density during MLF in a Zinfandel wine was to determine if a correlation between malic acid concentration and density exists and to write a predictive curve which can be used to determine malic acid concentration from density measurements. The goal of the study of the pressure tube density meter during MLF was to assess the sensitivity, compatibility and potential for adapting the pressure tube technology used in Cypress Semiconductor’s Integrated Fermentation Control System (IFCS) to monitor malic acid concentration during MLF with a density derived predictive curve. Daily samples were taken from three replicate 208 Liter fermenters and analyzed for density and L-malic acid concentration in a laboratory setting for the duration of MLF of a Zinfandel wine. The regression models fit to the data did not show evidence of a correlation between malic acid concentration and density with the coefficient of determination for each fermenter being R2Tank1 = 0.01092, R2Tank2 = 0.00085, R2Tank3= 0.01826 and R2Tank_all = 2.082-5. The high standard deviations in density for each data set (SDTank1 = 0.0051, SDTank2 = 0.0038, SDTank3 = 0.0046 and SDTank_all = 0.0045) implied a lack of sensitivity in testing methodology due to a volumetric variation not accounted for in density calculations. The data collection software disconnected from the IFCS units during alcoholic fermentation, halting data collection. Without data collection, it was impossible to assess the capabilities of the IFCS as a MLF sensor

In situ bending of thoracic stent grafts: Clinical application of a novel technique to improve conformance to the aortic arch

PurposeA straight thoracic stent graft often complies poorly with the curvature of the aortic arch. We have previously reported an in vitro model of a modified stent graft that can be bent in situ after deployment to improve conformance to the aortic arch. We now report the first clinical experience with this technique in three consecutive patients.MethodsBetween September 2007 and August 2008, three patients were treated for different pathologies of the aortic arch with a modified thoracic stent graft that was fitted with a sliding self-locking knot and a detachable Bowden cable. Transfemoral traction on the Bowden cable enables controlled shortening of the proximal part of the stent graft at the inner curve after deployment. The stent graft is thereby directed to allow for better apposition to the aortic wall.ResultsThe modified thoracic stent grafts were correctly orientated and deployed in all patients. Transfemoral traction on the Bowden cable successfully bent all stent grafts and improved vessel wall apposition without a residual gap on the inner curve. The Bowden cable was successfully released and withdrawn in all patients.ConclusionIn situ bending of thoracic stent grafts with a sliding self-locking knot is feasible and improves proximal apposition of the device at the inner curve of the aortic arch. More data and longer follow-up are required to confirm the applicability of this technique

Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting:systematic review and meta-analysis

Objective To compare patient outcomes of restrictive versus liberal blood transfusion strategies in patients with cardiovascular disease not undergoing cardiac surgery. Design Systematic review and meta-analysis. Data sources Randomised controlled trials involving a threshold for red blood cell transfusion in hospital. We searched (to 2 November 2015) CENTRAL, Medline, Embase, CINAHL, PubMed, LILACS, NHSBT Transfusion Evidence Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ISRCTN Register, and EU Clinical Trials Register. Authors were contacted for data whenever possible. Trial selection Published and unpublished randomised controlled trials comparing a restrictive with liberal transfusion threshold and that included patients with cardiovascular disease. Data extraction and synthesis Data extraction was completed in duplicate. Risk of bias was assessed using Cochrane methods. Relative risk ratios with 95% confidence intervals were presented in all meta-analyses. Mantel-Haenszel random effects models were used to pool risk ratios. Main outcome measures 30 day mortality, and cardiovascular events. Results 41 trials were identified; of these, seven included data on patients with cardiovascular disease. Data from a further four trials enrolling patients with cardiovascular disease were obtained from the authors. In total, 11 trials enrolling patients with cardiovascular disease (n=3033) were included for meta-analysis (restrictive transfusion, n=1514 patients; liberal transfusion, n=1519). The pooled risk ratio for the association between transfusion thresholds and 30 day mortality was 1.15 (95% confidence interval 0.88 to 1.50, P=0.50), with little heterogeneity (I(2)=14%). The risk of acute coronary syndrome in patients managed with restrictive compared with liberal transfusion was increased (nine trials; risk ratio 1.78, 95% confidence interval 1.18 to 2.70, P=0.01, I(2)=0%). Conclusions The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease. Effects on mortality and other outcomes are uncertain. These data support the use of a more liberal transfusion threshold (>80 g/L) for patients with both acute and chronic cardiovascular disease until adequately powered high quality randomised trials have been undertaken in patients with cardiovascular disease. Registration PROSPERO CRD42014014251

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Background Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. Methods We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction. Results There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m2 [95% confidence interval (95% CI): −0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m2 (95% CI: 0.13-0.31) lower BMI (P = 8 × 10−6). The effect size was larger in current [0.33 kg/m2 lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10−5], than in former smokers [0.16 kg/m2 (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001). Conclusions Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BM

In Vitro Pharmacological Characterization of RXFP3 Allosterism: An Example of Probe Dependency

Recent findings suggest that the relaxin-3 neural network may represent a new ascending arousal pathway able to modulate a range of neural circuits including those affecting circadian rhythm and sleep/wake states, spatial and emotional memory, motivation and reward, the response to stress, and feeding and metabolism. Therefore, the relaxin-3 receptor (RXFP3) is a potential therapeutic target for the treatment of various CNS diseases. Here we describe a novel selective RXFP3 receptor positive allosteric modulator (PAM), 3-[3,5-Bis(trifluoromethyl)phenyl]-1-(3,4-dichlorobenzyl)-1-[2-(5-methoxy-1H-indol-3-yl)ethyl]urea (135PAM1). Calcium mobilization and cAMP accumulation assays in cell lines expressing the cloned human RXFP3 receptor show the compound does not directly activate RXFP3 receptor but increases functional responses to amidated relaxin-3 or R3/I5, a chimera of the INSL5 A chain and the Relaxin-3 B chain. 135PAM1 increases calcium mobilization in the presence of relaxin-3NH2 and R3/I5NH2 with pEC50 values of 6.54 (6.46 to 6.64) and 6.07 (5.94 to 6.20), respectively. In the cAMP accumulation assay, 135PAM1 inhibits the CRE response to forskolin with a pIC50 of 6.12 (5.98 to 6.27) in the presence of a probe (10 nM) concentration of relaxin-3NH2. 135PAM1 does not compete for binding with the orthosteric radioligand, [125I] R3I5 (amide), in membranes prepared from cells expressing the cloned human RXFP3 receptor. 135PAM1 is selective for RXFP3 over RXFP4, which also responds to relaxin-3. However, when using the free acid (native) form of relaxin-3 or R3/I5, 135PAM1 doesn't activate RXFP3 indicating that the compound's effect is probe dependent. Thus one can exchange the entire A-chain of the probe peptide while retaining PAM activity, but the state of the probe's c-terminus is crucial to allosteric activity of the PAM. These data demonstrate the existence of an allosteric site for modulation of this GPCR as well as the subtlety of changes in probe molecules that can affect allosteric modulation of RXFP3

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Anaemia and blood transfusion in the critically ill patient with cardiovascular disease

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901

Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC):The Hot Start experience

A fast track “Hot Start” process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community. These were implemented to create a quality managed foundational collection of lines and associated data made available for distribution. Here we report on the successful outcome of this experience and work flow for banking and facilitating access to an otherwise disparate European resource, with lessons to benefit the international research community. eTOC: The report focuses on the EBiSC experience of rapidly establishing an operational capacity to procure, bank and distribute a foundational collection of established hiPSC lines. It validates the feasibility and defines the challenges of harnessing and integrating the capability and productivity of centres across Europe using commonly available resources currently in the field

AEDGE: Atomic Experiment for Dark Matter and Gravity Exploration in Space

Abstract: We propose in this White Paper a concept for a space experiment using cold atoms to search for ultra-light dark matter, and to detect gravitational waves in the frequency range between the most sensitive ranges of LISA and the terrestrial LIGO/Virgo/KAGRA/INDIGO experiments. This interdisciplinary experiment, called Atomic Experiment for Dark Matter and Gravity Exploration (AEDGE), will also complement other planned searches for dark matter, and exploit synergies with other gravitational wave detectors. We give examples of the extended range of sensitivity to ultra-light dark matter offered by AEDGE, and how its gravitational-wave measurements could explore the assembly of super-massive black holes, first-order phase transitions in the early universe and cosmic strings. AEDGE will be based upon technologies now being developed for terrestrial experiments using cold atoms, and will benefit from the space experience obtained with, e.g., LISA and cold atom experiments in microgravity. KCL-PH-TH/2019-65, CERN-TH-2019-12