23 research outputs found
Optical Arbitrary Waveform Measurement (OAWM) on the Silicon Photonic Platform
We demonstrate optical arbitrary waveform measurement (OAWM) using a silicon pho-tonic spectral slicer. Exploiting maximal-ratio combining (MRC), we demonstrate the viability of the scheme by reconstructing 100-GBd 64QAM signals with high quality
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Infrared Multiple Photon Dissociation Spectroscopy of Potassiated Proline
The structure of proline in [proline + K](+) has been investigated in the gas phase using high level DFT and MP2 calculations and infrared photo dissociation spectroscopy with a free electron laser (FELIX). The respective FELIX spectrum of [proline + K](+) matches convincingly the calculated spectra of two structurally closely related and nearly iso-energetic zwitterionic salt bridge (SB) structures. An additional unresolved band at similar to 1725 cm(-1) matching with the characteristic CO stretching mode of charge solvation (CS) structures points toward the presence of a minor population of these conformers of proline in [proline + K](+). However, theory predicts a significant energy gap of 18.9 kJmol(-1) (B3LYP/6-311++G(2d,2p)) or 15.6 kJ mol(-1) (MP2) between the lowest CS conformer of proline and the clearly favored SB structure
Systematic Study of the Structures of Potassiated Tertiary Amino Acids: Salt Bridge Structures Dominate
The gas-phase structures of a series of potassiated tertiary amino acids have been systematically investigated using infrared multiple photon dissociation (IRMPD) spectroscopy utilizing light generated by a free electron laser, ion mobility spectrometry (IMS), and computational modeling. The examined analytes comprise a set of five linear N,N-dimethyl amino acids derived from N,N-dimethyl glycine and three cyclic N-methyl amino acids including N-methyl proline. The number of methylene groups in either file alkyl chain of the linear members or in the ring of the cyclic members of the series is gradually varied. The spectra of the cyclic potassiated molecular ions are similar and well resolved, whereas the clear signals in the respective spectra of the linear analytes increasingly overlap with longer alkyl chains. Measured IRMPD spectra are compared to spectra calculated at the B3LYP/6-311++G(2d,2p) level of theory to identify the structures present in the experimental studies. On the basis of these experiments and calculations, all potassiated molecular ions of this series adopt salt bridge structures in the gas phase, involving bidentate coordination of the potassium cation to the carboxylate moiety. The assigned salt bridge structures are predicted to be the global minima on the potential energy surfaces. IMS cross-section measurements of the potassiated systems show a monotonic increase with growing system size, suggesting that the precursor ions adopt the same type of structure and comparisons between experimental and theoretical cross sections are consistent with salt bridge structures and the IRMPD results
Gas-phase structures of solution-phase zwitterions: Charge solvation or salt bridge?
Sodium and lithium adduct ions of a synthetic guanidiniocarbonylpyrrole-derivative are examined in the gas phase. A wavelength tunable free electron laser (FEL) was used for photo-dissociation spectroscopy experiments in the infrared (1400-1800 cm(-1)). The photo-dissociation spectra are compared to calculated IR spectra of structures identified by theory. All photo-dissociation spectra acquired are strikingly similar, indicating that all ions adopt analogous gas-phase structures. Additionally, the respective sodium adduct ions were examined with ion mobility mass spectrometry (IMS). Although computational efforts succeeded in finding a charge solvated conformer that matched both the photo-dissociation spectra and the IMS data, the predicted global minimum was a salt-bridge structure. (C) 2008 Elsevier B.V. All rights reserved