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The INHALE-HEP meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies, to evaluate whether inhaled nebulised UFH in hospitalised patients with COVID-19 who do not require immediate invasive mechanical ventilation, significantly reduces intubation (or death, for patients who died before intubation) at day 28 compared to standard care alone. Objective: In keeping with best practice and with the published protocol, a pre-specified statistical analysis plan has been described and made public before completion of patient recruitment and data collection into the INHALE-HEP meta-trial. Methods: Our statistical analysis plan was designed by the INHALE-HEP executive committee and statisticians and approved by the INHALE-HEP steering committee. We reviewed the data collected as specified in the meta-trial protocol and collected in individual contributing studies. We present information pertaining to data collection, pre-specified subgroups, and study outcomes. Primary and secondary outcomes are defined, and additional subgroup analyses of pre-defined variables are described. Results: We have described our methods for presenting the trial profile and baseline characteristics, as well as our Bayesian approach to monitoring and meta-analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. Conclusion: To minimise analytical bias, we have developed a statistical analysis plan and made this available to the public domain before completion of patient recruitment and data collection into the INHALE-HEP meta-trial.

The Rockets for Extended-source X-ray Spectroscopy (tREXS) are a funded series of sounding rocket instruments to detect diffuse soft X-ray emission from astrophysical sources. The first launch of tREXS is scheduled for Q4 2021, with a goal to observe the Cygnus Loop supernova remnant. tREXS house a four-channel grating spectrometer that uses passive, mechanical focusers, arrays of reflection gratings, and an extended focal plane based around Teledyne CIS 113 CMOS sensors. We present here an update on the instrument design, build, and calibrations in advance of the launch later this year.

The focal-plane camera on the Rockets for Extended-source X-ray Spectroscopy (tREXS) is a large-area detector array that takes advantage of the large-format, 3-side-buttable design of the Teledyne e2v Vega-CIS113 CMOS sensor. This paper discusses the initial design of the focal plane camera, results from testing that identified read noise performance issues, mechanical and electrical challenges of this initial design, and supply chain problems. The changes to the focal plane camera that were made due to these challenges are then presented, along with the final flight camera that has been designed to optimize noise performance and be able to be built within the schedule constraints of the tREXS mission.

The Rockets for Extended-source X-ray Spectroscopy (tREXS) are a series of NASA funded suborbital rockets that will make large field-of-view observations of the diffuse soft X-ray emission from the Cygnus Loop and Vela supernova remnants. The tREXS focal plane camera is made up of an array of 11 Vega-CIS113 CMOS detectors, with a 12th as the zero-order detector. To optimize the performance of the camera, a test setup was developed where a single CMOS detector can be characterized to determine which settings have the highest impact on detector performance characteristics such as readout noise. This paper will discuss this test setup, the initial testing that has occurred using an engineering grade detector, and the initial results on how changing bias potentials and pixel timings impact the readout noise. Improvements that will be made to the final focal plane camera electronics based on the findings in the initial testing will also be discussed.

The Rocket for Extended-Source X-ray Spectroscopy (tREXS) is a suborbital rocket payload that is designed to obtain the most highly resolved soft X-ray emission spectrum from the Cygnus Loop to date. This research will discuss the development and implementation of a guidance system that will replace the traditional pointing mechanism for a sub-orbital payload. Normally the pointing requirement for a sub-orbital flight is achieved using a NSROC altitude control system, which uses an ST5000 star tracker co-aligned with the X-ray optic. In tREXS design there is not space to use this star tracker; therefore, a design has been made that utilizes a side looking ST5000 to acquire the target field and an aspect camera for fine pointing. The aspect camera will stream frames of the target star field, that will be processed by the guidance algorithm. The algorithm will relay where to position the payload to target the Cygnus Loop.

Aims: inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID‐19. UFH has antiviral effects and prevents the SARS‐CoV‐2 virus' entry into mammalian cells. In addition, UFH has significant anti‐inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis.Methods: the INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID‐19 (INHALE‐HEP) metatrial is a prospective individual patient data analysis of on‐going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS‐CoV‐2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time‐to‐event analyses. Individual studies may have additional outcomes.Analysis: we use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention‐to‐treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow‐up or withdrawn.Trial registration, ethics and dissemination: the metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.

Introduction Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential for COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus’ entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anti-coagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods and intervention This meta-trial is a prospective collaborative individual patient data meta-analysis of randomised controlled trials and early phase studies. Individual studies are conducted in multiple countries. Adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, are randomised to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome is intubation (or death, for patients who died before intubation) at day 28, assessed in a time-to-event analysis. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have specific outcome measures in addition to the core set. Ethics and dissemination: The meta-trial is registered at ClinicalTrials.gov, ID NCT04635241. Results of this study will be shared with the WHO, published in scientific journals and presented at scientific meetings.

The Water Recovery X-ray Rocket (WRXR) mission was a sounding rocket flight that targeted the northern part of the Vela supernova remnant with a camera designed to image the diffracted X-rays using a grating spectrometer optimized for OVII, OVIII, and CVI emissions. The readout camera for WRXR utilized a silicon hybrid CMOS detector (HCD) with an active area of 36.9  36.9 mm. A modified H2RG X-ray HCD, with 1024  1024 active silicon pixels bonded to the H2RG read-out integrated circuit, was selected for this mission based on its characteristics, technology maturation, and ease of implementation into the existing payload. This required a new camera package for the HCD to be designed, built, calibrated, and operated. This detector and camera system were successfully operated in-flight and its characteristics were demonstrated using the on-board calibration X-ray source. In this paper, a detailed description of this process, from design concept to flight performance, will be given. A full integrated instrument calibration will also be discussed, as well as the temperature dependency measurements of gain variation, read noise, and energy resolution for the HCD.

High-resolution, high-throughput soft X-ray spectroscopy using reflection gratings has the potential to unlock answers to many of the questions about the high-energy Universe. To enable missions to use this technology in the future, the ability to precisely align reflection gratings needs to be demonstrated. The Water Recovery X-ray Rocket (WRXR), a soft X-ray spectrometer that successfully launched in April 2018 from the Kwajalein Atoll, required co-aligned X-ray reflection gratings. WRXR was designed to produce a moderate-resolution spectrum of the Vela supernova remnant over a large field-of-view. The grating module was manufactured, integrated onto the rocket payload, passed environmental testing and was successfully launched and recovered. This paper describes the grating and mirror alignment methodologies for WRXR, and their inherent systematic uncertainties. Improvements to the alignment method that are required to meet the tighter alignment tolerances of future X-ray spectrometers are also discussed.

The Water Recovery X-ray Rocket (WRXR) is a sounding rocket payload that launched from the Kwajalein Atoll in April 2018 and was the first NASA astrophysics sounding rocket payload to be recovered from water. WRXR's primary instrument is a grating spectrometer that consists of a mechanical collimator, X-ray reflection gratings, grazing-incidence mirrors, and a hybrid CMOS detector. We present here the design of the WRXR spectrometer’s gratings and mirrors.

A new generation of vanadium dioxide phase change switches have been designed, fabricated, and characterized. These switches were designed to dramatically reduce on-state shunt-capacitance associated with the switch's heater while also increasing the off-state resistance. The result is a switch architecture whose channel dimensions can be scaled to increase power handling while maintaining unparalleled low loss. We will present SPST switches with on-state insertion loss 35 dB from DC to 67 GHz while offering 1W power handling. A wide variety of SPNT switch designs is possible with MMW bandwidth. We have not identified any switch technology having reported superior bandwidth and low insertion loss.

The Water Recovery X-ray Rocket (WRXR) is a sounding rocket payload that will launch from the Kwajalein Atoll in April 2018 and seeks to be the first astrophysics sounding rocket payload to be water recovered by NASA. WRXR's primary instrument is a grating spectrometer that consists of a mechanical collimator, X-ray reflection gratings, grazing-incidence mirrors, and a hybrid CMOS detector. The instrument will obtain a spectrum of the diffuse soft X-ray emission from the northern part of the Vela supernova remnant and is optimized for 3rd and 4th order OVII emission. Utilizing a field of view of 3.25° × 3.25° and resolving power of λ/δλ ≈40-50 in the lines of interest, the WRXR spectrometer aims to achieve the most highly-resolved spectrum of Vela's diffuse soft X-ray emission. This paper presents introductions to the payload and the science target.

A monolithic 3-bit phase shifter has been fabricated and demonstrates broadband and low loss performance from 220 GHz to 240 GHz. The phase shifter utilizes an ultra-low loss vanadium dioxide switch for phase state control. The design uses a low-pass π-filter networks as phase shift elements for 45, 90 and 180 degree bits. This phase shifter's mean insertion loss of 7.6 dB is 3dB lower than any other passive phase shifter we could identify in literature and comparable to the best active vector-sum devices. The RMS phase error is a competitive 6.8 degrees at 230GHz and averages only 8 dB over the band from 220 to 240 GHz. This phase shifter's complete circuit footprint is < 0.1mm2 easily fitting within (λ/2)2 ∼ 0.4 mm2 array spacing. A second topology was also demonstrated that consists of a one-port transmission line reflection phase shifter (TLPS) using a variable length, short-circuit terminated synthetic transmission line. This device demonstrates an average insertion loss of 5.2 dB and RMS phase error of 30 degrees. We can find no passive phase shifter with comparable performance or compactness to either of the devices presented here.

The Water Recovery X-Ray Rocket (WRXR) was a suborbital rocket payload that was launched and recovered in April 2018. The WRXR flew two technologies being developed for future large x-ray missions: x-ray reflection gratings and a hybrid CMOS detector (HCD). The large-format replicated gratings on the WRXR were measured in ground calibrations to have absolute single-order diffraction efficiency of ∼60 % , ∼50 % , and ∼35 % at CVI, OVII, and OVIII emission energies, respectively. The HCD was operated with ∼6 e − read noise and ∼88 eV energy resolution at 0.5 keV. The WRXR was also part of a two-payload campaign that successfully demonstrated NASA sounding rocket water recovery technology for science payloads. The primary instrument, a soft x-ray grating spectrometer, targeted diffuse emission from the Vela supernova remnant over a field-of-view >10 deg2. The flight data show that the detector was operational during flight and detected x-ray events from an on-board calibration source, but there was no definitive detection of x-ray events from Vela. Flight results are presented along with a discussion of factors that could have contributed to the null detection.

Processing data from life sciences experiments presents many challenges, these include the volume of data to be processed and the complexity of the processing needed in order to present meaningful results back to the experimenters. This is particularly evident in the field of proteomics where the complex datasets provided by mass spectrometers require extensive preprocessing and the use of search algorithms before they can be used effectively. Many tools currently exist to carry out this processing but they are focused on batch based workloads where the mass spectrometer finishes its analysis and then the data is processed on a file by file basis. Usually this work is carried out on local PC hardware, which can also cause a data management problem. The research described in this paper leads to a distributed cluster-based architecture designed to process the mass spectrometer output in a real-time streaming fashion. In this way the mass spectrometers in a laboratory together with a central computing platform constitute an internet of things problem which can be solved using modern open-source technology and cloud computing.

We report a TSV-last, heterogeneous 3D integration process for millimeter wave solid state tiles for use in the demonstration of a W-band active electronically scanned array (AESA) radar system. Each phased array tile consists of a high speed SiGe BiCMOS beamformer chip, vertically integrated with an advanced, multi-metallization level glass substrate which includes an RF interposer and a patch antenna array. This paper will briefly describe the SiGe and glass circuit layers, along with the main components of the 3D integration processing and assembly. Electrical testing of the SiGe and glass chips was conducted at various points during the integration processing, including DC and RF measurements after the two chips were bonded together. Additionally, DC testing of TSV chains was completed along with thermal cycling. The results of this work indicated a successful initial prototype demonstration of 3D heterogeneous integrated phased array tiles, which can be used for a multi-tile subarray assembly and subsequent sensor system demonstration.

Several vanadium dioxide based single-pole single- throw (SPST) series switch geometries have been fabricated and demonstrate unequalled broadband low loss and isolation from DC to 280 GHz. A switch geometry having insertion loss of only 1.3 dB at 220 GHz and isolation of 15.7 dB also shows excellent S-parameter uniformity across the wafer. This uniformity indicates the maturity of the VO2 switch fabrication process. Furthermore, we have developed a model and comprehensive set of modeling parameters that will guide our future device development efforts. This model predicts that a millimeter-wave SPST switch having insertion loss < 1 dB and isolation > 12 at 220 GHz can be fabricated utilizing our existing device process. Such a switch will be vital for enabling applications such as electronically scanned phased arrays at millimeter-wave and terahertz frequencies.

The thermally driven metal insulator transition in vanadium dioxide (VO2) is used to create a low loss millimeter wave switch which operates up to and beyond W-band frequencies. We have built RF switches using vanadium dioxide thin films fabricated within a section of inverted transmission line with integrated on chip heaters to provide local thermal control. On heating the films above the metal insulator transition we obtain record low switch insertion loss of 0.13 dB at 50 GHz and 0.5 dB at 110 GHz. The switch cut-off frequency is high, fc ~ 45 THz, due to the low on state resistance and off state capacitance. We have investigated the device physics of these switches including self-latching of the devices under high RF powers, and demonstrated their integration with silicon germanium RF circuits where the switch heater current sources and control logic are also integrated into the same silicon germanium circuit.

A new ultra-low-loss and broad band millimeter wave switch technolog y based on the reversible metal/insulator phase transition of vanadium dioxide has been developed. We report having fabricated series configured, single-pole single­ throw (SPST) switches having measured S-parameters from DC to 110 GHz. The on-state insertion loss is 0.2 dB and off-state isolation is 21 dB at 50 GHz. The resulting impedance contrast ratio, ZOFF / ZON, is greater than 500: 1 at 50GHz (i.e. cut-off frequency Ic - 40 THz). As a demonstration of the technolog y's utilit y, we also present the results of a 2-bit real time dela y phase shifter incorporating a pair of V02 SP4T switches. This switch technolog y's high impedance contrast ratio combined with its compactness, ease of integration, and low voltage operation make it an enabler of previousl y unachievable high-performance millimeter wave FPGAs.

We report on progress in developing a travelling wave tube amplifier with significant gain and power at 220 GHz. This paper provides an overview of the program, describing fabrication and test of slow-wave structures with bandwidths exceeding 50 GHz centered at 220 GHz, the production of a sheet electron beam, development of a solid state preamplifier delivering 50 mW to the tube with > 17 dB of gain and beam-wave simulation of the entire circuit leading to expected output powers of over 50 W. Two further papers from the group are also submitted to IVEC: from UC Davis describing the interaction structure fabrication and hot test, and from CPI describing the sheet electron beam, TWT design and beam - wave simulations. The tube is currently under test and results will be reported in this paper.

We report on a 44-GHz Transceiver Array architecture that integrates all required functionality for rf beamforming and radiation using a single 16-channel Silicon-Germanium rf beamforming integrated circuit, a 4×4 array of wide-scan patch antennas, and a compact, rugged, micromachined three-dimensional structure for rf and dc interconnect and thermal management. The subarray tile is fabricated using a wafer-scale millimeter-wave system and circuit integration method we call BATCH that has been developed to allow the embedding of one or more semiconductor dice having varied function and material into a compact chip-scale module. This circuit integration technology includes low loss planar transmission line interconnects and patch antennas with planar feeds, all embedded in a micromachined silicon interposer and suitable for high-volume batch fabrication.

A wafer-scale microwave system and circuit integration method has been developed that allows the embedding of multiple semiconductor dice having varied function and material into a compact chip-scale module. This circuit integration technology includes low loss planar transmission line interconnects and integrated precision thin film resistors, capacitors and inductors; all of these structures are embedded in a micromachined silicon interposer. To demonstrate this interposer-based monolithic microwave integrated circuit (iMMIC) technology a Class-A Ku-band power amplifier has been designed and fabricated utilizing a discrete Triquint 1.2 mm X 0.35 µm pHEMT. A compact single stage amplifier produced 1 Watt of saturated output power at 14 GHz with a drain efficiency of 42.9 %, and 7.1 dB power gain. Wafer-scale micro-lithographic processing as well as selection of known-good-die for integration, will improve yield and reduced cost compared to current state-of-the-art hybrid technology. In this paper, we discuss architecture, design methodology, and the results of our demonstrated power amplifier in this new technology.

An indium-phosphide (InP) double-heterojunction bipolar transistor (DHBT) process for compact millimeter-wave power amplifier MMICs has been developed with integrated 15 mum thick layers of BCB dielectric. The thick BCB layers provide low-loss millimeter-wave transmission lines with much smaller dimensions compared to conventional microstrip placed directly on the semiconductor substrate. A single layer BCB process with two metal layers is used for microstrip circuits, and a two-layer BCB process (30 mum total thickness) with three metal layers is used for stripline MMICs. The stripline MMICs inherent shielding enables new MMIC packaging concepts such as three dimensional embedded circuits that are enabling for low-cost phased array antennas architectures. A two-stage cascode power amplifier has been fabricated and characterized using microstrip lines on a single thick layer of BCB. The compact 6 mm2 Ka-band PA demonstrated 1.1 Watts of saturated output power at 38 GHz, a dc power added efficiency (PAE) was 28.6%, and a small signal gain of 14.9 dB. The measured die area power density is 18.3 W/cm2. These results demonstrate the potential of thick BCB microstrip and stripline MMICs to enable compact power amplifiers for space constrained millimeter-wave applications.