Chemical and physical influences on aerosol activation in liquid clouds: a study based on observations from the Jungfraujoch, Switzerland

A simple statistical model to predict the number of aerosols which activate to form cloud droplets in warm clouds has been established, based on regression analysis of data from four summertime Cloud and Aerosol Characterisation Experiments (CLACE) at the high-altitude site Jungfraujoch (JFJ). It is shown that 79 % of the observed variance in droplet numbers can be represented by a model accounting only for the number of potential cloud condensation nuclei (defined as number of particles larger than 80 nm in diameter), while the mean errors in the model representation may be reduced by the addition of further explanatory variables, such as the mixing ratios of O3, CO, and the height of the measurements above cloud base. The statistical model has a similar ability to represent the observed droplet numbers in each of the individual years, as well as for the two predominant local wind directions at the JFJ (northwest and southeast). Given the central European location of the JFJ, with air masses in summer being representative of the free troposphere with regular boundary layer in-mixing via convection, we expect that this statistical model is generally applicable to warm clouds under conditions where droplet formation is aerosol limited (i.e. at relatively high updraught velocities and/or relatively low aerosol number concentrations). A comparison between the statistical model and an established microphysical parametrization shows good agreement between the two and supports the conclusion that cloud droplet formation at the JFJ is predominantly controlled by the number concentration of aerosol particles

Work stream on differentiated treatment:Final report

This report analyses practices of differentiated treatment, whereby a platform applies dissimilar conditions to business users in equivalent situations, and explores the extent to which such practices constitute a potential source of “unfairness” in the relationship between platforms and businesses in the online platform economy. A distinction is made between practices of self-favouring, whereby a platform gives preferential treatment to its own vertically integrated activities over those of rivals, and more general practices of differentiated treatment where one or more business users are treated more favourably than one or more others. The report aims to provide guidance on how to assess the impact of differentiated treatment by online platforms from a technical, economic and legal perspective, and identifies areas requiring further scrutiny because of the especially problematic nature of certain practices implemented by platforms. Special scrutiny seems particularly needed for practices of differentiated treatment by vertically integrated platforms that are dominant or whose consumers single-home and have high switching costs. In these circumstances, the relevant harms can outweigh the efficiencies of differentiated treatment. Another area of attention is differentiated treatment that significantly harms business users and for which the platform does not have a legitimate justification. The extent to which legitimate reasons invoked by a platform can justify harm to businesses is a key issue for future consideration. Significant harm to business users may translate into consumer detriment through less choice and diversity of offerings. Specific future prohibitions of certain problematic practices of differentiated treatment to promote diversity, fairness or equality of opportunities for businesses should be coupled with effective monitoring and enforcement mechanisms. Two areas are of particular concern: 1) the observability of differentiated treatment by platforms arising from techniques such as personalisation and localisation; (2) the availability of effective redress for businesses against the restriction, suspension or termination of service by platforms

Mammalian kinetochores count attached microtubules in a sensitive and switch-like manner.

The spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. Each mammalian kinetochore binds many microtubules, but how many attached microtubules are required to turn off the checkpoint, and how the kinetochore monitors microtubule numbers, are not known and are central to understanding SAC mechanisms and function. To address these questions, here we systematically tune and fix the fraction of Hec1 molecules capable of microtubule binding. We show that Hec1 molecules independently bind microtubules within single kinetochores, but that the kinetochore does not independently process attachment information from different molecules. Few attached microtubules (20% occupancy) can trigger complete Mad1 loss, and Mad1 loss is slower in this case. Finally, we show using laser ablation that individual kinetochores detect changes in microtubule binding, not in spindle forces that accompany attachment. Thus, the mammalian kinetochore responds specifically to the binding of each microtubule and counts microtubules as a single unit in a sensitive and switch-like manner. This may allow kinetochores to rapidly react to early attachments and maintain a robust SAC response despite dynamic microtubule numbers

Alternative therapies for GERD : a way to personalized antireflux surgery

Gastroesophageal reflux disease (GERD) is a commondisorder, known to affect about20%of theWestern population. Although conventional medical or surgical treatment has proven effective, there is certainly room for improvements. As only 10% of GERD patients are finally treated by antireflux surgery, a large therapeutic window exists. This treatment gap consists of patients who are not effectively treated with proton pump inhibitor but do not want to run the potential risks of conventional surgery. During the last two decades, several novel and intriguing options for the surgical treatment of GERD have been introduced and found their way into clinical use. The following summary will give an update of certain alternative therapeutic options to treat GERD or its pathological consequences

Fairness als zentrale Herausforderung moderner Aufnahmeverfahren

In der Praxis wird zumeist angenommen, dass die Ergebnisse in einem Aufnahmeverfahren individuelle Unterschiede in den zu erfassenden Fähigkeiten fair messen. Der vorliegende Beitrag gibt einen Überblick über Modelle zur Fairness von Aufnahmeverfahren und deren Überprüfung in der Praxis anhand von Beispielen zum Aufnahmeverfahren für Medizinische Studiengänge in Österreich (MedAT). Der Beitrag arbeitet zudem auch den engen Zusammenhang zwischen Fairness und anderen Gütekriterien heraus und veranschaulicht die Vorteile einer stark theoriegeleiteten automatischen Itemgenerierung (AIG), um auf die erhöhten Qualitätsanforderungen bei modernen Aufnahmeverfahren reagieren zu können

Probing RNA dynamics via longitudinal exchange and CPMG relaxation dispersion NMR spectroscopy using a sensitive 13C-methyl label

The refolding kinetics of bistable RNA sequences were studied in unperturbed equilibrium via 13C exchange NMR spectroscopy. For this purpose a straightforward labeling technique was elaborated using a 2′-13C-methoxy uridine modification, which was prepared by a two-step synthesis and introduced into RNA using standard protocols. Using 13C longitudinal exchange NMR spectroscopy the refolding kinetics of a 20 nt bistable RNA were characterized at temperatures between 298 and 310 K, yielding the enthalpy and entropy differences between the conformers at equilibrium and the activation energy of the refolding process. The kinetics of a more stable 32 nt bistable RNA could be analyzed by the same approach at elevated temperatures, i.e. at 314 and 316 K. Finally, the dynamics of a multi-stable RNA able to fold into two hairpin- and a pseudo-knotted conformation was studied by 13C relaxation dispersion NMR spectroscopy

Recruitment of the γ-Tubulin Ring Complex to Drosophila Salt-stripped Centrosome Scaffolds

Extracting isolated Drosophila centrosomes with 2 M KI generates salt-resistant scaffolds that lack the centrosomal proteins CP190, CP60, centrosomin, and γ-tubulin. To clarify the role of these proteins in microtubule nucleation by centrosomes and to identify additional centrosome components required for nucleation, we have developed an in vitro complementation assay for centrosome function. Centrosome aster formation is reconstituted when these inactive, salt-stripped centrosome scaffolds are supplemented with a soluble fraction of a Drosophila embryo extract. The CP60 and CP190 can be removed from this extract without effect, whereas removing the γ-tubulin destroys the complementing activity. Consistent with these results, we find no evidence that these three proteins form a complex together. Instead, γ-tubulin is found in two distinct protein complexes of 240,000 and ∼3,000,000 D. The larger complex, which is analogous to the Xenopus γ-tubulin ring complex (γTuRC) (Zheng, Y., M.L. Wong, B. Alberts, and T. Mitchison. 1995. Nature. 378:578–583), is necessary but not sufficient for complementation. An additional factor found in the extract is required. These results provide the first evidence that the γTuRC is required for microtubule nucleation at the centrosome

Chemical and physical influences on aerosol activation in liquid clouds: a study based on observations from the Jungfraujoch, Switzerland

A simple statistical model to predict the number of aerosols which activate to form cloud droplets in warm clouds has been established, based on regression analysis of data from four summertime Cloud and Aerosol Characterisation Experiments (CLACE) at the high-altitude site Jungfraujoch (JFJ). It is shown that 79 % of the observed variance in droplet numbers can be represented by a model accounting only for the number of potential cloud condensation nuclei (defined as number of particles larger than 80 nm in diameter), while the mean errors in the model representation may be reduced by the addition of further explanatory variables, such as the mixing ratios of O3, CO, and the height of the measurements above cloud base. The statistical model has a similar ability to represent the observed droplet numbers in each of the individual years, as well as for the two predominant local wind directions at the JFJ (northwest and southeast). Given the central European location of the JFJ, with air masses in summer being representative of the free troposphere with regular boundary layer in-mixing via convection, we expect that this statistical model is generally applicable to warm clouds under conditions where droplet formation is aerosol limited (i.e. at relatively high updraught velocities and/or relatively low aerosol number concentrations). A comparison between the statistical model and an established microphysical parametrization shows good agreement between the two and supports the conclusion that cloud droplet formation at the JFJ is predominantly controlled by the number concentration of aerosol particles

Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults

Objective: To provide a management approach for adults with calcium channel blocker poisoning. Data Sources, Study Selection, and Data Extraction: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. Data Synthesis: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block without significant alteration in cardiac inotropism (2D); 4) in patients with refractory shock or who are periarrest, we recommend incremental doses of high-dose insulin (1D) and IV lipid-emulsion therapy (1D) if not already tried. We suggest venoarterial extracorporeal membrane oxygenation, if available, when refractory shock has a significant cardiogenic component (2D), and using pacemaker in the presence of unstable bradycardia or high-grade arteriovenous block in the absence of myocardial dysfunction (2D) if not already tried; 5) in patients with cardiac arrest, we recommend IV calcium in addition to the standard advanced cardiac life-support (1D), lipid-emulsion therapy (1D), and we suggest venoarterial extracorporeal membrane oxygenation if available (2D). Conclusion: We offer recommendations for the stepwise management of calcium channel blocker toxicity. For all interventions, the level of evidence was very low

Exposure-based interventions for the management of individuals with high levels of needle fear across the lifespan: A clinical practice guideline and call for further research

Needle fear typically begins in childhood and represents an important health-related issue across the lifespan. Individuals who are highly fearful of needles frequently avoid health care. Although guidance exists for managing needle pain and fear during procedures, the most highly fearful may refuse or abstain from such procedures. The purpose of a clinical practice guideline (CPG) is to provide actionable instruction on the management of a particular health concern; this guidance emerges from a systematic process. Using evidence from a rigorous systematic review interpreted by an expert panel, this CPG provides recommendations on exposure-based interventions for high levels of needle fear in children and adults. The AGREE-II, GRADE, and Cochrane methodologies were used. Exposure-based interventions were included. The included evidence was very low quality on average. Strong recommendations include the following. In vivo (live/in person) exposure-based therapy is recommended (vs. no treatment) for children seven years and older and adults with high levels of needle fear. Non-in vivo (imaginal, computer-based) exposure (vs. no treatment) is recommended for individuals (over seven years of age) who are unwilling to undergo in vivo exposure. Although there were no included trials which examined children < 7 years, exposure-based interventions are discussed as good clinical practice. Implementation considerations are discussed and clinical tools are provided. Utilization of these recommended practices may lead to improved health outcomes due to better health care compliance. Research on the understanding and treatment of high levels of needle fear is urgently needed; specific recommendations are provided