Statistical Signal Properties of the Pressure-Reactivity Index (PRx)

Objectives: The pressure-reactivity index (PRx) is defined in terms of the moving correlation coefficient between intracranial pressure (ICP) and mean arterial pressure (MAP) and is a measure of cerebral autoregulation ability. Histograms of PRx against cerebral perfusion pressure (CPP) show U-shaped behaviour- the minimum reflecting optimal cerebral autoregulation (CPPopt). However U-shaped behavior may also occur by chance. To date there has been no evaluation of the statistical properties of these signals. Materials and Methods: We simulated PRx/CPP distributions using synthetic ICP and MAP signals from Gaussian noise with known cross-correlation. We calculated the statistical distribution of extrema in the PRx/CPP relationship. Results: The calculation of PRx on random data is statistically biased to show a U-shaped behavior when the signals are positively cross-correlated (equivalent to PRx>0). For PR<0, the bias is towards inverse U-shaped behavior. We demonstrate that this bias is eliminated by Fisher transforming the PRx data before CPPopt analysis. Conclusions: Cross-correlated signals are biased to show a U-shaped distribution. A “CPPopt-like” behavior will be observed more often than not even from random ICP and MAP signals that do not exhibit autoregulation unless PRx is Fisher transformed. Care must be taken in interpreting CPPopt in terms of physiology calculated from untransformed dat

Ozone’s Impact on Public Health: Contributions from Indoor Exposures to Ozone and Products of Ozone-Initiated Chemistry

OBJECTIVE: The associations between ozone concentrations measured outdoors and both morbidity and mortality may be partially due to indoor exposures to ozone and ozone-initiated oxidation products. In this article I examine the contributions of such indoor exposures to overall ozone-related health effects by extensive review of the literature as well as further analyses of published data. FINDINGS: Daily inhalation intakes of indoor ozone (micrograms per day) are estimated to be between 25 and 60% of total daily ozone intake. This is especially noteworthy in light of recent work indicating little, if any, threshold for ozone’s impact on mortality. Additionally, the present study estimates that average daily indoor intakes of ozone oxidation products are roughly one-third to twice the indoor inhalation intake of ozone alone. Some of these oxidation products are known or suspected to adversely affect human health (e.g., formaldehyde, acrolein, hydroperoxides, fine and ultrafine particles). Indirect evidence supports connections between morbidity/mortality and exposures to indoor ozone and its oxidation products. For example, cities with stronger associations between outdoor ozone and mortality tend to have residences that are older and less likely to have central air conditioning, which implies greater transport of ozone from outdoors to indoors. CONCLUSIONS: Indoor exposures to ozone and its oxidation products can be reduced by filtering ozone from ventilation air and limiting the indoor use of products and materials whose emissions react with ozone. Such steps might be especially valuable in schools, hospitals, and childcare centers in regions that routinely experience elevated outdoor ozone concentrations

Assessing connectivity between an overlying aquifer and a coal seam gas resource using methane isotopes, dissolved organic carbon and tritium

Coal seam gas (CSG) production can have an impact on groundwater quality and quantity in adjacent or overlying aquifers. To assess this impact we need to determine the background groundwater chemistry and to map geological pathways of hydraulic connectivity between aquifers. In south-east Queensland (Qld), Australia, a globally important CSG exploration and production province, we mapped hydraulic connectivity between the Walloon Coal Measures (WCM, the target formation for gas production) and the overlying Condamine River Alluvial Aquifer (CRAA), using groundwater methane (CH4) concentration and isotopic composition (δ13C-CH4), groundwater tritium (3H) and dissolved organic carbon (DOC) concentration. A continuous mobile CH4 survey adjacent to CSG developments was used to determine the source signature of CH4 derived from the WCM. Trends in groundwater δ13C-CH4 versus CH4 concentration, in association with DOC concentration and 3H analysis, identify locations where CH4 in the groundwater of the CRAA most likely originates from the WCM. The methodology is widely applicable in unconventional gas development regions worldwide for providing an early indicator of geological pathways of hydraulic connectivity

A study of empyema thoracis and role of intrapleural streptokinase in its management

BACKGROUND: Clinical spectrum, microbiology and outcome of empyema thoracis are changing. Intrapleural instillation of fibrinolytic agents is being increasingly used for management of empyema thoracis. The present study was carried out to describe the clinical profile and outcome of patients with empyema thoracis including those with chronic empyema and to study the efficacy and safety of intrapleural streptokinase in its management. METHODS: Clinical profile, etiological agents, hospital course and outcome of 31 patients (mean age 40 ± 16 years, M: F 25: 6) with empyema thoracis treated from 1998 to 2003 was analyzed. All patients were diagnosed on the basis of aspiration of frank pus from pleural cavity. Clinical profile, response to therapy and outcome were compared between the patients who received intrapleural streptokinase (n = 12) and those who did not (n = 19). RESULTS: Etiology was tubercular in 42% of the patients (n = 13) whereas the rest were bacterial. Amongst the patients in which organisms could be isolated (n = 13, 42%) Staphylococcus aureus was the commonest (n = 5). Intrapleural streptokinase was instilled in 12 patients. This procedure resulted in increase of drainage of pleural fluid in all patients. Mean daily pleural fluid drainage after streptokinase instillation was significantly higher for patients who received intrapleural streptokinase than those who did not (213 ml vs 57 ml, p = 0.006). Only one patient who was instilled streptokinase eventually required decortication, which had to be done in five patients (16.1%). Mean hospital stay was 30.2 ± 17.6 days whereas two patients died. CONCLUSIONS: Tubercular empyema is common in Indian patients. Intrapleural streptokinase appears to be a useful strategy to preserve lung function and reduce need for surgery in patients with late stage of empyema thoracis

Effects of air pollution and the introduction of the London Low Emission Zone on the prevalence of respiratory and allergic symptoms in schoolchildren in East London: a sequential cross-sectional study

The adverse effects of traffic-related air pollution on children’s respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8–9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00–1.02), NO2 (1.03, 1.00–1.06), PM10 (1.16, 1.04–1.28) and PM2.5 (1.38, 1.08–1.78), all per μg/m3 of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions

Do Web-based Mental Health Literacy Interventions Improve the Mental Health Literacy of Adult Consumers? Results From a Systematic Review

Background: Low levels of mental health literacy (MHL) have been identified as an important contributor to the mental health treatment gap. Interventions to improve MHL have used traditional media (eg, community talks, print media) and new platforms (eg, the Internet). Evaluations of interventions using conventional media show improvements in MHL improve community recognition of mental illness as well as knowledge, attitude, and intended behaviors toward people having mental illness. However, the potential of new media, such as the Internet, to enhance MHL has yet to be systematically evaluated. Objective: Study aims were twofold: (1) To systematically appraise the efficacy of Web-based interventions in improving MHL. (2) To establish if increases in MHL translated into improvement in individual health seeking and health outcomes as well as reductions in stigma toward people with mental illness. Methods: We conducted a systematic search and appraisal of all original research published between 2000 and 2015 that evaluated Web-based interventions to improve MHL. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to report findings. Results: Fourteen studies were included: 10 randomized controlled trials and 4 quasi-experimental studies. Seven studies were conducted in Australia. A variety of Web-based interventions were identified ranging from linear, static websites to highly interactive interventions such as social media games. Some Web-based interventions were specifically designed for people living with mental illness whereas others were applicable to the general population. Interventions were more likely to be successful if they included “active ingredients” such as a structured program, were tailored to specific populations, delivered evidenced-based content, and promoted interactivity and experiential learning.Conclusions: Web-based interventions targeting MHL are more likely to be successful if they include active ingredients. Improvements in MHL see concomitant improvements in health outcomes, especially for individuals with mild to moderate depression. The most promising interventions suited to this cohort appear to be MoodGYM and BluePages, 2 interventions from Australia. However, the relationship between MHL and formal and informal help seeking is less clear; self-stigma appears to be an important mediator with results showing that despite improvements in MHL and community attitudes to mental illness, individuals with mental illness still seek help at relatively low rates. Overall, the Internet is a viable method to improve MHL. Future studies could explore how new technology interfaces (eg, mobile phones vs computers) can help improve MHL, mental health outcomes, and reduce stigma

Quantitative analysis of optical coherence tomography for neovascular age-related macular degeneration using deep learning

PURPOSE: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of optical coherence tomography (OCT) scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD), and make the raw segmentation output data openly available for further research. DESIGN: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. PARTICIPANTS: 2473 first-treated eyes and another 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017. METHODS: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first and second eyes, by visual acuity (VA) and by race/ethnicity, and correlations between volumes. MAIN OUTCOME MEASURES: Volumes of segmented features (mm3), central subfield thickness (CST) (μm). RESULTS: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED and SRF. Eyes from black individuals had higher SRF, RPE and serous PED volumes, compared with other ethnic groups. Greater volumes of the vast majority of features were associated with worse VA. CONCLUSION: We report the results of large scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care, and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community

Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle. © 2012 Clause et al

Molecular Interpretation of ACTH-β-Endorphin Coaggregation: Relevance to Secretory Granule Biogenesis

Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system