Search

Anti-cancer host defense mechanisms are traditionally considered to consist of tumor suppressor genes and immune surveillance by cells of the innate and adaptive immune systems. However, there is mounting evidence that components of the acute phase protein response (APPR), and, in particular, certain cationic host defense peptides (HDPs), also contribute to anti-cancer host defense. In a number of in vitro studies, certain HDPs have been shown to be cytotoxic to tumor cells either directly through cancer cell membrane destabilization and lysis or through the initiation of apoptosis in the cancer cell. In addition, many cancer cells elaborate the pro-inflammatory cytokine interleukin-6, which in turn produces an APPR that involves the release of HDPs. It is therefore possible that the release of pro-inflammatory cytokines by cancer cells initiates a poorly understood anti-tumor response by the host that involves HDP induction. We hypothesize that the APPR may form an important anti-cancer host defense response. This may be an important consideration in light of cancer treatments designed to decrease systemic inflammation. Blunting of the anti-cancer effect of the APPR may also contribute to the increased cancer rates seen in chronic immunosuppressive states.

Background: Little information is available regarding expected phlebotomy cycle time (total time needed to draw a blood specimen) in inpatient settings. Examining this variable in 4 hospitals in Calgary, Alberta, Canada, we determined the distribution of phlebotomy cycle times and compared this by hospital and by phlebotomist experience. Methods: Between April 2014 and August 2014, we observed phlebotomy timing at 4 adult acute care hospital locations. Phlebotomists were stratified into 3 experience levels: 0 to 2 years, 2 to 5 years, and more than 5 years. We observed a total of 110 different phlebotomists. Results: We observed no statistical difference between experience levels ( P = .07) or hospital location ( P = .44) on mean phlebotomy cycle time. Conclusions: The mean (SD) phlebotomy cycle time was 259 (52) seconds per patient for normal phlebotomy procedures. If expected minimum and maximum phlebotomy times are defined as mean +/- 2 SD, the expected cycle time range is 196 to 404 seconds. * Abbreviations : RGH : Rockyview General Hospital FMC : Foothills Medical Centre PLC : Peter Lougheed Centre SHC : South Health Campus IV : intravenous ANOVA : analysis of variance

Objectives Approaches to determining optimal locations for patient service centers (phlebotomy clinics) have not been addressed in the published literature. Using the city of Calgary, Alberta, Canada, as a test case, our objective is to present a novel method for determining underserviced geographic areas within a city to guide the choice of potential new patient service center locations. Methods Data on travel distances for 198,883 phlebotomy visits as well as population data from the 2011 Canada Census were used for this study. Using geospatial mapping techniques, we produced maps of the city showing actual relative travel distances for patients as well as the geographic distribution of population density of patients undergoing phlebotomies. Results There was a striking pattern of increased travel distances in certain parts of the city. These also corresponded to geographic areas with greater density of patients seeking phlebotomies. Conclusions This analysis provided clear, objective evidence of communities that are currently relatively underserved by patient service centers. This approach could be used by other laboratories to plan the location of new patient service centers.

Objectives: Very little is known about the relative contributions of physician specialty groups and individual physicians to overall clinical laboratory expenditures. The objectives of this study were to determine the costs of clinical laboratory test expenditures attributable to 30 medical specialties and the associated per capita physician expenditures for an entire major Canadian city. Only chemistry, hematology, and microbiology tests were included in this study. Methods: Retrospective cohort study involving all physicians in Calgary, Canada, and surrounding areas (n = 3,499) and secondary data on laboratory test orders. Results: Data were obtained on approximately 20 million test requests. The mean clinical laboratory test expenditure, in Canadian dollars, per physician was $27,945 for all physicians combined. Total expenditures by primary care physicians (family physicians and general practitioners) accounted for 58% of total expenditures. Conclusions: There was wide variation in clinical laboratory test expenditures among specialties and on a per capita basis within medical specialties.

Objectives 1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3 + 4 and a 4 + 3 group. Design and methods Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7–10. The Gleason grade 7–10 group was further divided into 4 + 3 and 3 + 4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. Results 4622 men between the ages of 40–89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC = 0.570–0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC = 0.572–0.699). There were marked increases in the area under curves when 3 + 4 and 4 + 3 Gleason 7 cancers were separated. Conclusions Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3 + 4 and 4 + 3 group.

This paper presents a case study of traffic travel time estimation for the Deerfoot Trail highway in Calgary, AB, Canada. We analyzed the travel time for 12 hours per day for 5 consecutive months. The collected data are posted by Google maps, which are collected using hypertext transfer protocol requests. This paper provides a construction of the Holt-Winters forecasting model that streamlines the estimation of travel time for a specific hour of the day. The Holt-Winters model with exponential smoothing average has the best estimate of travel time. The model goodness of fit for the data collected at 07:00AM shows that the multiplicative Holt-Winters model has the best performance (mean square error 15.733 with R2 value of 0.8435). A fleet driver can use the results to decide to travel at a given hour. Moreover, decision makers can use the results to plan for road events.

Modern clinical decision support based on data analytics requires a framework that incorporates distributed processing platforms, sustainable data models, and inference algorithms. The ultimate objective of this chapter is to identify the common components of a user-centered analytics framework that can reason using different clinical historical Big Data. Those components emerge through two case studies that identify potential analytics to support the decisions of laboratory managers. In the case studies, the outputs are visualizing and estimating of clinical test volumes, which will lead to optimum purchasing and fiscal planning. We particularly focus on the reusable business intelligence (BI) components that can help running similar business processes from a single manager’s perspective, as well as the BI components that can be reused by several managers in a clinical laboratory setting. This is the first attempt at design and implementation of a user-centered framework for clinical laboratory settings as a BI platform.

The extreme polymorphism of mammalian major histocompatibility (MHC) Class I and Class II alleles has been attributed to inbreeding avoidance, heterozygote advantage and pathogen driven selection for rare MHC alleles. However, MHC alleles can be classified into a limited number of allele supertypes based on the specificity of their peptide binding grooves (about 10 supertypes in the case of human MHC Class I alleles). The paradox is that if antigen presentation can be accomplished by a limited number of binding groove motifs, why are these loci so polymorphic? An unexplored driver of this complexity may be selection pressure to enhance the antigenicity and immune recognition of transplacentally acquired lymphoid allografts during pregnancy. The exchange of lymphoid cells between mother and fetus probably occurs in all pregnancies and may lead to fetal and/or maternal lymphoid microchimerism, a known cause of autoimmune disease. Natural selection may have favoured increased polymorphism at MHC Class I and Class II loci in order to improve immune surveillance of these cells and thereby reduce the incidence of maternal and fetal autoimmune disease. At the same time, selection may have favoured the retention of a limited set of allele supertypes which optimally present immunodominant antigens.

To provide an update on the clinical usefulness of nonfasting versus fasting lipid testing to improve patient compliance, patient safety, and clinical assessment in cholesterol testing.Recommendations are identified as supported by good, fair, and poor (conflicting or insufficient) evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care.Screening for dyslipidemia as a risk factor for coronary artery disease and management of lipid-lowering medications are key parts of primary care. Recent evidence has questioned the fasting requirement for lipid testing. In population-based studies, total cholesterol, high-density lipoprotein cholesterol, and non-low-density lipoprotein cholesterol all varied by an average of 2% with fasting status. For routine screening, nonfasting cholesterol measurement is now a reasonable alternative to a fasting cholesterol measurement. For patients with diabetes, the fasting requirement might be an important safety issue because of problems with hypoglycemia. For the monitoring of triglyceride and low-density lipoprotein cholesterol levels in patients taking lipid-lowering medications, fasting becomes more important.Fasting for routine lipid level determinations is largely unnecessary and unlikely to affect patient clinical risk stratification, while nonfasting measurement might improve patient compliance and safety.

Community fecal immunochemical testing (FIT) screening programs are important for detecting early disease and can be effective when promoted by primary care physicians. Screening rates remain low across Canada and may be associated with sociodemographic factors.Fecal immunochemical testing results for a new community-based screening program were obtained from Calgary Laboratory Services from November 18, 2013 to May 31, 2014. Screening rates were determined for specific age and sex cohorts and sociodemographic factors were inferred from census Canada data. Poisson regression and generalized estimating equations were used to test associations of screening rate with sociodemographic variables.A total of 27,572 results were screened and included in our analysis. Recent immigrants (RR = 0.18, P =.0001), Aboriginal First Nations (RR = 0.39, P = 0.01), Aboriginal Metis (RR = 0.14, P = 0.0003), visible minority Black (RR = 0.35, P = 0.0002), and higher education (RR = 0.65, P =.0001) were associated with decreased screening. Visible minority Chinese (RR = 1.72, P =.0001) were more likely to be screened. Household income was not associated with screening rate. Older individuals and females were less likely to be screened.There is significant geographic variation in screening rates in Calgary. These are associated with a number of sociodemographic factors.

Objectives The introduction of the Papanicolaou (Pap) test in Canada has led to a decline in both the incidence of, and mortality from, cervical cancer. However, cervical cancer in women under the age of 25 is rare, and the updated Canadian Task Force on Preventive Health Care recommendations advise against screening by Pap test in this age group. Screening under the age of 25 can lead to false-positive results or to treatment of lesions that may spontaneously regress. The purpose of this observational study was to determine how many Pap tests are performed in women less than 25 years of age despite current guidelines. Methods Data were obtained from the Laboratory Information System of Calgary Laboratory Services for women under and over the age of 25 who underwent Pap testing between September and December 2012 and between February and May 2013. Results Approximately 4% of women aged 15 to 19 and 33% of women aged 20 to 24 had Pap tests after the new guidelines were released. Conclusion Women under the age of 25 continue to undergo unnecessary screening for cervical cancer. This excessive screening may cause physical and psychological harm and may result in unnecessary health care expenditures.

There are conflicting recommendations regarding the use of prostate specific antigen (PSA) as a screening test. Integral to this debate is an understanding of who is currently being tested. The purpose of this study was to provide a detailed account of PSA testing practices in a major Canadian city (Calgary, Alberta) and to identify variables that may affect access to the PSA test.PSA test counts were retrieved from Calgary Laboratory Services' Laboratory Information System from January 1, 2011 to December 31, 2011. A total of 75,914 individual PSA tests were included in our analysis. The frequency of PSA testing was plotted onto a dissemination area map of Calgary using ArcGIS software. Associations with sociodemographic variables were tested using Poisson regression.The median PSA value was 0.93 μg/L and the median age at collection was 58 years. Forty-three percent of men aged 60-69 received a PSA test. Visible minority status 'Black' (P=0.0002) and Métis status (P=0.0075) were associated with lower PSA testing frequencies, while median household income (P=0.0001) and university education (P=0.0001) were associated with higher PSA testing frequencies.There are areas in Calgary which are significantly over or under tested relative to the mean. The amount of PSA testing in men50 years of age is increasing, which is contrary to PSA testing guidelines.

Background Folate deficiency is rare in western countries and therefore blood tests for folate level have limited indications. One such indication is red cell macrocytosis, however it is unclear if the association of macrocytosis with folate deficiency is robust enough to serve as a risk marker. Our objective is to determine whether macrocytosis is a useful marker for folate deficiency. Findings Paired data from the Calgary Laboratory Services Information System was analyzed using receiver operating characteristic (ROC) curves to determine strength of association between mean corpuscular volume and serum folate. Strength of association was analyzed for serum folate cut-off values of 12, 10, 8, and 6 nmol/L. Overall, 0.2% of individuals were folate deficient (

Background: It is unclear whether vitamin D deficiency is associated with a higher risk of cardiovascular disease, and through what biochemical pathways this could occur. We investigated the relationship between serum 25-OH vitamin D and typical cardiovascular risk markers as well as incident myocardial infarction (MI) in a large group of high-risk individuals from the community of Calgary, Alberta, Canada. Methods: Calgary Laboratory Services databases were queried for age, sex, body mass index (BMI), personal healthcare number (PHN) and first available serum 25-OH vitamin D measure from patients who received an electrocardiogram or urine creatinine clearance test from 2010-2013. Data was linked by PHN to first available laboratory results for total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol, fasting glucose and HbA1c as well as Alberta Health Services hospital discharge data for first myocardial infarction (ICD-10: I21.1-9) occurring after 25-OH vitamin D measurement. Multiple linear and logistic regression were used to examine all associations. Results: There were 36 000-50 000 complete patient records for analysis of each of the risk markers, with a median follow-up of 8-11 months. A 30 mmol/L increase in serum 25-OH vitamin D was associated with significantly (p Conclusion: In a high-risk group of community patients from Calgary, Alberta, Canada, higher serum 25-OH vitamin D was associated with a lower risk of MI, which was explained by changes in commonly measured cardiovascular risk markers. Further study is needed to determine whether changes in cardiovascular risk markers are causally related to changes in 25-OH vitamin D.

Peripheral blood smear image examination is a part of the routine work of every laboratory. The manual examination of these images is tedious, time-consuming and suffers from interobserver variation. This has motivated researchers to develop different algorithms and methods to automate peripheral blood smear image analysis. Image analysis itself consists of a sequence of steps consisting of image segmentation, features extraction and selection and pattern classification. The image segmentation step addresses the problem of extraction of the object or region of interest from the complicated peripheral blood smear image. Support vector machine (SVM) and artificial neural networks (ANNs) are two common approaches to image segmentation. Features extraction and selection aims to derive descriptive characteristics of the extracted object, which are similar within the same object class and different between different objects. This will facilitate the last step of the image analysis process: pattern classification. The goal of pattern classification is to assign a class to the selected features from a group of known classes. There are two types of classifier learning algorithms: supervised and unsupervised. Supervised learning algorithms predict the class of the object under test using training data of known classes. The training data have a predefined label for every class and the learning algorithm can utilize this data to predict the class of a test object. Unsupervised learning algorithms use unlabeled training data and divide them into groups using similarity measurements. Unsupervised learning algorithms predict the group to which a new test object belong to, based on the training data without giving an explicit class to that object. ANN, SVM, decision tree and K-nearest neighbor are possible approaches to classification algorithms. Increased discrimination may be obtained by combining several classifiers together.

Metastases to the pineal gland are rare and reported cases have consisted primarily of gastrointestinal and lung primary malignancies. Here we present the case of a 66-year-old female with autosomal dominant polycystic kidney and liver disease who was found at autopsy to have an unrecognized infiltrating ductal adenocarcinoma of the pancreas with metastases to the liver, lungs and pineal gland. As far as we are aware, this is the first report of a metastasis of infiltrating ductal adenocarcinoma of the pancreas to the pineal gland.

Context: Many hematology laboratories have adopted semi-automated digital platforms for routine use and the evidence supporting their use is increasing. Aims: The CellaVision platforms are among the most thoroughly studied digital hematology platforms; we wished to determine the accuracy of CellaVision for reticulocyte counting. Design, Materials and Methods: We compared reticulocyte counts performed manually, using the Beckman Coulter LH750 automated analyzer and with the CellaVision DM96 platform. We analyzed the results for pair-wise correlation and bias, and precision. Statistical Analyses Used: Analyses were performed using Statistical Package for the Social Sciences software (SPSS), including Spearman's rho correlation coefficient, Friedman's two-way Analysis Of Variance (ANOVA) for comparison of distributions; bias was compared by way of mean and standard deviation. Results: The CellaVision reticulocyte counts correlated most strongly with those of the analyzer (often considered the benchmark test); the reticulocyte count distributions were noted not to be significantly different from each other across all three methods. The mean and standard deviation of bias were lowest in the comparison of CellaVision and LH750 counts. Conclusions: Our data provide additional support for the accuracy of digital hematology applications using the CellaVision DM96 platform.

Microscopic examination of a properly prepared blood smear is valuable in complete blood count (CBC) and differential blood count (DBC). A hematopathologist may spend enormous time manually inspecting the good working area (GWA) of the blood smear under a light microscope system to perform CBC or DBC. In this paper we focus on automatic localization of the GWA by classifying microscopic images of blood smears using different machine learning algorithms into three areas: Clumped, Good, and Sparse. The features used are the statistical and texture features. This approach yields a good localization of GWA in images acquired by a low cost light microscope system, scanned under magnifying power of x100 oil-immersed objective. Our experiment using images with resolution (3488×2616 pixels) of Giemsa-stained blood smears shows that the proposed method has an accuracy of 82% for the localizing the GWA and 79.73% for all areas in a validation set of 301 images.

Background The purpose of this study was to assess the current usage, utilization and future direction of digital photography of gross surgical specimens in pathology laboratories across Canada. Methods An online survey consisting of 23 multiple choice and free-text questions regarding gross digital photography was sent out to via email to laboratory staff across Canada involved in gross dissection of surgical specimens. Results Sixty surveys were returned with representation from most of the provinces. Results showed that gross digital photography is utilized at most institutions (90.0%) and the primary users of the technology are Pathologists (88.0%), Pathologists’ Assistants (54.0%) and Pathology residents (50.0%). Most respondents felt that there is a definite need for routine digital imaging of gross surgical specimens in their practice (80.0%). The top two applications for gross digital photography are for documentation of interesting/ complex cases (98.0%) and for teaching purposes (84.0%). The main limitations identified by the survey group are storage space (42.5%) and security issues (40.0%). Respondents indicated that future applications of gross digital photography mostly include teaching (96.6%), presentation at tumour boards/ clinical rounds (89.8%), medico-legal documentation (72.9%) and usage for consultation purposes (69.5%). Conclusions The results of this survey indicate that pathology staff across Canada currently utilizes gross digital images for regular documentation and educational reasons. They also show that the technology will be needed for future applications in teaching, consultation and medico-legal purposes.

Utilization, particularly in chemistry and molecular testing, is growing rapidly in Canada at a time when laboratory budgets are shrinking. Canadian laboratories face particular challenges as the prevailing funding model limits the scope for new revenue generation. Aggressive and coordinated interventions to reduce over-utilization will be necessary to ensure the long-term viability of the current system.

Chronic lymphocytic leukemia (CLL) is the most common type of blood cancer in Canadian adults. The relative 5-year survival rates for CLL in Canada is decreasing. CLL cell morphology maybe similar to normal lymphocytes and require a hematopathologist examination for diagnosis. There are a low number of related works on image analysis in CLL. This paper focuses on lymphocyte color cell segmentation using Support Vector Machine (SVM) and k-means clustering algorithms. The algorithm overcomes the occlusion problem when lymphocytes are tightly bound to the surrounding Red Blood Cells. Over and under-segmentation problems are significantly reduced. In this paper we used 440 lymphocyte images (normal and CLL), in which 140 images are used for segmentation accuracy measurement and 12 images for SVM training. The algorithm obtained 98.43% maximum accuracy for nucleus segmentation, and 98.69% for cell segmentation. The cytoplasm region can be extracted by 99.85% maximum accuracy with simple mask subtraction.

Background Increasing laboratory test utilization is a major challenge facing clinical laboratories. However, in most instances we lack population level information on the patient groups to which increased testing is directed. Much recent work has been published on the sociodemographic correlates of 25-hydroxyvitamin D deficiency. An unanswered question, however, is whether testing is preferentially directed towards individuals with a higher likelihood of deficiency. In this paper we examine this question by combining laboratory information system data on testing rates with Census Canada data. Methods We examined 1,436 census dissemination areas within the city of Calgary, Alberta, Canada. For each census dissemination area we determined age and sex-specific 25-hydroxyvitamin D testing rates over a one year period. We then compared these testing rates with the following sociodemographic variables obtained from Census Canada: first nations status, education level, household income, visible minority status, and recent immigrant status. Results Overall, 6.9% of males in the city of Calgary were tested during the study period. Females were 1.7 times more likely to be tested than males. Testing rate increased with increasing age, with 16.8% of individuals 66 years and over tested during the one-year study period. Individuals having at least some university education were less likely to be tested (RR = 0.60; p < 0.0001). Interestingly, although visible minorities were over twice as likely to be tested as compared to non-visual minorities (RR = 2.25; p < 0.0001), recent immigrants, a group known to exhibit low 25 hydroxyvitamin D levels, were significantly less likely to be tested than non-recent immigrants (RR = 0.72; p = 0.0174). While median household income was modestly associated with increased testing (RR = 1.02; p < 0.0001), First Nations status and non-English speaking were not significant predictors of 25-hydroxyvitamin D testing. Conclusions Testing for 25-hydroxyvitamin D is in part directed toward populations at higher risk of deficiency (visible minorities) and at higher risk of osteoporosis (older females), but a particularly high risk group (recent immigrants) is being tested at a lower rate than other patient groups.

To determine the relative effects of population size, FP and GP supply, and other specialist supply on chemistry and hematology test volumes (ie, number of tests performed).Population-level analysis using secondary data from the Calgary Health Zone for 2004 to 2009.Calgary, Alta.The relative effects of population size, FP and GP supply, and other specialist supply on laboratory test use.Population size was the strongest predictor of test volumes in a multivariate analysis. The FP and GP supply was significantly negatively correlated with chemistry test volume (partial r(2) = 0.186, P = .045). There was a trend toward decreasing use of hematology tests with increasing FP and GP supply (partial r(2) = 0.117, P = .119).The relationship between FP and GP supply and laboratory test use is complex, but increasing numbers of FPs do not necessarily indicate an increase in laboratory test use and might be associated with a decrease in test use when other factors are controlled for.

Pathology informatics has evolved to varying levels around the world. The history of pathology informatics in different countries is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice to enhance efficiency, better manage (e.g., digitize) laboratory information, as well as exploit emerging information technologies. Under the surface, however, lie powerful resource, regulatory, and societal forces that helped shape our discipline into what it is today. In this monograph, for the first time in the history of our discipline, we collectively perform a global review of the field of pathology informatics. In doing so, we illustrate how general far-reaching trends such as the advent of computers, the Internet and digital imaging have affected pathology informatics in the world at large. Major drivers in the field included the need for pathologists to comply with national standards for health information technology and telepathology applications to meet the scarcity of pathology services and trained people in certain countries. Following trials by a multitude of investigators, not all of them successful, it is apparent that innovation alone did not assure the success of many informatics tools and solutions. Common, ongoing barriers to the widespread adoption of informatics devices include poor information technology infrastructure in undeveloped areas, the cost of technology, and regulatory issues. This review offers a deeper understanding of how pathology informatics historically developed and provides insights into what the promising future might hold.

Chronic lymphocytic leukemia (CLL) is the most common type of blood cancer in Canadian adults. CLL cells are abnormal lymphocytes, which tend to be slightly larger than normal resting lymphocytes and have a condensed appearance to their chromatin. There is a low number of related works on this disease. This paper presents a method to segment normal and CLL lymphocytes into two parts: nucleus, and cytoplasm using a watershed algorithm and optimal thresholding. The goal of this work is reducing the over and under segmentation error of the watershed algorithm by suppressing 1% of the local minima. We tested 140 microscopic lymphocyte images (normal and CLL), and the algorithm obtained 99.92% maximum accuracy for nucleus segmentation, and 99.85% maximum accuracy for cell segmentation. The cytoplasm can be extracted with a 99.63% maximum accuracy with simple mask subtraction. The code for the presented algorithm is shared on the MATLAB® file exchange website.

Introduction: Rapid and accurate determination of platelet count is an important factor in diagnostic medicine. Traditional microscopic methods are labor intensive with variable results and are highly dependent on the individual training. Recent developments in automated peripheral blood differentials using a computerized system have shown many advantages as a viable alternative. The purpose of this paper was to determine the reliability and accuracy of the CellaVision DM 96 system with regards to platelet counts. Materials and Methods: One hundred twenty seven peripheral blood smears were analyzed for platelet count by manual microscopy, an automated hematology analyzer (Beckman Counter LH 780 or Unicel DXH 800 analyzers) and with the CellaVision DM96 system. Results were compared using the correlations and Bland-Altman plots. Results: Platelet counts from the DM96 system showed an R 2 of 0.94 when compared to manual platelet estimates and an R 2 of 0.92 when compared to the automated hematology analyzer results. Bland-Altman plots did not show any systematic bias.

Digital pathology is a rapidly evolving niche in the world of pathology and is likely to increase in popularity as technology improves. We performed a questionnaire for pathologists and pathology residents across Canada, in order to determine their current experiences and attitudes towards digital pathology; which modalities digital pathology is best suited for; and to assess the need for training in digital pathology amongst pathology residents and staff. An online survey consisting of 24 yes/no, multiple choice and free text questions regarding digital pathology was sent out via E-mail to all members of the Canadian Association of Pathologists and pathology residents across Canada. Survey results showed that telepathology (TP) is used in approximately 43% of institutions, primarily for teaching purposes (65%), followed by operating room consults (46%). Seventy-one percent of respondents believe there is a need for TP in their practice; 85% use digital images in their practice. The top two favored applications for digital pathology are teaching and consultation services, with the main advantage being easier access to cases. The main limitations of using digital pathology are cost and image/diagnostic quality. Sixty-two percent of respondents would attend training courses in pathology informatics and 91% think informatics should be part of residency training. The results of the survey indicate that Pathologists and residents across Canada do see a need for TP and the use of digital images in their daily practice. Integration of an informatics component into resident training programs and courses for staff Pathologists would be welcomed.

In traits which are normally bilaterally symmetrical, asymmetries may arise as a result of genomic or environmental stress. Such asymmetries are called fluctuating asymmetry. Symmetry is known to be decreased in a variety of disorders of developmental origin, and thus could potentially serve as a risk marker for disorders with a developmental component. We examined this idea by conducting a case-control study of 49 developmentally delayed children and 51 controls. Using two dermatoglyphic characters as a measure of symmetry (finger print concordance and A-B triradial ridge count difference), we found odds ratios of 2.32 (95% CI 0.65-3.17) and 2.11 (95% CI 0.57-3.27) ; depending on which character was measured. These results suggest that fluctuating asymmetry may have potential as a risk marker for developmental disorders, and that this area of research warrants further research.

Environmental and/or genetic stresses may cause a breakdown in developmental homeostasis, resulting in increased bilateral asymmetry of morphological traits. The degree of these deviations (termed "fluctuating asymmetry") is thought to correlate with the severity of the stress. If these stresses also play a role in the appearance of developmental disorders, then increased morphological asymmetry may serve as a risk marker for disorders of developmental origin. This would be possible if 1) the environmental stress that caused a breakdown in developmental stability also contributed to the appearance of the disorder, and/or 2) the genetic predisposition (liability) to the disorder and increased susceptibility to fluctuating asymmetry have a common cause. Although a number of authors have reported associations between increased fluctuating asymmetry and disorders of presumed developmental origin, the usefulness of fluctuating asymmetry as a risk marker has not been established. One obstacle to this assessment is the lack of odds ratios reported by previous authors.

Background: Demand forecasting is the area of predictive analytics devoted to predicting future volumes of services or consumables. Fair understanding and estimation of how demand will vary facilitates the optimal utilization of resources. In a medical laboratory, accurate forecasting of future demand, that is, test volumes, can increase efficiency and facilitate long-term laboratory planning. Importantly, in an era of utilization management initiatives, accurately predicted volumes compared to the realized test volumes can form a precise way to evaluate utilization management initiatives. Laboratory test volumes are often highly amenable to forecasting by time-series models; however, the statistical software needed to do this is generally either expensive or highly technical. Method: In this paper, we describe an open-source web-based software tool for time-series forecasting and explain how to use it as a demand forecasting tool in clinical laboratories to estimate test volumes. Results: This tool has three different models, that is, Holt-Winters multiplicative, Holt-Winters additive, and simple linear regression. Moreover, these models are ranked and the best one is highlighted. Conclusion: This tool will allow anyone with historic test volume data to model future demand.

Various pre-analytical factors affect clinical laboratory test results, including patient preparation, specimen collection, anticoagulants, and preservatives used for collecting specimens. The most assessable specimens are blood and urine. For analysis using blood, important factors such as the presence of anticoagulants in plasma and in whole blood, hematocrit variability, and the differences in serum characteristics associated with blood coagulation should be considered. Optimal anticoagulant-to-blood ratio is crucial to prevent clot formation while avoiding interference with analyte measurement, including dilution effects associated with liquid anticoagulants. Other factors to consider regarding blood collection tubes include differences between plastic and glass surfaces, surfactants, tube stopper lubricants, and gel separators, which all affect analyte measurement. There are also pre-analytical factors that affect test results using urine specimens. These issues are addressed in this chapter.

We thank Dr. Hamilton for his interest in our article and for providing more recent literature than was available at the time we submitted our manuscript. There are multiple points of view toward allergy testing. But the bottom line, as emphasized by Dr. Hamilton and in our article, is that serum

Serum 25-OH vitamin D levels were compared in 254 hip fracture subjects and 2,402 matched control subjects. There was a significant inverse association between 25-OH vitamin D and hip fracture only between 0 and 70 nmol/L. Vitamin D is integral to bone metabolism, however the utility of serum 25-OH vitamin D as a risk marker for hip fractures is controversial. We conducted a case–control study of patients admitted to the hospitals with hip fractures in Calgary, Alberta, (catchment population 1.4 million) between January 1, 2007 and August 31, 2011. We searched the laboratory information system of Calgary Laboratory Services for serum 25-OH vitamin D levels within 6 months prior to admission on patients admitted to hospital with hip fractures. Cases were identified through the Calgary Laboratory Services laboratory information system and were matched to controls for age, sex, and month of testing. The hip fracture–25-OH vitamin D association was examined using multiple linear and spline regression. Of 305 subjects initially identified with hip fractures, serum 25-OH vitamin D levels were available for 254 (83 %). These were matched to 2,402 control subjects. We observed a significant (p

For health scientists, knowledge translation refers to the process of facilitating uptake of knowledge into clinical practice or decision making. Since high-quality clinical research that is not applied cannot improve outcomes, knowledge translation is critical for realizing the value and potential for all types of health research. Knowledge translation is particularly relevant for areas within health care where gaps in care are known to exist, which is the case for some areas of management for people with chronic kidney disease (CKD), including assessment of proteinuria. Given that proteinuria is a key marker of cardiovascular and renal risk, forthcoming international practice guidelines will recommend including proteinuria within staging systems for CKD. While this revised staging system will facilitate identification of patients at higher risk for progression of CKD and mortality who benefit from intervention, strategies to ensure its appropriate uptake will be particularly important. This article describes key elements of effective knowledge translation strategies based on the knowledge-to-action cycle framework and describes options for effective knowledge translation interventions related to the new CKD guidelines, focusing on recommendations related to assessment for proteinuria specifically. The article also presents findings from a multidisciplinary meeting aimed at developing knowledge translation intervention strategies, with input from key stakeholders (researchers, knowledge users, decision makers and collaborators), to facilitate implementation of this guideline. These considerations are relevant for dissemination and implementation of guidelines on other topics and in other clinical settings.

Objective To compare unsatisfactory rates between the two major liquid-based cytology (LBC) platforms, namely ThinPrep (Hologic) and SurePath (Becton Dickinson). Design The authors performed both a systematic review and a meta-analysis. Inclusion criteria were English language, data presented on unsatisfactory rates for either ThinPrep or SurePath, utilising actual patient samples (ie, not laboratory manipulated samples) and no manipulation using acetic acid to increase the satisfactory rate. The authors searched PubMed for articles using the keywords ‘SurePath’ or ‘ThinPrep’ and ‘unsatisfactory’. References of retrieved studies were searched for additional articles. Key researchers in the field were also contacted. Participants and interventions Eligible studies were reviewed for rates of unsatisfactory cervical cytology smears processed on either the ThinPrep or SurePath platforms (compared with a general linear model) or data on unsatisfactory rates for both platforms for the same laboratory and the same patient population (compared with a meta-analysis using a random effects model and pooled RR). Primary Outcome Measure Unsatisfactory rate of cervical cytology smears. Results A total of 1 120 418 cervical cytology smears were reported in 14 different studies using the SurePath platform for an overall unsatisfactory rate (weighted average) of 0.3%. 28 studies reported on 1 148 755 smears prepared using the ThinPrep platform for an overall unsatisfactory rate (weighted average) of 1.3%. The general linear model did not show a difference between LBC platforms when other variables were controlled for; however, the power to detect a difference (0.087) was very low. The meta-analysis performed on four studies where both ThinPrep and SurePath results were reported from the same laboratory showed fewer unsatisfactory tests from the SurePath platform (RR 0.44, 95% CI 0.25 to 0.77, p=0.004). Conclusions Multiple factors affect LBC unsatisfactory rates. In a meta-analysis, cervical cytology samples prepared on the SurePath platform show significantly fewer unsatisfactory smears than those prepared on the ThinPrep platform., Article summary Article focus Two major LBC platforms are commonly used (ThinPrep (Hologic) and SurePath (Becton Dickinson)) These employ different sample preparation methodologies, which may result in different unsatisfactory rates. Key messages Multiple factors are associated with LBC unsatisfactory rates. Cervical cytology samples prepared on the SurePath platform show significantly fewer unsatisfactory smears than those prepared on the ThinPrep platform. Unsatisfactory samples represent a missed opportunity for screening Strengths and limitations of this study Large sample size from multiple studies Relatively few studies performed a head-to-head evaluation of the two platforms Restriction to English literature and use of only one bibliographic search base (Medline) are limitations.

Background The role that the peritumoral stroma plays in the growth of tumours is currently poorly understood. In this manuscript the morphometric characteristics of basal cell carcinoma subtypes and their associated peritumoral stromas are presented. Methods Ninety eight digitized basal cell carcinoma histology slides were categorized as infiltrative, nodular, or superficial subtypes, and were analysed using a combination of manual and computer-assisted approaches. The morphometric characteristics of the tumour nests and their associated peritumoral stroma were quantified, and the presence of a marked immune reaction or elastosis was noted. Results The tumour to stroma ratio was different among each tumour subtype. Elastosis was identified in a greater proportion of the infiltrative tumours. Conclusions Quantitative differences exist between the peritumoral stroma of basal cell carcinoma subtypes. Future work exploring the relation between these morphometric differences and biochemical variations in peritumoral stroma may further our understanding of the biology of carcinoma development. Trial Registration Not applicable.

Begging for food is one of the most conspicuous behaviours performed by nestling birds. Recent models suggest that the form and intensity of begging evolved not only to communicate nutritional requirements to parents but also as a mechanism for competing against siblings to obtain a greater share of parental resources. In an interspecific comparison of passerine birds, we show that the loudness of nestling begging calls increases as the relatedness amongst the members of a brood declines. Species with high levels of mixed parentage, as well as the brood-parasitic brown-headed cowbird ( Molothrus ater ), begged louder than their closest monogamous and non-parasitic relatives. These results support the hypothesis that sibling relatedness influences begging behaviour in birds, and suggests that increased intensity of begging can evolve whenever female promiscuity or brood parasitism lowers the coefficient of relatedness among nestmates.

Fluctuating asymmetry of the first tarsal segment of the proleg of the forest tent caterpiller moth Malacosoma disstria Hbn. (Lepidoptera: Lasiocampidae) was significantly inversely related to survival ability in the lab. The monitoring of population levels of fluctuating asymmetry could have important implications in pest management of this and other species by providing an indication of the health of a population.

Introduction: Delta checks use two specimen test results taken in succession in order to detect test result changes greater than expected physiological variation. One of the most common and serious errors detected by delta checks is specimen mix-up errors. The positive and negative predictive values of delta checks for detecting specimen mix-up errors, however, are largely unknown. Materials and Methods: We addressed this question by first constructing a stochastic dynamic model using repeat test values for five analytes from approximately 8000 inpatients in Calgary, Alberta, Canada. The analytes examined were sodium, potassium, chloride, bicarbonate, and creatinine. The model simulated specimen mix-up errors by randomly switching a set number of pairs of second test results. Sensitivities and specificities were then calculated for each analyte for six combinations of delta check equations and cut-off values from the published literature. Results: Delta check specificities obtained from this model ranged from 50% to 99%; however the sensitivities were generally below 20% with the exception of creatinine for which the best performing delta check had a sensitivity of 82.8%. Within a plausible incidence range of specimen mix-ups the positive predictive values of even the best performing delta check equation and analyte became negligible. Conclusion: This finding casts doubt on the ongoing clinical utility of delta checks in the setting of low rates of specimen mix-ups.

Increased type I error resulting from multiple statistical comparisons remains a common problem in the scientific literature. This may result in the reporting and promulgation of spurious findings. One approach to this problem is to correct groups of P-values for "family-wide significance" using a Bonferroni correction or the less conservative Bonferroni-Holm correction or to correct for the "false discovery rate" with a Benjamini-Hochberg correction. Although several solutions are available for performing this correction through commercially available software there are no widely available easy to use open source programs to perform these calculations. In this paper we present an open source program written in Python 3.2 that performs calculations for standard Bonferroni, Bonferroni-Holm and Benjamini-Hochberg corrections.

Objectives Cervical cytology smears reported as unsatisfactory for interpretation represent an unrealized screening opportunity and may have significant laboratory and patient costs. Identifying patients at higher risk for an unsatisfactory smear could alert clinicians to take extra care in the acquisition of the smear. Few studies have examined patient characteristics that could predict an unsatisfactory cervical cytology smear. The purpose of this study was to determine the effect of patient age, day of the menstrual cycle, postmenopausal status, postpartum status, and the use of oral contraceptives on the rate of unsatisfactory cervical cytology smears. Methods We performed a case–control study of all unsatisfactory cervical cytology smears at a large tertiary care teaching hospital over one year compared with a random sample of smears that were satisfactory for interpretation. Data were obtained from the cytology requisitions. Continuous variables were tested with unpaired t tests, and dichotomous variables were analyzed with chi-square tests. Multivariate significance was tested with binary logistic regression analysis. Results Of all cervical cytology smears, 1.1% were reported as unsatisfactory. In univariate analyses increased age, earlier date in the menstrual cycle, and postpartum status were associated with unsatisfactory smears. However, following Bonferroni correction for multiple comparisons and multivariate regression analysis, only increased age remained a significant predictor of an unsatisfactory cervical cytology smear. Conclusion Older women are at greater risk of having an unsatisfactory cervical cytology smear. Clinicians and public health officials must be aware of this risk and must encourage optimal collection techniques for women in this demographic group.

A number of different human leukocyte antigen (HLA) allele associations with chronic myelogenous leukemia (CML) have been previously reported. The specific associations reported in one population, however, are rarely replicated in other populations. We attempted to explore these associations by performing a meta-analysis of published studies. Following a Medline search, we identified four studies which presented raw data on all allele associations with CML (significant and non-significant). Meta-analysis of these revealed a significant risk association with the HLA-A*02 (pooled odds ratio 1.33, 95% confidence interval 1.10-1.61) allele and a significant protective effect with the HLA-B*35 allele (pooled odds ratio 0.64, 95% confidence interval 0.48-0.86). To our knowledge this is the first study to demonstrate the epidemiologic association between HLA-A*02 and the risk of CML, and we discuss this in the context of recent immunological studies reporting data on BCR-ABL fusion peptide presentation and subsequent immune response. Our findings suggest that individual epidemiological studies may lack statistical power, or may have other interfering factors which prevent the unmasking of overall associations. Meta-analyses of published studies may overcome these limitations and may prove useful in uncovering allele-disease associations.