Acute promyelocytic leukaemia is characterized by stable incidence and improved survival that is restricted to patients managed in leukaemia referral centres: a pan-Canadian epidemiological study.

Timely diagnosis and care are major determinants of the outcome in acute promyelocytic leukaemia (APL), a malignancy whose incidence may be increasing. The Canadian Cancer Registry (CCR) and health system represent valuable settings to study APL epidemiology. We analysed the CCR, which contains data on all Canadians with APL. To provide clinical information lacking in the CCR, we obtained data from five leukaemia referral centres during a similar time period. Between 1993 and 2007, there were 399 APL in Canada. Age-standardized incidence was 0·083/100,000 and was stable over time. The early death (ED) rate was 21·8% (10·6% in patients <50 years old and 35·5% for those aged >50 years), with no improvement over time. Five-year overall survival (OS) was 54·6% (73·3% in patients <50 years; 29·1% older patients). In the referral cohort, 131 patients were diagnosed between 1999 and 2010. ED was 14·6% and 2-year OS was 76·5%. Within this cohort, ED and OS improved over time, although advanced patient age remained an adverse determinant of OS. In Canada, APL incidence is unexpectedly low and temporally stable. ED was higher than reported in clinical trials, but similar to reports from other registries. In contrast, ED was lower in referral centres and improved with time.

Action Thresholds for Summer Fungicide Sprays and Sequential Classification of Apple Scab Incidence.

The objectives of this study were to establish scab incidence thresholds at which summer fungicide sprays should be initiated and to develop sequential sampling for classification plans to facilitate decision making. The relationship between proportion of scabbed leaves per shoot and percent scabbed fruits at harvest was established based on data collected in both experimental and commercial orchards. Action threshold at which fungicide spray program should be initiated in order to maintain fruit scab at harvest below 2% was established at 0.006 scabbed leaves per shoot; hence incidence thresholds of 0.005 and 0.01 scabbed leaves per shoot were evaluated. Sequential sampling for classification procedures (SSCP), using the Wald's sequential probability ratio test (SPRT), were developed based on a beta-binomial distribution and using parameter estimates of the binary power law. Monte Carlo simulations were used to establish the probability of classifying mean scab incidence as less than the action thresholds (pth = 0.005 and pth = 0.01). Operating characteristic (OC) and average sample number (ASN) curves were established for eight combinations of stop lines and error levels (α and ß). Based on the results of the Monte Carlo simulations, four sets of stop lines (two for each pth threshold) were selected for further evaluation. Bootstrap simulations of 50 data sets indicated that both the OC and ASN curves for each of the four pairs of stop lines were similar to OC and ASN values determined by Monte Carlo simulation. When validated with data not used to construct the models, the SSCPs provided the appropriate classification in 98 and 95% of the simulations for the pth = 0.005 and pth = 0.01 (α = 0.05 and ß = 0.10), respectively. The sequential sampling plans developed in this study should allow for rapid and accurate classification of the incidence of apple scab on leaves, and aid in sampling for summer scab management decision making.

Airway smooth muscle cells express functional neurokinin-1 receptors and the nerve-derived preprotachykinin-a gene: regulation by passive sensitization.

Preprotachykinin-A (PPT-A) gene-derived neuropeptides, namely substance P (SP) and neurokinin (NK)A, and their receptors participate in allergen-induced airway responses. Whether airway smooth muscle cells (ASMC) may react directly to SP through expression of the NK-1 receptor or express the gene for the synthesis of SP, the PPT-A gene, is unknown. We demonstrated using reverse transcription-polymerase chain reaction that tracheal SMC (TSMC) from atopic Brown Norway rats contained mRNA transcripts for the full-length isoform of the NK-1 receptor. Flow cytometric analysis indicated that the NK-1 receptor was expressed on the surface of TSMC. This receptor was functional as demonstrated by calcium mobilization in response to SP stimulation. The expression of the NK-1 receptor was not altered in passively sensitized TSMC in response to antigenic stimulation, although this stimulation increased the expression of the chemokine RANTES (regulated on activation, normal T cells expressed and secreted). Using different sets of PCR primers, we showed that TSMC also express the beta, alpha, and its alternative splicing product delta, and possibly the gamma mRNA transcript isoforms of the PPT-A gene. Gene sequencing of the PCR-amplified beta isoform confirmed that it is a transcript product of the rat PPT-A gene, and the production of SP by TSMC was confirmed by enzyme immunoassay. We also showed the beta isoform increased after cell stimulation with rat sera, whether sensitized or not. In conclusion, both the PPT-A gene and NK-1 receptors are expressed by TSMC, which suggests the possibility of autocrine neuropeptidergic mechanisms in these cells. However, these mechanisms are not upregulated by passive sensitization.