No effect of omeprazole on pH of exhaled breath condensate in cough associated with gastro-oesophageal reflux

BACKGROUND: Endogenous airway acidification evaluated as pH in exhaled breath condensate (EBC) has been described in patients with chronic cough. Proton pump inhibitors improve gastro-oesophageal reflux (GOR)-associated cough. METHODS: We examined pH levels in EBC and capsaicin cough response in 13 patients with chronic cough (mean age 41 years, SD 9) associated with GOR before and after omeprazole treatment (40 mg/day for 14 days) and its relationship with clinical response. RESULTS: Omeprazole abolished symptoms associated with GOR. Patients with chronic cough had an EBC pH of 8.28 (SD 0.13) prior to treatment but this did not change with omeprazole treatment. There was a significant improvement in the Leicester Cough Questionnaire symptom scores from 80.8 points (SD 13.2) to 95.1 (SD 17) (p = 0.02) and in a 6-point scale of cough scores, but there was no change in capsaicin cough response. CONCLUSION: An improvement in GOR-associated cough was not associated with changes in EBC pH or capsaicin cough response. These parameters are not useful markers of therapeutic response

BET bromodomains regulate transforming growth factor-beta-induced proliferation and cytokine release in asthmatic airway smooth muscle

Airway smooth muscle (ASM) mass is increased in asthma, and ASM cells from patients with asthma are hyperproliferative and release more IL-6 and CXCL8. The BET (bromo- and extra-terminal) family of proteins (Brd2, Brd3, and Brd4) govern the assembly of histone acetylation-dependent chromatin complexes. We have examined whether they modulate proliferation and cytokine expression in asthmatic ASM cells by studying the effect of BET bromodomain mimics JQ1/SGCBD01 and I-BET762. ASM cells from healthy individuals and nonsevere and severe asthmatics were pretreated with JQ1/SGCBD01 and I-BET762 prior to stimulation with FCS and TGF-β. Proliferation was measured by BrdU incorporation. IL-6 and CXCL8 release was measured by ELISA, and mRNA expression was measured by quantitative RT-PCR. ChIP using a specific anti-Brd4 antibody and PCR primers directed against the transcriptional start site of IL-6 and CXCL8 gene promoters was performed. Neither JQ1/SGCBD01 nor I-BET762 had any effect on ASM cell viability. JQ1/SGCBD01 and I-BET762 inhibited FCS+TGF-β-induced ASM cell proliferation and IL-6 and CXCL8 release in healthy individuals (≥ 30 nm) and in nonsevere and severe asthma patients (≥100 nm), with the latter requiring higher concentrations of these mimics. JQ1/SGCBD01 reduced Brd4 binding to IL8 and IL6 promoters induced by FCS+TGF-β. Mimics of BET bromodomains inhibit aberrant ASM cell proliferation and inflammation with lesser efficiency in those from asthmatic patients. They may be effective in reducing airway remodeling in asthma

The Place of Scripture in the Trajectories of a Distinct Religious Identity among Ravidassias in Britain: Guru Granth Sahib or Amritbani Guru Ravidass

This article highlights narratives, collected as informant testimonies, relating to trajectories of a distinct religious identity among the Ravidassia community in Britain. Current tensions surround the replacement of the Guru Granth Sahib with the Amritbani Guru Ravidass in Ravidassia places of worship. This is primarily in response to cartographies of the Ravidassia identity as distinct from Sikh identity. The opinions of Ravidassia individuals, from a varied age range, expressed in interviews conducted at various periods during 2010–2012, are considered in relation to dominant discourses emphasising the importance of one hegemonic ‘Ravidassia’ scripture. The interview data highlight three main positions among the followers of Guru Ravidass: (1) Ravidassias seeking a distinct identity but preferring to retain the Guru Granth Sahib in Ravidassia places of worship, (2) Ravidassias demanding a distinct identity by installing the Amritbani Guru Ravidass, (3) Ravidassias wanting to maintain their link with the Panth as Sikhs or as Ravidassi Sikhs

Fundamental MHD scales -- II: the kinematic phase of the supersonic small-scale dynamo

The small-scale dynamo (SSD) amplifies weak magnetic fields exponentially fast via kinetic motions. While there exist well-established theories for SSDs in incompressible flows, many astrophysical SSDs operate in supersonic turbulence. To understand the impact of compressibility on amplified magnetic fields, we perform an extensive set of visco-resistive SSD simulations, covering a wide range of sonic Mach number $\mathcal{M}$, hydrodynamic Reynolds number Re, and magnetic Prandtl number Pm. We develop robust methods for measuring kinetic and magnetic energy dissipation scales $\ell_\nu$ and $\ell_\eta$, as well as the scale at which magnetic fields are strongest $\ell_p$ during the kinematic phase of these simulations. We show that $\ell_\nu/\ell_\eta \sim$ Pm$^{1/2}$ is a universal feature in the kinematic phase of Pm $\geq 1$ SSDs, regardless of $\mathcal{M}$ or Re, and we confirm earlier predictions that SSDs operating in incompressible plasmas (either $\mathcal{M} \leq 1$ or Re $<$ Re$_{\rm crit} \approx 100$) concentrate magnetic energy at the smallest scales allowed by magnetic dissipation, $\ell_p \sim \ell_\eta$, and produce fields organised with field strength and field-line curvature inversely correlated. However, we show that these predictions fail for compressible SSDs ($\mathcal{M} > 1$ and Re $>$ Re$_{\rm crit}$), where shocks concentrate magnetic energy in large-scale, over-dense, coherent structures, with size $\ell_p \sim (\ell_{\rm turb} / \ell_{\rm shock})^{1/3} \ell_\eta \gg \ell_\eta$, where $\ell_{\rm shock} \sim \mathcal{M}^2 / [$Re $(\mathcal{M} - 1)^2]$ is shock width, and $\ell_{\rm turb}$ is the turbulent outer scale; magnetic field-line curvature becomes almost independent of the field strength. We discuss the implications for galaxy mergers and for cosmic-ray transport models in the interstellar medium that are sensitive to field-line curvature statistics.Comment: 25 pages, 15 figures, submitted to MNRAS, json-file w/ dat

A Single Multiplex CytoBas Assay Incorporating Eight Major Components for Accurate Detection of Allergen Sensitization in Asthma and Allergic Rhinitis

Background: Allergic rhinitis and asthma can be triggered by a variety of aeroallergens, including house dust mites (HDM), tree and grass pollen, and household pets. Identification of the relevant allergen is critical for lifestyle changes and treatments, including allergen immunotherapy. We here assessed the diagnostic performance and clinical utility of a single flow cytometry staining of basophils with major aeroallergen components (AeroDiff CytoBas). Methods: In 156 atopic patients with allergic rhinitis/asthma and 21 non-atopic individuals, allergen-specific IgE levels were determined by ImmunoCAP, and component-specific IgE by ELISA. PBMCs were analyzed by flow cytometry with basophil markers and eight fluorochrome-conjugated allergen component tetramers. Results: Patients were stratified for sensitization to each of the four allergens. Allergen-component staining in a single multiplex CytoBas assay and component-specific IgE serology performed similarly for Der p 2, Lol p 1, Fel d 1, and Can f 1 (ROC AUC: 0.76–0.97 vs. 0.73–0.93). CytoBas had greater diagnostic accuracy than component-specific IgE serology (p &lt; 0.001) for HDM sensitization using Der f 1 or Der p 1, and grass pollen using Lol p 5 or Phl p 1. Furthermore, the combined evaluation of Der p 1 and Der p 2 with CytoBas was 96.3% sensitive and 90.7% specific for HDM sensitization. The combined evaluation of Lol p 1 and Lol p 5 achieved 95.4% sensitivity and 96.4% specificity for ryegrass pollen sensitization. Conclusion: AeroDiff CytoBas has similar to superior diagnostic accuracy compared to singleplex IgE serology, with the additional advantage of a single assay to evaluate multiple allergens. This enables precise and efficient component-resolved diagnosis of aeroallergen sensitization to guide personalized treatment for patients with allergic rhinitis and/or asthma.</p

Trajectory analyses of adherence patterns in a real-life moderate to severe asthma population

Background: Global Initiative for Asthma step 5 therapies (GINA-5), other than inhaled corticosteroids and long-acting β-agonists in fixed dose combinations (ICS/LABA FDC), often entail more expensive (eg, monoclonal biologics) or less safe (eg, maintenance oral corticosteroids [OCS]) treatments. It is therefore important to assess poor inhaler adherence as a possible cause of suboptimal response to ICS/LABA FDC before additional GINA-5. Objective: To determine rates of, and time to, additional GINA-5 after first-year ICS/LABA FDC use, and their association with inhaler adherence. Methods: Patients initiating ICS/LABA FDC between 2013 and 2017 were identified from Australian national dispensing data. Group-based trajectory modeling was used to estimate medication adherence patterns. Multivariable Cox proportional hazards models were used to examine the association between adherence trajectories and GINA-5 addition during 2-year follow-up. Results: In total, 3062 new ICS/LABA FDC users were identified, of whom 120 (3.9%) received additional GINA-5 (OCS: 89; long-acting muscarinic antagonists: 39; biologics: &lt;3). Mean time to commencing additional GINA-5 was 705.2 (standard deviation, 1.7) days. Adherence trajectories were nonpersistent use (20%), seasonal use (8%), poor adherence (58%), and good adherence (13%). Although poor adherence was associated with longer time to additional GINA-5 (adjusted hazard ratio: 0.58; 95% confidence interval: 0.35-0.95), over 80% of additional GINA-5 was commenced in poorly adherent patients. Use of ≥2 OCS/antibiotic courses also predicted additional GINA-5. Conclusions: Almost 1 in 20 people with asthma commenced additional GINA-5 after ICS/LABA initiation, most of whom (&gt;80%) were poorly adherent to inhaled preventers. There is a substantial unmet need for inhaler adherence to be addressed before prescribing additional GINA-5.</p

Quantitative and Qualitative Trade-Off Analysis of Drowsy Driver Detection Methods: Single Electrode Wearable EEG Device, Multi-Electrode Wearable EEG Device, and Head-Mounted Gyroscope

Drowsy driving impairs motorists’ ability to operate vehicles safely, endangering both the drivers and other people on the road. The purpose of the project is to find the most effective wearable device to detect drowsiness. Existing research has demonstrated several options for drowsiness detection, such as electroencephalogram (EEG) brain wave measurement, eye tracking, head motions, and lane deviations. However, there are no detailed trade-off analyses for the cost, accuracy, detection time, and ergonomics of these methods. We chose to use two different EEG headsets: NeuroSky Mindwave Mobile (single-electrode) and Emotiv EPOC (14- electrode). We also tested a camera and gyroscope-accelerometer device. We can successfully determine drowsiness after five minutes of training using both single and multi-electrode EEGs. Devices were evaluated using the following criteria: time needed to achieve accurate reading, accuracy of prediction, rate of false positives vs. false negatives, and ergonomics and portability. This research will help improve detection devices, and reduce the number of future accidents due to drowsy driving

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Subcutaneous immunotherapy for bee venom allergy induces epitope spreading and immunophenotypic changes in allergen-specific memory B cells

Background: Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic disorders. We have recently discovered that allergen-specific memory B cells (Bmem) are phenotypically altered after 4 months of sublingual AIT for ryegrass pollen allergy. Whether these effects are shared with subcutaneous allergen immunotherapy (SCIT) and affect the epitope specificity of Bmem remain unknown.Objective: The study aimed to evaluate the phenotype and antigen receptor sequences of Bmem specific to the major bee venom (BV) allergen Api m 1 before and after ultra-rush SCIT for BV allergy. Methods: Recombinant Api m 1 protein tetramers were generated to evaluate basophil activation in a cohort of individuals with BV allergy before and after BV SCIT. Comprehensive flow cytometry was performed to evaluate and purify Api m 1–specific Bmem. Immunoglobulin genes from single Api m 1–specific Bmem were sequenced and structurally modeled onto Api m 1. Results: SCIT promoted class switching of Api m 1–specific Bmem to IgG2 and IgG4 with increased expression of CD23 and CD29. Furthermore, modeling of Api m 1–specific immunoglobulin from Bmem identified a suite of possible new and diverse allergen epitopes on Api m 1 and highlighted epitopes that may preferentially be bound by immunoglobulin after SCIT. Conclusions: AIT induces shifting of epitope specificity and phenotypic changes in allergen-specific Bmem.<p/