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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