Impact of mental health and personality traits on the incidence of chronic cough in the Canadian Longitudinal Study on Aging

BACKGROUND: Chronic cough is a common troublesome condition, but risk factors for developing chronic cough are poorly understood. The aim of this study was to understand the relationship between mental health disorders, personality traits and chronic cough. METHODS: The Canadian Longitudinal Study on Aging is a prospective, nationally generalisable, random sample of adults aged 45–85 years at baseline recruited between 2011 and 2015, and followed-up 3 years later. Chronic cough was defined as a daily cough over the last 12 months. Incident chronic cough was defined as those participants who reported new-onset chronic cough between baseline and follow-up 1. Current depressive symptoms and psychological distress were assessed using the Center for Epidemiologic Study Short Depression Scale (CESD-10) and Kessler Psychological Distress Scale (K-10), respectively. The “Big Five” personality traits were assessed using the Ten-Item Personality Inventory. Relative risks are reported using a multivariate mutually adjusted model. RESULTS: At follow-up 1, 2506 participants (11.1%) reported new-onset chronic cough during the ∼3-year interval. Depressive symptoms (CESD-10 ≥10: relative risk 1.22 (95% CI 1.03–1.44)) and psychological distress (K-10 ≥22: relative risk 1.20 (95% CI 1.07–1.36)) at baseline were both independent predictors of a higher risk of incident chronic cough. Prevalent and incident chronic cough were also independently associated with an increased risk of developing depressive symptoms and psychological distress. Personality traits did not influence the development of chronic cough but did increase the risk of depressive symptoms and psychological distress. CONCLUSIONS: This study shows that there is a bidirectional relationship between chronic cough, and depressive symptoms and psychological distress, and personality traits do not independently influence the development of chronic cough

Molecular-Based Optical Diagnostics for Hypersonic Nonequilibrium Flows

This manuscript describes Molecular-Based Optical Diagnostics for Hypersonic Nonequilibrium Flows. This is a book chapter and has no formal abstract

Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps

<p>Abstract</p> <p>Background</p> <p>Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM) maintenance and reliever therapy (Symbicort SMART^®Turbuhaler^®) in patients previously prescribed treatments from Global Initiative for Asthma (GINA) Steps 2, 3 or 4.</p> <p>Methods</p> <p>This is a <it>post hoc </it>analysis of the results of five large clinical trials (>12000 patients) comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined.</p> <p>Results</p> <p>At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) (plus short-acting β₂-agonist [SABA] as reliever), and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P < 0.01) and at treatment Step 4 versus higher maintenance dose ICS/LABA (P < 0.001). BUD/FORM maintenance and reliever therapy also achieved significantly higher rates of current clinical control and significantly lower exacerbation rates at most treatment steps compared with a higher maintenance dose ICS + SABA (Steps 2-4 for control and Steps 3 and 4 for exacerbations). With all treatments, the proportion of patients achieving current clinical control was lower with increasing treatment steps.</p> <p>Conclusions</p> <p>BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.</p

Predicting risk of postpartum haemorrhage during the intrapartum period in a general obstetric population

Objective: To develop and validate (both internally and externally) a prediction model examining a combination of risk factors in order to predict postpartum haemorrhage (PPH) in a general obstetric Irish population of singleton pregnancies. Study design: We used data from the National Maternal and Newborn Clinical Management System (MN-CMS), including all singleton deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019. We defined PPH as an estimated blood loss of = 1000 ml following the birth of the baby. Multivariable logistic regression with backward stepwise selection was used to develop the prediction model. Candidate predictors included maternal age, maternal body mass index, parity, previous caesarean section, assisted fertility, gestational age, fetal macrosomia, mode of delivery and history of PPH. Discrimination was assessed using the area under the receiver operating characteristic curve (ROC) C-statistic. We used bootstrapping for internal validation to assess overfitting, and conducted a temporal external validation using data from all singleton deliveries at CUMH during 2020. Results: Out of 6,077 women, 5,807 with complete data were included in the analyses, and there were 270 (4.65%) cases of PPH. Four variables were considered the best combined predictors of PPH, including parity (specifically nulliparous), macrosomia, mode of delivery (specifically operative vaginal delivery, emergency caesarean section and prelabour caesarean section), and history of PPH. These predictors were used to develop a nomogram to provide individualised risk assessment for PPH. The original apparent C-statistic was 0.751 (95% CI: 0.721, 0.779) suggesting good discriminative performance. There was minimal optimism adjustment to the C-statistic after bootstrapping, indicating good internal performance (optimism adjusted C-statistic: 0.748). Results of external validation were comparable with the development model suggesting good reproducibility. Conclusions: Four routinely collected variables (parity, fetal macrosomia, mode of delivery and history of PPH) were identified when predicting PPH in a general obstetric Irish population of singleton pregnancies. Use of our nomogram could potentially assist with individualised risk assessment of PPH and inform clinical decision-making allowing those at highest risk of PPH be actively managed

Predicting perineal trauma during childbirth using data from a general obstetric population [version 2; peer review: 2 approved]

Background: Perineal trauma is a common complication of childbirth and can have serious impacts on long-term health. Few studies have examined the combined effect of multiple risk factors. We developed and internally validated a risk prediction model to predict third and fourth degree perineal tears using data from a general obstetric population. Methods: Risk prediction model using data from all singleton vaginal deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019 and 2020. Third/fourth degree tears were diagnosed by an obstetrician or midwife at time of birth and defined as tears that extended into the anal sphincter complex or involved both the anal sphincter complex and anorectal mucosa. We used univariable and multivariable logistic regression with backward stepwise selection to develop the models. Candidate predictors included infant sex, maternal age, maternal body mass index, parity, mode of delivery, birthweight, post-term delivery, induction of labour and public/private antenatal care. We used the receiver operating characteristic (ROC) curve C-statistic to assess discrimination, and bootstrapping techniques were used to assess internal validation. Results: Of 8,403 singleton vaginal deliveries, 8,367 (99.54%) had complete data on predictors for model development. A total of 128 women (1.53%) had a third/fourth degree tear. Three variables remained in the final model: nulliparity, mode of delivery (specifically forceps delivery or ventouse delivery) and increasing birthweight (per 100 gram increase) (C-statistic: 0.75, 95% CI: 0.71, 0.79). We developed a nomogram to calculate individualised risk of third/fourth degree tears using these predictors. Bootstrapping indicated good internal performance. Conclusions: Use of our nomogram can provide an individualised risk assessment of third/fourth degree tears and potentially aid counselling of women on their potential risk

The presence of Aspergillus fumigatus in asthmatic airways is not clearly related to clinical disease severity

Background: It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus, in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. Methods: Sixty‐nine patients characterized by asthma severity (GINA) and level of control (ACQ‐7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus‐specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. Results: In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL‐4, IL‐6, IL‐10, IL‐13 and TNF‐α correlated with BAL fungal presence, while plasma IL‐17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL‐6 and BAL IL‐13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus. Conclusions: Fungi were present in a large proportion of our asthmatic patients’ airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control

Allergen-induced airway inflammation and its therapeutic intervention

Allergen inhalation challenge has been useful for examining the mechanisms of allergen-induced airway inflammation and the associated physiological changes and for documenting the efficacy of drugs to treat asthma. Allergen inhalation by a sensitized subject results in acute bronchoconstriction, beginning within 15-30 min and lasting 1-3 hr, which can be followed by the development of a late asthmatic response. Individuals who develop both an early and late response after allergen have more marked increases in airway hyperresponsiveness, and greater increases in allergen-induced airway inflammation, particularly in airway eosinophils and basophils. All of the currently available and effective treatments for asthma modify some aspects of allergen-induced responses. These medications include short-acting and long-acting inhaled β2-agonists, inhaled corticosteroids, cromones, methylxanthines, leukotriene inhibitors, and anti-IgE monoclonal antibody. In addition, allergen inhalation challenge has become a useful method which can, in a very limited number of patients, provide key information on the therapeutic potential of new drugs being developed to treat asthma

Modelling and testing of a historic steel suspension footbridge in Ireland

Daly's Bridge is a historic steel suspension footbridge in Ireland, known locally as the 'Shaky Bridge' for its noticeable movement under pedestrian loading. Although there is concern regarding the performance of the structure, testing or modelling has not been carried out to date and inadequate information exists in relation to carrying out such analyses. In this paper, Daly's Bridge is instrumented and tested for the first time and a model of the bridge is established and improved in the process. Apart from ambient vibration, excitation from traversing pedestrians and cyclists is considered. Video analysis of dynamic deflection, a wavelet-packet-based technique using acceleration responses and dynamic measurements from a cheap smartphone accelerometer application are used to identify and compare the natural frequency of the bridge. The work contributes to the evidence base of full-scale measurements from instrumenting and analysing responses of aging pedestrian bridges, highlighting the complexity, challenges, opportunities and limitations related to the varied levels of information available from disparate sources. The study also highlights the need to investigate to what extent cheap sensors can be successfully used as compared to their more expensive and sophisticated counterparts

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer