Summary
Background
The effects of environmental factors and ambient concentrations of grass pollen on allergic asthma are yet to be established.
Objective
We sought to estimate the independent ...effects of grass pollen concentrations in the air over Melbourne on asthma hospital admissions for the 1992–1993 pollen season.
Methods
Daily grass pollen concentrations were monitored over a 24‐h period at three stations in Melbourne. The outcome variable was defined as all‐age asthma hospital admissions with ICD9‐493 codes. The ambient air pollutants were average daily measures of ozone, nitrogen dioxide and sulphur dioxide, and the airborne particle index representing fine particulate pollution. Semi‐parametric Poisson regression models were used to estimate these effects, adjusted for air temperature, humidity, wind speed, rainfall, day‐of‐the‐week effects and seasonal variation.
Results
Grass pollen was a strong independent non‐linear predictor of asthma hospital admissions in a multi‐pollutant model (P=0.01). Our data suggest that grass pollen had an increasing effect on asthma hospital admissions up to a threshold of 30 grains/m3, and that the effect remains stable thereafter.
Conclusion
Our findings suggest that grass pollen levels influence asthma hospital admissions. High grass pollen days, currently defined as more than 50 grains/m3, are days when most sensitive individuals will experience allergic symptoms. However, some asthmatic patients may be at a significant risk even when airborne grass pollen levels are below this level. Patients with pollen allergies and asthma would be advised to take additional preventive medication at lower ambient concentrations.
Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which ...combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown.
This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28.
A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval CI, 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range IQR, 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated.
Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals.
NCT05142319.
Over 2021, COVID-19 vaccination programs worldwide focused on raising population immunity through the primary COVID-19 vaccine series. In Singapore, two mRNA vaccines (BNT162b2 and mRNA-1273) and the ...inactivated vaccine CoronaVac are currently authorized under the National Vaccination Programme for use as the primary vaccination series. More than 90% of the Singapore population has received at least one dose of a COVID-19 vaccine as of December 2021. With the demonstration that vaccine effectiveness wanes in the months after vaccination, and the emergence of Omicron which evades host immunity from prior infection and/or vaccination, attention in many countries has shifted to how best to maintain immunity through booster vaccinations.
The objectives of this phase 3, randomized, subject-blinded, controlled clinical trial are to assess the safety and immunogenicity of heterologous boost COVID-19 vaccine regimens (intervention groups 1-4) compared with a homologous boost regimen (control arm) in up to 600 adult volunteers. As non-mRNA vaccine candidates may enter the study at different time points depending on vaccine availability and local regulatory approval, participants will be randomized at equal probability to the available intervention arms at the time of randomization. Eligible participants will have received two doses of a homologous mRNA vaccine series with BNT162b2 or mRNA-1273 at least 6 months prior to enrolment. Participants will be excluded if they have a history of confirmed SARS or SARS-CoV-2 infection, are immunocompromised, or are pregnant. Participants will be monitored for adverse events and serious adverse events by physical examinations, laboratory tests and self-reporting. Blood samples will be collected at serial time points pre-vaccination/screening (day - 14 to day 0), day 7, day 28, day 180, day 360 post-vaccination for assessment of antibody and cellular immune parameters. Primary endpoint is the level of anti-SARS-CoV-2 spike immunoglobulins at day 28 post-booster and will be measured against wildtype SARS-CoV-2 and variants of concern. Comprehensive immune profiling of the humoral and cellular immune response to vaccination will be performed.
This study will provide necessary data to understand the quantity, quality, and persistence of the immune response to a homologous and heterologous third booster dose of COVID-19 vaccines. This is an important step in developing COVID-19 vaccination programs beyond the primary series.
ClinicalTrials.gov NCT05142319 . Registered on 2 Dec 2021.
Structural phase transitions run in families of crystalline solids. Perovskites, for example, feature a remarkable number of structural transformations that produce a wealth of exotic behaviors, ...including ferroelectricity, magnetoresistance, metal–insulator transitions and superconductivity. In superatomic crystals and other such materials assembled from programmable building blocks, phase transitions offer pathways to new properties that are both tunable and switchable. Here we describe Co6Te8(PEt3)6C702, a novel superatomic crystal with two separate phase transitions that drastically transform the collective material properties. A coupled structural-electronic phase transition triggers the emergence of a new electronic band in the fullerene sublattice of the crystal, increasing its electrical conductivity by 2 orders of magnitude, while narrowing its optical gap and increasing its spin density. Independently, an order–disorder transition transforms Co6Te8(PEt3)6C702 from a phonon crystal to a phonon glass. These results introduce a family of materials in which functional phase transformations may be manipulated by varying the constituent building blocks.
Through atomistic computational analysis of thermal transport in nanocrystal arrays (NCAs), we find that vibrational states couple elastically across the organic–inorganic interfaces with a resulting ...flux that depends on the ligand grafting density and the overlap between the core and ligand vibrational spectra. The modeling was performed using molecular dynamics simulations and lattice dynamics calculations on a gold-dodecanethiol NCA built using a robust self-assembly methodology. Our approach is validated by comparing the predicted NCA thermal conductivities against experimental measurements Ong et al. Nat. Mater. 2013, 12, 410, with agreement found in both magnitude and trends. The self-assembly methodology enables prediction of general NCA behavior and detailed probing of experimentally inaccessible nanoscale phenomena.
•Commonly reported symptoms are headache, throat pain and lethargy.•A large number of healthcare workers report more than four symptoms.•Those with physical symptoms had higher rates of depression, ...anxiety, stress, PTSD.•Those with physical symptoms had higher mean scores in the IES-R, DASS subscales.•Association between physical symptoms and psychological outcomes may be bidirectional.
Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers.
Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated.
Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54–5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36–3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27–7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12–4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales.
Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.
We report on multifrequency observations performed during 2012 December-2013 August of the first narrow-line Seyfert 1 galaxy detected in gamma rays, PMN J0948+0022 (z equal to 0.5846). A gamma-ray ...flare was observed by the Large Area Telescope on board Fermi during 2012 December-2013 January, reaching a daily peak flux in the 0.1-100 GeV energy range of (155 plus or minus 31)×10(exp −8) ph cm (exp −2) s (exp −1) on 2013 January 1, corresponding to an apparent isotropic luminosity of approximately 1.5×10)exp 48) erg s(exp −1). The gamma-ray flaring period triggered Swift and VERITAS observations in addition to radio and optical monitoring by OVRO, MOJAVE, and CRTS. A strong flare was observed in optical, UV, and X- rays on 2012 December 30, quasi-simultaneously to the gamma-ray flare, reaching a record flux for this source from optical to gamma rays. VERITAS observations at very high energy (E greater than 100 GeV) during 2013 January 6-17 resulted in an upper limit of F(sub greater than 0.2 TeV) less than 4.0 × 10(exp −12) ph cm(exp −2) s(exp −1). We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
Aims/hypothesis
Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor ...prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts.
Methods
We conducted a meta-analysis of EWASs in blood collected 7–10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK).
Results
The meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (
p
values <1.1 × 10
−7
). Sixty-four out of 76 (84.2%) CpG sites were confirmed by directionally consistent effects and
p
values <0.05 in an independent cohort of Indian Asians. However, on adjustment for baseline BMI only four CpG sites remained genome-wide significant, and addition of the 76 CpG methylation risk score to a prediction model including established predictors of type 2 diabetes (age, sex, BMI and HbA
1c
) showed no improvement (AUC 0.757 vs 0.753). Gene set enrichment analysis of the full epigenome-wide results clearly showed enrichment of processes linked to insulin signalling, lipid homeostasis and inflammation.
Conclusions/interpretation
By combining results from five European cohorts, and thus significantly increasing study sample size, we identified 76 CpG sites associated with incident type 2 diabetes. Replication of 64 CpGs in an independent cohort of Indian Asians suggests that the association between DNA methylation levels and incident type 2 diabetes is robust and independent of ethnicity. Our data also indicate that BMI partly explains the association between DNA methylation and incident type 2 diabetes. Further studies are required to elucidate the underlying biological mechanisms and to determine potential causal roles of the differentially methylated CpG sites in type 2 diabetes development.
Graphical abstract
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