Coastal proximity and mental health among urban adults in England: The moderating effect of household income

This is the final version. Available on open access from Elsevier via the DOI in this recordAfter adjusting for covariates, self-reported general health in England is higher among populations living closer to the coast, and the association is strongest amongst more deprived groups. We explored whether similar findings were present for mental health using cross-sectional data for urban adults in the Health Survey for England (2008-2012, N ≥25,963). For urban adults, living ≤1 km from the coast, in comparison to >50 km, was associated with better mental health as measured by the GHQ12. Stratification by household income revealed this was only amongst the lowest-earning households, and extended to ≤5 km. Our findings support the contention that, for urban adults, coastal settings may help to reduce health inequalities in England.National Institute for Health Research (NIHR)European Union Horizon 202

The impact of current CH4 and N2O atmospheric loss process uncertainties on calculated ozone abundances and trends

The atmospheric loss processes of N2O and CH4, their estimated uncertainties, lifetimes, and impacts on ozone abundance and long-term trends are examined using atmospheric model calculations and updated kinetic and photochemical parameters and uncertainty factors from SPARC [2013]. The uncertainty ranges in calculated N2O and CH4 global lifetimes computed using the SPARC estimated uncertainties are reduced by nearly a factor of two compared with uncertainties from Sander et al. [2011]. Uncertainties in CH4 loss due to reaction with OH and O(1D) have relatively small impacts on present day global total ozone (±0.2-0.3%). Uncertainty in the Cl + CH4 reaction affects the amount of chlorine in radical vs. reservoir forms and has a modest impact on present day SH polar ozone (~±6%), and on the rate of past ozone decline and future recovery. Uncertainty in the total rate coefficient for the O(1D) + N2O reaction results in a substantial range in present day stratospheric odd nitrogen (±20-25%) and global total ozone (±1.5-2.5%). Uncertainty in the O(1D) + N2O reaction branching ratio for the O2 + N2 and 2*NO product channels results in moderate impacts on odd nitrogen (±10%) and global ozone (±1%),with uncertainty in N2O photolysis resulting in relatively small impacts (±5% in odd nitrogen, ±0.5% in global ozone). Uncertainties in the O(1D) + N2O reaction and its branching ratio also affect the rate of past global total ozone decline and future recovery, with a range in future ozone projections of ±1-1.5% by 2100, relative to present day

A data-centric approach to generative modelling for 3D-printed steel.

The emergence of additive manufacture (AM) for metallic material enables components of near arbitrary complexity to be produced. This has potential to disrupt traditional engineering approaches. However, metallic AM components exhibit greater levels of variation in their geometric and mechanical properties compared to standard components, which is not yet well understood. This uncertainty poses a fundamental barrier to potential users of the material, since extensive post-manufacture testing is currently required to ensure safety standards are met. Taking an interdisciplinary approach that combines probabilistic mechanics and uncertainty quantification, we demonstrate that intrinsic variation in AM steel can be well described by a generative statistical model that enables the quality of a design to be predicted before manufacture. Specifically, the geometric variation in the material can be described by an anisotropic spatial random field with oscillatory covariance structure, and the mechanical behaviour by a stochastic anisotropic elasto-plastic material model. The fitted generative model is validated on a held-out experimental dataset and our results underscore the need to combine both statistical and physics-based modelling in the characterization of new AM steel products

A data-centric approach to generative modelling for 3D-printed steel.

The emergence of additive manufacture (AM) for metallic material enables components of near arbitrary complexity to be produced. This has potential to disrupt traditional engineering approaches. However, metallic AM components exhibit greater levels of variation in their geometric and mechanical properties compared to standard components, which is not yet well understood. This uncertainty poses a fundamental barrier to potential users of the material, since extensive post-manufacture testing is currently required to ensure safety standards are met. Taking an interdisciplinary approach that combines probabilistic mechanics and uncertainty quantification, we demonstrate that intrinsic variation in AM steel can be well described by a generative statistical model that enables the quality of a design to be predicted before manufacture. Specifically, the geometric variation in the material can be described by an anisotropic spatial random field with oscillatory covariance structure, and the mechanical behaviour by a stochastic anisotropic elasto-plastic material model. The fitted generative model is validated on a held-out experimental dataset and our results underscore the need to combine both statistical and physics-based modelling in the characterization of new AM steel products

Surveillance recommendations based on an exploratory analysis of respiratory syncytial virus reports derived from the European Influenza Surveillance System

BACKGROUND: Respiratory syncytial virus (RSV) is an important pathogen that can cause severe illness in infants and young children. In this study, we assessed whether data on RSV collected by the European Influenza Surveillance Scheme (EISS) could be used to build an RSV surveillance system in Europe. METHODS: Influenza and RSV data for the 2002–2003 winter season were analysed for England, France, the Netherlands and Scotland. Data from sentinel physician networks and other sources, mainly hospitals, were collected. Respiratory specimens were tested for influenza and RSV mainly by virus culture and polymerase chain reaction amplification. RESULTS: Data on RSV were entered timely into the EISS database. RSV contributed noticeably to influenza-like illness: in England sentinel RSV detections were common in all age groups, but particularly in young children with 20 (40.8%) of the total number of sentinel swabs testing positive for RSV. Scotland and France also reported the highest percentages of RSV detections in the 0–4 year age group, respectively 10.3% (N = 29) and 12.2% (N = 426). In the Netherlands, RSV was detected in one person aged over 65 years. CONCLUSION: We recommend that respiratory specimens collected in influenza surveillance are also tested systematically for RSV and emphasize the use of both community derived data and data from hospitals for RSV surveillance. RSV data from the EISS have been entered in a timely manner and we consider that the EISS model can be used to develop an RSV surveillance system equivalent to the influenza surveillance in Europe

CAM therapies among primary care patients using opioid therapy for chronic pain

<p>Abstract</p> <p>Background</p> <p>Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy.</p> <p>Method</p> <p>A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population.</p> <p>Results</p> <p>Patients were treated for a variety of pain problems including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162), acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n = 62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful.</p> <p>Conclusion</p> <p>This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.</p

Network-Based Approach for Modeling and Analyzing Coronary Angiography

Significant intra-observer and inter-observer variability in the interpretation of coronary angiograms are reported. This variability is in part due to the common practices that rely on performing visual inspections by specialists (e.g., the thickness of coronaries). Quantitative Coronary Angiography (QCA) approaches are emerging to minimize observer's error and furthermore perform predictions and analysis on angiography images. However, QCA approaches suffer from the same problem as they mainly rely on performing visual inspections by utilizing image processing techniques. In this work, we propose an approach to model and analyze the entire cardiovascular tree as a complex network derived from coronary angiography images. This approach enables to analyze the graph structure of coronary arteries. We conduct the assessments of network integration, degree distribution, and controllability on a healthy and a diseased coronary angiogram. Through our discussion and assessments, we propose modeling the cardiovascular system as a complex network is an essential phase to fully automate the interpretation of coronary angiographic images. We show how network science can provide a new perspective to look at coronary angiograms

Teprotumumab for Thyroid-Associated Ophthalmopathy

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves’ disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. / METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves’ ophthalmopathy–specific quality-of-life questionnaire. Adverse events were assessed. / RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. / CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997.

Secreted Phospholipase A2 Involvement in Neurodegeneration: Differential Testing of Prosurvival and Anti-Inflammatory Effects of Enzyme Inhibition

There is increased interest in the contribution of secreted phospholipase A2 (sPLA2) enzymes to neurodegenerative diseases. Systemic treatment with the nonapeptide CHEC-9, a broad spectrum uncompetitive inhibitor of sPLA2, has been shown previously to inhibit neuron death and aspects of the inflammatory response in several models of neurodegeneration. A persistent question in studies of sPLA2 inhibitors, as for several other anti-inflammatory and neuroprotective compounds, is whether the cell protection is direct or due to slowing of the toxic aspects of the inflammatory response. To further explore this issue, we developed assays using SY5Y (neuronal cells) and HL-60 (monocytes) cell lines and examined the effects of sPLA2 inhibition on these homogeneous cell types in vitro. We found that the peptide inhibited sPLA2 enzyme activity in both SY5Y and HL-60 cultures. This inhibition provided direct protection to SY5Y neuronal cells and their processes in response to several forms of stress including exposure to conditioned medium from HL-60 cells. In cultures of HL-60 cells, sPLA2 inhibition had no effect on survival of the cells but attenuated their differentiation into macrophages, with regard to process development, phagocytic ability, and the expression of differentiation marker CD36, as well as the secretion of proinflammatory cytokines TNF-α and IL-6. These results suggest that sPLA2 enzyme activity organizes a cascade of changes comprising both cell degeneration and inflammation, processes that could theoretically operate independently during neurodegenerative conditions. The effectiveness of sPLA2 inhibitor CHEC-9 may be due to its ability to affect both processes in isolation. Testing potential anti-inflammatory/neuroprotective compounds with these human cell lines and their conditioned media may provide a useful screening tool prior to in vivo therapeutic applications

Cambogin Is Preferentially Cytotoxic to Cells Expressing PDGFR

Platelet-derived growth factor receptors (PDGFRs) have been implicated in a wide array of human malignancies, including medulloblastoma (MB), the most common brain tumor of childhood. Although significant progress in MB biology and therapeutics has been achieved during the past decades, MB remains a horrible challenge to the physicians and researchers. Therefore, novel inhibitors targeting PDGFR signaling pathway may offer great promise for the treatment of MB. In the present study, we investigated the cytotoxicity and mechanisms of cambogin in Daoy MB cells. Our results show that cambogin triggers significant S phase cell cycle arrest and apoptosis via down regulation of cyclin A and E, and activation of caspases. More importantly, further mechanistic studies demonstrated that cambogin inhibits PDGFR signaling in Daoy and genetically defined mouse embryo fibroblast (MEF) cell lines. These results suggest that cambogin is preferentially cytotoxic to cells expressing PDGFR. Our findings may provide a novel approach by targeting PDGFR signaling against MB