The next generation magnetic spectrometer in space, AMS-100, is designed to have a geometrical acceptance of 100 m 2 sr and to be operated for at least ten years at the Sun–Earth Lagrange Point 2. ...Compared to existing experiments, it will improve the sensitivity for the observation of new phenomena in cosmic rays, and in particular in cosmic antimatter, by at least a factor of 1000. The magnet design is based on high temperature superconductor tapes, which allow the construction of a thin solenoid with a homogeneous magnetic field of 1 Tesla inside. The inner volume is instrumented with a silicon tracker reaching a maximum detectable rigidity of 100 TV and a calorimeter system that is 70 radiation lengths deep, equivalent to four nuclear interaction lengths, which extends the energy reach for cosmic-ray nuclei up to the PeV scale, i.e. beyond the cosmic-ray knee. Covering most of the sky continuously, AMS-100 will detect high-energy gamma-rays in the calorimeter system and by pair conversion in the thin solenoid, reconstructed with excellent angular resolution in the silicon tracker.
The Delta (B.1.617.2) variant was the predominant UK circulating SARS-CoV-2 strain between May and December 2021. How Delta infection compares with previous variants is unknown. This prospective ...observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly the predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. 3581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta versus Alpha infection (including fever, sore throat, and headache) and some vice versa (dyspnoea). Symptom burden in the first week was higher with Delta versus Alpha infection; however, the odds of any given symptom lasting ≥ 7 days was either lower or unchanged. Illness duration ≥ 28 days was lower with Delta versus Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.49) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly reduced the risk of Delta infection (by 69-84%). We conclude that COVID-19 from Delta or Alpha infections is similar. The Delta variant is more transmissible than Alpha; however, current vaccines showed good efficacy against disease. This research framework can be useful for future comparisons with new emerging variants.
Summary
Background
High‐mobility group box 1 protein (HMGB1) belonging to endogenous danger signals prolongs eosinophil survival and acts as a chemoattractant.
Objective
The authors evaluated the ...role of HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation.
Methods
Firstly, HMGB1 expressions in induced sputum obtained from human asthmatics were determined. This was followed by an evaluation of the role of HMGB1 in a murine model of asthma using anti‐HMGB1 antibodies. Then the effect of HMGB1 on the receptor of advanced glycation end products (RAGE) expressions on CD11b‐CD11c+ cells isolated from a murine model of asthma were measured to elucidate the mechanisms involved.
Results
Sputum HMGB1 expressions were markedly higher in asthmatics than in normal controls, and were positively correlated with sputum eosinophilia and sputum TNF‐α, IL‐5 and IL‐13 expressions. In a murine model of asthma, HMGB1 expressions in lung tissue and HMGB1 levels in bronchoalveolar lavage fluid were significantly elevated and eosinophilic airway inflammation, non‐specific airway hyperresponsiveness, and pathological changes were attenuated by blocking HMGB1 activity. Furthermore, we found that enhanced RAGE expressions on CD11b‐CD11c+ also significantly decreased when HMGB1 activity was blocked.
Conclusion and Clinical Relevance
Our findings suggest that HMGB1 plays a key role in the pathogenesis of clinical and experimental asthma characterized by eosinophilic airway inflammation.
Aims To investigate whether fatty liver per se is an independent risk factor of incident type 2 diabetes mellitus (T2DM) in Koreans.
Methods We examined the clinical and laboratory data of 5372 ...non‐diabetic participants (3670 men and 1702 women; age 46.8 ± 8.4 years, range 20–79 years) who underwent voluntary medical check‐ups in 2000 and follow‐up examinations in 2005.
Results Two hundred and thirty‐three participants (4.3%) developed T2DM after 5 years. Univariate analysis showed that the development of diabetes was associated with: male sex; family history of diabetes; smoking; older age; higher body mass index (BMI), systolic and diastolic blood pressure, fasting plasma glucose (FPG), hepatic enzymes, total cholesterol and triglycerides; lower HDL cholesterol; and the presence of fatty liver on ultrasonography at baseline. In multiple logistic regression models, after adjusting for age, sex and alcohol consumption, patients with fatty liver were at significantly higher risk of developing T2DM compared to those without fatty liver relative risk (RR) 3.92, 95% confidence interval (CI) 2.89–5.31. After further adjustment for smoking, BMI, triglycerides, HDL cholesterol, FPG, alanine aminotransferase and ultrasonographer, fatty liver remained significantly associated with the development of T2DM (RR 1.51, 95% CI 1.04–2.20). Patients with moderate to severe fatty liver had higher risk ratios than patients with mild fatty liver. Exclusion of frequent drinkers did not attenuate the association.
Conclusions Fatty liver on ultrasonography is associated with the development of T2DM, independently of classical risk factors, in Korean adults.
Optical measurements using ultraviolet–visible (UV–VIS) spectrophotometric sensors and fluorescent dissolved organic matter (FDOM) sensors have recently been used as proxies of dissolved organic ...carbon (DOC) concentrations in streams and rivers at a high temporal resolution. Despite the merits of the sensors, temperature changes and particulate matter in water can interfere with the sensor readings, over- or underestimating DOC concentrations. However, little efforts have been made to compare responses of the two types of the sensors to critical interferences such as temperature and turbidity. The performance of a UV–VIS sensor and an FDOM sensor was compared in both laboratory experiments and in situ monitoring in a forest stream in Korea during three storm events. Although the UV–VIS sensor did not require temperature correction in laboratory experiments using the forest stream water, the deviations of its values from the DOC concentrations measured with a TOC analyzer increased linearly as turbidity increased. In contrast, the FDOM sensor outputs decreased significantly as temperature or turbidity increased, requiring temperature and turbidity correction for in situ monitoring of DOC concentrations. The results suggest that temperature correction is relatively straightforward but turbidity correction may not be simple because the attenuation of light by particles can significantly reduce the sensitivity of the sensors in highly turbid waters. Shifts in composition of fluorophores also need to be carefully tracked using periodically collected samples since light absorbance and fluorescence can vary as the concentrations of dominant fluorophores change.
Summary
Background
Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult‐onset asthma ...in community‐based populations.
Objective
We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community‐based adult populations.
Methods
The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin‐specific IgE using ImmunoCAP.
Results
Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin‐specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin‐specific IgE level was identified as the major determinant factor for total IgE level.
Conclusions and Clinical Relevance
Staphylococcal enterotoxin sensitization was independently associated with adult‐onset asthma in adult community populations. Strong correlations between the enterotoxin‐specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.
Summary
Background
Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects ...of human umbilical cord blood‐derived MSCs (huMSCs) remain largely unexamined for asthma.
Objective
This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)‐induced murine asthma model.
Methods
Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen‐specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells.
Results
Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA‐specific IgE and IgG1 levels along with Th2 cytokine production (IL‐4, IL‐5, and IL‐13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs.
Conclusions
Our results suggest that huMSC treatment reduces OVA‐induced allergic inflammation, which could be mediated by regulatory T cells.
This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer.
Patients with thyroid ...cancer of any histology that was resistant or not appropriate for 131I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate partial response (PR) + stable response ≥12 weeks. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD), progression-free survival (PFS), overall survival, duration of response, and safety.
Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks 95% confidence interval (CI) 14.9–78.5. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%).
Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation.
NCT01164176.
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