Ghost Factors of Laboratory Carbonate Chemistry Are Haunting Our Experiments.

AbstractFor many historical and contemporary experimental studies in marine biology, seawater carbonate chemistry remains a ghost factor, an uncontrolled, unmeasured, and often dynamic variable affecting experimental organisms or the treatments to which investigators subject them. We highlight how environmental variability, such as seasonal upwelling and biological respiration, drive variation in seawater carbonate chemistry that can influence laboratory experiments in unintended ways and introduce a signal consistent with ocean acidification. As the impacts of carbonate chemistry on biochemical pathways that underlie growth, development, reproduction, and behavior become better understood, the hidden effects of this previously overlooked variable need to be acknowledged. Here we bring this emerging challenge to the attention of the wider community of experimental biologists who rely on access to organisms and water from marine and estuarine laboratories and who may benefit from explicit considerations of a growing literature on the pervasive effects of aquatic carbonate chemistry changes.

The next generation cohort: a description of a cohort at high risk for childhood onset type 2 diabetes.

Children of mothers with youth-onset (<18 years) type 2 diabetes (T2D) are at increased risk of youth-onset T2D. In Canada, the highest reported prevalence of youth-onset T2D is in First Nation youth, some of whom harbor a unique genetic predisposition HNF1α polymorphism which has been associated with age of onset and clinical presentation. To describe the characteristics of the Next Generation birth cohort (n=260) at 7-9 years (n=88) and 14-16 years of age (n=27). This is a cross-sectional study of offspring exposed in utero to T2D (Next Generation Birth Cohort). Annual assessments from age 7 include height and weight, and biochemical testing (glucose, insulin, lipids, HbA1c). Descriptive statistics were employed. χ2 tests and repeated-measures ANOVA were used to compare categorical and continuous characteristics, respectively. In total, 11.9% of the total cohort have developed T2D. Of those 14-16.9 years of age, 16.0% have developed T2D. 92% of the offspring ages 7-9 and 70.3% of offspring ages 14-16 are overweight or obese. Children had a significantly higher body mass index z-score than adolescents (2.9 v. 1.5, P=0.001). Comparing the different HNF1α genotypes (G/G wildtype, G/S heterozygote, S/S homozygote); HbA1c (GG: 5.5% v. G/S: 5.7% v. S/S: 8.8%; P=0.0052), insulin (GG: 103 v. G/S: 202; P=0.05) and T2D status (G/G: 5.7% v. G/S: 28.1% v. S/S: 72.7%; P<0.0001) were significantly different between groups. T2D is very common among adolescents of mothers with youth-onset T2D. Early childhood obesity and the HNF1α G319S allele are associated with the incidence of T2D in the Next Gen offspring.

Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn's disease: real world experience from a multicentre cohort.

BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins-12 and -23, with efficacy in Crohn's disease (CD) demonstrated in clinical trials. AIM: To assess the real-world clinical, endoscopic and radiographic response and remission outcomes achieved with ustekinumab in medically-refractory CD. METHODS: A retrospective multicentre cohort study was performed on CD patients receiving ustekinumab between 2011 and 2016. The primary outcome was achievement of clinical and objective steroid-free response and remission at 3, 6 and 12 months. Clinical response and remission were defined by reduction in Harvey Bradshaw Index (HBI) of ≥3 points and an HBI ≤4 points respectively. Objective response was defined by improvement in endoscopic or radiographic CD, as assessed by ileocolonoscopy, contrast-enhanced ultrasound or CT/MR enterography. Objective remission was defined by endoscopic mucosal healing or complete resolution of inflammatory parameters on radiographic assessment. RESULTS: A total of 167 CD patients were treated with ustekinumab. 95.2% (159/167) previously failed anti-TNF therapy. Median follow-up was 45.6 weeks (IQR: 24.4-88.9). At 3 months, clinical response was achieved in 38.9% (65/167) and remission in 15.0% (25/167) of patients. At 6 months, clinical response was achieved in 60.3% (91/151) and remission in 25.2% (38/151) of patients. At 12 months, clinical response was achieved in 59.5% (66/111) and remission in 27.9% (31/111) of patients. Endoscopic or radiographic response was demonstrated in 54.5% (67/123) at 6 months and 55.8% (48/86) of patients at 12 months. CONCLUSIONS: Ustekinumab is an effective therapeutic option for inducing and maintaining clinical, endoscopic and radiographic response in patients with Crohn's disease failing anti-TNF therapy.

Coralline algae in a naturally acidified ecosystem persist by maintaining control of skeletal mineralogy and size.

To understand the effects of ocean acidification (OA) on marine calcifiers, the trade-offs among different sublethal responses within individual species and the emergent effects of these trade-offs must be determined in an ecosystem setting. Crustose coralline algae (CCA) provide a model to test the ecological consequences of such sublethal effects as they are important in ecosystem functioning, service provision, carbon cycling and use dissolved inorganic carbon to calcify and photosynthesize. Settlement tiles were placed in ambient pH, low pH and extremely low pH conditions for 14 months at a natural CO2 vent. The size, magnesium (Mg) content and molecular-scale skeletal disorder of CCA patches were assessed at 3.5, 6.5 and 14 months from tile deployment. Despite reductions in their abundance in low pH, the largest CCA from ambient and low pH zones were of similar sizes and had similar Mg content and skeletal disorder. This suggests that the most resilient CCA in low pH did not trade-off skeletal structure to maintain growth. CCA that settled in the extremely low pH, however, were significantly smaller and exhibited altered skeletal mineralogy (high Mg calcite to gypsum (hydrated calcium sulfate)), although at present it is unclear if these mineralogical changes offered any fitness benefits in extreme low pH. This field assessment of biological effects of OA provides endpoint information needed to generate an ecosystem relevant understanding of calcifying system persistence.

Estimating the completeness of physician billing claims for diabetes case ascertainment using population-based prescription drug data.

INTRODUCTION: Changes in physician reimbursement policies may hinder the collection of billing claims in administrative data; this can result in biased estimates of disease prevalence and incidence. However, the magnitude of data loss is largely unknown. The purpose of this study was to estimate completeness of capture of disease cases for Manitoba physicians paid by fee-for-service (FFS) and non-fee-for-service (NFFS) methods. METHODS: Manitoba's administrative data were used to identify a cohort (≥ 20 years) with a new diabetes medication between 1 April, 2007, and 31 March, 2009. Cohort members were classified by payment method of the prescribing physician (i.e. FFS vs. NFFS). The cohort was then classified as missing or not missing a diabetes diagnosis using physician claims and hospital records. Then, χ2 statistics were used to test for differences in the characteristics of the two groups. RESULTS: The cohort consisted of 12 394 individuals; 86.4% had a prescription for a diabetes medication from an FFS physician. A total of 1172 physicians (81.8% FFS) prescribed these medications for the cohort. Cohort members with a prescription from an FFS physician were older and more likely to reside in the urban Winnipeg health region than those with a prescription from a NFFS physician. A greater percentage of NFFS physicians' cases were missing a diabetes diagnosis (18.7%vs. 14.9% for FFS physicians). CONCLUSION: The results suggest minimal loss of physician claims associated with remuneration policies in Manitoba. This method of assessing data completeness could be applied to other chronic diseases and jurisdictions to estimate completeness.

TITRE: Estimation de l'exhaustivité des données de facturation des médecins pour la détermination des cas de diabète au moyen des données sur les médicaments d'ordonnance. INTRODUCTION: Les changements dans les politiques de remboursement des me´decins peuvent faire obstacle a` la collecte des donne´es administratives de facturation des me´decins, ce qui pourrait mener a` des estimations biaise´es de la pre´valence et de l'incidence des maladies. L'ampleur de cette perte potentielle de donne´es demeure cependant largement inconnue. Notre e´tude vise a` estimer l'exhaustivite´ de la couverture des cas de maladie pour le Manitoba par les me´decins re´mune´re´s a` l'acte (RA) et par les me´decins non re´mune´re´s a` l'acte (NRA). MÉTHODOLOGIE: Les donne´es administratives du Manitoba ont servi a` cre´er une cohorte dont les membres (20 ans et plus) devaient avoir pris un nouveau me´dicament pour le diabe`te entre le 1er avril 2007 et le 31 mars 2009. Ces membres ont e´te´ classe´s par mode de paiement du me´decin prescripteur (c'est-a`-dire re´mune´re´s a` l'acte ou non re´mune´re´s a` l'acte), puis selon s'ils avaient ou non rec¸u de diagnostic de diabe`te d'apre`s les donne´es de facturation des me´decins et des dossiers d'hoˆpitaux. On a utilise´ des analyses statistiques w2 pour tester les diffe´rences de caracte´ristiques entre les deux groupes. RÉSULTATS: La cohorte se composait de 12 394 individus, dont 86,4 % avaient rec¸u une ordonnance de me´dicament pour le diabe`te d'un me´decin RA. Au total, 1 172 me´decins (81,8 % RA) ont prescrit ce type de me´dicaments pour la cohorte. Les membres de la cohorte ayant rec¸u une ordonnance d'un me´decin RA e´taient plus aˆge´s et plus susceptibles de re´sider dans la re´gion sanitaire deWinnipeg que ceux qui avaient rec¸u une ordonnance d'un me´decin NRA. Un plus grand pourcentage de cas traite´s par des me´decins NRA n'avait pas rec¸u de diagnostic de diabe`te (18,7 %, contre 14,9 % pour les me´decins RA). CONCLUSION : Les re´sultats sugge`rent une perte minimale de donne´es de facturation des me´decins associe´e aux politiques de re´mune´ration au Manitoba. Cette me´thode d'e´valuation de l'exhaustivite´ des donne´es pourrait eˆtre applique´e a` d'autres maladies chroniques et a` d'autres secteurs de compe´tence.

Adalimumab dose escalation is effective for managing secondary loss of response in Crohn's disease.

BACKGROUND: The efficacy of adalimumab in maintaining remission in Crohn's disease patients may wane over time, leading to secondary loss of response that is often managed with dose escalation. However, the response to adalimumab dose escalation and long-term outcomes after escalation have not been well evaluated. AIMS: To characterise the short- and long-term clinical responses to adalimumab dose escalation for secondary loss of response. METHODS: A retrospective cohort study evaluating Crohn's disease out-patients requiring adalimumab dose escalation for secondary loss of response from 2003 to 2013 was conducted. The primary outcome was the proportion of patients achieving symptomatic clinical response to dose escalation and subsequent development of tertiary loss of response. Duration of regained response was assessed by Kaplan-Meier analysis. RESULTS: Ninety-two CD patients met inclusion criteria with mean duration of follow-up of 170.2 weeks (±129.6 weeks). Disease distribution was predominantly ileal (37/92, 40.2%) or ileocolonic (43/92, 46.7%), with equal distribution of inflammatory (34.8%), stricturing (27.2%), and penetrating (38.0%) disease phenotypes. At 24 weeks post-dose escalation, 74/92 (80.4%) patients had symptomatic clinical response. Among responders, median duration of sustained response was 69.2 weeks (IQR 29.4-107.1) but 42/74 (56.8%) responders experienced subsequent tertiary loss of response at a median time of 47.9 weeks (IQR 24.7-80.3). C-reactive protein >10.0 mg/L at the time of dose escalation predicted tertiary loss of response in univariate analysis (OR 3.32, 95% CI: 1.18-9.37). CONCLUSIONS: In patients with Crohn's disease, adalimumab dose escalation is effective for recapturing symptomatic response after secondary loss of response, but more than half will eventually experience a tertiary loss of response.

The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti-TNF use: a time-trend study.

BACKGROUND: Medical therapy is standard treatment for ulcerative colitis with colectomy reserved for medically refractory disease or malignancy. The introductions of ciclosporin in 1994 and anti-TNF therapy in 2005 have extended medical management options. AIM: To determine whether the colectomy incidence rate for medically refractory ulcerative colitis has changed since the introduction of anti-TNF therapy. METHODS: Adult patients with a diagnosis of ulcerative colitis and who subsequently underwent an urgent or elective colectomy for medically refractory disease in Edmonton, Canada between 1 January 1998 and 31 December 2011 were identified. Log-linear regression was used to estimate the annual percent change in the total colectomy incidence rate (urgent and elective combined) and the urgent and elective incidence rates individually, before and after 2005, the year infliximab was approved for use in ulcerative colitis. Temporal trends of drug utilisation in this study population were also described. RESULTS: During 1998-2011, 481 patients with ulcerative colitis underwent a colectomy for medically refractory disease. There was negligible change in the total colectomy incidence rate from 1998 to 2005, with an annual percent change of 4.4% (95% confidence interval (CI): -1.12% to 10.16%). From 2005-2011, following the approval and increasing use of anti-TNF therapy, the total colectomy incidence rate decreased by 16.1% (95% CI: -21.32% to -10.54%) every year to 0.9 per 100 ulcerative colitis patients in 2011. CONCLUSION: The total incidence rate of colectomy for medically refractory ulcerative colitis has declined substantially since 2005, paralleling the increased use of anti-TNF therapy in this patient population.

Prevalence of Epstein-Barr Virus in a population of patients with inflammatory bowel disease: a prospective cohort study.

BACKGROUND: The Epstein-Barr Virus (EBV) is truly prolific, with a prevalence of more than 90% in the adult human population. There are, however, little data available on the prevalence of EBV among patients with Inflammatory Bowel Disease (IBD), a population that is frequently immunosuppressed and thus at risk for severe, often fatal, primary infection. AIM: To identify the prevalence of EBV in a population of patients with IBD and to compare it with that of the general population. METHODS: A database of 2500 IBD patients previously followed at the University of Alberta IBD Centre was queried; 60 of these patients were randomly chosen to participate. A total of 220 patients attending the IBD Centre for clinical appointment were also prospectively asked to participate. Participants completed serological testing for VCA-IgM, VCA-IgG and EBNA-IgG, to determine prior EBV exposure. RESULTS: A total of 263 patients underwent testing. Results for EBV seroprevalence of specific age groups were as follows: 18-20 years (n = 17), 29% seronegative; 21-25 years (n = 31), 29% seronegative; 26-30 years (n = 35), 31-35 years (n = 18) and 36-40 years (n = 25), 100% seropositive. Finally, 3% of those older than 40 (n = 117) were seronegative. EBV seroprevalence was similar for Crohn's disease and ulcerative colitis. Azathioprine was associated with seropositivity (P = 0.048). CONCLUSION: The prevalence of EBV seronegativity in the IBD population aged 18-25 years was similar to that described in the general population, and above age 25 years, seropositivity approached 100%.

Treatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort.

Aliment Pharmacol Ther 2010; 32: 522-528 Summary Background Randomized, controlled trials have demonstrated that anti-TNF agents are efficacious in inducing remission in cases of Crohn's disease and ulcerative colitis. However, response rates for anti-TNF agents in 'real life' clinical practice are less well-defined. Aims To examine the response rates and long-term outcomes of infliximab and adalimumab treatment for out-patients with ulcerative colitis and to study the variables associated with response rates. Methods In a prospective study, a single-centre out-patient cohort was treated and followed up according to a structured protocol of clinical care. Response to treatment was assessed using a physician's global assessment that focused on normalization of bowel frequency, absence of blood with defecation and tapering of corticosteroids to zero. Results Fifty-three ulcerative colitis patients were included in the study. Responses to induction therapy were 96.4% (27/28) for infliximab and 80% (20/25) for adalimumab (P = 0.0889). Responses to maintenance therapy were similar: infliximab 77.8% (14/18) and adalimumab 70.0% (14/20) (P = 0.7190). Multivariate analyses of the induction and maintenance responses did not reveal confounding elements. No new safety signals were identified. Conclusions This long-term follow-up of a single-centre cohort of ulcerative colitis patients demonstrates that 'real-life' out-patient treatment with infliximab and adalimumab is effective in induction and maintenance of response.

Meaningful nursing research.

Dr. Fawcett's editorial (Western Journal of Nursing Research, August 2000), staunchly criticizes research journals and researchers for their lack of attentiveness to nursing discipline-specific knowledge. She suggests that this lack of attentiveness posits nursing for extinction; in doing so, she raises fundamental questions about the relationship between nursing and nursing science. Despite a plethora of nursing literature, professional nursing remains an intangible concept for many nurses. The author addresses this issue from the perspective of her sense of self as a nurse.

Video-capture teleradiology for the after-hours reading of computerized tomography scans.

We evaluated the after-hours support that radiologists could provide from their homes to an urban hospital for reading emergency computerized tomography (CT) scans. During a six-month study period, 36 CT scans were acquired using a video-capture card in a PC and transmitted via an ordinary telephone line. The teleradiology interpretation and the formal report (from the hard copy) were compared with a reference or gold standard interpretation made by a radiologist and an emergency physician for 31 of the 36 cases. In comparison with the gold standard, there were 26 correct diagnoses by teleradiology (84%) and five incorrect (16%). Head CT scans accounted for 74% of the transmitted scans and all five of the cases with discrepant diagnoses. The cause of the single clinically relevant discrepancy was found to be unrelated to the use of teleradiology. In comparison with the formal report, the accuracy of the teleradiologist was not significantly different for all categories combined or for head CT scans alone. Video-capture technology provided a reliable means of transmitting CT scans for after-hours interpretation in emergency cases.

Effect of proinflammatory interleukins on jejunal nutrient transport.

AIM: We examined the effect of proinflammatory and anti-inflammatory interleukins on jejunal nutrient transport and expression of the sodium-glucose linked cotransporter (SGLT-1). METHODS: 3-O-methyl glucose and L-proline transport rates were examined in New Zealand White rabbit stripped, short circuited jejunal tissue. The effects of the proinflammatory cytokines interleukin (IL)-1alpha, IL-6, and IL-8, IL-1alpha plus the specific IL-1 antagonist, IL-1ra, and the anti-inflammatory cytokine IL-10 were investigated. In separate experiments, passive tissue permeability was assessed and brush border SGLT-1 expression was measured by western blot in tissues exposed to proinflammatory interleukins. RESULTS: The proinflammatory interleukins IL-6, IL-1alpha, and IL-8 significantly increased glucose absorption compared with control levels. This increase in glucose absorption was due to an increase in mucosal to serosal flux. IL-1alpha and IL-8 also significantly increased L-proline absorption due to an increase in absorptive flux. The anti-inflammatory IL-10 had no effect on glucose transport. The receptor antagonist IL-1ra blocked the ability of IL-1alpha to stimulate glucose transport. IL-8 had no effect on passive tissue permeability. SGLT-1 content did not differ in brush border membrane vesicles (BBMV) from control or interleukin treated tissue. CONCLUSIONS: These findings suggest that intestinal inflammation and release of inflammatory mediators such as interleukins increase nutrient absorption in the gut. The increase in glucose transport does not appear to be due to changes in BBMV SGLT-1 content.