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The Karolinska KI/K COVID-19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS-CoV-2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response towards SARS-CoV-2 infection in humans, as it occurred during the first wave. The Immune Atlas was built as an open resource for broad research and educational purposes. It contains a presentation of the response evoked by different immune and inflammatory cells in defined naïve patient-groups as they presented with moderate and severe COVID-19 disease. The present Resource Article describes how the Karolinska KI/K COVID-19 Immune Atlas allows scientists, students, and other interested parties to freely explore the nature of the immune response towards human SARS-CoV-2 infection in an online setting.

Summary. Background: Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants. Objectives: To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor – BAY 59-7939 – relative to enoxaparin in patients undergoing elective total hip replacement. Methods: In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6–8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5–9 days after surgery. Results: Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose–response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin. Conclusions: When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5–10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.

Objectives: There is an indication in the literature that there is a difference in tendon healing between genders. However comparisons in outcome are often not possible due to the small sample size of women with an acute Achilles tendon rupture. In most studies on patients with Achilles tendon rupture the women only account for less then 20% of the patients. The objective of this study was to evaluate if there are any differences in outcome between genders when combining the data from two large randomized controlled trials, which used identical outcome measures. Methods: Patients included in two consecutive randomized controlled trials, comparing surgical and non-surgical treatment, were included in the evaluation. Patients who had a re-rupture were excluded from the analysis. A total of 184 patients (154 males, 30 females) mean (SD) age of 40 (11) years were included. 96 (78 males, 18 females) were treated with surgery and 88 (76 males, 12 females) non-surgically. Patient reported outcome was evaluated with the Achilles tendon Total rupture Score (ATRS) and the functional outcome were measured with a single-leg standing heel-rise test (measurement of muscular endurance and heel-rise height) 6 and 12 months after injury in our research laboratory. Results: For the whole group there were no significant difference between treatments on ATRS at 6 and 12 months. The surgical group was significantly better then the non-surgical group in heel-rise endurance at 6 and 12 months and in heel-rise height recovery at 6 months (pConclusion: Females has a greater degree of deficit in heel-rise height as compared to males irrespective of treatment. Females have more symptoms compared to males after surgery both at 6 and 12 months but this difference is not found when treated non-surgically. Further research is needed to determine if women will benefit more from non-surgical compared to surgical treatment after an Achilles tendon rupture.

Interfaces of dye-sensitized TiO2 nanoparticles with electrolytes or hole conductors have been widely applied in photoelectrochemical cells. However, the fundamental understanding of their properties and function is still poor. Herein, we demonstrate that the spectral changes that occur in the-visible spectrum of dye-sensitized TiO2 films upon (a) Li+ titration, (b) potentiostatic electron accumulation in mesoporous TiO2, and (c) photoinduced electron injection into TiO2 can be explained by the Stark effect, which can then be used to characterize the change in the local electric field at the TiO2/dye/electrolyte interface. A quantitative analysis of the Stark effect indicates that the compact (Helmholtz) layer capacitance at the TiO2/dye/electrolyte interface strongly affects the strength of the local electric field. Systematic studies show that the Helmholtz layer capacitance depends strongly on the Li+ concentration and surface dye coverage but is independent of the concentrations of other electrolytic species and the light intensity. These results illustrate the potential of Stark spectroscopy for the in situ study of the TiO2/dye/electrolyte interfaces and provide substantial new insights into these widely applied interfaces related to photoelectrochemistry and other research fields.

At distances close enough to the Sun, when comets are characterised by a significant outgassing, the cometary neutral density may become large enough for both the cometary plasma and the cometary gas to be coupled, through ion-neutral and electron-neutral collisions. This coupling enables the formation of an unmagnetised expanding cometary ionosphere around the comet nucleus, also called diamagnetic cavity, within which the solar wind magnetic field cannot penetrate. The instruments of the Rosetta Plasma Consortium (RPC), onboard the Rosetta Orbiter, enable us to better constrain the structure, dynamics and stability of the plasma around comet 67P/CG. Recently, magnetic field measurements (RPC-MAG) have shown the existence of such a diamagnetic region around comet 67P/CG [Götz et al., 2016]. Contrary to a single, large scale, diamagnetic cavity such as what was observed around comet Halley, Rosetta have crossed several diamagnetic structures along its trajectory around comet 67P/CG. Using electron density measurements from the Mutual Impedance Probe (RPC-MIP) during the different diamagnetic cavity crossings, identified by the flux gate magnetometer (RPC-MAG), we map the unmagnetised plasma density around comet 67P/CG. Our aims is to better constrain the structure, dynamics and stability of this inner cometary plasma layer characterised by cold electrons (as witnessed by the Langmuir Probes RPC-LAP). The ionisation ratio in these unmagnetised region(s) is computed from the measured electron (RPC-MIP) and neutral gas (ROSINA/COPS) densities. In order to assess the importance of solar EUV radiation as a source of ionisation, the observed electron density will be compared to a the density expected from an ionospheric model taking into account solar radiation absorption. The crossings of diamagnetic region(s) by Rosetta show that the unmagnetised cometary plasma is particularly homogeneous, compared to the highly dynamical magnetised plasma observed in adjacent magnetised regions. Moreover, during the crossings of multiple, successive diamagnetic region(s) over time scales of tens of minutes or hours, the plasma density is almost identical in the different unmagnetised regions, suggesting that these unmagnetised regions may be a single diamagnetic structure crossed several times by Rosetta.

AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations

The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides. During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO2) have been developed and tested. The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used. In the present study, the phys. chem. of the phosphopeptide binding to TiO2 is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D). Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions. The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO2 surface increases in a nonlinear fashion with increasing degree of phosphorylation. An exception was detected, however, where pos. cooperativity between the peptides existed and the Langmuir model no longer applied. The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of pos. charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides. Regardless of the net peptide charge, the TiO2-phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin. This study highlights and explains some of the most common problems with the TiO2-based enrichment methods used today.

First observed in 1969, comet 67P/Churyumov-Gerasimenko was escorted for almost two years along its 6.45-yr elliptical orbit by ESA's Rosetta orbiter spacecraft. When a comet is sufficiently close to the Sun, the sublimation of ice leads to an outgassing atmosphere and the formation of a coma, and a dust and plasma tail. Comets are critical to decipher the physics of gas release processes in space. The latter result in mass-loaded plasmas, which more than three decades after the Active Magnetospheric Particle Tracer Explorers (AMPTE) space release experiments are still not fully understood. Using a 3D fully kinetic approach, we study the solar wind interaction with comet 67P/Churyumov-Gerasimenko, focusing in particular on the ion-electron dynamics for various outgassing rates. A detailed kinetic treatment of the electron dynamics is critical to fully capture the complex physics of mass-loading plasmas and to describe the strongly inhomogeneous plasma dynamics observed by Rosetta, down to electron kinetic scales.