Based on our data, we propose that increased pro-inflammatory cytokine signalling parallel to a defective type II IFN response is a key mediator of critical COVID-19 pathophysiology; thereby making (a combination of) specific anti-cytokine monoclonal antibodies (e.g. anti-IL-6) or broad-activity immunomodulatory drugs (e.g. colchicine, azithromycin) interesting candidates for interventional clinical trials. Moreover, systemic hyperinflammation might be prevented by targeting neutrophils or NETs (e.g. DNase therapy) in the lung (early in the disease course) to prevent clinical deterioration. The demonstrated efficacy of dexamethasone66, whose mechanism of action is poorly understood but likely dampens both the dysregulated immune response and neutrophil activation seen in our study, supports further investigation along these avenues.
Black Box Analog Design HG-2 - ChangelogVersion 1.8.1 (Jun 28, 2022)- General: Fixed potential blacklisting of VST2 on Windows- General: Fixed potential crashes on Windows- General: Fixed processing being Mono with VST2 in FL Studio- General: Fixed value readouts not being present when clicking knobVersion 1.8 (Mar 15, 2022)- General: added native Apple Silicon compatibility for VST3, VST2 and AU- General: added macOS Monterey support- General: added Windows 11 and Windows 10 21H1 support - General: discontinued Windows 7 support- General: discontinued macOS 10.9 and 10.11 support- General: fixed metering behavior in block sizes of 2048 samples and higherVersion 1.7 (Mar 22, 2021)- General: Compatibility with Logic on Apple Silicon devices via the Rosetta-2 layer- General: Fixed possible artefacts when freezing or bouncing tracks in Pro Tools- General: Fixed automation highlighting disappearing in Studio One- General: Improved license dialog visibility in dark mode- Fixed artefacts at render start when freezing or bouncing- Added scalable UI feature- Improved metering behaviorVersion 1.6 (May 27, 2020)- General: Qualified for use with the Windows 10 May 2020 Update- General: VST3: Fixed potential hangs in a DAW upon loading- General: Fixed logical issues in undo / redo behavior- General: Fixed UI resizing issues in Ableton Live on Windows- General: Fixed audio processing initialization issues on amp and delay productsVersion 1.5 (Nov 06, 2019)- General: Qualified for use with macOS 10.15 Catalina- General: Qualified for use with Windows 10 November 2019 Update- General: Fixed plugin validation in Logic under macOS Catalina- General: Fixed preset name restore in Logic when reopening a session- General: Fixed opening authorization dialog triggering automation- General: Improved instantiation times for plugins- General: Improved license functionality and branding for subscription- General: Removed 32-bit support on macOS and WindowsVersion 1.4 (Jul 10, 2019)- General: macOS 10.14.5 Update compatibility- General: Windows 10 1903 Update compatibility- General: Fixed activation issue in Windows hosts set to non-English language (e.g. Cakewalk)- General: AU: Fixed issue with increased CPU and memory on reopening UI- General: VST3: Fixed issue with adapting to host knob mode, and now prioritizing linear- General: VST3: Fixed issue with VST3 preset permissions- General: VST3: Improved synchronization between parameter states and some UI functions, e.g. toolbar resetVersion 1.3 (Nov 16, 2018)- General: macOS Mojave compatibility- General: Windows October 2018 update compatibility- General: adding Windows High DPI support for VST2/3 plugins- General: Fixed potential crashes in Cubase and other VST2 / VST3 DAWs- General: Fixed potential CPU spikes and audio dropouts- General: Fixed rendering in Pro Tools on the start of a session- General: Fixed missing presets in Wavelab and other VST3 DAWs- General: Improving keyboard control, fixing issues with catched keys preventing it from passing through to DAW- General: Fixed parallel use of host sessions (e.g. with Live)Version 1.2 (May 24, 2018)- General: Microsoft Windows Redstone 4 compatibility- General: Added computer keyboard control for plugin parameters- General: Fixed Mouse scroll wheel not working in Windows 8- General: Fixed an issue where plugins will not validate or load after a certain amount of plugins have been loaded (Windows)- General: Fixed visual GUI freezes when adjusting DAW parameters, meters, analyzers (Mac)- General: Fixed possible issue with Pick Pack licenses- General: Small licenser stability fix- Fixed bug where plugin produces a buzzing sound when inserted Version 1.1 (Oct 23, 2017)- General: Mac OS High Sierra compatibility- General: Fixed possible crash on online activation (Mac OS High Sierra)- General: Fixed Logic Pro X not validating AU plugins (Mac OS High Sierra)- General: Fixed CPU spikes and crashes with Cubase (Windows)- General: Fixed bug that could lead to "AAE -6 error" in ProTools (Windows)- General: Fixed crash with FL Studio- General: Fixed crash when cross-opening plugins in various hosts- General: Fixed crash when using mixdown in Audition- General: Fixed crash in Final Cut Pro- General: Fixed delayed parameter handling and crackling issues in Cubase with VST3- General: Fixed bug where plugin settings were not saved in Harrison Mixbus- General: Fixed bug that led to AAE error -9317 in ProTools when instantiating plugin- General: Fixed bug where plugins did not render properly when "x ray" option is enabled in Sonar- General: Modifications to factory presets were lost when reopening session- General: Fixed mouse wheel behaviour with second monitor setup (Windows)- Some plugins: Value labels do not appear every time when clicking on parameter in UI- General: Faster instantiation time for plugins (Windows)- General: Adding support for automation highlighting in Presonus StudioOneVersion 1.0.2 (Mar 3, 2017)- Fixed issue that generated pumping audio [BXBUGS-1810]- Minor toolbar UI fix [BXBUGS-1834]- General: Fixed mousewheel issue with multi-monitor environment on Windows [BXBUGS-1371]- General: Fixed multi-instantiation of a plugin causing BitWig to crash [BXBUGS-1532]- General: Fixed multi-instantiation of any 2 plugins in different hosts leading to crash [BXBUGS-1678]Version 1.0.1 (Feb 7, 2016)- Updated manualVersion 1.0- Release version 2b1af7f3a8