Droplet activation, separation, and compositional analysis: laboratory studies and atmospheric measurements

Droplets produced in a cloud condensation nuclei chamber (CCNC) as a function of supersaturation have been separated from unactivated aerosol particles using counterflow virtual impaction. Residual material after droplets were evaporated was chemically analyzed with an Aerodyne Aerosol Mass Spectrometer (AMS) and the Particle Analysis by Laser Mass Spectrometry (PALMS) instrument. Experiments were initially conducted to verify activation conditions for monodisperse ammonium sulfate particles and to determine the resulting droplet size distribution as a function of supersaturation. Based on the observed droplet size, the counterflow virtual impactor cut-size was set to differentiate droplets from unactivated interstitial particles. Validation experiments were then performed to verify that only droplets with sufficient size passed through the counterflow virtual impactor for subsequent analysis. A two-component external mixture of monodisperse particles was also exposed to a supersaturation which would activate one of the types (hygroscopic salts) but not the other (polystyrene latex spheres or adipic acid). The mass spectrum observed after separation indicated only the former, validating separation of droplets from unactivated particles. Results from ambient measurements using this technique and AMS analysis were inconclusive, showing little chemical differentiation between ambient aerosol and activated droplet residuals, largely due to low signal levels. When employing as single particle mass spectrometer for compositional analysis, however, we observed enhancement of sulfate in droplet residuals

Droplet activation, separation, and compositional analysis: laboratory studies and atmospheric measurements [Discussion paper]

Droplets produced in a cloud condensation nucleus chamber as a function of supersaturation have been separated from unactivated aerosol particles using counterflow virtual impaction. Residual material after droplets were evaporated was chemically analyzed with an Aerodyne Aerosol Mass Spectrometer and the Particle Analysis by Laser Mass Spectrometry instrument. Experiments were initially conducted to verify activation conditions for monodisperse ammonium sulfate particles and to determine the resulting droplet size distribution as a function of supersaturation. Based on the observed droplet size, the counterflow virtual impactor cut-size was set to differentiate droplets from unactivated interstitial particles. Validation experiments were then performed to verify that only droplets with sufficient size passed through the counterflow virtual impactor for subsequent analysis. A two-component external mixture of monodisperse particles was also exposed to a supersaturation which would activate one of the types (ammonium sulfate) but not the other (polystyrene latex spheres). The mass spectrum observed after separation indicated only the former, validating separation of droplets from unactivated particles. Results from atmospheric measurements using this technique indicate that aerosol particles often activate predominantly as a function of particle size. Chemical composition is not irrelevant, however, and we observed enhancement of sulfate in droplet residuals using single particle analysis

Immersionmode ice nucleationmeasurements with the new Portable Immersion Mode Cooling chAmber (PIMCA)

The new Portable Immersion Mode Cooling chAmber (PIMCA) has been developed for online immersion freezing of single-immersed aerosol particles. PIMCA is a vertical extension of the established Portable Ice Nucleation Chamber (PINC). PIMCA immerses aerosol particles into cloud droplets before they enter PINC. Immersion freezing experiments on cloud droplets with a radius of 5–7 μm at a prescribed supercooled temperature (T) and water saturation can be conducted, while other ice nucleation mechanisms (deposition, condensation, and contact mode) are excluded. Validation experiments on reference aerosol (kaolinite, ammonium sulfate, and ammonium nitrate) showed good agreement with theory and literature. The PIMCA-PINC setup was tested in the field during the Zurich AMBient Immersion freezing Study (ZAMBIS) in spring 2014 in Zurich, Switzerland. Significant concentrations of submicron ambient aerosol triggering immersion freezing at T > 236 K were rare. The mean frozen cloud droplet number concentration was estimated to be 7.22·105 L−1 for T < 238 K and determined from the measured frozen fraction and cloud condensation nuclei (CCN) concentrations predicted for the site at a typical supersaturation of SS = 0.3%. This value should be considered as an upper limit of cloud droplet freezing via immersion and homogeneous freezing processes. The predicted ice nucleating particle (INP) concentration based on measured total aerosol larger than 0.5 μm and the parameterization by DeMott et al. (2010) at T = 238 K is INPD10=54 ± 39 L−1. This is a lower limit as supermicron particles were not sampled with PIMCA-PINC during ZAMBIS

Tricarbonyliron(0) complexes of bio-derived η4 cyclohexadiene ligands: An approach to analogues of oseltamivir

AbstractWe have prepared novel [η4] and [η5]+ tricarbonyliron complexes from an unusual enantiopure cyclohexadiene ligand that possesses a quaternary stereocentre; this in turn is prepared through biotransformation of an aromatic ring. The cyclohexadiene ligand initially possessed two hydroxyl groups, both of which could be substituted with other functionality by means of an overall [η4] → [η5]+ → [η4] → [η5]+ → [η4] sequence. From six novel tricarbonyliron complexes which have been prepared, three have been characterised by x-ray crystallography. The reaction sequence we describe is potentially of relevance to the synthesis of analogues of the anti-influenza drug oseltamivir. In addition, the failure of an attempted addition of a bulky nitrogen nucleophile to an [η5]+ complex sheds light on the limits of reactivity for such additions. Thus, two bulky nucleophiles which are each known to add successfully to unencumbered [η5]+ complexes seemingly cannot be added sequentially to adjacent positions on the cyclohexadiene ligand

Structural Analysis to Determine the Core of Hypoxia Response Network

The advent of sophisticated molecular biology techniques allows to deduce the structure of complex biological networks. However, networks tend to be huge and impose computational challenges on traditional mathematical analysis due to their high dimension and lack of reliable kinetic data. To overcome this problem, complex biological networks are decomposed into modules that are assumed to capture essential aspects of the full network's dynamics. The question that begs for an answer is how to identify the core that is representative of a network's dynamics, its function and robustness. One of the powerful methods to probe into the structure of a network is Petri net analysis. Petri nets support network visualization and execution. They are also equipped with sound mathematical and formal reasoning based on which a network can be decomposed into modules. The structural analysis provides insight into the robustness and facilitates the identification of fragile nodes. The application of these techniques to a previously proposed hypoxia control network reveals three functional modules responsible for degrading the hypoxia-inducible factor (HIF). Interestingly, the structural analysis identifies superfluous network parts and suggests that the reversibility of the reactions are not important for the essential functionality. The core network is determined to be the union of the three reduced individual modules. The structural analysis results are confirmed by numerical integration of the differential equations induced by the individual modules as well as their composition. The structural analysis leads also to a coarse network structure highlighting the structural principles inherent in the three functional modules. Importantly, our analysis identifies the fragile node in this robust network without which the switch-like behavior is shown to be completely absent

Interprofessional and interdisciplinary simulation-based training leads to safe sedation procedures in the emergency department

BACKGROUND Sedation is a procedure required for many interventions in the Emergency department (ED) such as reductions, surgical procedures or cardioversions. However, especially under emergency conditions with high risk patients and rapidly changing interdisciplinary and interprofessional teams, the procedure caries important risks. It is thus vital but difficult to implement a standard operating procedure for sedation procedures in any ED. Reports on both, implementation strategies as well as their success are currently lacking. This study describes the development, implementation and clinical evaluation of an interprofessional and interdisciplinary simulation-based sedation training concept. METHODS All physicians and nurses with specialised training in emergency medicine at the Berne University Department of Emergency Medicine participated in a mandatory interdisciplinary and interprofessional simulation-based sedation training. The curriculum consisted of an individual self-learning module, an airway skill training course, three simulation-based team training cases, and a final practical learning course in the operating theatre. Before and after each training session, self-efficacy, awareness of emergency procedures, knowledge of sedation medication and crisis resource management were assessed with a questionnaire. Changes in these measures were compared via paired tests, separately for groups formed based on experience and profession. To assess the clinical effect of training, we collected patient and team satisfaction as well as duration and complications for all sedations in the ED within the year after implementation. We further compared time to beginning of procedure, time for duration of procedure and time until discharge after implementation with the one year period before the implementation. Cohen's d was calculated as effect size for all statistically significant tests. RESULTS Fifty staff members (26 nurses and 24 physicians) participated in the training. In all subgroups, there is a significant increase in self-efficacy and knowledge with high effect size (d z  = 1.8). The learning is independent of profession and experience level. In the clinical evaluation after implementation, we found no major complications among the sedations performed. Time to procedure significantly improved after the introduction of the training (d = 0.88). DISCUSSION Learning is independent of previous working experience and equally effective in raising the self-efficacy and knowledge in all professional groups. Clinical outcome evaluation confirms the concepts safety and feasibility. CONCLUSION An interprofessional and interdisciplinary simulation-based sedation training is an efficient way to implement a conscious sedation concept in an ED

Impedance Analysis of Complex Formation Equilibria in Phosphatidylcholine Bilayers Containing Decanoic Acid or Decylamine

Bilayer lipid membranes composed of phosphatidylcholine and decanoic acid or phosphatidylcholine and decylamine were investigated using electrochemical impedance spectroscopy. Interaction between membrane components causes significant deviations from the additivity rule. Area, capacitance, and stability constant values for the complexes were calculated based on the model assuming 1:1 stoichiometry, and the model was validated by comparison of these values to experimental results. We established that phosphatidylcholine and decylamine form highly stable 1:1 complexes. In the case of decanoic acid-modified phosphatidylcholine membranes, complexes with stoichiometries other than 1:1 should be taken into consideration

MOLNUPIRAVIR COMPARED TO NIRMATRELVIR/RITONAVIR FOR COVID-19 IN HIGH-RISK PATIENTS WITH HAEMATOLOGICAL MALIGNANCY IN EUROPE. A MATCHED-PAIRED ANALYSIS FROM THE EPICOVIDEHA REGISTRY

Introduction: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections, which reduce both hospitalization and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, while molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir, because it displays less frequent drug-drug interactions and contraindications. A caveat connected to molnupiravir derives from the mode of action inducing viral mutations. In clinical trials on patients without haematological malignancy, mortality rate reduction of molnupiravir appeared less pronounced than that of nirmatrelvir/ritonavir. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, we here assess the effectiveness of molnupiravir compared to nirmatrelvir/ritonavir in our cohort of patients with haematological malignancies. Methods: Clinical data of patients treated either with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and baseline haematological malignancy severity to controls treated with nirmatrelvir/ritonavir. Results: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (IQR 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 57% (n=66) of the patients had controlled baseline haematological malignancy, 13% (n=15) stable, and 30% (n=35) had active disease at COVID-19 onset in each of the groups. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of vaccinated patients was observed in both groups (molnupiravir n=77, 66% vs nirmatrelvir/ritonavir n=87, 75%), those treated with nirmatrelvir/ritonavir had more often received four doses (n=27, 23%) as compared to patients treated with molnupiravir (n=5, 4%, p&lt;0.001). No differences were detected in COVID-19 severity (p=0.39) or hospitalization (p=1.0). No statistically significant differences were identified in overall mortality rate (p=0.78) or in survival probability (d30 p=0.19, d60 p=0.67, d90 p=0.68, last day of follow up p=0.68). In all patients, deaths were either attributed to COVID-19 or the infection contributed to death as per treating physician's judgement. Conclusions: In high-risk patients with haematological malignancies and COVID-19, molnupiravir showed rates of hospitalization and mortality comparable to those of nirmatrelvir/ritonavir in this matched-pair analysis. Molnupiravir appears to be a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy