Search

Background: Proton pump inhibitors (PPIs) are highly effective in treating gastroesophageal reflux disease (GERD). However, persistent, troublesome reflux symptoms despite PPI use are common, and a proportion of individuals with these persistent symptoms is considered to have refractory GERD (rGERD). There are limited data on patients’ experience with persistent reflux-like symptoms to guide healthcare professionals in managing this troublesome condition. Methods: An international, population-based, online survey was conducted among adults who reported persistent reflux-like symptoms; 24 questions were posed regarding the participants’ symptoms, diagnosis, treatment, and comorbid conditions. Descriptive analyses were performed to characterize participants’ experience with diagnosis and their satisfaction with treatment. All data were self-reported. Results: Of 565 initial respondents, 283 (51%) answered the question regarding being formally diagnosed by a healthcare professional with GERD and/or rGERD. The 197 (70%) participants who answered “yes” made up the survey population. Heartburn (65%) and acid regurgitation (62%) were the most common troublesome symptoms. PPI use was reported by 145 (74%) respondents, but only 30% were satisfied with PPI therapy. The most common alternative therapies included antacid/alginates (63%), histamine H2-receptor antagonists (33%), mucosal protectants (25%), and lifestyle modifications (84%). Conclusions: In this population-based survey, nearly one-third of participants with persistent reflux-like symptoms had not received a formal diagnosis of GERD or rGERD. Although most participants diagnosed with GERD/rGERD had received PPI therapy, persistent symptoms, dissatisfaction with PPI therapy, and concerns about long-term PPI use were common. These data emphasize the need for patient input when developing management strategies for GERD and persistent reflux-like symptoms or rGERD.

Objectives We estimated and compared the travel related carbon emissions of the annual meeting of the Canadian Association of Gastroenterology between the two most common geographical locations of the meeting. Methods We modelled the car, train and flight travel journey of each registrant to two annual meetings. One was held in Toronto, close to where the majority of Gastroenterogists live, the other in Banff in the west of the country. We used validated carbon emission outputs per kilometer of travel. Results The average per capita distance travelled to the Toronto meeting was 2845 km, resulting in 0.540 tonnes (t) of CO2equivalent (CO2e) emitted per person. When the meeting was held in Banff emissions were 41% higher than those in Toronto with an average distance travelled of 3949 km and 0.760t of CO2e emitted per person. Almost all of the travel related carbon emissions for both meetings were generated by flying. Conclusions Even when held close to the largest population centre, there is a large environmental impact from travel to annual meetings. Importantly, choice of meeting location has a very big impact on difference in carbon emissions. Societies need to consider the site of meetings and reduce the number of in-person attendees if they wish to reduce their carbon footprint. Hybrid models participants should be considered. Our analysis also suggests, other medical societies who wish to model their annual meetings can use a simplified model, using flying distance only, to estimate travel-related emissions.

Refractory reflux-like symptoms have a substantial impact on patients and healthcare providers. The aim of the survey was to qualitatively assess the needs and attitudes of practicing clinicians around the management of refractory reflux symptoms and refractory gastroesophageal reflux disease (rGERD).An International Working Group for the Classification of Oesophagitis (IWGCO) steering committee invited clinicians to complete an online survey including 17 questions.Of the 113 clinicians who completed the survey, 70% were GIs, 20% were primary care physicians, and 10% were other specialties. Functional heartburn was considered the most common reason for an incomplete response to proton pump inhibitor (PPI) therapy (82%), followed by stress/anxiety (69%). More GIs identified esophageal hypersensitivity as a cause, while more non-GIs identified esophageal dysmotility and non-reflux-related esophageal conditions. As the first step, most clinicians would order investigations (70-88%). Overall, 72% would add supplemental therapy for patients with partial response, but only 58% for those with non-response. Antacid/alginate was the most common choice overall, while non-GIs were more likely to add a prokinetic than were GIs (47.8 vs. 24.1%). Approximately 40% of clinicians would switch PPIs in patients with partial response, but only 29% would do so in non-responders. Preferences for long-term therapy were highly variable. The most common initial investigation was upper endoscopy. Choice of esophageal manometry and pH monitoring was more variable, with no clear preference for whether pH monitoring should be conducted on, or off, PPI therapy.The survey identified a number of challenges for clinicians, especially non-GI physicians, treating patients with refractory reflux-like symptoms or rGERD on a daily basis.

This study argues that the massive growing interest in Chinese language in Japanese universities in the 1990s was more complicated than it seemed. ‘Chinese fever’ at the beginning of the new millen...

This paper examines a remarkable artifact of international business education, a four-book business Chinese language series published in Shanghai from 1916 to 1933 by a Japanese business school. La...

Leukaemia cells re-program their microenvironment to provide proliferation support and protection from standard chemotherapy, molecularly targeted therapies, and immunotherapy. Although much is becoming known about molecules that drive niche-dependent treatment resistance; means of targeting these in the clinics has remained a key obstacle. To address this challenge, we have developed human induced pluripotent stem cell engineered niches ex vivo to reveal insights into druggable cancer-niche dependencies. We show that mesenchymal (iMSC) and vascular niche-like (iANG) cells support ex vivo proliferation of patient-derived leukaemia cells, impact dormancy and mediate therapy resistance. iMSC protected both non-cycling and cycling blasts against dexamethasone treatment while iANG protected only dormant blasts. Leukaemia proliferation and protection from dexamethasone induced-apoptosis was dependent on direct cell-cell contact and mediated by CDH2. To explore the therapeutic potential of disrupting this cell-cell interaction, we tested the CDH2 antagonist ADH-1 (previously in phase I / II for solid tumours) in a very aggressive patient-derived xenograft leukaemia mouse model. ADH-1 showed high in vivo efficacy. ADH-1/ dexamethasone combination therapy was superior to dexamethasone alone with no ADH1 conferred additional toxicity. These findings provide a proof-of-concept starting point to develop novel, potentially safer therapeutics that target niche-mediated cancer cell dependencies in haematological malignancies.SummaryCDH2 mediated niche-dependent cancer proliferation and treatment resistance is clinically targetable via ADH-1, a low toxic agent that could be potentially repurposed for future clinical trials in acute leukaemia.

Delays in triage processes in the emergency department (ED) can compromise patient safety. The aim of this study was to provide proof-of-concept that a self-check-in kiosk could decrease the time needed to identify ambulatory patients arriving in the ED. We compared the use of a novel automated self-check-in kiosk to identify patients on ED arrival to routine nurse-initiated patient identification.We performed a prospective trail with random weekly allocation to intervention or control processes during a 10-week study period. During intervention weeks, patients used a self-check-in kiosk to self-identify on arrival. This electronically alerted triage nurses to patient arrival times and primary complaint before triage. During control weeks, kiosks were unavailable and patients were identified using routine nurse-initiated triage. The primary outcome was time-to-first-identification, defined as the interval between ED arrival and identification in the hospital system.Median (interquartile range) time-to-first-identification was 1.4 minutes (1.0-2.08) for intervention patients and 9 minutes (5-18) for control patients. Regression analysis revealed that the adjusted time-to-first-identification was 13.6 minutes (95% confidence interval 12.8-14.5) faster for the intervention group.A self-check-in kiosk significantly reduced the time-to-first-identification for ambulatory patients arriving in the ED.Les délais d'attente inhérents au processus de triage des malades au service des urgences (SU) peuvent mettre en péril leur sécurité. L’étude visait donc à valider le principe selon lequel l'utilisation d'un guichet d'auto-inscription diminuerait le temps nécessaire pour signaler l'arrivée des malades ambulatoires au SU. A été comparé le processus d'utilisation d'un guichet d'auto-inscription d'un nouveau type pour signaler l'arrivée des malades au SU avec le processus habituel d'inscription des malades par le personnel infirmier.L’étude consistait en un essai prospectif, à répartition aléatoire et hebdomadaire, d'inscription, réalisé selon le processus expérimental ou le processus témoin, sur une période de 10 semaines. Durant les semaines d'expérimentation, les malades se dirigeaient vers le guichet d'auto-inscription à leur arrivée; un signal électronique informait le personnel infirmier affecté au triage de l'heure d'arrivée des malades et des motifs de consultation avant le triage lui-même. Durant les semaines témoins, les guichets étaient fermés et les malades étaient inscrits selon le processus habituel de triage effectué par le personnel infirmier. Le principal critère d’évaluation était le temps écoulé avant le signal d'arrivée, défini comme l'intervalle entre l'arrivée des malades au SU et leur inscription dans le système de l'hôpital.Le temps médian (écart interquartile) écoulé avant le signal d'arrivée était de 1,4 minute (1,0–2,08) durant les semaines d'expérimentation contre 9 minutes (5 –18) durant les semaines témoins. D'après les résultats de l'analyse de régression, le temps rajusté écoulé avant le signal d'arrivée était de 13,6 minutes (IC à 95% : 12,8–14,5) plus court dans le groupe d'expérimentation que dans le groupe témoin.L'utilisation d'un guichet d'auto-inscription a permis de réduire considérablement le temps écoulé avant le signal d'arrivée des malades ambulatoires au SU.

In 1987 archaeologists from nine African countries and colleagues from Sweden began a co-operation programme to study urbanism in eastern and southern Africa under the auspices of The Urban Origins ...

Background and Aim The value of a multidisciplinary group and patient engagement in guideline groups is uncertain. We compared the recommendations of two guidelines that used the same data during the same time frame but with different participants to obtain a “real world” perspective on influence of the composition of guideline groups. Methods The Canadian Association of Gastroenterology (CAG) and the American College of Gastroenterology (ACG) recently updated their clinical practice guidelines for the management of Irritable Bowel Syndrome (IBS). Both the CAG and ACG used the same methodology and methodologist and were presented with the same data for interpretation. The ACG group consisted of predominantly academic gastroenterologists, while the CAG group also included general practitioners, a psychiatrist, a psychologist and a patient representative. The CAG group were also asked what components of the group were valuable. Results There were 14 statements with the same or similar recommendations. There were 10 statements in the CAG guideline not addressed by the ACG guideline and five recommendations where the opposite was the case. There was one statement that the two groups both addressed, but each group came to different conclusions. CAG members were in 100% agreement that involving a patient and having a multidisciplinary team was valuable and may have played a role in these differing interpretations of the same data in an IBS guideline. Conclusions There has been little uptake of patient involvement and multidisciplinary teams in guideline groups. However, this study provides a unique example of added benefit through broader group representation.

Prevention of central nervous system (CNS) relapse is critical for cure of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite this, mechanisms of CNS infiltration are poorly understood, and the timing, frequency, and properties of BCP-ALL blasts entering the CNS compartment are unknown. We investigated the CNS-engrafting potential of BCP-ALL cells xenotransplanted into immunodeficient NOD.Cg- ITALIC! Prkdc (ITALIC! scid) ITALIC! Il2rg (ITALIC! tm1Wjl)/SzJ mice. CNS engraftment was seen in 23 of 29 diagnostic samples (79%): 2 of 2 from patients with overt CNS disease and 21 of 27 from patients thought to be CNS negative by diagnostic lumbar puncture. Histologic findings mimic human pathology and demonstrate that leukemic cells transit the blood-cerebrospinal fluid barrier situated close to the dural sinuses, the site of recently discovered CNS lymphatics. Retrieval of blasts from the CNS showed no evidence for chemokine receptor-mediated selective trafficking. The high frequency of infiltration and lack of selective trafficking led us to postulate that CNS tropism is a generic property of leukemic cells. To test this, we performed serial dilution experiments which showed CNS engraftment in 5 of 6 mice after transplant of as few as 10 leukemic cells. Clonal tracking techniques confirmed the polyclonal nature of CNS-infiltrating cells, with multiple clones engrafting in both the CNS and periphery. Overall, these findings suggest that subclinical seeding of the CNS is likely to be present in most BCP-ALL patients at original diagnosis, and efforts to prevent CNS relapse should concentrate on effective eradication of disease from this site rather than targeting entry mechanisms.

Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of cases of childhood precursor B-cell acute lymphoblastic leukemia. These abnormalities are too complex to engineer faithfully in animal models and are unrepresented in leukemia cell lines. As a resource for future functional and preclinical studies, we have created xenografts from the leukemic blasts of patients with intrachromosomal amplification of chromosome 21 and characterized them by in-vivo and ex-vivo luminescent imaging, flow immunophenotyping, and histological and ultrastructural analyses of bone marrow and the central nervous system. Investigation of up to three generations of xenografts revealed phenotypic evolution, branching genomic architecture and, compared with other B-cell acute lymphoblastic leukemia genetic subtypes, greater clonal diversity of leukemia-initiating cells. In support of intrachromosomal amplification of chromosome 21 as a primary genetic abnormality, it was always retained through generations of xenografts, although we also observed the first example of structural evolution of this rearrangement. Clonal segregation in xenografts revealed convergent evolution of different secondary genomic abnormalities implicating several known tumor suppressor genes and a region, containing the B-cell adaptor, PIK3AP1, and nuclear receptor co-repressor, LCOR, in the progression of B-cell acute lymphoblastic leukemia. Tracking of mutations in patients and derived xenografts provided evidence for co-operation between abnormalities activating the RAS pathway in B-cell acute lymphoblastic leukemia and for their aggressive clonal expansion in the xeno-environment. Bi-allelic loss of the CDKN2A/B locus was recurrently maintained or emergent in xenografts and also strongly selected as RNA sequencing demonstrated a complete absence of reads for genes associated with the deletions.

Introduction: Uganda remains seismically vulnerable to earthquakes, which constitute one of the most deadly naturally triggered disasters in the world. This is not surprising given the country’s location in the East African Rift Valley System. Method: This paper draws mainly on the authors’ live event experience and some media reports to narratively outline the nature of a sizable earthquake, which measured a magnitude of 5.7 on the Richter scale that struck Uganda and other countries within the Lake Victoria Basin region on 10th September 2016 in the afternoon. Results: Rakai - a district in central region was the worst affected in Uganda. It witnessed the death of four people; 20 people were admitted to the hospital with injuries; a total of 590 people were affected; and serious structural damages mainly in buildings were reported, leaving many either razed to the ground or left with cracks. Discussions: Although this earthquake was less devastating in terms of injuries and fatalities compared to two previous earthquakes in Uganda, based on the Modified Mercalli Intensity Scale it was still considered to be severe. Therefore, this paper identified some proactive lessons as far as earthquake risk reduction in Uganda is concerned, which among others include: encouraging earthquake-resistant buildings; the safety of essential infrastructure; earthquake early warning systems supported by free global technologies; and the safety of rescue workers along with prioritizing the psychosocial needs of rescue teams. With all this in mind, the September 2016 earthquake should serve as a timely reminder that there is a real need for the proactive ex-ante earthquake preparedness rather than risking an expensive post-ante approach to responding to any future devastating earthquakes in Uganda. Keywords: Earthquake, Uganda, disaster risk reduction, ex-ante approach, post-ante approach

Through funding from the Canadian International Development Agency’s (CIDA) China Program, the University of Regina (UofR), Canada, implemented two major development projects with the Educational Institute of Jilin province (EIJP) from 1990 to 2001. This paper re-examines this historic cooperation. The paper argues that prevailing theories of sustainable development which had been percolating in education faculties of Canadian universities in the 1990s allowed the UofR/EIJP program to transcend a simple international aid paradigm and to focus on the mutual benefit of the partners. At the same time, we observe that despite the enormous goodwill and institutional learning achieved through the UofR/EIJP program the project failed to live up to its significant potential. The paper concludes with some practical measures that institutions might implement to ensure important cooperative projects can build robust international capacity sustainable for the long term.

This article examines the Guide to Kuan Hua, arguably the world’s first business Chinese textbook series, exploring how a group of business communication experts in late 19th-century China created instructional materials that allowed foreigners to function efficiently in China’s business and bureaucratic environment. Rather than simply focusing on the mechanics of language, editors of the series fostered in students a set of literacies that would help them cope with the tumultuous change in 19th-century China. This study suggests that the experience of 19th-century textbook editors may inform our approach to complex intercultural communication challenges in today’s globalized world.

The CAG is a professional organization that seeks to promote the discipline of gastroenterology in Canada and internationally through a series of activities aligned with a Strategic Plan (renewed and updated every five years) in order to advance our mandate of (i) supporting and engaging in the study of the organs of the digestive tract in health and disease, (ii) promoting the advancement of the science and art of gastroenterology by providing leadership in patient care, research, education, and continuing professional development (CPD), and (iii) promoting and maintaining the highest ethical standards (https://www.cag-acg.org/about/what-is-the-cag/).

Changes in gene dosage are a major driver of cancer, known to be caused by a finite, but increasingly well annotated, repertoire of mutational mechanisms1. This can potentially generate correlated copy-number alterations across hundreds of linked genes, as exemplified by the 2% of childhood acute lymphoblastic leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21 (iAMP21)2, 3. We used genomic, cytogenetic and transcriptional analysis, coupled with novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here we show that individuals born with the rare constitutional Robertsonian translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the general population. In such cases, amplification is initiated by a chromothripsis event involving both sister chromatids of the Robertsonian chromosome, a novel mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge cycles are typically the initiating event, often followed by chromothripsis. In both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently involve duplications of the entire abnormal chromosome. The end-product is a derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage optimized for leukaemic potential, showing constrained copy-number levels over multiple linked genes. Thus, dicentric chromosomes may be an important precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes somatically. Furthermore, our data illustrate that several cancer-specific mutational processes, applied sequentially, can coordinate to fashion copy-number profiles over large genomic scales, incrementally refining the fitness benefits of aggregated gene dosage changes.

This paper discusses changing patterns of resource utilisation over time in the locality of Chibuene, Vilankulos, situated on the coastal plain of southern Mozambique. The macroscopic charcoal, bone and shell assemblages from archaeological excavations are presented and discussed against the off-site palaeoecological records from pollen, fungal spores and microscopic charcoal. The Chibuene landscape has experienced four phases of land use and resource utilisation that have interacted with changes in the environment. Phase 1 (a.d. 400–900), forest savanna mosaic, low intensity cattle herding and cultivation, trade of resources for domestic use. Phase 2 (a.d. 900–1400), forest savanna mosaic, high intensity/extensive cultivation and cattle herding. Phase 3 (a.d. 1400–1800), savanna woodland and progressive decrease in forests owing to droughts. Decline of agricultural activities and higher reliance on marine resources. Possible trade of resources with the interior. Phase 4 (a.d. 1800–1900), open savanna with few forest patches. Warfare and social unrest. Collapse of trade with the interior. Decline in marine resources and wildlife. Loss of cattle herds. Expansion of agriculture locally and introduction of New World crops and clearing of Brachystegia trees. The study shows the importance of combining different environmental resources for elucidating how land use and natural variability have changed over time.

BACKGROUND: Funders of health research in Canada seek to determine how their funding programs impact research capacity and knowledge creation.OBJECTIVE: To evaluate the impact of a focused grants and award program that was cofunded by the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes, and the Canadian Association of Gastroenterology; and to measure the impact of the Program on the career paths of funded researchers and assess the outcomes of research supported through the Program.METHODS: A survey of the recipients of grants and awards from 2000 to 2008 was conducted in 2012. The CIHR Funding Decisions database was searched to determine subsequent funding; a bibliometric citation analysis of publications arising from the Program was performed.RESULTS: Of 160 grant and award recipients, 147 (92%) completed the survey. With >$17.4 million in research funding, support was provided for 131 fellowship awards, seven career transition awards, and 22 operating grants. More than three-quarters of grant and award recipients continue to work or train in a research-related position. Combined research outputs included 545 research articles, 130 review articles, 33 book chapters and 11 patents. Comparative analyses indicate that publications supported by the funding program had a greater impact than other Canadian and international comparators.CONCLUSIONS: Continuity in support of a long-term health research funding partnership strengthened the career development of gastroenterology researchers in Canada, and enhanced the creation and dissemination of new knowledge in the discipline.

Archaeological data can be represented in quantitative models to test theories of societal growth, development, and resilience. This chapter describes the results of simulations employing integrated agent-based, cellular automata, and network models to represent elements of the ancient Maya social-ecological system. The purpose of the model is to better understand the complex dynamics of the Maya civilization and to test quantitative indicators of resilience as predictors of system sustainability or decline. The model examines the relationship between population growth, agricultural production, pressure on ecosystem services, forest succession, value of trade, and the stability of trade networks. These combine to allow agents representing Maya settlements to develop and expand within a landscape that changes under climate variation and responds to anthropogenic pressure. The model is able to reproduce spatial patterns and timelines somewhat analogous to that of the ancient Maya, although this model requires refinement and further archaeological data for calibration.

Historical ecological approaches to settlement aggregation and complexity reject modernist and post-modernist reliance on linear neo-evolutionary categorization of cities in relation to earlier farming communities. Instead, urban centres and multi-urban systems are viewed as components of complex heterarchically and hierarchically organized landscapes. Resilience theory has been applied in several archaeological efforts to characterize urban development of specific centres. Building on experience from the recently concluded Urban Mind project this chapter argues for a historical ecology approach to track the long-term cultural and environmental dynamics of multi-centred urban systems. Linking human cognition, social memory, ecosystem services, urban metabolism and food security, and institutions of urban governance, it uses data on long-term urban histories in the eastern Mediterranean, southern Africa, and Mesoamerica to identify implications for future urban planning initiatives.

The debate on the peopling of Madagascar has long been dominated by historical linguistics and the observed similarities between Malagasy and Austronesian languages. It is clear from the linguistic evidence that there have been several periods of human contact with, or migration to, Madagascar—and that these also brought different domesticates to the island (Allibert 1998, 2007; Beaujard 2011a,b; Boivin et al. 2013). Genetics is currently the main tool being used to understand the peopling of Madagascar (Hurles et al. 2005; Tofanelli et al. 2009; Murray et al. 2012; Pierron et al. 2014). However, despite recent advances in the field of genetic studies we still know very little about either the first colonisation on Madagascar or about the contacts between the populations of Madagascar, the Austronesian influence zone, and the African mainland. Moreover, Verin and Wright (1999) have warned that inferences from linguistic and genetic studies can be misleading, and that there is often a disjuncture between language and human biology on the one hand and material culture and identity on the other.

Migrations and interactions between Madagascar and the eastern Africa, 500 BC – 1000 AD: : the archeological perspective

Cities are rapidly increasing in importance as a major factor shaping the Earth system, and therefore, must take corresponding responsibility. With currently over half the world's population, cities are supported by resources originating from primarily rural regions often located around the world far distant from the urban loci of use. The sustainability of a city can no longer be considered in isolation from the sustainability of human and natural resources it uses from proximal or distant regions, or the combined resource use and impacts of cities globally. The world's multiple and complex environmental and social challenges require interconnected solutions and coordinated governance approaches to planetary stewardship. We suggest that a key component of planetary stewardship is a global system of cities that develop sustainable processes and policies in concert with its non-urban areas. The potential for cities to cooperate as a system and with rural connectivity could increase their capacity to effect change and foster stewardship at the planetary scale and also increase their resource security. © Royal Swedish Academy of Sciences 2012.

The south-east coast of Africa in the later first millennium was busy with boats and the movement of goods from across the Indian Ocean to the interior. The landing places were crucial mediators in this process, in Africa as elsewhere. Investigations at the beach site of Chibuene show that a local community was supplying imported beads to such interior sites as Schroda, with the consequent emergence there of hierarchical power structures.

The Integrated History and future of People on Earth (IHOPE) initiative is a global network of researchers and research projects with its International Program Office (IPO) now based at the Stockho ...

OBJECTIVE: To determine staffing and practice patterns for after-hours endoscopy service in CanadaMETHODS: A link to a web-based survey was sent by e-mail to all clinical members of the Canadian Association of Gastroenterology in February 2011. A priori, it was planned to compare variations in practice among gastroenterologists (GIs) performing endoscopy in different regions of Canada, between pediatric and adult GIs, and between university and community hospitals.RESULTS: Of 422 potential respondents, 168 (40%) responded. Of the 139 adult GIs, 61% performed after-hours endoscopy in the endoscopy suite where daytime procedures were performed, 62% had a trained endoscopy nurse available for all procedures, 38% had access to propofol sedation, 12% reprocessed the endoscopes themselves or with the help of a resident, 4% had out-of-hospital patients come directly to their endoscopy suite and 53% were highly satisfied. The adult endoscopists practising at community hospitals were more likely to have an anesthetist attend the procedure. Regional differences were noted, with more involvement of anesthetists (13%) and availability of propofol (50%) in Ontario, more frequent reprocessing of endoscopes in the central reprocessing units in British Columbia (78%) and almost universal availability of a trained endoscopy nurse (96%) with concomitant higher endoscopist satisfaction (84% highly satisfied) in Alberta.CONCLUSIONS: More than one-third of surveyed endoscopists across the country do not have a trained endoscopy nurse to assist in after-hours endoscopy – the time period when urgent patients often present and typically require therapeutic endoscopic interventions. There are significant regional differences in the practice of after-hours endoscopy in Canada.

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct subgroup of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has a dismal outcome when treated with standard therapy. For improved diagnosis and risk stratification, the initiating genetic events need to be elucidated. To investigate the genetic basis of BCP-ALL, genomes of 94 iAMP21 patients were interrogated by arrays, FISH, and multiplex ligation-dependent probe amplification. Most copy number alterations targeted chromosome 21, reinforcing the complexity of this chromosome. The common region of amplification on chromosome 21 was refined to a 5.1-mb region that included RUNX1, miR-802, and genes mapping to the Down syndrome critical region. Recurrent abnormalities affecting genes in key pathways were identified: IKZF1 (22%), CDKN2A/B (17%), PAX5 (8%), ETV6 (19%), and RB1 (37%). Investigation of clonal architecture provided evidence that these abnormalities, and P2RY8-CRLF2, were secondary to chromosome 21 rearrangements. Patient outcome was uniformly poor with standard therapy irrespective of the presence or absence of these changes. This study has provided evidence that chromosome 21 instability is the only anomaly among those so far investigated that is common to all iAMP21 patients, and therefore the initiating event is likely to be found among the complex structural rearrangements of this abnormal chromosome.

BACKGROUND: Point-of-care practice audits allow documentation of procedural outcomes to support quality improvement in endoscopic practice.OBJECTIVE: To evaluate a colonoscopists’ practice audit tool that provides point-of-care data collection and peer-comparator feedback.METHODS: A prospective, observational colonoscopy practice audit was conducted in academic and community endoscopy units for unselected patients undergoing colonoscopy. Anonymized colonoscopist, patient and practice data were collected using touchscreen smart-phones with automated data upload for data analysis and review by participants. The main outcome measures were the following colonoscopy quality indicators: colonoscope insertion and withdrawal times, bowel preparation quality, sedation, immediate complications and polypectomy, and biopsy rates.RESULTS: Over a span of 16 months, 62 endoscopists reported on 1279 colonoscopy procedures. The mean cecal intubation rate was 94.9% (10th centile 84.2%). The mean withdrawal time was 8.8 min and, for nonpolypectomy colonoscopies, 41.9% of colonoscopists reported a mean withdrawal time of less than 6 min. Polypectomy was performed in 37% of colonoscopies. Independent predictors of polypectomy included the following: endoscopy unit type, patient age, interval since previous colonoscopy, bowel preparation quality, stable inflammatory bowel disease, previous colon polyps and withdrawal time. Withdrawal times of less than 6 min were associated with lower polyp removal rates (mean difference −11.3% [95% CI −2.8% to −19.9%]; P=0.01).DISCUSSION: Cecal intubation rates exceeded 90% and polypectomy rates exceeded 30%, but withdrawal times were frequently shorter than recommended. There are marked practice variations consistent with previous observations.CONCLUSION: Real-time, point-of-care practice audits with prompt, confidential access to outcome data provide a basis for targeted educational programs to improve quality in colonoscopy practice.

Significant gains have been achieved by the CAG during the past five years. The CAG remains dedicated to professional education, research and patient care in all areas of digestive health and disease in support of the economic and social health of all Canadians. All of the goals and targets associated with the five principal initiatives of the 2004 strategic plan have been addressed, and most have been fully or partially achieved. The organization is active on many fronts by engaging partners, strengthening existing programs, addressing areas where goals and targets have not been achieved and creating new initiatives. The focus of these activities is to provide value to you, the member, by improving digestive health and disease programs. We believe the CAG is well positioned to meet the opportunities and challenges in the years to come. To this end, a new five-year strategic plan is in development and will be presented to the membership in the near future. The CAG leadership welcomes your comments and suggestions to enhance the ongoing development and operation of the organization.

BACKGROUND: The cost-effectiveness of initial strategies in managing Canadian patients with uninvestigated upper gastrointestinal symptoms remains controversial.OBJECTIVE: To assess the cost-effectiveness of six management approaches to uninvestigated upper gastrointestinal symptoms in the Canadian setting.METHODS: The present study analyzed data from four randomized trials assessing homogeneous and complementary populations of Canadian patients with uninvestigated upper gastrointestinal symptoms with comparable outcomes. Symptom-free months, quality-adjusted life-years (QALYs) and direct costs in Canadian dollars of two management approaches based on the Canadian Dyspepsia Working Group (CanDys) Clinical Management Tool, and four additional strategies (two empirical antisecretory agents, and two prompt endoscopy) were examined and compared. Prevalence data, probabilities, utilities and costs were included in a Markov model, while sensitivity analysis used Monte Carlo simulations. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were determined.RESULTS: Empirical omeprazole cost $226 per QALY ($49 per symptom-free month) per patient. CanDys omeprazole and endoscopy approaches were more effective than empirical omeprazole, but more costly. Alternatives using H2-receptor antagonists were less effective than those using a proton pump inhibitor. No significant differences were found for most incremental cost-effectiveness ratios. As willingness to pay (WTP) thresholds rose from $226 to $24,000 per QALY, empirical antisecretory approaches were less likely to be the most cost-effective choice, with CanDys omeprazole progressively becoming a more likely option. For WTP values ranging from $24,000 to $70,000 per QALY, the most clinically relevant range, CanDys omeprazole was the most cost-effective strategy (32% to 46% of the time), with prompt endoscopy-proton pump inhibitor favoured at higher WTP values.CONCLUSIONS: Although no strategy was the indisputable cost-effective option, CanDys omeprazole may be the strategy of choice over a clinically relevant range of WTP assumptions in the initial management of Canadian patients with uninvestigated dyspepsia.

The B-cell receptor (BCR) and its immature form, the precursor-BCR (pre-BCR), have a central role in the control of B-cell development, which is dependent on a sequence of cell-fate decisions at specific antigen-independent checkpoints. Pre-BCR expression provides the first checkpoint, which controls differentiation of pre-B to immature B-cells in normal haemopoiesis. Pre-BCR signalling regulates and co-ordinates diverse processes within the pre-B cell, including clonal selection, proliferation and subsequent maturation. In B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), B-cell development is arrested at this checkpoint. Moreover, malignant blasts avoid clonal extinction by hijacking pre-BCR signalling in favour of the development of BCP-ALL. Here, we discuss three mechanisms that occur in different subtypes of BCP-ALL: (i) blocking pre-BCR expression; (ii) activating pre-BCR-mediated pro-survival and pro-proliferative signalling, while inhibiting cell cycle arrest and maturation; and (iii) bypassing the pre-BCR checkpoint and activating pro-survival signalling through pre-BCR independent alternative mechanisms. A complete understanding of the BCP-ALL-specific signalling networks will highlight their application in BCP-ALL therapy.

The management of Helicobacter pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies.H. pylori negative patients with dyspepsia symptoms of at least moderate severity (or =4 on a seven-point Likert scale) were recruited from 35 centers. Patients were randomized to a 4-wk treatment of omeprazole 20 mg od, ranitidine 150 mg bid, cisapride 20 mg bid, or placebo, followed by on-demand therapy for an additional 5 months. Treatment success was defined as no or minimal symptoms (scoreor = 2 out of 7), and was assessed after 4 wk and at 6 months.Five hundred and twelve patients were randomized and included in the intention-to-treat (ITT) analysis. At 4 wk, success rates (95% CI) were: omeprazole 51% (69/135; 43-60%), ranitidine 36% (50/139, 28-44%), cisapride 31% (32/105, 22-39%), and placebo 23% (31/133, 16-31%). Omeprazole was significantly better than all other treatments (p0.05). The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31% (42/135, 23-39%) compared with cisapride 13% (14/105, 7-20%), and placebo 14% (18/133, 8-20%) (p= 0.001), but not ranitidine 21% (29/139, 14-27%) (p= 0.053). The mean number of on-demand study tablets consumed and rescue antacid used was comparable across groups. Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine.Treatment with omeprazole provides superior symptom relief compared to ranitidine, cisapride, and placebo in the treatment of H. pylori negative primary care dyspepsia patients.

With the objective of identifying candidate tumor suppressor genes, we used fluorescence in situ hybridization to map leukemia-related deletions of the long arm of chromosome 6 (6q). Twenty of 24 deletions overlapped to define a 4.8-Mb region of minimal deletion between markers D6S1510 and D6S1692 within chromosome 6 band q16. Using reverse transcription-PCR, we found evidence of expression in hematopoietic cells for 3 of 15 genes in the region (GRIK2, C6orf111, and CCNC). Comparison between our own and published deletion data singled out GRIK2 as the gene most frequently affected by deletions of 6q in acute lymphocytic leukemia (ALL). Sequence analysis of GRIK2 in 14 ALL cases carrying heterozygous 6q deletions revealed a constitutional and paternally inherited C to G substitution in exon 6 encoding for an amino acid change in one patient. The substitution was absent among 232 normal alleles tested, leaving open the possibility that heterozygous carriers of such mutations may be susceptible to ALL. Although low in all normal hematopoietic tissues, quantitative reverse transcription-PCR showed higher baseline GRIK2 expression in thymus and T cells than other lineages. Among T-cell ALL patients, 6q deletion was associated with a statistically significant reduction in GRIK2 expression (P = 0.0001). By contrast, elevated GRIK2 expression was measured in the myelomonocytic line THP-1 and in one patient with common ALL. Finally, we detected significant levels of GRIK2 expression in prostate, kidney, trachea, and lung, raising the possibility that this gene may be protective against multiple tumor types.

Background & Aims. The acid inhibitory effect of proton pump inhibitors is reported to be greater in the presence than in the absence of an H. pylori infection. This study was undertaken to test the hypothesis that the acid inhibitory effect of omeprazole given twice a day is greater in H. pylori infected healthy volunteers than in the same individuals following eradication because of differences in the pharmacodynamics of omeprazole, greater duodenogastric reflux, the effects of ammonia produced by the H. pylori, or lower gastric juice concentrations of selected cytokines, which may inhibit gastric acid secretion. Materials and Methods. We undertook 24-hour pH-metry in 12 H. pylori-positive healthy volunteers: (1) when on no omeprazole; (2) when on omeprazole 20 mg bid for 8 days; (3) 2 months after eradication of H. pylori and when on no omeprazole; and (4) after eradication of H. pylori and when on omeprazole 20 mg twice a day. Results. In subjects given omeprazole, eradication of H. pylori reduced pH and percentage pH ≥ 3, as well as increasing the area under the H+ concentration-time curve. These differences were not due to alterations in (1) gastric juice concentrations of IL-1α, IL-8, IL-13, epidermal growth factor, or bile acids; (2) serum gastrin concentrations; or (3) the pharmacokinetics of omeprazole. There was no change in the difference in the H+ concentration-time curve ‘without omeprazole’ minus ‘with omeprazole’, when comparing ‘after’ versus ‘before’ eradication of H. pylori. Conclusions. Eradication of H. pylori was not associated with an alteration in the acid inhibitory potency when comparing the difference in gastric acidity ‘with’ versus ‘without’ omeprazole. When the results were expressed by simply taking into account the acid measurements while on omeprazole before versus after eradication of H. pylori, the acid inhibition with omeprazole was greater in the presence than in the absence of a H. pylori infection. The clinical significance of the small difference is not clear.

The annual survey of Canadian Association of Gastroenterology (CAG) members’ educational needs was conducted online this past April. One hundred eightyseven individuals (one fifth of the membership) completed the needs assessment. The topic most in demand for future educational events was inflammatory bowel disease, both from the clinical and basic science perspectives. Other highly rated topics were endoscopy, pharmacological therapeutics, celiac disease and pancreatitis/pancreatic disease. Educational materials were judged to be the most valuable component of exhibit areas. Results of the needs assessment were used to shape the 2004 Canadian Digestive Diseases Week (CDDW) program.

This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.

A primary goal of the Canadian Association of Gastroenterology (CAG) and its Foundation, the Canadian Digestive Health Foundation (CDHF), in collaboration with the Canadian Institutes of Health Research (CIHR) and the CAG-CDHF partners, is to promote excellence in research. This research will lead to new discoveries that will translate into improved health for Canadians. Moreover, this partnership will sustain and increase this capacity through high-quality education and research training of talented young scientists and clinicians in gastroenterology. The CAG strategic plan is to sustain its strong support of biomedical research while increasing support for research in CIHR pillars 3 and 4 including outcomes research, quality assurance and knowledge translation. The present report, on behalf of the research committee (Table 1), outlines another very successful year for this partnership program. TABLE 1 Members of the Canadian Association of Gastroenterology Research Committee 2011 Details relating to eligibility and application processes for all of the following awards are available on the CAG website (www.cag-acg.org/research). The review and assessment of every application complies with CIHR standards and guidelines, and any potential conflicts of interest are meticulously identified and avoided.