Background Viruses are frequently associated with acute exacerbations of asthma, but the extent to which they contribute to the level of day-to-day symptom control is less clear. Objective We sought ...to explore the relationship between viral infections, host and environmental factors, and respiratory symptoms in children. Methods Sixty-seven asthmatic children collected samples twice weekly for an average of 10 weeks. These included nasal wash fluid and exhaled breath for PCR-based detection of viral RNA, lung function measurements, and records of medication use and asthma and respiratory symptoms in the previous 3 days. Atopy, mite allergen exposure, and vitamin D levels were also measured. Mixed-model regression analyses were performed. Results Human rhinoviruses (hRVs) were detected in 25.5% of 1232 nasal samples and 11.5% of breath samples. Non-hRV viruses were detected in less than 3% of samples. hRV in nasal samples was associated with asthma symptoms (cough and phlegm: odds ratio = 2.0; 95% CI = 1.4-2.86, P = .0001; wheeze and chest tightness: odds ratio = 2.34, 95% CI = 1.55-3.52, P < .0001) and with cold symptoms, as reported concurrently with sampling and 3 to 4 days later. No differences were found between the 3 hRV genotypes (hRV-A, hRV-B, and hRV-C) in symptom risk. A history of inhaled corticosteroid use, but not atopic status, mite allergen exposure, or vitamin D levels, modified the association between viruses and asthma symptoms. Conclusion The detection of nasal hRV was associated with a significantly increased risk of day-to-day asthma symptoms in children. Host, virus genotype, and environmental factors each had only a small or no effect on the relationship of viral infections to asthma symptoms.
To the Editor: The Childhood Asthma Prevention Study is a randomized controlled trial to test the effectiveness of house dust mite (HDM) avoidance and dietary fatty acid modification during the first ...5 years of life as strategies for the primary prevention of asthma and allergy in high-risk children. Â HDM intervention Diet intervention Outcome Active (%) Control (%) Absolute risk reductionlow * (95% CI) Active (%) Control (%) Absolute risk reductionlow * (95% CI) Atopy 43.9 46.1 2.2 (-7.5 to 12.0) 45.1 45.0 -0.2 (-9.9 to 9.6) HDM allergy 33.2 37.9 4.7 (-4.6 to 14.1) 38.2 32.8 -5.4 (-14.8 to 3.9) Wheeze 29.6 25.7 -3.9 (-12.2 to 4.4) 31.7 23.2 -8.6 (-16.8 to -0.4) AHR 18.5 18.4 0.1 (-8.1 to 8.0) 18.0 19.0 1.0 (-7.1 to 9.0) Asthma 23.2 21.7 -1.4 (-9.2 to 6.3) 24.8 20.0 -4.8 (-12.5 to 2.9) Poor asthma control 8.6 10.9 2.2 (-3.2 to 7.7) 10.4 9.1 -1.3 (-6.8 to 4.1) Eczema 14.4 15.0 0.6 (-6.1 to 7.3) 15.3 14.2 -1.1 (-7.8 to 5.6) Rhinitis 32.3 27.8 -4.5 (-12.9 to 4.0) 30.4 29.6 -0.9 (-9.4 to 7.6) Serum total IgE >1000 IU 9.7 8.6 -1.1 (-7.5 to 5.3) 8.5 9.9 1.5 (-4.9 to 7.8) Specific anti-HDM IgE positive 43.0 42.4 -0.7 (-11.3 to 9.9) 44.8 40.4 -4.5 (-15.0 to 6.1) FeNO >15 ppb 12.2 11.9 -0.3 (-6.7 to 6.1) 13.4 10.8 -2.6 (-9.0 to 3.8) Table I Effect of the interventions on clinical outcomes assessed at 8 years of age AHR, Airway hyperresponsiveness; FeNO, fraction of exhaled nitric oxide.
We present a search for neutrino induced events containing a single, exclusive photon using data from the NOMAD experiment at the CERN SPS where the average energy of the neutrino flux is ≃25 GeV. ...The search is motivated by an excess of electron-like events in the 200–475 MeV energy region as reported by the MiniBooNE experiment. In NOMAD, photons are identified via their conversion to e+e− in an active target embedded in a magnetic field. The background to the single photon signal is dominated by the asymmetric decay of neutral pions produced either in a coherent neutrino–nucleus interaction, or in a neutrino–nucleon neutral current deep inelastic scattering, or in an interaction occurring outside the fiducial volume. All three backgrounds are determined in situ using control data samples prior to opening the ‘signal-box’. In the signal region, we observe 155 events with a predicted background of 129.2±8.5±3.3. We interpret this as null evidence for excess of single photon events, and set a limit. Assuming that the hypothetical single photon has a momentum distribution similar to that of a photon from the coherent π0 decay, the measurement yields an upper limit on single photon events, <4.0×10−4 per νμ charged current event. Narrowing the search to events where the photon is approximately collinear with the incident neutrino, we observe 78 events with a predicted background of 76.6±4.9±1.9 yielding a more stringent upper limit, <1.6×10−4 per νμ charged current event.
We provide guidance for considering equity in rapid reviews through examples of published COVID-19 rapid reviews.
This guidance was developed based on a series of methodological meetings, review of ...internationally renowned guidance such as the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for equity-focused systematic reviews (PRISMA-Equity) guideline. We identified Exemplar rapid reviews by searching COVID-19 databases and requesting examples from our team.
We proposed the following key steps: 1. involve relevant stakeholders with lived experience in the conduct and design of the review; 2. reflect on equity, inclusion and privilege in team values and composition; 3. develop research question to assess health inequities; 4. conduct searches in relevant disciplinary databases; 5. collect data and critically appraise recruitment, retention and attrition for populations experiencing inequities; 6. analyse evidence on equity; 7. evaluate the applicability of findings to populations experiencing inequities; and 8. adhere to reporting guidelines for communicating review findings. We illustrated these methods through rapid review examples.
Implementing this guidance could contribute to improving equity considerations in rapid reviews produced in public health emergencies, and help policymakers better understand the distributional impact of diseases on the population.
In recent years, large losses of migrating adult sockeye salmon (
Oncorhynchus nerka
) from the Fraser River, British Columbia, Canada, have resulted in reductions in catches and productivity. We ...investigated patterns of mortality and the occurrence of the myxosporean parasite
Parvicapsula minibicornis
in adult sockeye salmon from Cultus Lake, tributary to the Fraser River. Using data from a captive broodstock program, we found that early migrants to Cultus Lake had less severe P. minibicornis infections and were more likely to survive to maturity than those fish that arrived later after they had presumably held in the warmer Fraser River. We found P. minibicornis in kidneys and gills of spawners. In some fish, significant histopathology in the gills that included severe inflammation and hyperplasia of the gill lamellae was observed;; the severity of the disease was correlated with the severity of P. minibicornis infections. Kidney and gill pathologies were more prevalent and more severe in fish that died before spawning compared with those that matured successfully. Gill disease associated with P. minibicornis infections had not been previously identified in Fraser River sockeye salmon, and its role in the loss of spawners needs further investigation.
We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in ...patients receiving weekly paclitaxel could improve outcomes in such patients.
In dose escalation, weekly paclitaxel (80mg/m2) was given 6/7weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small-cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively.
The dose-escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. On the basis of toxicity and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80mg/m2 paclitaxel with 50mg vistusertib bd 3/7days for 6/7weeks. In the HGSOC expansion, RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively, with median progression-free survival (mPFS) of 5.8months (95% CI: 3.28–18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%), and the mPFS was 5.8months (95% CI: 2.76–21.25).
In this phase I trial, we report a highly active and well-tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC.
ClinicialTrials.gov identifier: CNCT02193633
There is a lack of quantitative information about the generation of virus aerosols by infected subjects. The exhaled aerosols generated by coughing, talking, and breathing were sampled in 50 subjects ...using a novel mask, and analyzed using PCR for nine respiratory viruses. The exhaled samples from a subset of 10 subjects who were PCR positive for rhinovirus were also examined by cell culture for this virus. Of the 50 subjects, among the 33 with symptoms of upper respiratory tract infections, 21 had at least one virus detected by PCR, while amongst the 17 asymptomatic subjects, 4 had a virus detected by PCR. Overall, rhinovirus was detected in 19 subjects, influenza in 4 subjects, parainfluenza in 2 subjects, and human metapneumovirus in 1 subject. Two subjects were co-infected. Of the 25 subjects who had virus-positive nasal mucus, the same virus type was detected in 12 breathing samples, 8 talking samples, and in 2 coughing samples. In the subset of exhaled samples from 10 subjects examined by culture, infective rhinovirus was detected in 2. These data provide further evidence that breathing may be a source of respirable particles carrying infectious virus. J. Med. Virol. 81:1674-1679, 2009.
We have developed a mask sampler for exhaled respiratory viruses. Among a group of 9 patients with cold symptoms who had virus-positive nasal mucus specimens, as analyzed by multiplexed polymerase ...chain reaction, virus-positive mask samples were obtained after coughing (20 times), talking (20 min), or breathing (20 min) from 6, 5, and 3 patients, respectively.
Studies of the spin and parity quantum numbers of the Higgs boson are presented, based on proton–proton collision data collected by the ATLAS experiment at the LHC. The Standard Model spin–parity ...JP=0+ hypothesis is compared with alternative hypotheses using the Higgs boson decays H→γγ, H→ZZ⁎→4ℓ and H→WW⁎→ℓνℓν, as well as the combination of these channels. The analysed dataset corresponds to an integrated luminosity of 20.7 fb−1 collected at a centre-of-mass energy of s=8TeV. For the H→ZZ⁎→4ℓ decay mode the dataset corresponding to an integrated luminosity of 4.6 fb−1 collected at s=7TeV is included. The data are compatible with the Standard Model JP=0+ quantum numbers for the Higgs boson, whereas all alternative hypotheses studied in this Letter, namely some specific JP=0−,1+,1−,2+ models, are excluded at confidence levels above 97.8%. This exclusion holds independently of the assumptions on the coupling strengths to the Standard Model particles and in the case of the JP=2+ model, of the relative fractions of gluon-fusion and quark–antiquark production of the spin-2 particle. The data thus provide evidence for the spin-0 nature of the Higgs boson, with positive parity being strongly preferred.
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