Digital Pixel Test Structures implemented in a 65 nm CMOS process

The ALICE ITS3 (Inner Tracking System 3) upgrade project and the CERN EP R&D on monolithic pixel sensors are investigating the feasibility of the Tower Partners Semiconductor Co. 65 nm process for use in the next generation of vertex detectors. The ITS3 aims to employ wafer-scale Monolithic Active Pixel Sensors thinned down to 20 to 40 um and bent to form truly cylindrical half barrels. Among the first critical steps towards the realisation of this detector is to validate the sensor technology through extensive characterisation both in the laboratory and with in-beam measurements. The Digital Pixel Test Structure (DPTS) is one of the prototypes produced in the first sensor submission in this technology and has undergone a systematic measurement campaign whose details are presented in this article. The results confirm the goals of detection efficiency and non-ionising and ionising radiation hardness up to the expected levels for ALICE ITS3 and also demonstrate operation at +20 C and a detection efficiency of 99% for a DPTS irradiated with a dose of $10^{15}$ 1 MeV n$_{\mathrm{eq}}/$cm$^2$. Furthermore, spatial, timing and energy resolutions were measured at various settings and irradiation levels.Comment: Updated threshold calibration method. Implemented colorblind friendly color palette in all figures. Updated reference

Optimization of a 65 nm CMOS imaging process for monolithic CMOS sensors for high energy physics

The long term goal of the CERN Experimental Physics Department R&D on monolithic sensors is the development of sub-100nm CMOS sensors for high energy physics. The first technology selected is the TPSCo 65nm CMOS imaging technology. A first submission MLR1 included several small test chips with sensor and circuit prototypes and transistor test structures. One of the main questions to be addressed was how to optimize the sensor in the presence of significant in-pixel circuitry. In this paper this optimization is described as well as the experimental results from the MLR1 run confirming its effectiveness. A second submission investigating wafer-scale stitching has just been completed. This work has been carried out in strong synergy with the ITS3 upgrade of the ALICE experiment

Optimization of a 65 nm CMOS imaging process for monolithic CMOS sensors for high energy physics

The long term goal of the CERN Experimental Physics Department R&D on monolithic sensors is the development of sub-100nm CMOS sensors for high energy physics. The first technology selected is the TPSCo 65nm CMOS imaging technology. A first submission MLR1 included several small test chips with sensor and circuit prototypes and transistor test structures. One of the main questions to be addressed was how to optimize the sensor in the presence of significant in-pixel circuitry. In this paper this optimization is described as well as the experimental results from the MLR1 run confirming its effectiveness. A second submission investigating wafer-scale stitching has just been completed. This work has been carried out in strong synergy with the ITS3 upgrade of the ALICE experiment

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

Non peer reviewe

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Series Production and Test of Hybrid Modules for the ALICE ITS Upgrade

ALICE is one of the four experiments at the LHC located at CERN. As part of the upgrade of the detector, the current Inner Tracking System (ITS) will be replaced by an all silicon detector constructed from pixel sensors with a pitch of 27 x 29 μm$^2$ using CMOS Monolithic Active Pixel Sensors (MAPs) technology. The goal of this upgrade is to enable precise measurements of low momenta particles by significantly improving the impact parameter resolution, tracking efficiency and readout capacity. The detector consists of 7 concentric layers split into two barrels, an inner barrel and an outer barrel. To construct a layer in the detector several sensors are arranged and glued to an Flexible Printed Circuit (FPC) and electrically connected through wirebonds to create a hybrid module. These modules are then joined together to make the staves and then finally the barrels that vary in size depending on the layer. The module production was carried out at five assembly sites and has now mfinished. In total over 2500 modules were produced with a yield of 84% for detector grade modules. Each module underwent wire pull tests to assess the quality of the bonds, extensive electrical tests to evaluate the functionality of the module and classify it based on the results. Metrology was also carried out on selected modules to better understand the mechanical properties and the quality of the assembly during the construction phase. This proceeding will present the assembly procedure of the modules, give details and results of the tests carried out and a summary of the production as a whole

Simulation and evaluation of HV-CMOS pixel sensors for the CLIC vertex detector

The next steps in particle physics will involve colliders that are able to investigate the TeV energy scale so that many of the unanswered questions can be addressed. The Compact Linear Collider (CLIC) aims to do this through collisions of electrons and positrons at a high luminosity and at centre-of-mass energies of up to 3 TeV. In addition to the accelerator, a detector system is under development that targets precision physics measurements in an environment with a high rate of beam-induced backgrounds. One of the sub-detectors that faces particularly challenging requirements is the pixel vertex detector. To achieve its goals, hybrid readout chips either bump-bonded to planar sensors or capacitively coupled to High-Voltage CMOS (HV-CMOS) sensors, fabricated in a commercial 180nm technology, are under study. Both of these sensor options have a small pitch of 25 x 25μm2 and are hybridised to 65nm CLICpix readout ASICs. Initial investigations have shown the feasibility of such technologies, but further, and more detailed studies are needed. This is done through a series of simulations and measurements to assess the suitability of each technology for the CLIC vertex detector. Simulations of the custom designed CCPDv3 HV-CMOS sensor have been carried out using the Sentaurus Technology Computer Aided Design (TCAD) simulation software. Firstly, a comparison of a 2D model and a resource intensive 3D model was carried out, showing an agreement within 15% of the sensor properties, such as electric field, depletion depth and charge collection. However, there is a difference of 40% for the capacitance, indicating 3D simulations are better suited to capacitance measurements. The 2D model was then expanded to include a multi-pixel model for studies of charge sharing. Lab characterisations of planar sensor assemblies were undertaken to determine the quality of the bump-bonds and define regions with an acceptable level of working pixels for three assemblies. Calibrations were performed to convert the Time-over-Threshold (ToT) energy measurements and Digital-to-Analogue (DAC) threshold voltage steps into physical units. For the HV-CMOS assemblies, the analogue output of several pixels was compared to the ToT response of the CLICpix readout chip so that the simulation results could be converted to ToT and compared to the beam test data. The performance of the HV-CMOS assemblies was assessed at the CERN SPS using 120 GeV/c secondary beams. This was done over an incident angle range of 0–80° and showed excellent efficiency above 99.7% and a spatial resolution of 5–7μm after etacorrection was applied to correct for non-linear charge sharing. The measurements were then compared to the simulations, showing a good agreement for the currentvoltage, breakdown and charge collection properties. The validated simulations were used to investigate possible prospects for improved performance that can be applied in future sensor designs. Two avenues of investigation were explored: increasing the bulk resistivity and biasing from the backside. The largest improvement was for a back bias model with a resistivity of 1k$\Omega$cm

TCAD simulations of High-Voltage-CMOS Pixel structures for the CLIC vertex detector

The requirements for precision physics and the experimental conditions at CLIC result in stringent constraints for the vertex detector. Capacitively coupled active pixel sensors with 25 μm pitch implemented in a commercial 180 nm High-Voltage CMOS (HV-CMOS) process are currently under study as a candidate technology for the CLIC vertex detector. Laboratory calibration measurements and beam tests with prototypes are complemented by detailed TCAD and electronic circuit simulations, aiming for a comprehensive understanding of the signal formation in the HV-CMOS sensors and subsequent readout stages. In this note 2D and 3D TCAD simulation results of the prototype sensor, the Capacitively Coupled Pixel Detector version three (CCPDv3), will be presented. These include the electric field distribution, leakage current, well capacitance, transient response to minimum ionising particles and charge-collection