pH-gradient chromatofocusing of proteins on a chip

We present a novel microfluidic system for the pH-gradient focusing of proteins with the integration of 16 parallel micro-mixers, a micro-column, and a multiplexer. In this work we successfully achieved the creation of 16 non-linear gradients and the generation of a solid-phase micro-column for the realization of anion exchange chromatography on a single chip. With the device we demonstrated the separation of a protein mixture of R-phycoerythrin and FITC-BSA based on pH-gradient chromatofocusing

FRODO 2.0: An Open-Source Framework for Distributed Constraint Optimization

Distributed Constraint Optimization (DCOP) is a field that has recently been getting more and more attention from academia and industry. However, very few open-source, off-the-shelf tools are currently available to solve DCOPs; examples are FRODO, DisChoco and DCOPolis. A DCOP platform should possess the following key qualities: the framework should be reliable and extensively tested, deployable in a truly distributed setting, and modular so that it is easy to customize and extend. This paper introduces the Java-based FRODO 2.0 framework, which possesses all three qualities. It is a complete re-design of the FRODO framework, released under the GNU Affero GPL license

FRODO: An Open-Source Framework for Distributed Constraint Optimization

Distributed Constraint Optimization (DCOP) is a field that has recently been getting more and more attention from academia and industry. However, very few open-source, off-the-shelf tools are currently available to solve DCOPs; examples are FRODO, DisChoco and DCOPolis. A DCOP platform should possess the following key qualities: the framework should be reliable and extensively tested, deployable in a truly distributed setting, and modular so that it is easy to customize and extend. This poster presents the Java-based FRODO 2.0 framework, which possesses all three qualities. It is a complete re-design of the FRODO framework, released under the GNU Affero GPL license

Association of obesity, diabetes and hypertension with cognitive impairment in older age

Background: Age-related cognitive impairment is rising in prevalence but is not yet fully characterized in terms of its epidemiology. Here, we aimed to elucidate the role of obesity, diabetes and hypertension as candidate risk factors. Methods: Original baseline data from 3 studies (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis of cross-sectional associations of diabetes, hypertension, blood pressure, obesity (body mass index [BMI] ≥30 kg/m²) and BMI with presence of cognitive impairment in log-binomial regression analyses. Cognitive impairment was defined as scoring more than 2 standard deviations below controls on at least one of 5–11 cognitive tests. Underweight participants (BMI<18.5 kg/m2 ) were excluded. Results were pooled across studies in fixed-effects inverse variance models. Results: Analyses totaled 1545 participants with a mean age of 61 years (OCTOPUS) to 70 years (SuDoCo). Cognitive impairment was found in 29.0% of participants in DECS, 8.2% in SuDoCo and 45.6% in OCTOPUS. In pooled analyses, after adjustment for age, sex, diabetes and hypertension, obesity was associated with a 1.29-fold increased prevalence of cognitive impairment (risk ratio [RR] 1.29; 95% CI 0.98, 1.72). Each 1 kg/m² increment in BMI was associated with 3% increased prevalence (RR 1.03; 95% CI 1.00, 1.06). None of the remaining risk factors were associated with impairment. Conclusion: Our results show that older people who are obese have higher prevalence of cognitive impairment compared with normal weight and overweight individuals, and independently of co-morbid hypertension or diabetes. Prospective studies are needed to investigate the temporal relationship of the association

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control: A randomized controlled trial

Introduction: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. Methods: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol-Glucose Regulation for Intensive care Patients (GRIP

Effect of high-dose dexamethasone on perioperative lactate levels and glucose control:a randomized controlled trial

INTRODUCTION: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. METHODS: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol--Glucose Regulation for Intensive care Patients (GRIP)--was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC₁₅). ICU length of stay and mortality were observed as well. RESULTS: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC₁₅ 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC₁₅ 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). CONCLUSIONS: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. TRIAL REGISTRATION: ClinicalTrials.gov NCT00293592 . Registered 16 February 2006

Rapid Response to Remdesivir in Hospitalised COVID-19 Patients:A Propensity Score Weighted Multicentre Cohort Study

Introduction: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients’ respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. Methods: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. Results: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79–1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48–1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (&lt; 7 days) (OR 2.84, 95% CI 1.07–7.56). Conclusion: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.</p

Surface water temperature, salinity, and density changes in the northeast Atlantic during the last 45,000 years: Heinrich events, deep water formation, and climatic rebounds

We developed a new method to calculate sea surface salinities (SSS) and densities (SSD) from planktonic foraminiferal delta(18)O and sea surface temperatures (SST) as determined from planktonic foraminiferal species abundances. SST, SSS, and SSD records were calculated for the last 45,000 years for Biogeochemical Oceanic Flux Study (BOFS) cores 5K and 8K recovered from the northeast Atlantic. The strongest feature is the dramatic drop in all three parameters during the Heinrich ''ice-rafting'' events. We modelled the possibility of deepwater formation in the northeast Atlantic from the SSD records, by assuming that the surface waters at our sites cooled as they flowed further north. Comparison with modelled North Atlantic deepwater densities indicates that there could have been periods of deepwater formation between 45,000 and 30,000 C-14 years B.P. (interrupted by iceberg meltwater input of Heinrich event 3 and 4, at 27,000 and 38,000 C-14 years B.P.) and during the Holocene. No amount of cooling in the northeast Atlantic between 30,000 and 13,000 years could cause deep water to form, because of the low salinities resulting from the high meltwater inputs from icebergs. Our records indicate that after each Heinrich event there were periods of climatic rebound, with milder conditions persisting for up to 2000 years, as indicated by the presence of warmer and more saline water masses. After these warm periods conditions returned to average glacial levels. These short term cold and warm episodes in the northeast Atlantic ate superimposed on the general trend towards colder conditions of the Last Glacial Maximum (LGM). Heinrich event 1 appears to be unique as it occurs as insolation rose and was coeval with the initial melting of the Fennoscandian ice sheet. We propose that meltwater input of Heinrich event 1 significantly reduced North Atlantic Deep Water formation reducing the heat exchange between the low and high latitudes, thus delaying deglaciation by about 1500 radiocarbon years (2000 calendar years)

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom