Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.

Murine allele and transgene symbols: ensuring unique, concise, and informative nomenclature.

In addition to naturally occurring sequence variation and spontaneous mutations, a wide array of technologies exist for modifying the mouse genome. Standardized nomenclature, including allele, transgene, and other mutation nomenclature, as well as persistent unique identifiers (PUID) are critical for effective scientific communication, comparison of results, and integration of data into knowledgebases such as Mouse Genome Informatics (MGI), Alliance for Genome Resources, and International Mouse Strain Resource (IMSR). As well as being the authoritative source for mouse gene, allele, and strain nomenclature, MGI integrates published and unpublished genomic, phenotypic, and expression data while linking to other online resources for a complete view of the mouse as a valuable model organism. The International Committee on Standardized Genetic Nomenclature for Mice has developed allele nomenclature rules and guidelines that take into account the number of genes impacted, the method of allele generation, and the nature of the sequence alteration. To capture details that cannot be included in allele symbols, MGI has further developed allele to gene relationships using sequence ontology (SO) definitions for mutations that provide links between alleles and the genes affected. MGI is also using (HGVS) variant nomenclature for variants associated with alleles that will enhance searching for mutations and will improve cross-species comparison. With the ability to assign unique and informative symbols as well as to link alleles with more than one gene, allele and transgene nomenclature rules and guidelines provide an unambiguous way to represent alterations in the mouse genome and facilitate data integration among multiple resources such the Alliance of Genome Resources and International Mouse Strain Resource.

Relationship between welfare and individual ranging behaviour in commercial free-range laying hens.

Laying hens housed in free-range systems have access to an outdoor range, and individual hens within a flock differ in their ranging behaviour. Whether there is a link between ranging and laying hen welfare remains unclear. We analysed the relationships between ranging by individual hens on a commercial free-range layer farm and behavioural, physiological and health measures of animal welfare. We hypothesised that hens that access the range more will be (1) less fearful in general and in response to novelty and humans, (2) have better health in terms of physical body condition and (3) have a reduced physiological stress response to behavioural tests of fear and health assessments than hens that use the range less. Using radio frequency identification tracking across two flocks, we recorded individual hens' frequency, duration and consistency of ranging. We also assessed how far hens ventured into the range based on three zones: 0 to 2.4, 2.4 to 11.4 or >11.4 m from the shed. We assessed hen welfare using a variety of measures including: tonic immobility, open field, novel object, human approach, and human avoidance (HAV) behavioural tests; stress-induced plasma corticosterone response and faecal glucocorticoid metabolites; live weight, comb colour, and beak, plumage, footpad, and keel bone condition. Range use was positively correlated with plasma corticosterone response, faecal glucocorticoid metabolites, and greater flight distance during HAV. Hens that used the range more, moved towards rather than away from the novel object more often than hens that ranged less. Distance ranged from the shed was significantly associated with comb colour and beak condition, in that hens with darker combs and more intact beaks ranged further. Overall the findings suggest that there is no strong link between outdoor range usage and laying hen welfare. Alternatively, it may be that hens that differed in their ranging behaviour showed few differences in measures of welfare because free-range systems provide hens with adequate choice to cope with their environment. Further research into the relationship between individual range access and welfare is needed to test this possibility.

The Vertical Dust Profile over Gale Crater, Mars.

We create a vertically coarse, but complete, vertical profile of dust mixing ratio from the surface to the upper atmosphere over Gale Crater, Mars, using the frequent joint atmospheric observations of the orbiting Mars Climate Sounder (MCS) and the Mars Science Laboratory (MSL) Curiosity rover. Using these data and an estimate of planetary boundary layer (PBL) depth from the MarsWRF general circulation model, we divide the vertical column into three regions. The first region is the Gale Crater PBL, the second is the MCS-sampled region, and the third is between these first two. We solve for a well-mixed dust mixing ratio within this third (middle) layer of atmosphere to complete the profile. We identify a unique seasonal cycle of dust within each atmospheric layer. Within the Gale PBL, dust mixing ratio maximizes near southern hemisphere summer solstice (Ls = 270°) and minimizes near winter solstice (Ls = 90-100°) with a smooth sinusoidal transition between them. However, the layer above Gale Crater and below the MCS-sampled region more closely follows the global opacity cycle and has a maximum in opacity near Ls = 240° and exhibits a local minimum (associated with the "solsticial pause" in dust storm activity) near Ls = 270°. With knowledge of the complete vertical dust profile, we can also assess the frequency of high-altitude dust layers over Gale. We determine that 36% of MCS profiles near Gale Crater contain an "absolute" high-altitude dust layer wherein the dust mixing ratio is the maximum in the entire vertical column.

Pharmacodynamic comparison of LY3023703, a novel microsomal prostaglandin e synthase 1 inhibitor, with celecoxib.

To assess the safety, tolerability, and pharmacology of LY3023703, a microsomal prostaglandin E synthase 1 (mPGES1) inhibitor, a multiple ascending dose study was conducted. Forty-eight subjects received LY3023703, celecoxib (400 mg), or placebo once daily for 28 days. Compared with placebo, LY3023703 inhibited ex vivo lipopolysaccharide-stimulated prostaglandin E2 (PGE2 ) synthesis 91% and 97% on days 1 and 28, respectively, after 30-mg dosing, comparable to celecoxib's effect (82% inhibition compared to placebo). Unlike celecoxib, which also inhibited prostacyclin synthesis by 44%, LY3023703 demonstrated a maximal increase in prostacyclin synthesis of 115%. Transient elevations of serum aminotransferase were observed in one subject after 30-mg LY3023703 dosing (10× upper limit of normal (ULN)), and one subject after 15-mg dosing (about 1.5× ULN). Results from this study suggest that mPGES1 inhibits inducible PGE synthesis without suppressing prostacyclin generation and presents a novel target for inflammatory pain.

Gap and channeled plasmons in tapered grooves: a review.

Tapered metallic grooves have been shown to support plasmons - electromagnetically coupled oscillations of free electrons at metal-dielectric interfaces - across a variety of configurations and V-like profiles. Such plasmons may be divided into two categories: gap-surface plasmons (GSPs) that are confined laterally between the tapered groove sidewalls and propagate either along the groove axis or normal to the planar surface, and channeled plasmon polaritons (CPPs) that occupy the tapered groove profile and propagate exclusively along the groove axis. Both GSPs and CPPs exhibit an assortment of unique properties that are highly suited to a broad range of cutting-edge nanoplasmonic technologies, including ultracompact photonic circuits, quantum-optics components, enhanced lab-on-a-chip devices, efficient light-absorbing surfaces and advanced optical filters, while additionally affording a niche platform to explore the fundamental science of plasmon excitations and their interactions. In this Review, we provide a research status update of plasmons in tapered grooves, starting with a presentation of the theory and important features of GSPs and CPPs, and follow with an overview of the broad range of applications they enable or improve. We cover the techniques that can fabricate tapered groove structures, in particular highlighting wafer-scale production methods, and outline the various photon- and electron-based approaches that can be used to launch and study GSPs and CPPs. We conclude with a discussion of the challenges that remain for further developing plasmonic tapered-groove devices, and consider the future directions offered by this select yet potentially far-reaching topic area.

Inhibition of thiol isomerase activity diminishes endothelial activation of plasminogen, but not of protein C.

INTRODUCTION: Cell surface thiol isomerase enzymes, principally protein disulphide isomerase (PDI), have emerged as important regulators of platelet function and tissue factor activation via their action on allosteric disulphide bonds. Allosteric disulphides are present in other haemostasis-related proteins, and we have therefore investigated whether thiol isomerase inhibition has any influence on two endothelial activities relevant to haemostatic regulation, namely activation of protein C and activation of plasminogen, with subsequent fibrinolysis. MATERIALS AND METHODS: The study was performed using the human microvascular endothelial cell line HMEC-1. Thiol isomerase gene expression was measured by RT-PCR and activation of protein C and plasminogen by cell-based assays using chromogenic substrates S2366 and S2251, respectively. Cell mediated fibrinolysis was measured by monitoring absorbance at 405 nm following fibrin clot formation on the surface of HMEC-1 monolayers. RESULTS AND CONCLUSIONS: A variety of thiol isomerase enzymes, including PDI, were expressed by HMEC-1 cells and thiol reductase activity detectable on the cell surface was inhibited by both RL90 anti-PDI antibody and by the PDI inhibitor quercetin-3-rutinoside (rutin). In cell-based assays, activation of plasminogen, but not of protein C, was inhibited by RL90 antibody and, to a lesser extent, by rutin. Fibrin clot lysis occurring on a HMEC-1 monolayer was also significantly slowed by RL90 antibody and by rutin, but RL90-mediated inhibition was abolished in the presence of exogenous tissue plasminogen activator (tPA). We conclude that thiol isomerases, including PDI, are involved in fibrinolytic regulation at the endothelial surface, although not via a direct action on tPA. These findings broaden understanding of haemostatic regulation by PDI, and may aid in development of novel anti-thrombotic therapeutic strategies targeted via the fibrinolysis system.

Invariant natural killer T cells in children with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in which dietary antigens (in particular, milk) play a major role. EoE is most likely a mixed IgE and non-IgE food-mediated reaction in which overexpression of Th2 cytokines, particularly IL-13, play a major role; however, the cells responsible for IL-13 overexpression remain elusive. Th2-cytokines are secreted following the ligation of invariant natural killer T cell receptors to sphingolipids (SLs). Sphingolipids (SLs) are presented via the CD1d molecule on the INKTs surface. Cow's milk-derived SL has been shown to activate iNKTs from children with IgE-mediated food allergies to milk (FA-MA) to produce Th2 cytokines. The role of iNKTs and milk-SL in EoE pathogenesis is currently unknown. OBJECTIVE: The aim of this study was to investigate the role of iNKTs and milk-SL in EoE. METHODS: Peripheral blood mononuclear cells (PBMCs) from 10 children with active EoE (EoE-A), 10 children with controlled EoE (EoE-C) and 16 healthy controls (non-EoE) were measured ex vivo and then incubated with α-galactosylceramide (αGal) and milk-SL. INKTs from peripheral blood (PB) and oesophageal biopsies were studied. RESULTS: EoE-A children had significantly fewer peripheral blood iNKTs with a greater Th2-response to αGal and milk-SM compared with iNKTs of EoE-C and non-EoE children. Additionally, EoE-A children had increased iNKT levels in oesophageal biopsies compared with EoE-C children. CONCLUSION: Milk-SLs are able to activate peripheral blood iNKTs in EoE-A children to produce Th2 cytokines. Additionally, iNKT levels are higher at the site of active oesophageal eosinophilic inflammation. CLINICAL RELEVANCE: This study suggests that sphingolipids (SLs) contained in milk may drive the development of EoE by promoting an iNKT-cell-mediated Th2-type cytokine response that facilitates eosinophil-mediated allergic inflammation.

An investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana.

INTRODUCTION: Several factors influence the severity of Plasmodium falciparum; here, we investigate the impact of alpha+-thalassaemia genotype on P. falciparum parasitemia and prevalence of severe anaemia amongst microcytic children from Kumasi, Ghana. METHODS: Seven hundred and thirty-two children (≤10 years) with P. falciparum were categorised into normocytic and microcytic (mean cell volume ≤76 fL). Microcytic individuals were genotyped for the -α(3.7) deletional thalassaemia mutation and parasite densities determined. RESULTS: Amongst microcytic patients both parasite densities and prevalence of severe malaria parasitemia (≥100 000/µL) were significantly lower (P < 0.001) in the presence of an alpha+-thalassaemia genotype compared with non-alpha+-thalassaemia genotype. There was no evidence that alpha+-thalassaemia protected against severe anaemia. The protection conferred by alpha-thalassaemia genotype against severe P. falciparum parasitemia did not change with increasing age. CONCLUSION: The severity of P. falciparum parasitemia was significantly lower in both the homozygous and heterozygous alpha+-thalassaemia groups compared with microcytic individuals with non-alpha+-thalassaemia genotype. The protective effect, from severe malaria, of the alpha+-thalassaemia allele does not alter with age.

Metal and nutrient dynamics on an aged intensive green roof.

Runoff and rainfall quality was compared between an aged intensive green roof and an adjacent conventional roof surface. Nutrient concentrations in the runoff were generally below Environmental Quality Standard (EQS) values and the green roof exhibited NO3(-) retention. Cu, Pb and Zn concentrations were in excess of EQS values for the protection of surface water. Green roof runoff was also significantly higher in Fe and Pb than on the bare roof and in rainfall. Input-output fluxes revealed the green roof to be a potential source of Pb. High concentrations of Pb within the green roof soil and bare roof dusts provide a potential source of Pb in runoff. The origin of the Pb is likely from historic urban atmospheric deposition. Aged green roofs may therefore act as a source of legacy metal pollution. This needs to be considered when constructing green roofs with the aim of improving pollution remediation.

Rainwater runoff retention on an aged intensive green roof.

Urban areas are characterised by large proportions of impervious surfaces which increases rainwater runoff and the potential for surface water flooding. Increased precipitation is predicted under current climate change projections, which will put further pressure on urban populations and infrastructure. Roof greening can be used within flood mitigation schemes to restore the urban hydrological balance of cities. Intensive green roofs, with their deeper substrates and higher plant biomass, are able to retain greater quantities of runoff, and there is a need for more studies on this less common type of green roof which also investigate the effect of factors such as age and vegetation composition. Runoff quantities from an aged intensive green roof in Manchester, UK, were analysed for 69 rainfall events, and compared to those on an adjacent paved roof. Average retention was 65.7% on the green roof and 33.6% on the bare roof. A comprehensive soil classification revealed the substrate, a mineral soil, to be in good general condition and also high in organic matter content which can increase the water holding capacity of soils. Large variation in the retention data made the use of predictive regression models unfeasible. This variation arose from complex interactions between Antecedant Dry Weather Period (ADWP), season, monthly weather trends, and rainfall duration, quantity and peak intensity. However, significantly lower retention was seen for high rainfall events, and in autumn, which had above average rainfall. The study period only covers one unusually wet year, so a longer study may uncover relationships to factors which can be applied to intensive roofs elsewhere. Annual rainfall retention for Manchester city centre could be increased by 2.3% by a 10% increase in intensive green roof construction. The results of this study will be of particular interest to practitioners implementing greenspace adaptation in temperate and cool maritime climates.

Measurement of quality of recovery using the QoR-40: a quantitative systematic review.

BACKGROUND: Several rating scales have been developed to measure quality of recovery after surgery and anaesthesia, but the most extensively used is the QoR-40, a 40-item questionnaire that provides a global score and subscores across five dimensions: patient support, comfort, emotions, physical independence, and pain. It has been evaluated in a variety of settings, but its overall psychometric properties (validity, reliability, ease of use, and interpretation) and clinical utility are uncertain. METHODS: We undertook a quantitative systematic review of studies evaluating psychometric properties of the QoR-40. Data were combined in meta-analyses using random effects models. This resulted in a total sample of 3459 patients from 17 studies originating in nine countries. RESULTS: We confirmed content, construct, and convergent [pooled r=0.58, 95% confidence interval (CI): 0.51-0.65] validity. Reliability was confirmed by excellent intraclass correlation (pooled α=0.91, 95% CI: 0.88-0.93), test-retest reliability (pooled r=0.90, 95% CI: 0.86-0.92), and inter-rater reliability (intraclass correlation=0.86). The clinical utility of the QoR-40 instrument was supported by high patient recruitment into evaluation studies (97%), and an excellent completion and return rate (97%). The mean time to complete the QoR-40 was 5.1 (95% CI: 4.4-5.7) min. CONCLUSIONS: The QoR-40 is a widely used and extensively validated measure of quality of recovery. The QoR-40 is a suitable measure of postoperative quality of recovery in a range of clinical and research situations.

Extensive epidermal naevus in a foal.

CASE REPORT: A 2-month-old Standardbred filly was presented for examination and treatment of extensive congenital skin lesions that had a linear distribution on the left front leg extending from the dorsal midline to the metacarpal region. The lesions were surgically excised under general anaesthesia. Surgical excision was curative and there were no signs of recurrence 6 weeks after surgery. The number and distribution of lesions were more extensive than in previously reported cases of congenital papillomas, which have also been described as epidermal growth abnormalities (naevi or hamartomas). Early reports of congenital papillomas suggest in-utero infection with papillomavirus may be responsible, despite a lack of histological features associated with papillomavirus infection. Papillomavirus immunohistochemistry has subsequently proven negative in tested cases. CONCLUSIONS: The presence at birth, their appearance and the extensive distribution of lesions in this case is similar to verrucous epidermal naevus of humans. A name change from congenital papilloma to epidermal naevus is proposed for this condition in horses.

Tissint martian meteorite: a fresh look at the interior, surface, and atmosphere of Mars.

Tissint (Morocco) is the fifth martian meteorite collected after it was witnessed falling to Earth. Our integrated mineralogical, petrological, and geochemical study shows that it is a depleted picritic shergottite similar to EETA79001A. Highly magnesian olivine and abundant glass containing martian atmosphere are present in Tissint. Refractory trace element, sulfur, and fluorine data for the matrix and glass veins in the meteorite indicate the presence of a martian surface component. Thus, the influence of in situ martian weathering can be unambiguously distinguished from terrestrial contamination in this meteorite. Martian weathering features in Tissint are compatible with the results of spacecraft observations of Mars. Tissint has a cosmic-ray exposure age of 0.7 ± 0.3 million years, consistent with those of many other shergottites, notably EETA79001, suggesting that they were ejected from Mars during the same event.

A maize line resistant to herbivory constitutively releases (E) -beta-caryophyllene.

Various pests, such as those in the order Lepidoptera, frequently feed on young maize (Zea mays) plants and pose a significant threat to plant development and survival. To manage this problem, maize generates a wide variety of responses to attack by pests, from activation of wound-response pathways to the release of volatile compounds. Mp708, an inbred line resistant to feeding by the larvae of the fall armyworm (Spodoptera frugiperda J.E. Smith Lepidoptera: Noctuidae), has been developed through traditional breeding methods, but its underlying mechanisms of resistance are still not completely understood. Mp708 has been shown to have a moderately high constitutive expression of jasmonic acid (JA) before infestation by fall armyworm. However, Tx601, a genotype susceptible to feeding by fall armyworm, activates JA pathway only in response to feeding, suggesting that Mp708 is "primed" to respond swiftly to an attack. Current research indicates that fall armyworm show a lack of preference to feeding on Mp708, leading to the hypothesis that volatiles constitutively released by the plant may also play an important role in its resistance. Analysis of volatiles released by Mp708 and Tx601 in the presence and absence of fall armyworm larvae identified (E)-beta-caryophyllene, a terpenoid associated with resistance, released constitutively in Mp708. Fall armyworm fed samples of both Mp708 and Tx601 showed high transcript number of tps23, the gene responsible for the synthesis of (E)-beta-caryophyllene. In addition, fall armyworm larvae show a preference for Tx601 whorl tissue over Mp708 tissue, and the dosage of Tx601 whorl with (E)-beta-caryophyllene repels the fall armyworm.

Derivation of the uncontrolled donation after circulatory determination of death protocol for New York city.

Evidence from Europe suggests establishing out-of-hospital, uncontrolled donation after circulatory determination of death (UDCDD) protocols has potential to substantially increase organ availability. The study objective was to derive an out-of-hospital UDCDD protocol that would be acceptable to New York City (NYC) residents. Participatory action research and the SEED-SCALE process for social change guided protocol development in NYC from July 2007 to September 2010. A coalition of government officials, subject experts and communities necessary to achieve support was formed. Authorized NY State and NYC government officials and their legal representatives collaboratively investigated how the program could be implemented under current law and regulations. Community stakeholders (secular and religious organizations) were engaged in town hall style meetings. Ethnographic data (meeting minutes, field notes, quantitative surveys) were collected and posted in a collaborative internet environment. Data were analyzed using an iterative coding scheme to discern themes, theoretical constructs and a summary narrative to guide protocol development. A clinically appropriate, ethically sound UDCDD protocol for out-of-hospital settings has been derived. This program is likely to be accepted by NYC residents since the protocol was derived through partnership with government officials, subject experts and community participants.

Pulmonary function measurements immediately after exercise are correlated with neutrophil percentage in tracheal aspirates in horses with poor racing performance.

Inflammatory airway disease (IAD) is common in racehorses, and is a cause of wastage in the industry. IAD has been diagnosed by measurement of percent neutrophils (N%) in tracheal aspirates (TA). The aim of this study was to investigate whether spirometric indices of pulmonary function were correlated with N% in TAs. Limits to breathing were measured by analyses of relationships between relative times and relative respiratory gas flows during inspiration and expiration in individual breaths recorded after exercise. Horses with higher N% had significantly lower relative gas flows at the same relative times during inspiration and expiration, suggesting a limit to breathing. These findings confirm a physiological basis for the measurement of N% in TA after exercise for diagnosis of IAD. Spirometric pulmonary function testing using analyses of individual breaths after exercise has application for assessment of pulmonary function and poor exercise performance.

Intravascular large B cell lymphoma: an elusive cause of pyrexia of unknown origin diagnosed postmortem.

Intravascular large B cell lymphoma (IVLBCL) is a rare cause of pyrexia of unknown origin. Because of its protean clinical manifestations, diagnosis is elusive and is often made postmortem. We report here a case of IVLBCL that evaded diagnosis despite multiple investigations in vivo for pyrexia of unknown origin over a 5‐month period.

Galantamine-induced improvements in cognitive function are not related to alterations in alpha(4)beta (2) nicotinic receptors in early Alzheimer's disease as measured in vivo by 2-[18F]fluoro-A-85380 PET.

INTRODUCTION: The nicotinic acetylcholine receptor (nAChR) system plays a regulatory role in a number of cognitive processes. Cholinesterase inhibitors (i.e., galantamine) that potentiate cholinergic neurotransmission improve cognitive function in Alzheimer's disease (AD); however, the relationship between these effects and associated changes in nAChRs are yet to be established in vivo. MATERIALS AND METHODS: 2-[18F]Fluoro-A-85380 (2-FA) binds to nAChRs and with positron emission tomography (PET) imaging provides a composite measure of receptor density and ligand affinity. This study aimed to: (1) quantify nAChRs in vivo in 15 drug-naïve patients with mild AD before and after chronic treatment with galantamine, using 2-FA and PET, and (2) examine the relationship between treatment-induced changes in nAChRs and improvements in cognitive function. Participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of approximately 200 MBq of 2-FA on two occasions (before and after 12 weeks, galantamine treatment). A 3-day washout period preceded the second scan. Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). RESULTS: Performance on global measures of cognition significantly improved following galantamine treatment (p < 0.05). This improvement extended to specific cognitive measures of language and verbal learning. No significant differences in nAChR DV(S) before and after galantamine treatment were found. The treatment-induced improvement in cognition was not correlated with regional or global nAChR DV(S), suggesting that changes in nAChRs may not be responsible for the improvements in cognition following galantamine in patients with mild AD.

An approach to the management of chronic myeloid leukemia in British Columbia.

Chronic myeloid leukemia (cml) is a myeloproliferative disorder whose therapy has changed dramatically since the late 1990s. With the introduction of the tyrosine kinase inhibitor (tki) imatinib mesylate, the treatment outcomes for patients with cml have improved markedly, and hematopoietic stem-cell transplantation is no longer routinely offered as first-line therapy for most patients in chronic phase.However, resistance to tki therapy is increasingly being recognized, and alternative therapy is needed for this group of patients. In addition, the development of models predicting response to tki therapy is desired, so that appropriate treatment strategies can be used for individual patients. The present report serves to outline the approach to the treatment of cml in British Columbia and to highlight areas of ongoing research.