Comparison of airway deposition distributions of particles in healthy and diseased workers in an Egyptian industrial site

The objective of this study is the prediction and comparison of airway deposition patterns of an industrial aerosol in healthy workers and workers suffering from silicosis. Mass concentrations and related size distributions of particulate matter were measured in the industrial area of Samalut in Minia, Egypt. A novel stochastic lung deposition model, simulating the symptoms of silicosis by chronic bronchial (Br) obstruction and emphysema in the acinar (Ac) region, was applied to compute mass deposition fractions, deposition density, deposition rate and deposition density rate distributions in healthy and diseased workers. In the case of healthy workers, both mass deposition fractions and deposition rates are highest in the first half of the Ac region of the lung, while the corresponding deposition density and deposition density rate distributions exhibit a maximum in the large Br airways. In the case of diseased lungs, bullous emphysema causes a large deposition peak in the region of the bronchioli respiratorii. Regional mass deposition fractions adopt maximum values in the extrathoracic region, except during mouth breathing for bullous emphysema, where Ac deposition can be the most prominent. In general, lung deposition is significantly higher in diseased than in healthy lungs. Indeed, workers suffering from silicosis receive significantly higher Ac doses than healthy workers exposed to the same aerosol. Thus, this illness may progress faster if a diseased worker remains in a strongly polluted area.     

Pathfinders in oncology from the end of the 19th century to the first description of Ewing sarcoma

During the period 1884 to 1922, the only option in cases of operable cancers was radical surgery, and only a minority of patients were cured. Sporadic attempts were made to treat inoperable cancer patients with bacterial toxins; however, with the discovery of x-ray and radium, the era of radiation treatment as an alternative to surgery began. The discovery of transmissible cancers and experimental growth of cancer cells offered new information and not only led to a better understanding of the cellular composition of cancers but also yielded important information that ultimately paved the way to chemotherapy. These efforts also advanced the understanding of the pathogenesis of tumors and induced new clinical and pathologic classifications and subspecializations. It is important to emphasize that many of the initiatives and discoveries made in Europe in the second half of the 19th century were first put into clinical practice in the United States during the first 2 decades of the 20th century, including the use of x-ray and radium for irradiation and as diagnostic tools. All things considered, the progress made between 1884 and 1922 came about through the hard work of many eminent individuals; however, there were 7 foresighted pathfinders (3 surgeons, 2 pathologists, 1 internist, and 1 physicist) who—despite their widely diverse backgrounds, personalities, and expertise—made remarkable contributions to oncology to an extent that is still felt today.     

Enantiomeric separation of antimalarial drugs by capillary electrophoresis using neutral and negatively charged cyclodextrins

Capillary electrophoresis (CE) methods for chiral resolution of five antimalarial drugs (primaquine, tafenoquine, mefloquine, chloroquine and quinacrine) were developed by using a wide selection of neutral and anionic cyclodextrin (CD) derivatives. The use of sulfobutyl-β-CD and carboxymethyl-β-CD (CMBCD) resulted in good resolution of quinacrine and tafenoquine, respectively. New results are presented for resolutions of chloroquine and mefloquine. Application of carboxyalkyl- and sulfobutyl-CD derivatives provided improved resolution for primaquine. The impurity in primaquine sample detected by CE was identified as quinocide by MS and NMR. CMBCD provided not only the best separation of primaquine from quinocide but also the simultaneous complete resolution of both compounds.     

Genetics of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease. IPF is a complex disease, with environmental and genetic factors variably contributing to disease susceptibility and outcomes. A host of common gene variants with modest effect size impart disease risk in patients with sporadic IPF, while rare variants with large effect size influence disease risk in those with familial interstitial pneumonia. In this review, we highlight several common and rare variants underpinning IPF risk and call attention to recently published studies informing our understanding of this risk.     

A sequence labeling approach to link medications and their attributes in clinical notes and clinical trial announcements for information extraction

Objective

The goal of this work was to evaluate machine learning methods, binary classification and sequence labeling, for medication–attribute linkage detection in two clinical corpora.

Data and methods

We double annotated 3000 clinical trial announcements (CTA) and 1655 clinical notes (CN) for medication named entities and their attributes. A binary support vector machine (SVM) classification method with parsimonious feature sets, and a conditional random fields (CRF)-based multi-layered sequence labeling (MLSL) model were proposed to identify the linkages between the entities and their corresponding attributes. We evaluated the system''s performance against the human-generated gold standard.

Results

The experiments showed that the two machine learning approaches performed statistically significantly better than the baseline rule-based approach. The binary SVM classification achieved 0.94 F-measure with individual tokens as features. The SVM model trained on a parsimonious feature set achieved 0.81 F-measure for CN and 0.87 for CTA. The CRF MLSL method achieved 0.80 F-measure on both corpora.

Discussion and conclusions

We compared the novel MLSL method with a binary classification and a rule-based method. The MLSL method performed statistically significantly better than the rule-based method. However, the SVM-based binary classification method was statistically significantly better than the MLSL method for both the CTA and CN corpora. Using parsimonious feature sets both the SVM-based binary classification and CRF-based MLSL methods achieved high performance in detecting medication name and attribute linkages in CTA and CN.     

Job insecurity and prognosis after myocardial infarction: The SHEEP Study

Background

The prognostic role of job insecurity in coronary heart disease is unknown. We aimed to analyze whether job insecurity predicts mortality and recurrent events after a first acute myocardial infarction (AMI).

Methods

We studied non-fatal AMI cases involved in the Stockholm Heart Epidemiology Program who were in paid employment and younger than 65 years (n = 676). Shortly after their AMI, patients completed a questionnaire about job insecurity, demographic, work-related, clinical and lifestyle factors and participated in a clinical examination three months after discharge from the hospital. They were followed for 8.5 years for mortality and cardiovascular events.

Results

After adjusting for previous morbidity, demographic and work-related factors, job insecurity was associated with an increased risk of the combined endpoint of cardiac death and non-fatal AMI, of total mortality and of heart failure; the hazard ratios (HR) and the 95% confidence intervals (CI) were 1.50 (1.02-2.22), 1.69 (1.04-2.75) and 1.62 (1.07-2.44), respectively. Similar associations, but with less statistical power were observed between job insecurity and cardiac death (HR (95% CI): 1.57 (0.80-3.09)) and stroke (HR (95% CI): 1.46 (0.71-3.02)), respectively. Adjustment for potential mediators, i.e. sleep problems, health behaviour, hypertension, blood lipids, glucose, inflammatory and coagulation factors did not alter considerably the relationship between job insecurity and the combination of cardiac mortality and non-fatal AMI.

Conclusions

Our results suggest that job insecurity is an adverse prognostic factor in patients with a first AMI. Future studies are needed to confirm this finding and to determine the mechanisms underlying the observed relationship.     

MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen-restricted Th2-deviated CD4(+) T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC-Th2 axis.