Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

In-situ thermoelectric temperature monitoring and “Closed-loop integrated control” system for concentrator photovoltaic-thermoelectric hybrid receivers

This work demonstrates a new technique that capitalizes on the inherent flexibility of the thermoelectric module to provide a multifunctional platform, and exhibits a unique advantage only available within CPV-TE hybrid architectures. This system is the first to use the thermoelectric itself for hot-side temperature feedback to a PID control system, needing no additional thermocouple or thermistor to be attached to the cell - eliminating shading, and complex mechanical designs for mounting. Temperature measurement accuracy and thermoelectric active cooling functionality is preserved. Dynamic “per-cell” condition monitoring and protection is feasible using this technique, with direct cell-specific temperature measurement accurate to 1°C demonstrated over the entire experimental range. The extrapolation accuracy potential of the technique was also evaluated

Novel hybrid III:V concentrator photovoltaic-thermoelectric receiver designs

This paper presents the design, manufacture and electrical characterization of novel hybrid III:V Concentrator Photovoltaic-Thermoelectric receivers. Addition of an encapsulating and spectral homogenizing single active surface secondary optic lens increased the solar cell electrical power output from 7.66mW (ALPHA no cooling) to 18.20mW (KAPPA with TE cooling). The effective optical concentration of the optics, based on short circuit current, was x2.4. A linear irradiance vs maximum power receiver output relationship was observed (R2=0.9978), confirming good optical alignment during manufacture and likewise internal current matching of the series-connected triple-junction cell. An in-depth COMSOL model for simulated evaluation of the synergistic thermally-dependent parameters inherent to hybrid devices was built and experimentally validated

Experimental comparison of a III:V triple-junction concentrator photovoltaic-thermoelectric (CPV-TE) hybrid module with commercial CPV and flat plate silicon modules

Concentrator Photovoltaic-Thermoelectric (CPV-TE) hybrid devices have the potential to address areas of limitation within concentrator photovoltaic devices, using the inherent flexibility and controllability of thermoelectrics. In this work, a full CPV-TE module was designed and fabricated using commercial Primary and Secondary Optical Elements (POEs and SOEs respectively). The SOE-CPV-TE hybrid receivers were characterized prior to integration within the module, and connected into a string of three receivers. The acceptance angle of the POE-SOE-CPV-TE hybrid module was experimentally characterized, and outdoor on-tracker data was obtained at the University of Jaén. For the first time, the performance of CPV-TE hybrid devices was evaluated within a 3-receiver string, and the efficiency of on-sun TE cooling was investigated.A preliminary break-even point was found at 0.3A, for active cooling verses non- cooling for the CPV-TE hybrid receivers. This highlights the future on-sun performance increases possible with further optimised CPV-TE module designs, including a low-power regime for optimised TE operation

Commercial photovoltaic system design for Cardiff City Hall

The rooftops of Cardiff City Hall were surveyed to establish potential areas for commercial-scale photovoltaic (PV) system design. The orientation and tilt angles of suitable unshaded roof areas were measured for accurate PV system simulation. The performance of two PV technologies, polycrystalline silicon (p-Si) and heterojunction with intrinsic thin layers (HIT) was investigated. From the analysis of simulation, experimental, environmental and economic data, HIT was found to be the best-performing PV technology for system installation. Superior performance of HIT under diffuse sunlight conditions, typical of the UK climate, was demonstrated. Additionally, the maximum power temperature coefficient, verified during experimental work, was lower than the p-Si alternative (−0·28 against −0·50%/°C). Electricity demand data for City Hall were analysed and 8·1% of the annual electricity demand (solar fraction) could be supplied by an 88 kWp HIT PV system. The HIT PV system modelled would significantly improve the energy performance of Cardiff City Hall, avoiding >40 000 kg carbon dioxide emissions annually. The levelised cost of energy from one array (B, £0·11/kWh) was less than the current day tariff rate for grid import (£0·1173). The economic and environmental benefits of well-designed high-efficiency PV systems in the UK at commercial scale are also demonstrated

Testing the effectiveness of the Developing Inclusive Youth program: A multisite randomized control trial

The Developing Inclusive Youth program is a classroom-based, individually administered video tool that depicts peer-based social and racial exclusion, combined with teacher-led discussions. A multisite randomized control trial was implemented with 983 participants (502 females; 58.5% White, 41.5% Ethnic/racial minority; Mage = 9.64 years) in 48 third-, fourth-, and fifth-grade classrooms across six schools. Children in the program were more likely to view interracial and same-race peer exclusion as wrong, associate positive traits with peers of different racial, ethnic, and gender backgrounds, and report play with peers from diverse backgrounds than were children in the control group. Many approaches are necessary to achieve antiracism in schools. This intervention is one component of this goal for developmental science.https://doi.org/10.1111/cdev.1378