Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent.

OBJECTIVES: To determine how the intrinsic severity of successively dominant SARS-CoV-2 variants changed over the course of the pandemic. METHODS: A retrospective cohort analysis in the NHS Greater Glasgow and Clyde (NHS GGC) Health Board. All sequenced non-nosocomial adult COVID-19 cases in NHS GGC with relevant SARS-CoV-2 lineages (B.1.177/Alpha, Alpha/Delta, AY.4.2 Delta/non-AY.4.2 Delta, non-AY.4.2 Delta/Omicron, and BA.1 Omicron/BA.2 Omicron) during analysis periods were included. Outcome measures were hospital admission, ICU admission, or death within 28 days of positive COVID-19 test. We report the cumulative odds ratio; the ratio of the odds that an individual experiences a severity event of a given level vs all lower severity levels for the resident and the replacement variant after adjustment. RESULTS: After adjustment for covariates, the cumulative odds ratio was 1.51 (95% CI: 1.08-2.11) for Alpha versus B.1.177, 2.09 (95% CI: 1.42-3.08) for Delta versus Alpha, 0.99 (95% CI: 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta, 0.49 (95% CI: 0.22-1.06) for Omicron versus non-AY.4.2 Delta, and 0.86 (95% CI: 0.68-1.09) for BA.2 Omicron versus BA.1 Omicron. CONCLUSIONS: The direction of change in intrinsic severity between successively emerging SARS-CoV-2 variants was inconsistent, reminding us that the intrinsic severity of future SARS-CoV-2 variants remains uncertain.

The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis.

OBJECTIVES: The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this. METHODS: In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death. RESULTS: Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants). CONCLUSIONS: The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.

Genomic epidemiology reveals multiple introductions of SARS-CoV-2 from mainland Europe into Scotland.

Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.

Fullerene Desymmetrization as a Means to Achieve Single-Enantiomer Electron Acceptors with Maximized Chiroptical Responsiveness.

Solubilized fullerene derivatives have revolutionized the development of organic photovoltaic devices, acting as excellent electron acceptors. The addition of solubilizing addends to the fullerene cage results in a large number of isomers, which are generally employed as isomeric mixtures. Moreover, a significant number of these isomers are chiral, which further adds to the isomeric complexity. The opportunities presented by single-isomer, and particularly single-enantiomer, fullerenes in organic electronic materials and devices are poorly understood however. Here, ten pairs of enantiomers are separated from the 19 structural isomers of bis[60]phenyl-C61-butyric acid methyl ester, using them to elucidate important chiroptical relationships and demonstrating their application to a circularly polarized light (CPL)-detecting device. Larger chiroptical responses are found, occurring through the inherent chirality of the fullerene. When used in a single-enantiomer organic field-effect transistor, the potential to discriminate CPL with a fast light response time and with a very high photocurrent dissymmetry factor (gph  = 1.27 ± 0.06) is demonstrated. This study thus provides key strategies to design fullerenes with large chiroptical responses for use as chiral components of organic electronic devices. It is anticipated that this data will position chiral fullerenes as an exciting material class for the growing field of chiral electronic technologies.

Natural optical activity as the origin of the large chiroptical properties in π-conjugated polymer thin films.

Polymer thin films that emit and absorb circularly polarised light have been demonstrated with the promise of achieving important technological advances; from efficient, high-performance displays, to 3D imaging and all-organic spintronic devices. However, the origin of the large chiroptical effects in such films has, until now, remained elusive. We investigate the emergence of such phenomena in achiral polymers blended with a chiral small-molecule additive (1-aza[6]helicene) and intrinsically chiral-sidechain polymers using a combination of spectroscopic methods and structural probes. We show that - under conditions relevant for device fabrication - the large chiroptical effects are caused by magneto-electric coupling (natural optical activity), not structural chirality as previously assumed, and may occur because of local order in a cylinder blue phase-type organisation. This disruptive mechanistic insight into chiral polymer thin films will offer new approaches towards chiroptical materials development after almost three decades of research in this area.

Highly Efficient Inverted Circularly Polarized Organic Light-Emitting Diodes.

Circularly polarized (CP) electroluminescence has been demonstrated as a strategy to improve the performance of organic light-emitting diode (OLED) displays. CP emission can be generated from both small-molecule and polymer OLEDs (SM-OLEDs and PLEDs), but to date, these devices suffer from low dissymmetry factors (g-factor < 0.1), poor device performance, or a combination of the two. Here, we demonstrate the first CP-PLED employing an inverted device architecture. Through this approach, we demonstrate a highly efficient CP-PLED, with a current efficiency of 16.4 cd/A, a power efficiency of 16.6 lm/W, a maximum luminance of over 28,500 cd/m2, and a high EL dissymmetry (gEL) of 0.57. We find that the handedness of the emitted light is sensitive to the PLED device architecture: the sign of CP-EL from an identically prepared active layer reverses between inverted and conventional devices. The inverted structure affords the first demonstration of CP-PLEDs exhibiting both high efficiency and high dissymmetry-the two figures of merit which, until now, have been difficult to achieve at the same time. We also highlight device architecture and associated internal electric field to be a previously unexplored means to control the handedness of CP emission. Our findings significantly broaden the versatility of CP emissive devices and should enable their further application in a variety of other CP-dependent technologies.

A Systematic Review of Clinical Practice Guidelines for the Diagnosis and Management of Bronchiolitis.

BACKGROUND: Bronchiolitis is the leading cause of hospital admission for respiratory disease among infants aged <1 year. Clinical practice guidelines can benefit patients by reducing the performance of unnecessary tests, hospital admissions, and treatment with lack of a supportive evidence base. This review aimed to identify current clinical practice guidelines worldwide, appraise their methodological quality, and discuss variability across guidelines for the diagnosis and management of bronchiolitis. METHODS: A systematic literature review of electronic databases EMBASE, Global Health, and Medline was performed. Manual searches of the gray literature, national pediatric society websites, and guideline-focused databases were performed, and select international experts were contacted to identify additional guidelines. The Appraisal of Guidelines for Research and Evaluation assessment tool was used by 2 independent reviewers to appraise each guideline. RESULTS: Thirty-two clinical practice guidelines met the selection criteria. Quality assessment revealed significant shortcomings in a number of guidelines, including lack of systematic processes in formulating guidelines, failure to state conflicts of interest, and lack of consultation with families of affected children. There was widespread agreement about a number of aspects, such as avoidance of the use of unnecessary diagnostic tests, risk factors for severe disease, indicators for hospital admission, discharge criteria, and nosocomial infection control. However, there was variability, even within areas of consensus, over specific recommendations, such as variable thresholds for oxygen therapy. Guidelines showed significant variability in recommendations for the pharmacological management of bronchiolitis, with conflicting recommendations over whether use of nebulized epinephrine, hypertonic saline, or bronchodilators should be routinely trialled. CONCLUSIONS: Future guidelines should aim to be compliant with international standards for clinical guidelines to improve their quality and clarity and to promote their adoption into practice. Variable recommendations between guidelines may reflect the evolving evidence base for bronchiolitis management, and platforms should be created to understand this variability and promote evidence-based recommendations.

Inverting the Handedness of Circularly Polarized Luminescence from Light-Emitting Polymers Using Film Thickness.

The emission of circularly polarized light is central to many applications, including data storage, optical quantum computation, biosensing, environmental monitoring, and display technologies. An emerging method to induce (chiral) circularly polarized (CP) electroluminescence from the active layer of polymer light-emitting diodes (polymer OLEDs; PLEDs) involves blending achiral polymers with chiral small-molecule additives, where the handedness/sign of the CP light is controlled by the absolute stereochemistry of the small molecule. Through the in-depth study of such a system we report an interesting chiroptical property: the ability to tune the sign of CP light as a function of active layer thickness for a fixed enantiomer of the chiral additive. We demonstrate that it is possible to achieve both efficient (4.0 cd/A) and bright (8000 cd/m2) CP-PLEDs, with high dissymmetry of emission of both left-handed (LH) and right-handed (RH) light, depending on thickness (thin films, 110 nm: gEL = 0.51, thick films, 160 nm: gEL = -1.05, with the terms "thick" and "thin" representing the upper and lower limits of the thickness regime studied), for the same additive enantiomer. We propose that this arises due to an interplay between localized CP emission originating from molecular chirality and CP light amplification or inversion through a chiral medium. We link morphological, spectroscopic, and electronic characterization in thin films and devices with theoretical studies in an effort to determine the factors that underpin these observations. Through the control of active layer thickness and device architecture, this study provides insights into the mechanisms that result in CP luminescence and high performance from CP-PLEDs, as well as demonstrating new opportunities in CP photonic device design.

Nanoscale Ion-Doped Polymer Transistors.

Organic transistors with submicron dimensions have been shown to deviate from the expected behavior due to a variety of so-called "short-channel" effects, resulting in nonlinear output characteristics and a lack of current saturation, considerably limiting their use. Using an electrochemically doped polymer in which ions are dynamically injected and removed from the bulk of the semiconductor, we show that devices with nanoscale channel lengths down to 50 nm exhibit output curves with well-defined linear and saturation regimes. Additionally, they show very large on-currents on par with their microscale counterparts, large on-to-off ratios of 108, and record-high width-normalized transconductances above 10 S m-1. We believe this work paves the way for the fabrication of high-gain, high-current polymer integrated circuits such as sensor arrays operating at voltages below |1 V| and prepared using simple solution-processing methods.

Emergent Properties of an Organic Semiconductor Driven by its Molecular Chirality.

Chiral molecules exist as pairs of nonsuperimposable mirror images; a fundamental symmetry property vastly underexplored in organic electronic devices. Here, we show that organic field-effect transistors (OFETs) made from the helically chiral molecule 1-aza[6]helicene can display up to an 80-fold difference in hole mobility, together with differences in thin-film photophysics and morphology, solely depending on whether a single handedness or a 1:1 mixture of left- and right-handed molecules is employed under analogous fabrication conditions. As the molecular properties of either mirror image isomer are identical, these changes must be a result of the different bulk packing induced by chiral composition. Such underlying structures are investigated using crystal structure prediction, a computational methodology rarely applied to molecular materials, and linked to the difference in charge transport. These results illustrate that chirality may be used as a key tuning parameter in future device applications.

Circularly Polarized Phosphorescent Electroluminescence with a High Dissymmetry Factor from PHOLEDs Based on a Platinahelicene.

Circularly polarized (CP) light is of interest in areas such as quantum optical computing, optical spintronics, biomedicine, and high efficiency displays. Direct emission of CP light from organic light-emitting diodes (OLEDs) has been a focus of research as it has the immediate application of increasing efficiency and simplifying device architecture in OLED based displays. High dissymmetry (gEL) factor values have been reported for devices employing fluorescent polymers, but these CP-OLEDs are limited in their ultimate efficiencies by the type of emissive electronic transitions involved. In contrast, phosphorescent OLEDs (PHOLEDs) can emit light from triplet excited states and can therefore achieve very high efficiencies. However, CP-PHOLEDs are significantly understudied, and the two previous reports suffered from very low brightness or gEL values. Here, we use a platinahelicene complex to construct a CP-PHOLED that achieves both a display level brightness and a high gEL factor. The dissymmetry of CP emission reached with this proof-of-concept single-layer helicene-based device is sufficient to provide real-world benefits over nonpolarized emission and paves the way toward chiral metal complex-based CP-PHOLED displays.

Quantitative analysis and optimization of gravure printed metal ink, dielectric, and organic semiconductor films.

Here we demonstrate the optimization of gravure printed metal ink, dielectric, and semiconductor formulations. We present a technique for nondestructively imaging printed films using a commercially available flatbed scanner, combined with image analysis to quantify print behavior. Print speed, cliché screen density, nip pressure, the orientation of print structures, and doctor blade extension were found to have a significant impact on the quality of printed films, as characterized by the spreading of printed structures and variation in print homogeneity. Organic semiconductor prints were observed to exhibit multiple periodic modulations, which are correlated to the underlying cell structure.

Induction of circularly polarized electroluminescence from an achiral light-emitting polymer via a chiral small-molecule dopant.

By simply doping the conventional light-emitting polymer F8BT with a helically chiral aromatic molecule, it is shown that substantial levels of CP-electroluminescence can be generated directly. Both photoluminescent and electroluminescent emission from the polymer are observed to become circularly polarized, with the sign of the CP emission directly determined by the handedness of the dopant.