753 research outputs found
A Comparison of Methods for Poverty Estimation in Developing Countries
Small area estimation is a widely used indirect estimation technique for micro-level geographic profiling. Three unit level small area estimation techniques-the ELL or World Bank method, empirical best prediction (EBP) and M-quantile (MQ) - can estimate micro-level Foster, Greer, & Thorbecke (FGT) indicators: poverty incidence, gap and severity using both unit level survey and census data. However, they use different assumptions. The effects of using model-based unit level census data reconstructed from cross-tabulations and having no cluster level contextual variables for models are discussed, as are effects of small area and cluster level heterogeneity. A simulation-based comparison of ELL, EBP and MQ uses a model-based reconstruction of 2000/2001 data from Bangladesh and compares bias and mean square error. A three-level ELL method is applied for comparison with the standard two-level ELL that lacks a small area level component. An important finding is that the larger number of small areas for which ELL has been able to produce sufficiently accurate estimates in comparison with EBP and MQ has been driven more by the type of census data available or utilised than by the model per se
A comparison of sensitivity-specificity imputation, direct imputation and fully Bayesian analysis to adjust for exposure misclassification when validation data are unavailable.
: Measurement error is an important source of bias in epidemiological studies. We illustrate three approaches to sensitivity analysis for the effect of measurement error: imputation of the 'true' exposure based on specifying the sensitivity and specificity of the measured exposure (SS); direct imputation (DI) using a regression model for the predictive values; and adjustment based on a fully Bayesian analysis. : We deliberately misclassify smoking status in data from a case-control study of lung cancer. We then implement the SS and DI methods using fixed-parameter (FBA) and probabilistic (PBA) bias analyses, and Bayesian analysis using the Markov-Chain Monte-Carlo program WinBUGS to show how well each recovers the original association. : The 'true' smoking-lung cancer odds ratio (OR), adjusted for sex in the original dataset, was OR = 8.18 [95% confidence limits (CL): 5.86, 11.43]; after misclassification, it decreased to OR = 3.08 (nominal 95% CL: 2.40, 3.96). The adjusted point estimates from all three approaches were always closer to the 'true' OR than the OR estimated from the unadjusted misclassified smoking data, and the adjusted interval estimates were always wider than the unadjusted interval estimate. When imputed misclassification parameters departed much from the actual misclassification, the 'true' OR was often omitted in the FBA intervals whereas it was always included in the PBA and Bayesian intervals. : These results illustrate how PBA and Bayesian analyses can be used to better account for uncertainty and bias due to measurement error.<br/
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Reproducibility of gene expression across generations of Affymetrix microarrays
BACKGROUND: The development of large-scale gene expression profiling technologies is rapidly changing the norms of biological investigation. But the rapid pace of change itself presents challenges. Commercial microarrays are regularly modified to incorporate new genes and improved target sequences. Although the ability to compare datasets across generations is crucial for any long-term research project, to date no means to allow such comparisons have been developed. In this study the reproducibility of gene expression levels across two generations of Affymetrix GeneChips(® )(HuGeneFL and HG-U95A) was measured. RESULTS: Correlation coefficients were computed for gene expression values across chip generations based on different measures of similarity. Comparing the absolute calls assigned to the individual probe sets across the generations found them to be largely unchanged. CONCLUSION: We show that experimental replicates are highly reproducible, but that reproducibility across generations depends on the degree of similarity of the probe sets and the expression level of the corresponding transcript
Self-stabilised fractality of sea-coasts through damped erosion
Erosion of rocky coasts spontaneously creates irregular seashores. But the
geometrical irregularity, in turn, damps the sea-waves, decreasing the average
wave amplitude. There may then exist a mutual self-stabilisation of the waves
amplitude together with the irregular morphology of the coast. A simple model
of such stabilisation is studied. It leads, through a complex dynamics of the
earth-sea interface, to the appearance of a stationary fractal seacoast with
dimension close to 4/3. Fractal geometry plays here the role of a morphological
attractor directly related to percolation geometry.Comment: 4 pages, 5 figure
Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study
Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.
Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years.
Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.
Trial registration number NCT01836692; Pre-result
Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway
Neutrophil apoptosis and subsequent nonphlogistic clearance by surrounding phagocytes are key to the successful resolution of neutrophilic inflammation, with dysregulated apoptosis reported in multiple human inflammatory diseases. Enhancing neutrophil apoptosis has proresolution and anti-inflammatory effects in preclinical models of inflammation. Here we investigate the ability of the flavones apigenin, luteolin, and wogonin to induce neutrophil apoptosis in vitro and resolve neutrophilic inflammation in vivo. Human neutrophil apoptosis was assessed morphologically and by flow cytometry following incubation with apigenin, luteolin, and wogonin. All three flavones induced time- and concentration-dependent neutrophil apoptosis (apigenin, EC(50)=12.2 μM; luteolin, EC(50)=14.6 μM; and wogonin, EC(50)=28.9 μM). Induction of apoptosis was caspase dependent, as it was blocked by the broad-spectrum caspase inhibitor Q-VD-OPh and was associated with both caspase-3 and caspase-9 activation. Flavone-induced apoptosis was preceded by down-regulation of the prosurvival protein Mcl-1, with proteasomal inhibition preventing flavone-induced Mcl-1 down-regulation and apoptosis. The flavones abrogated the survival effects of mediators that prolong neutrophil life span, including lipoteichoic acid, peptidoglycan, dexamethasone, and granulocyte-macrophage colony stimulating factor, by driving apoptosis. Furthermore, wogonin enhanced resolution of established neutrophilic inflammation in a zebrafish model of sterile tissue injury. Wogonin-induced resolution was dependent on apoptosis in vivo as it was blocked by caspase inhibition. Our data show that the flavones induce neutrophil apoptosis and have potential as neutrophil apoptosis-inducing anti-inflammatory, proresolution agents.—Lucas, C. D., Allen, K. C., Dorward, D. A., Hoodless, L. J., Melrose, L. A., Marwick, J. A., Tucker, C. S., Haslett, C., Duffin, R., Rossi, A. G. Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway
Highly controlled, reproducible measurements of aerosol emissions from combustion of a common African biofuel source
Particulate emissions from biomass burning can both alter the atmosphere's radiative
balance and cause significant harm to human health. However, due to the large
effect on emissions caused by even small alterations to the way in which
a fuel burns, it is difficult to study particulate production of biomass
combustion mechanistically and in a repeatable manner. In order to address
this gap, in this study, small wood samples sourced from Côte D'Ivoire in
West Africa were burned in a highly controlled laboratory environment. The
shape and mass of samples, available airflow and surrounding thermal
environment were carefully regulated. Organic aerosol and refractory black
carbon emissions were measured in real time using an Aerosol Mass
Spectrometer and a Single Particle Soot Photometer, respectively. This
methodology produced remarkably repeatable results, allowing aerosol
emissions to be mapped directly onto different phases of combustion.
Emissions from pyrolysis were visible as a distinct phase before flaming was
established. After flaming combustion was initiated, a black-carbon-dominant
flame was observed during which very little organic aerosol was produced,
followed by a period that was dominated by organic-carbon-producing
smouldering combustion, despite the presence of residual flaming. During
pyrolysis and smouldering, the two phases producing organic aerosol, distinct
mass spectral signatures that correspond to previously reported variations in
biofuel emissions measured in the atmosphere are found. Organic aerosol
emission factors averaged over an entire combustion event were found to be
representative of the time spent in the pyrolysis and smouldering phases,
rather than reflecting a coupling between emissions and the mass loss of the
sample. Further exploration of aerosol yields from similarly carefully
controlled fires and a careful comparison with data from macroscopic fires
and real-world emissions will help to deliver greater constraints on the
variability of particulate emissions in atmospheric systems
Pituitary apoplexy following shoulder arthroplasty: a case report
<p>Abstract</p> <p>Introduction</p> <p>Pituitary apoplexy following a major surgical procedure is a catastrophic event and the diagnosis can be delayed in a previously asymptomatic patient. The decision on thromboprophylaxis in shoulder replacements in the absence of definite guidelines, rests on a careful clinical judgment.</p> <p>Case presentation</p> <p>A previously healthy 62-year-old Caucasian male patient who underwent shoulder arthroplasty developed hyponatremia resistant to correction with saline replacement. The patient had a positive family history of deep vein thrombosis and pulmonary embolism and heparin thromboprophylaxis was considered on clinical grounds. The patient developed hyponatremia resistant to conventional treatment and later developed ocular localizing signs with oculomotor nerve palsy. The diagnosis was delayed due to other confounding factors in the immediate post-operative period. Subsequent workup confirmed a pituitary adenoma with features of pituitary insufficiency. The patient was managed successfully on conservative lines with a multidisciplinary approach.</p> <p>Conclusions</p> <p>A high index of suspicion is required in the presence of isolated post-operative hyponatremia resistant to medical correction. A central cause, in particular pituitary adenoma, should be suspected early. Thromboprophylaxis in shoulder replacements needs careful consideration as it may be a contributory factor in precipitating this life-threatening condition.</p
Revealing the chemical characteristics of Arctic low-level cloud residuals – in situ observations from a mountain site
The role aerosol chemical composition plays in Arctic
low-level cloud formation is still poorly understood. In this study we
address this issue by combining in situ observations of the chemical
characteristics of cloud residuals (dried liquid cloud droplets or ice
crystals) and aerosol particles from the Zeppelin Observatory in
Ny-Ålesund, Svalbard (approx. 480 m a.s.l.). These measurements were
part of the 1-year-long Ny-Ålesund Aerosol and Cloud Experiment
2019–2020 (NASCENT). To obtain the chemical composition of cloud residuals
at molecular level, we deployed a Filter Inlet for Gases and AEROsols
coupled to a Chemical Ionization Mass Spectrometer (FIGAERO-CIMS) with
iodide as the reagent ion behind a ground-based counterflow virtual impactor
(GCVI). The station was enshrouded in clouds roughly 15 % of the time
during NASCENT, out of which we analyzed 14 cloud events between December
2019 and December 2020. During the entire year, the composition of the cloud
residuals shows contributions from oxygenated organic compounds, including
organonitrates, and traces of the biomass burning tracer levoglucosan. In
summer, methanesulfonic acid (MSA), an oxidation product of dimethyl sulfide
(DMS), shows large contributions to the sampled mass, indicating marine
natural sources of cloud condensation nuclei (CCN) and ice nucleating
particle (INP) mass during the sunlit part of the year. In addition, we
also find contributions of the inorganic acids nitric acid and sulfuric acid,
with outstanding high absolute signals of sulfuric acid in one cloud
residual sample in spring and one in late summer (21 May and 12 September 2020), probably caused by high anthropogenic sulfur emissions near the
Barents Sea and Kara Sea. During one particular cloud event, on 18 May 2020,
the air mass origin did not change before, during, or after the
cloud. We therefore chose it as a case study to investigate cloud impact on
aerosol physicochemical properties. We show that the overall chemical
composition of the organic aerosol particles was similar before, during, and
after the cloud, indicating that the particles had already undergone one or
several cycles of cloud processing before being measured as residuals at the
Zeppelin Observatory and/or that, on the timescales of the observed cloud event, cloud
processing of the organic fraction can be neglected. Meanwhile, there were on
average fewer particles but relatively more in the accumulation mode after
the cloud. Comparing the signals of sulfur-containing compounds of cloud
residuals with aerosols during cloud-free conditions, we find that sulfuric
acid had a higher relative contribution to the cloud residuals than to
aerosols during cloud-free conditions, but we did not observe an increase in
particulate MSA due to the cloud. Overall, the chemical composition,
especially of the organic fraction of the Arctic cloud residuals, reflected
the overall composition of the general aerosol population well. Our results
thus suggest that most aerosols can serve as seeds for low-level clouds in
the Arctic.</p
Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung
Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation
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