Evaluation of the national governmental efforts between 1997 and 2010 in reducing health inequalities in England.

OBJECTIVES: The pandemic has compounded existing inequalities. In the UK, there have been calls for a new cross-government health inequalities strategy. This study aims to evaluate the effectiveness of national governmental efforts between 1997 and 2010, referred to as the National Health Inequalities Strategy (NHIS). STUDY DESIGN: population-based observational study. METHODS: Using Global Burden of Disease data, age-standardised years of life lost due to premature mortality (YLL) rates per 10,000 were extracted for 150 Upper Tier Local Authority (UTLA) regions in England for every year between 1990 and 2019. The slope index of inequality was calculated using YLL rates for all causes, individual conditions, and risk factors. Joinpoint regression was used to assess the trends of any changes which arose before, during or after the NHIS. RESULTS: Absolute inequalities in YLL rates for all causes remained stable between 1990 and 2000, before decreasing over the following 10 years. After 2010, improvements slowed. A similar trend can be observed amongst inequalities in YLLs for individual causes, including ischaemic heart disease, stroke, breast cancer and lung cancer amongst females, and ischaemic heart disease stroke, diabetes and self-harm amongst males. This trend was also observed amongst certain risk factors, notably blood pressure, cholesterol, tobacco and dietary risks. Inequalities were generally greater in males than in females; however, trends were similar across both sexes. The NHIS coincided with significant reductions in inequalities in YLLs due to ischaemic heart disease and lung cancer. CONCLUSIONS: The findings suggest that the NHIS coincided with a reduction in health inequalities in England. Policy makers should consider a new cross-government strategy to tackle health inequalities drawing from the success of the previous NHIS.

Barriers to conducting cancer trials in Canada: an analysis of key informant interviews.

Background: In Canada, there is growing evidence that oncology clinical trials units (ctus) and programs face serious financial challenges. Investment in cancer research in Canada has declined almost 20% in the 5 years since its peak in 2011, and the costs of conducting leading-edge trials are rising. Clinical trials units must therefore be strategic about which studies they open. We interviewed Canadian health care professionals responsible for running cancer trials programs to identify the barriers to sustainability that they face. Methods: One-on-one telephone interviews were conducted with clinicians and clinical research professionals at oncology ctus in Canada. We asked for their perspectives about the barriers to conducting trials at their institutions, in their provinces, and nationwide. Interviews were digitally recorded, transcribed, anonymized, and coded in the NVivo software application (version 11: QSR International, Melbourne, Australia). The initial coding structure was informed by the interview script, with new concepts drawn out and coded during analysis, using a constant comparative approach. Results: Between June 2017 and November 2018, 25 interviews were conducted. Key barriers that participants identified were■ insufficient stable funding to support trials infrastructure and retain staff;■ the need to adopt strict cost-recovery policies, leading to fewer academic trials in portfolios; and■ an overreliance on industry to fund clinical research in Canada. Conclusions: Funding uncertainties have led ctus to increasingly rely on industry sponsorship and more stringent feasibility thresholds to remain solvent. Retaining skilled trials staff can create efficiencies in opening and running studies, with spillover effects of more trials being open to patients. More academic studies are needed to curb industry's influence.

A new double crystal calibration system for absolute x-ray emission measurements down to ∼1 keV energies.

Over the past few years, work has been conducted at AWE to accurately characterize x-ray diffraction crystals to allow for absolute measurements of x-ray emission for our Orion opacity campaigns. Diffraction crystals are used in spectrometers on Orion to record the dispersed spectral features emitted by the laser produced plasma to obtain a measurement of the plasma conditions. Previously, based on a Manson x-ray source, our calibration system struggled to attain a high signal at the low energies required in calibration for the use of aluminum as a tracer for higher atomic number experiments. Here, we present data from the newly commissioned CTX400 x-ray source, a twin anode water cooled system, showing it to be a bright source even for ∼1 keV energies. Rocking curve measurements for three of the most commonly used crystals, namely, pentaerythritol, cesium acid phthalate, and germanium, are presented for both convex and flat forms.

Flexible scheme to truncate the hierarchy of pure states.

The hierarchy of pure states (HOPS) is a wavefunction-based method that can be used for numerically modeling open quantum systems. Formally, HOPS recovers the exact system dynamics for an infinite depth of the hierarchy. However, truncation of the hierarchy is required to numerically implement HOPS. We want to choose a "good" truncation method, where by "good" we mean that it is numerically feasible to check convergence of the results. For the truncation approximation used in previous applications of HOPS, convergence checks are numerically challenging. In this work, we demonstrate the application of the "n-particle approximation" to HOPS. We also introduce a new approximation, which we call the "n-mode approximation." We then explore the convergence of these truncation approximations with respect to the number of equations required in the hierarchy in two exemplary problems: absorption and energy transfer of molecular aggregates.

Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract Infections.

The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group, and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but unrelated adverse events. A short-course regimen of 5 days of finafloxacin resulted in high eradication and improved clinical outcome rates compared to those for treatment with ciprofloxacin for 10 days. In contrast to those of ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment (800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500 mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral administration at day 3. The primary endpoint was the combined microbiological and clinical response at the TOC visit in the microbiological intent-to-treat population. (This study has been registered at ClinicalTrials.gov under identifier NCT01928433.).

Calibration of X-ray spectrometers for opacity experiments at the Orion laser facility (invited).

Accurately calibrated and characterised x-ray diagnostics are a key requirement in the fielding of experiments on the Orion laser where absolute measurements of x-ray emission are used to underpin the validity of models of emissivity and opacity. Diffraction crystals are used in spectrometers on Orion to record the dispersed spectral features emitted by the laser produced plasma to obtain a measurement of the plasma conditions. The ability to undertake diffraction crystal calibrations supports the successful outcome of these Orion experiments. This paper details the design and commissioning of a system to undertake these calibrations in the energy range 2.0 keV to approximately 8.5 keV. Improvements to the design are detailed which will extend the commissioned range of energies to below 1 keV.

Detection-enhanced steady state entanglement with ions.

Driven dissipative steady state entanglement schemes take advantage of coupling to the environment to robustly prepare highly entangled states. We present a scheme for two trapped ions to generate a maximally entangled steady state with fidelity above 0.99, appropriate for use in quantum protocols. Furthermore, we extend the scheme by introducing detection of our dissipation process, significantly enhancing the fidelity. Our scheme is robust to anomalous heating and requires no sympathetic cooling.

ORION laser target diagnostics.

The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

A soft x-ray transmission grating imaging-spectrometer for the National Ignition Facility.

A soft x-ray transmission grating spectrometer has been designed for use on high energy-density physics experiments at the National Ignition Facility (NIF); coupled to one of the NIF gated x-ray detectors it records 16 time-gated spectra between 250 and 1000 eV with 100 ps temporal resolution. The trade-off between spectral and spatial resolution leads to an optimized design for measurement of emission around the peak of a 100-300 eV blackbody spectrum. Performance qualification results from the NIF, the Trident Laser Facility and vacuum ultraviolet beamline at the National Synchrotron Light Source, evidence a <100 µm spatial resolution in combination with a source-size limited spectral resolution that is <10 eV at photon energies of 300 eV.

Influence of chylomicron remnants on human monocyte activation in vitro.

BACKGROUND AND AIMS: Atherosclerosis is known to be an inflammatory disease and there is increasing evidence that chylomicron remnants (CMR), the lipoproteins which carry dietary fats in the blood, cause macrophage foam cell formation and inflammation. In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is increased, and clearance of CMR from blood may be delayed, however, whether CMR contribute directly to monocyte activation and subsequent egress into the arterial wall has not been established. Here, the contribution of CMR to activation of monocyte pro-inflammatory pathways was assessed using an in vitro model. METHODS AND RESULTS: Primary human monocytes and CMR-like particles (CRLP) were used to measure several endpoints of monocyte activation. Treatment with CRLP caused rapid and prolonged generation of reactive oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were secreted in nanogram quantities by the cells in the absence of CRLP. IL-8 secretion was transiently increased after CRLP treatment, and CRLP maintained secretion in the presence of pharmacological inhibitors of IL-8 production. In contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by addition of exogenous MCP-1. CONCLUSION: Our findings indicate that CRLP activate human monocytes and augment their migration in vitro by reducing cellular MCP-1 expression. Our data support the current hypothesis that CMR contribute to the inflammatory milieu of the arterial wall in early atherosclerosis, and suggest that this may reflect direct interaction with circulating blood monocytes.

Part 5. Public health and air pollution in Asia (PAPA): a combined analysis of four studies of air pollution and mortality.

BACKGROUND: In recent years, Asia has experienced rapid economic growth and a deteriorating environment caused by the increasing use of fossil fuels. Although the deleterious effects of air pollution from fossil-fuel combustion have been demonstrated in many Western nations, few comparable studies have been conducted in Asia. Time-series studies of daily mortality in Asian cities can contribute important new information to the existing body of knowledge about air pollution and health. Not only can these studies verify important health effects of air pollution in local regions in Asia, they can also help determine the relevance of existing air pollution studies to mortality and morbidity for policymaking and environmental controls. In addition, the studies can help identify factors that might modify associations between air pollution and health effects in various populations and environmental conditions. Collaborative multicity studies in Asia-especially when designed, conducted, and analyzed using a common protocol-will provide more robust air pollution effect estimates for the region as well as relevant, supportable estimates of local adverse health effects needed by environmental and public-health policymakers. SPECIFIC OBJECTIVES: The Public Health and Air Pollution in Asia (PAPA*) project, sponsored by the Health Effects Institute, consisted of four studies designed to assess the effects of air pollution on mortality in four large Asian cities, namely Bangkok, in Thailand, and Hong Kong, Shanghai, and Wuhan, in China. In the PAPA project, a Common Protocol was developed based on methods developed and tested in NMMAPS, APHEA, and time-series studies in the literature to help ensure that the four studies could be compared with each other and with previous studies by following an established protocol. The Common Protocol (found at the end of this volume) is a set of prescriptive instructions developed for the studies and used by the investigators in each city. It is flexible enough to allow for adjustments in methods to optimize the fit of health-effects models to each city's data set. It provides the basis for generating reproducible results in each city and for meta-estimates from combined data. By establishing a common methodology, factors that might influence the differences in results from previous studies can more easily be explored. Administrative support was provided to ensure that the highest quality data were used in the analysis. It is anticipated that the PAPA results will contribute to the international scientific discussion of how to conduct and interpret time-series studies of air pollution and will stimulate the development of high-quality routine systems for recording daily deaths and hospital admissions for time-series analysis. METHODS: Mortality data were retrieved from routine databases with underlying causes of death coded using the World Health Organization (WHO) International Classification of Diseases, 9th revision or 10th revision (ICD-9, ICD-10). Air quality measurements included nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matter with aerodynamic diameter < or = 10 microm (PM10), and ozone (O3) and were obtained from several fixed-site air monitoring stations that were located throughout the metropolitan areas of the four cities and that met the standards of procedures for quality assurance and quality control carried out by local government units in each city. Using the Common Protocol, an optimized core model was established for each city to assess the effects of each of the four air pollutants on daily mortality using generalized linear modeling with adjustments for time trend, seasonality, and other time-varying covariates by means of a natural-spline smoothing function. The models were adjusted to suit local situations by correcting for influenza activity, autocorrelation, and special weather conditions. Researchers in Hong Kong, for example, used influenza activity based on frequency of respiratory mortality; researchers in Hong Kong and Shanghai used autoregressive terms for daily outcomes at lag days; and researchers in Wuhan used additional smoothing for periods with extreme weather conditions. RESULTS AND DISCUSSION: For mortality due to all natural (nonaccidental) causes at all ages, the effects of air pollutants per 10-microg/m3 increase in concentration was found to be higher in Bangkok than in the three Chinese cities, with the exception of the effect of NO2 in Wuhan. The magnitude of the effects for cardiovascular and respiratory mortality were generally higher than for all natural mortality at all ages. In addition, the effects associated with PM10 and O3 in all natural, cardiovascular; and respiratory mortality were found to be higher in Bangkok than in the three Chinese cities. The explanation for these three findings might be related to consistently higher daily mean temperatures in Bangkok, variations in average time spent outdoors by the susceptible populations, and the fact that less air conditioning is available and used in Bangkok than in the other cities. However, when pollutant concentrations were incorporated into the excess risk estimates through the use of interquartile range (IQR), the excess risk was more comparable across the four cities. We found that the increases in effects among older age groups were greater in Bangkok than in the other three cities. After excluding data on extremely high concentrations of PM10 in Bangkok, the effect estimate associated with PM10 concentrations decreased in Bangkok (suggesting a convex relationship between risk and PM10, where risk levels off at high concentrations) instead of increasing, as it did in the other cities. This leveling off of effect estimates at high concentrations might be related to differences in vulnerability and exposure of the population to air pollution as well as to the sources of the air pollutant. IMPLICATIONS OF THE STUDY: The PAPA project is the first coordinated Asian multicity air pollution study ever published; this signifies the beginning of an era of cooperation and collaboration in Asia, with the development of a common protocol for coordination, data management, and analysis. The results of the study demonstrated that air pollution in Asia is a significant public health burden, especially given the high concentrations of pollutants and high-density populations in major cities. When compared with the effect estimates reported in the research literature of North America and Western Europe, the study's effect estimates for PM10 were generally similar and the effect estimates for gaseous pollutants were relatively higher. In Bangkok, however, a tropical city where total exposures to outdoor pollution might be higher than in most other cities, the observed effects were greater than those reported in the previous (i.e., Western) studies. In general, the results suggested that, even though social and environmental conditions across Asia might vary, it is still generally appropriate to apply to Asia the effect estimates for other health outcomes from previous studies in the West. The results also strongly support the adoption of the global air quality guidelines recently announced by WHO.

Characterization of cardiac brain natriuretic peptide release in patients with paroxysmal atrial fibrillation undergoing left atrial ablation.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is associated with elevated levels of brain natriuretic peptide (BNP). The exact cardiac source and implications of this are currently unknown, as are the effects of left atrial ablation on cardiac BNP release. We sought to investigate BNP levels at different cardiac sites in PAF patients before and after left atrial ablation and compare these with a non-atrial fibrillation control cohort. METHODS AND RESULTS: Twenty PAF patients (52+/-10 years, 70% men; left ventricular ejection fraction, 55+/-3%) undergoing ablation were studied, BNP levels were measured at different cardiac sites before and after ablation and compared with a control cohort undergoing ablation for left lateral accessory pathways (10 patients, 41+/-11 years; left ventricular ejection fraction, 55+/-4%). In both cohorts, the coronary sinus BNP levels were the greatest. The PAF cohort had significantly greater BNP levels than the control cohort at all sites before and after ablation. Ablation of the left atrium was associated with a significant decrease in coronary sinus BNP levels (P=0.05) and transcardiac BNP gradient (P=0.03). This was not observed in the control cohort. CONCLUSIONS: BNP levels are elevated in PAF, with the highest levels in the coronary sinus. Ablation of the left atrium was associated with an immediate decrease of BNP levels, implicating this as the source.

Soft x-ray measurements using photoconductive type-IIa and single-crystal chemical vapor deposited diamond detectors.

Photoconductive detectors (PCDs) are routinely used alongside vacuum x-ray diodes (XRDs) to provide an alternative x-ray flux measurement at laser facilities such as HELEN at AWE Aldermaston, UK, and Omega at the Laboratory for Laser Energetics. To evaluate diamond PCDs as an alternative to XRD arrays, calibration measurements made at the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory are used to accurately calculate the x-ray flux from a laser-heated target. This is compared to a flux measurement using the Dante XRD diagnostic. Estimates indicate that the photoinduced conductivity from measurements made at Omega are too large, and calculations using the radiometric calibrations made at the NSLS agree with this hypothesis. High-purity, single-crystal, chemical vapor deposited (CVD) diamond samples are compared to natural type-IIa PCDs and show promising high resistivity effects, the corollary of which preliminary results show is a slower response time.

Evaluation of the sensitivity and fading characteristics of an image plate system for x-ray diagnostics.

Image plates (IPs) are a reusable recording media capable of detecting ionizing radiation, used to diagnose x-ray emission from laser-plasma experiments. Due to their superior performance characteristics in x-ray applications [C. C. Bradford, W. W. Peppler, and J. T. Dobbins III, Med. Phys. 26, 27 (1999) and J. Digit. Imaging. 12, 54 (1999)], the Fuji Biological Analysis System (BAS) IPs are fielded on x-ray diagnostics for the HELEN laser by the Plasma Physics Department at AWE. The sensitivities of the Fuji BAS IPs have been absolutely calibrated for absolute measurements of x-ray intensity in the energy range of 0-100 keV. In addition, the Fuji BAS IP fading as a function of time was investigated. We report on the characterization of three Fuji BAS IP responses to x-rays using a radioactive source, and discrete x-ray line energies generated by the Excalibur soft x-ray facility and the Defense Radiological Standards Centre filter-fluorescer hard x-ray system at AWE.

Digital photography as a novel technique of measuring ocular surface dimensions.

PURPOSE: To introduce a novel technique for measuring ocular surface dimensions using digital photography and computerized image analysis in the context of ptosis repair surgery. METHODS: Digital photographs and patient questionnaires on dry eye symptoms were obtained from 31 patients before and after ptosis repair. Patients were examined preoperatively and at 1 and 6 weeks postoperatively. Adobe Photoshop 7.0 (Adobe Systems Incorporated, 345 Parkl Avenue, San Jose, CA 95110-2704, USA) was used to digitally measure palpebral fissure height, fissure width, and ocular surface area (OSA). Similar digital measurements were obtained on 30 control subjects as well. Digital calculations of OSA for control, preoperative, and postoperative groups were compared with other published techniques. RESULTS: Graphical comparison between our method of measuring OSA and the mathematical estimations proposed by previous studies suggests that our method is more precise in measuring OSA, and that it is also better able to identify individual variations of OSA from general population trends. CONCLUSION: Digital ocular photography combined with computerized image analysis is a fast, easy to use, and reliable method of measuring ocular surface dimensions. In addition to ptosis surgery, this method can be used in other ocular surface studies.

Adrenergic receptors in the ptotic human eyelid: correlation with phenylephrine testing and surgical success in ptosis repair.

PURPOSE: To investigate the relationship between adrenergic receptors in Müller muscle and response to phenylephrine testing in patients undergoing ptosis surgery. This study also compares outcomes of Fasanella and Putterman approaches to posterior ptosis repair. METHODS: Prospective analysis of 71 patients undergoing posterior ptosis surgery. Eyelid height was measured before and after phenylephrine. Müller muscle was examined for alpha-1D, alpha-2C, beta-1, and beta-2 receptors. Specimens were graded on receptor staining intensity. Patients were seen 1 week and 6 weeks following surgery. Surgical outcomes were scored on a scale of 1 (most favorable) to 3 (least favorable). RESULTS: Adrenergic receptors were found in decreasing order: alpha-1D, beta-1, alpha-2C, and beta-2. Receptor grade significantly predicted eyelid height for alpha-2C receptors (p = .03). Mean outcome scores for 36 Putterman (1.10) and 35 Fasanella (1.27) procedures were not significantly different. CONCLUSIONS: Alpha 1D, alpha-2C, and beta-2 receptors are documented within human Müller muscle. Human eyelid elevation response to phenylephrine is inversely related to the amount of alpha-2C receptor staining in Müller muscle. Fasanella and Putterman procedures have equal outcomes, independent of adrenergic receptors.

Hypothalamic-pituitary-adrenal axis activity in obese men with and without sleep apnea: effects of continuous positive airway pressure therapy.

CONTEXT: Previous studies on the association between the hypothalamic-pituitary-adrenal axis activity and sleep apnea (SA) and obesity are inconsistent and/or limited. OBJECTIVE: In this study, we evaluated the activity of the hypothalamic-pituitary-adrenal axis in nonpsychologically distressed obese subjects with and without SA and examined the impact of continuous positive airway pressure (CPAP) in SA patients. DESIGN AND PARTICIPANTS: In study I, four-night sleep laboratory recordings and serial 24-h plasma measures of cortisol were obtained in 45 obese men with and without apnea and nonobese controls. Sleep apneic patients were reassessed after 3 months of CPAP use. In study II, 38 obese men with and without sleep apnea and nonobese controls were challenged with ovine CRH administration after four nights in the sleep laboratory. RESULTS: The sleep patterns were similar between obese and nonobese controls. Twenty-four-hour plasma cortisol levels were highest in nonobese controls, intermediate in obese apneic patients, and lowest in obese controls (8.8 +/- 0.4 vs. 8.1 +/- 0.3 vs. 7.5 +/- 0.3 microg/dl, P < 0.05). CPAP tended to reduce cortisol levels in the apneic patients (difference -0.7 +/- .4 microg/dl, P = 0.1). CRH administration resulted in a higher ACTH response in both obese groups, compared with nonobese controls; the three groups were not different in cortisol response. CONCLUSIONS: Nonpsychologically distressed, normally sleeping, obese men had low cortisol secretion. The cortisol secretion was slightly activated by SA and returned to low by CPAP use. The low cortisol secretion in obesity through its inferred hyposecretion of hypothalamic CRH might predispose the obese to sleep apnea.

Dietary fats induce human monocyte activation in vitro.

In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is amplified, and migration of monocytes into the walls of the aorta and large arteries is increased, due partly to de novo expression or activation of monocyte adhesion molecules. Although there is increasing evidence that CMRs (chylomicron remnants) are strongly atherogenic, the outcomes of interactions between blood monocytes and circulating CMRs are not known. Here, we have studied the effects of CRLPs (CMR-like particles) on THP-1 human monocyte oxidative burst. The particles induced a significant increase in reactive oxygen species within 1 h, which persisted for 24 h. We suggest that monocyte-CMR interactions may be important in early atherosclerosis when many activated monocytes are found in susceptible areas of the artery wall.