Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than ...18 years compared with the same data that are available in adults.
COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6–17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 1010 viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12–17 years were enrolled before those aged 6–11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12–17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344).
Between Feb 15 and April 2, 2021, 262 participants (150 57% participants aged 12–17 years and 112 43% aged 6–11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 n=105 at day 28 and n=106 at day 84) or control (n=51 n=26 at day 28 and n=25 at day 84). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6–11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12–17 years with a longer interval between doses (geometric means of 73 371 arbitrary units AU/mL 95% CI 58 685–91 733 and 299 half-maximal inhibitory concentration IC50; 95% CI 230–390) compared with those aged 12–17 years who received their vaccines 28 days apart (43 280 AU/mL 95% CI 35 852–52 246 and 150 IC50 95% CI 116–194). Humoral responses were higher in those aged 6–11 years than in those aged 12–17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 95% CI 1·07–2·07 for anti-SARS-CoV-2 IgG and 2·96 1·89–4·62 for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination.
ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6–17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial.
AstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research.
In this work we present a new multi-resonance thermally activated delayed fluorescence (MR-TADF) emitter paradigm, demonstrating that the structure need not require the presence of acceptor atoms. ...Based on an
in silico
design, the compound
DiICzMes
4
possesses a red-shifted emission, enhanced photoluminescence quantum yield, and smaller singlet-triplet energy gap, Δ
E
ST
, than the parent indolocarbazole that induces MR-TADF properties. Coupled cluster calculations accurately predict the magnitude of the Δ
E
ST
when the optimized singlet and triplet geometries are used. Slow yet optically detectable reverse intersystem crossing contributes to low efficiency in organic light-emitting diodes using
DiICzMes
4
as the emitter. However, when used as a terminal emitter in combination with a TADF assistant dopant within a hyperfluorescence device architecture, maximum external quantum efficiencies of up to 16.5% were achieved at CIE (0.15, 0.11). This represents one of the bluest hyperfluorescent devices reported to date. Simultaneously, recognising that MR-TADF emitters do not require acceptor atoms reveals an unexplored frontier in materials design, where yet greater performance may yet be discovered.
We present a new multi-resonance thermally activated delayed fluorescence (MR-TADF) emitter paradigm, demonstrating that the structure need not require the presence of acceptor atoms.
Developing high‐efficiency purely organic blue organic light‐emitting diodes (OLEDs) that meet the stringent industry standards is a major current research challenge. Hyperfluorescent device ...approaches achieve in large measure the desired high performance by combining the advantages of a high‐efficiency thermally activated delayed fluorescence (TADF) assistant dopant with a narrowband deep‐blue multi‐resonant TADF (MR‐TADF) terminal emitter. However, this approach requires suitable spectral overlap to support Förster resonance energy transfer (FRET) between the two. Here, a color tuning of a recently reported MR‐TADF B,N‐heptacene core through control of the boron substituents is demonstrated. While there is little impact on the intrinsic TADF properties—as both singlet and triplet energies decrease in tandem—this approach improves the emission color coordinate as well as the spectral overlap for blue hyperfluorescence OLEDs (HF OLEDs). Crucially, the red‐shifted and more intense absorption allows the new MR‐TADF emitter to pair with a high‐performance TADF assistant dopant and achieve maximum external quantum efficiency (EQEmax) of 15% at color coordinates of (0.15 and 0.10). The efficiency values recorded for the device at a practical luminance of 100 cd m–2 are among the highest reported for HF TADF OLEDs with CIEy ≤ 0.1.
Pairing terminal emitters with suitable assistant dopants in hyperfluorescence organic light‐emitting diodes can be restrictive. Here, exchanging boron substituents simultaneously tunes both the emission and absorption spectra of a multi‐resonant TADF B,N‐heptacene, allowing use with available blue TADF cohosts. This approach may circumvent the need for deeper‐blue TADF cohosts by instead expanding hyperfluorescence compatibility to more stable cyan or green materials.
Manually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary ...in their level of public accessibility, and the complexity of the models used to capture clinical knowledge. CIViC (Clinical Interpretation of Variants in Cancer - www.civicdb.org) is a fully open, free-to-use cancer variant interpretation knowledgebase that incorporates highly detailed curation of evidence obtained from peer-reviewed publications and meeting abstracts, and currently holds over 6300 Evidence Items for over 2300 variants derived from over 400 genes. CIViC has seen increased adoption by, and also undertaken collaboration with, a wide range of users and organizations involved in research. To enhance CIViC's clinical value, regular submission to the ClinVar database and pursuit of other regulatory approvals is necessary. For this reason, a formal peer reviewed curation guideline and discussion of the underlying principles of curation is needed. We present here the CIViC knowledge model, standard operating procedures (SOP) for variant curation, and detailed examples to support community-driven curation of cancer variants.
Extensive research has been devoted to the development of thermally activated delayed fluorescence emitters, especially those showing pure-blue emission for use in lighting and full-color display ...applications. Toward that goal, herein we report a novel weak donor, 1,4-azaborine (AZB), with complementary electronic and structural properties compared to the widely used dimethylacridan (DMAC) or carbazole (Cz) donors. Coupled with a triazine acceptor, AZB-Ph-TRZ is the direct structural analogue of the high-performance and well-studied green TADF emitter DMAC-TRZ and has ΔE ST = 0.39 eV, a photoluminescence quantum yield (ΦPL) of 27%, and λPL = 415 nm in 10 wt % doped mCP films. The shortened analogue AZB-TRZ possesses red-shifted emission with a reduced singlet–triplet gap (ΔE ST = 0.01 eV) and fast reverse intersystem crossing (k RISC of 5 × 106 s–1) in mCP. Despite a moderate ΦPL of 34%, OLEDs with AZB-TRZ in mCP showed sky-blue emission with CIE1931(x,y) of (0.22,0.39) and a maximum external quantum efficiency (EQEmax) of 10.5%. Expanding the chemist’s toolkit for the design of blue donor–acceptor TADF materials will enable yet further advances in the future, as AZB is paired with a wider range of acceptor groups.
The biological challenges facing humanity are complex, multi-factorial, and are intimately tied to the future of our health, welfare, and stewardship of the Earth. Tackling problems in diverse areas, ...such as agriculture, ecology, and health care require linking vast datasets that encompass numerous components and spatio-temporal scales. Here, we provide a new framework and a road map for using experiments and computation to understand dynamic biological systems that span multiple scales. We discuss theories that can help understand complex biological systems and highlight the limitations of existing methodologies and recommend data generation practices. The advent of new technologies such as big data analytics and artificial intelligence can help bridge different scales and data types. We recommend ways to make such models transparent, compatible with existing theories of biological function, and to make biological data sets readable by advanced machine learning algorithms. Overall, the barriers for tackling pressing biological challenges are not only technological, but also sociological. Hence, we also provide recommendations for promoting interdisciplinary interactions between scientists.
Purpose
Our aim was to determine whether perioperatively administered corticosteroid treatment has any beneficial effect on the outcome of stapes surgery, with special regard to the audiological ...results and early postoperative morbidity.
Methods
84 CO
2
laser stapedotomies performed in our institute between 2013 and 2018 were included in our investigation. All cases underwent preoperative and mid-term postoperative pure-tone audiometric evaluation. Vestibular complications were also evaluated. The cases were subdivided into two groups, 23 patients received perioperative i.v. methylprednisolone treatment (“S”) while the other 61 patients (“nS”) did not receive any adjuvant pharmacological therapy. The data were analyzed retrospectively using IBM SPSS Statistics.
Results
CO
2
laser stapedotomy proved to be a successful intervention with a significant improvement in ABG and AC thresholds as well. Long-term BC levels were significantly better compared to preoperative ones in the S group; however, in the nS group, no difference could be shown. Hearing and ABG gain were significantly superior in group S 28.1 dB (SD11.2) vs. 18.1 dB (SD 10.9) and 23.9 dB(SD 9.8) vs. 17.2 dB (SD 9.5), respectively.
Conclusion
No significant inner ear damage was detectable in the results of our CO
2
laser stapedotomy method; however, the positive effect of corticosteroid treatment could be demonstrated through the postoperative hearing levels. We found no statistical difference in early postoperative morbidity. According to our data, the routine administration of corticosteroids during stapes surgery could be an issue worthy of consideration. The effects of perioperative treatment vs that on the first day after surgery, and topical vs. systemic treatment could be the subject of further investigation in a prospective manner.
An elicitation method increased the synthesis of anthraquinone derivatives occurring in cell suspension cultures of
Rubia tinctorum L. High performance liquid chromatography coupled with diode array ...detection and mass spectrometry (HPLC–DAD–MS) was used for the detection and quantification of the two glycosides, lucidin primeveroside and ruberithric acid and eight aglycones, namely pseudopurpurin, lucidin, alizarin, purpurin, alizarin-2-methylether, lucidin-ω-ethylether, nordamnacanthal and munjistin ethyl ester. The improved elicitor treatment of the suspension cultures increased the amounts of the natural dyes; the different elicitors, such as fungal polysaccharides and endogenous signal molecules (salicylic and jasmonic acid) provided specific yields of anthraquinone derivatives. After 7 days of elicitation, the total yield of anthraquinones increased from ≈70
mg
g
−1 to ≈262
mg
g
−1 while the amounts of lucidin primeveroside and ruberithric acid grew threefold and the quantity of pseudopurpurin increased by a factor of 28.
Our aim was to determine whether perioperatively administered corticosteroid treatment has any beneficial effect on the outcome of stapes surgery, with special regard to the audiological results and ...early postoperative morbidity.
84 CO
laser stapedotomies performed in our institute between 2013 and 2018 were included in our investigation. All cases underwent preoperative and mid-term postoperative pure-tone audiometric evaluation. Vestibular complications were also evaluated. The cases were subdivided into two groups, 23 patients received perioperative i.v. methylprednisolone treatment ("S") while the other 61 patients ("nS") did not receive any adjuvant pharmacological therapy. The data were analyzed retrospectively using IBM SPSS Statistics.
CO
laser stapedotomy proved to be a successful intervention with a significant improvement in ABG and AC thresholds as well. Long-term BC levels were significantly better compared to preoperative ones in the S group; however, in the nS group, no difference could be shown. Hearing and ABG gain were significantly superior in group S 28.1 dB (SD11.2) vs. 18.1 dB (SD 10.9) and 23.9 dB(SD 9.8) vs. 17.2 dB (SD 9.5), respectively.
No significant inner ear damage was detectable in the results of our CO
laser stapedotomy method; however, the positive effect of corticosteroid treatment could be demonstrated through the postoperative hearing levels. We found no statistical difference in early postoperative morbidity. According to our data, the routine administration of corticosteroids during stapes surgery could be an issue worthy of consideration. The effects of perioperative treatment vs that on the first day after surgery, and topical vs. systemic treatment could be the subject of further investigation in a prospective manner.
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