THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

Global strategy for asthma management and prevention

ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogenesis of atherosclerotic CAD. It will recount the evidence that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree. A decade ago, the treatment of hypercholesterolemia and hypertension was expected to eliminate CAD by the end of the 20th century. Lately, however, that optimistic prediction has needed revision. Cardiovascular diseases are expected to be the main cause of death globally within the next 15 years owing to a rapidly increasing prevalence in developing countries and eastern Europe and the rising incidence of obesity and diabetes in the Western world. 1 Cardiovascular diseases cause 38 percent of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. These facts force us to revisit cardiovascular disease and consider new strategies for prediction, prevention, and treatment.

/pdf/inflammation-atherosclerosis-and-coronary-artery-disease-23ryhxhuc2.pdf

Inflammation, Atherosclerosis, and Coronary Artery Disease

ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).

/pdf/2015-esc-guidelines-for-the-management-of-acute-coronary-6did6h5nxk.pdf

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)

ACCF
: American College of Cardiology Foundation
ACS
: acute coronary syndrome
AHA
: American Heart Association
CAD
: coronary artery disease
CABG
: coronary artery bypass grafting
CKMB
: creatine kinase MB isoform
cTn
: cardiac troponin
CT
: computed tomography
CV
: coefficient of variation
ECG
: electrocardiogram
ESC
: European Society of Cardiology
FDG
: fluorodeoxyglucose
h
: hour(s)
HF
: heart failure
LBBB
: left bundle branch block
LV
: left ventricle
LVH
: left ventricular hypertrophy
MI
: myocardial infarction
mIBG
: meta-iodo-benzylguanidine
min
: minute(s)
MONICA
: Multinational MONItoring of trends and determinants in CArdiovascular disease)
MPS
: myocardial perfusion scintigraphy
MRI
: magnetic resonance imaging
mV
: millivolt(s)
ng/L
: nanogram(s) per litre
Non-Q MI
: non-Q wave myocardial infarction
NSTEMI
: non-ST-elevation myocardial infarction
PCI
: percutaneous coronary intervention
PET
: positron emission tomography
pg/mL
: pictogram(s) per millilitre
Q wave MI
: Q wave myocardial infarction
RBBB
: right bundle branch block
sec
: second(s)
SPECT
: single photon emission computed tomography
STEMI
: ST elevation myocardial infarction
ST–T
: ST-segment –T wave
URL
: upper reference limit
WHF
: World Heart Federation
WHO
: World Health Organization

Myocardial infarction (MI) can be recognised by clinical features, including electrocardiographic (ECG) findings, elevated values of biochemical markers (biomarkers) of myocardial necrosis, and by imaging, or may be defined by pathology. It is a major cause of death and disability worldwide. MI may be the first manifestation of coronary artery disease (CAD) or it may occur, repeatedly, in patients with established disease. Information on MI rates can provide useful information regarding the burden of CAD within and across populations, especially if standardized data are collected in a manner that …

/pdf/third-universal-definition-of-myocardial-infarction-1nbq846anm.pdf

Third universal definition of myocardial infarction

The origin of myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) was investigated in the first part of the study. Radioimmunoassay of the cellular and supernatant MPO content as well as the peroxidase-antiperoxidase (PAP) technique were employed to determine the cellular source of MPO. The concentrations of MPO were measured in serum and BAL in the second part of the study. The aim was to determine whether the capillary bed was also a source of MPO. Neutrophil numbers in BALs obtained from 20 healthy subjects correlated significantly to the concentrations of MPO in cell-free BAL supernatants (r = 0.643, P less than or equal to 0.01). The cellular content of MPO in mixed BAL cells was significantly correlated to the number of neutrophils in the mixture (r = 0.536, P less than 0.05), but not to the number of any other cells. Moreover, the PAP-technique identified MPO in lung tissue neutrophils in resection specimens obtained from three patients undergoing surgery. This technique also revealed strong MPO activity in all BAL neutrophils and a weak activity in merely 4% of the alveolar macrophages in cytospin preparations obtained from seven BALs. High BAL/serum ratio of MPO concentrations suggests that MPO is of local origin, rather than passively diffused from the circulating pool. We therefore conclude that strong evidence suggests that MPO in BAL originates from lung neutrophils and that BAL MPO content may be used to estimate the neutrophil presence or activation in epithelium lining fluid.

Myeloperoxidase in human lung lavage. I. A marker of local neutrophil activity.

Eosinophil peroxidase produces hypobromous acid in the airways of stable asthmatics

Background: Bronchial asthma is characterized by airways smooth muscle hypertrophy and infiltration of mast cells in the bronchial mucosa. The aim of this investigation was to study the distribution of mast cells in different compartments in the bronchial mucosa of allergic and nonallergic asthma in relation to airways remodeling.



Methods:  Bronchial biopsies were obtained from 29 subjects with allergic and nonallergic asthma and healthy controls. The biopsies were stained for mast cells by means of the tryptase specific antibody AA1. Extracellular deposition of mast cell products were judged on a semi-quantitative scale. Mast cells per mm2 were counted in epithelium, lamina propria and the smooth muscle compartment. Smooth muscle was visualized by actin antibodies and the proportion of staining of the biopsy estimated. Laminin and tenascin layers were visualized by their respective antibodies.



Results:  Airways smooth muscle thickness was greater in allergic vs nonallergic asthma (P < 0.001). Mast cells were increased in all three compartments in both allergic and nonallergic asthma, with significantly higher numbers in smooth muscles in allergic asthma (P < 0.03). The extracellular deposition of mast cell products was more common in allergic than nonallergic asthma in lamina propria and smooth muscles (P = 0.025; P = 0.002, respectively). In patients with allergic asthma the numbers of mast cells with extracellular deposition of mast cell products were significantly correlated to the thickness of the laminin and tenascin layers.



Conclusion:  Our results suggest that there are large differences between allergic and nonallergic asthmatics as to mast cell activation and airways smooth muscle thickness. Our data implies that mast cells are causally involved in structural alterations in allergic asthma.

The extracellular deposition of mast cell products is increased in hypertrophic airways smooth muscles in allergic asthma but not in nonallergic asthma

Background: There is growing concern about the respiratory health aspects of the indoor air quality in schools.



Methods: A standardized investigation, including nasal lavage (NAL), measurement of the nasal cavity by acoustic rhinometry, and hygienic measurements of airborne pollutants was performed in classrooms, outside the pollen season. All 279 school personnel working in the main buildings of 12 randomly selected primary schools in an urban community in central Sweden (Uppsala) were invited to enroll in the study; 234 (84%) participated. Eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme, and albumin were analyzed in NAL. Crude statistical analysis, as well as multiple regression analysis, was performed, controlling for room temperature, age, sex, current smoking, and a history of atopy.



Results: Most classrooms (83%) did not meet the Swedish ventilation standards. A lower degree of nasal patency was found at higher concentrations of respirable dust, nitrogen dioxide (NO2), formaldehyde, and total molds, and in the presence of Aspergillus sp. in the classroom air. The most consistent findings were observed for formaldehyde, NO2, and Aspergillus sp., related to both decreased nasal patency and increase of ECP and lysozyme in NAL. The presence of yeast was associated with an increase of ECP and lysozyme in NAL, but was not related to nasal patency.



Conclusions: Ventilation flow was below current hygienic standards in the classrooms. Air pollutants in the classroom air may influence nasal patency and inflammatory response in the nasal mucosa.

Indoor air pollutants in schools: nasal patency and biomarkers in nasal lavage.

The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen-atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure.

https://www.jacionline.org/article/S0091-6749(05)80050-8/pdf

Per Venge

Papers

Myeloperoxidase in human lung lavage. I. A marker of local neutrophil activity.

Eosinophil peroxidase produces hypobromous acid in the airways of stable asthmatics

The extracellular deposition of mast cell products is increased in hypertrophic airways smooth muscles in allergic asthma but not in nonallergic asthma

Indoor air pollutants in schools: nasal patency and biomarkers in nasal lavage.

Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season