Modeling uncertainty in the measurement of low-level analytes in environmental analysis

The use of analytical chemistry measurements in environmental monitoring is dependent on an assessment of measurement error. Models for variation in measurements are needed to quantify uncertainty in measurements, set limits of detection, and preprocess data for more sophisticated analysis in prediction, classification, and clustering. This article explains how a two-component error model can be used to accomplish all of these objectives. In addition, we present applications to quantitating biomarkers of exposure to toxic substances using gene expression microarrays.     

Initial experience with a respiratory therapist arterial line placement service

BACKGROUND: Indwelling arterial lines are commonly used in critical care. To standardize and improve the placement of these devices, we developed and implemented a respiratory therapist-based line placement service. As a measure of the quality of the service, we assessed the success and complications encountered in the first 119 line placement attempts of this new service. METHODS: The following were recorded for each artery on which cannulation was attempted: the number of the attempt on which cannulation was successful; if a different person was able to cannulate the artery after initial failure; and whether any complications occurred. Success rate compared to the number of attempts was tested with chi-square. RESULTS: Respiratory therapists were successful in placing 80% of attempted lines on the first try, including all 18 of 18 dorsal pedis attempts. Ninety-seven percent (115 of 119) of attempted arteries were ultimately cannulated. Success on second attempts by the same person was less than if a different, more experienced, person attempted the placement (p = 0.024). No complications were identified during the study. CONCLUSIONS: Initiation of a respiratory therapist-based arterial line placement service resulted in an acceptable cannulation success rate, without complications. Increased experience of the person attempting cannulation correlates with improved success.     

The coastal environment and human health: microbial indicators,pathogens, sentinels and reservoirs

Innovative research relating oceans and human health is advancing our understanding of disease-causing organisms in coastal ecosystems. Novel techniques are elucidating the loading, transport and fate of pathogens in coastal ecosystems, and identifying sources of contamination. This research is facilitating improved risk assessments for seafood consumers and those who use the oceans for recreation. A number of challenges still remain and define future directions of research and public policy. Sample processing and molecular detection techniques need to be advanced to allow rapid and specific identification of microbes of public health concern from complex environmental samples. Water quality standards need to be updated to more accurately reflect health risks and to provide managers with improved tools for decision-making. Greater discrimination of virulent versus harmless microbes is needed to identify environmental reservoirs of pathogens and factors leading to human infections. Investigations must include examination of microbial community dynamics that may be important from a human health perspective. Further research is needed to evaluate the ecology of non-enteric water-transmitted diseases. Sentinels should also be established and monitored, providing early warning of dangers to ecosystem health. Taken together, this effort will provide more reliable information about public health risks associated with beaches and seafood consumption, and how human activities can affect their exposure to disease-causing organisms from the oceans.     

The hexadentate hydroxypyridinonate TREN-(Me-3,2-HOPO) is a more orally active iron chelator than its bidentate analogue

Bidentate hydroxypyridinone chelators effectively complex and facilitate excretion of trivalent iron. To test the hypothesis that hexadentate chelators are more effective than bidentate chelators at low concentrations, urinary and biliary Fe excretions were determined in Fe-loaded rats before and after administration of a bidentate chelator, Pr-(Me-3,2-HOPO), or its hexadentate analogue, TREN-(Me-3,2-HOPO). The bidentate chelator slightly increased biliary Fe excretion in Fe-loaded rats after IV (90 micromol/kg) and PO (90 or 270 micromol/kg) administration, but chelation efficiency did not exceed 1%. The hexadentate chelator markedly increased biliary Fe excretion, achieving overall chelation efficiencies of 14% after IV administration of 30 micromol/kg and 8 or 3% after PO (30 or 90 micromol/kg) administration. The hexadentate chelator was significantly more effective than the bidentate chelator after IV injection and oral dosing. In chelator-treated Fe-loaded or saline-injected rats, >90% of the excreted Fe was in the bile. Oral TREN-(Me-3,2-HOPO), given to non-Fe-loaded rats, did not appreciably change Fe output, indicating that there was little Fe depletion in the absence of Fe overload. These results support the hypothesis that greater Fe chelation efficiency can be achieved with hexadentate than with bidentate chelators at lower, and presumably safer, concentrations. The results also demonstrate that TREN-(Me-3, 2-HOPO) is a promising, orally effective, Fe chelator.     

Controlled trial of continuous inflating pressure for hyaline membrane disease

A controlled trial of elective intervention with continuous inflating pressure (CIP) was performed in infants with severe hyaline membrane disease who weighed more than 1000 g at birth. Infants entered the trial if their arterial oxygen tension (PaO2) fell below 60 mmHg while breathing a fractional inspired oxygen concentration (F1O2) greater than 0-95. 11 out of 12 infants in the CIP-treated group and 10 out of 12 in the control group survived. 7 treated and 6 control infants required mechanical ventilation. When CIP was started the Pao2 of the treated infants increased, and they breathed high concentrations of oxygen for a significantly shorter period than the control infants. During the 31-month duration of the trial 107 other infants with severe hyaline membrane disease were admitted who did not meet the criteria for entry to the trial. 37 survived after breathing high concentrations of oxygen (F1O2 greater than 0-60) spontaneously without any ventilatory assistance, and the remaining 70 infants were already being ventilated on their arrival in the unit, usually because they had required mechanical ventilation during transfer from other hospitals. The neonatal survival rate for those infants born in this hospital during the study period was 88% (50 out of 57 infants) and for those referred from other hospitals it was 69% (51 out of 74 infants). The maximum further increase in overall survival rate that might have been achieved in our population of infants if CIP had been initiated very early in the course of the illness was 5%--i.e. from 77% (101/131) to 82% (107/131).     

Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.     

The Natural History of Flare‐Ups in Fibrodysplasia Ossificans Progressiva (FOP): A Comprehensive Global Assessment

Fibrodysplasia ossificans progressiva (FOP) leads to disabling heterotopic ossification (HO) from episodic flare‐ups. However, the natural history of FOP flare‐ups is poorly understood. A 78‐question survey on FOP flare‐ups, translated into 15 languages, was sent to 685 classically‐affected patients in 45 countries (six continents). Five hundred patients or knowledgeable informants responded (73%; 44% males, 56% females; ages: 1 to 71 years; median: 23 years). The most common presenting symptoms of flare‐ups were swelling (93%), pain (86%), or decreased mobility (79%). Seventy‐one percent experienced a flare‐up within the preceding 12 months (52% spontaneous; 48% trauma‐related). Twenty‐five percent of those who had received an intramuscular injection reported an immediate flare‐up at the injection site, 84% of whom developed HO. Axial flare‐ups most frequently involved the back (41.6%), neck (26.4%), or jaw (19.4%). Flare‐ups occurred more frequently in the upper limbs before 8 years of age, but more frequently in the lower limbs thereafter. Appendicular flare‐ups occurred more frequently at proximal than at distal sites without preferential sidedness. Seventy percent of patients reported functional loss from a flare‐up. Thirty‐two percent reported complete resolution of at least one flare‐up and 12% without any functional loss (mostly in the head or back). The most disabling flare‐ups occurred at the shoulders or hips. Surprisingly, 47% reported progression of FOP without obvious flare‐ups. Worldwide, 198 treatments were reported; anti‐inflammatory agents were most common. Seventy‐five percent used short‐term glucocorticoids as a treatment for flare‐ups at appendicular sites. Fifty‐five percent reported that glucocorticoids improved symptoms occasionally whereas 31% reported that they always did. Only 12% reported complete resolution of a flare‐up with glucocorticoids. Forty‐three percent reported rebound symptoms within 1 to 7 days after completing a course of glucocorticoids. This study is the first comprehensive global assessment of FOP flare‐ups and establishes a critical foundation for the design and evaluation of future clinical trials. © 2015 American Society for Bone and Mineral Research.