“We Used to Say Rats Fell from the Sky After a Flood:” Temporary Recovery of Muskrat Following Ice Jams in the Peace-Athabasca Delta

Elders and Indigenous land users in the Peace-Athabasca Delta (PAD) have observed a dramatic decline in the relative abundance of muskrat in recent decades (~1935–2014). The main explanation for the decline has been reduction in suitable habitat as a result of decades with reduced frequency of ice-jam flooding on the Peace River. Under favourable conditions, ice jams can cause flooding of perched basins within the PAD that would otherwise receive no recharge from floodwaters. To examine whether abundance of muskrat in the PAD is driven by flooding, we tested the predictions that the density of muskrat (estimated by winter counts of houses) (1) was inversely related to the number of years since major ice jam floods and (2) increased with water depth. An ongoing collaborative monitoring program initiated in 2011, combined with analysis of data from past surveys (1973–2015), allowed Indigenous land users and scientists to document a 10 to 100-fold increase in the density of muskrat houses in 24 basins, over the two years following ice-jam flood events in the PAD. During 1973–2015, in the periods between major floods, density of houses dropped by approximately 79% for every year after a significant flood. In 27 basins surveyed from 2011 to 2015, density of muskrat houses increased by two orders of magnitude in the two years following a flood in the spring of 2014. Density of muskrat houses had a non-linear relationship with estimated depth of water at the time of fall freeze-up; the highest densities of muskrat houses were in basins with about 60 – 250 cm of water at the time of freeze-up. The depth of snow at the time of surveys did not have a strong relationship with the density of muskrat houses. However, few houses were counted in basins with more than 20 cm of snow, likely because deeper snow made it more difficult to conduct surveys and spot houses. Factors other than an increase in the depth of water at fall freeze-up may provide the mechanisms by which flooding affects muskrat. Density of muskrat houses is clearly tied to ice-jam flooding in the PAD. However, the local mechanisms by which floods affect muskrat are best understood by Indigenous land users and remain poorly understood by Western science. Indigenous peoples continue to regard muskrat as an indicator of ecological and cultural health of the PAD. This study highlights the value of consistent ecological monitoring that includes Indigenous knowledge.Les aînés et les utilisateurs des terres autochtones du delta des rivières de la Paix et Athabasca ont observé une baisse draconienne de l’abondance du rat musqué au cours des dernières décennies (~1935-2014). La principale explication du déclin est la diminution d’abris convenables, et ce, en raison de plusieurs décennies marquées par la fréquence réduite d’inondations causées par des embâcles dans la rivière de la Paix. Dans des conditions favorables, les embâcles peuvent causer l’inondation des bassins perchés au sein du delta des rivières de la Paix et Athabasca qui autrement ne recevraient pas de recharge des eaux de crue. Afin d’examiner si l’abondance du rat musqué dans le delta des rivières de la Paix et Athabasca est favorisée par les inondations, nous avons testé des prévisions selon lesquelles la densité du rat musqué (estimée par le nombre d’abris en hiver) 1) était inversement liée au nombre d’années depuis les dernières importantes inondations causées par des embâcles et 2) augmentait avec la profondeur de l’eau. Un programme collaboratif de suivi continu lancé en 2011, combiné à l’analyse de données des relevés antérieurs (1973-2015), a permis aux utilisateurs des terres autochtones et aux scientifiques de multiplier de 10 à 100 fois la densité d’abris du rat musqué dans 24 bassins, au cours des deux années suivant des événementsd’inondation causés par des embâcles dans le delta des rivières de la Paix et Athabasca. Entre 1973 et 2015, durant les périodes se situant entre les inondations importantes, la densité d’abris a diminué d’environ 79 % chaque année suivant une inondation importante. Dans 27 bassins sondés entre 2011 et 2015, la densité d’abris du rat musqué a augmenté de deux ordres de grandeur au cours des deux années ayant suivi une inondation survenue au printemps de 2014. La densité d’abris du rat musqué avait une relation non linéaire avec la profondeur de l’eau estimée au moment de la prise des glaces en automne; les plus fortes densités d’abris du rat musqué se trouvaient dans les bassins ayant de 60 à 250 cm d’eau au moment de la prise des glaces. La profondeur de la neige au moment des relevés n’avait pas de relation solide avec la densité d’abris du rat musqué. Cependant, nous avons compté peu d’abris dans les bassins comptant plus de 20 cm de neige, probablement parce qu’il était plus difficile d’effectuer des relevés et de trouver les abris dans la neige plus épaisse. Des facteurs autres que l’augmentation de la profondeur de l’eau au moment de la prise des glaces en automne pourraient fournir les mécanismes par lesquels les inondations se répercutent sur les rats musqués. La densité d’abris du rat musqué est manifestement liée aux inondations causées par des embâcles dans le delta des rivières de la Paix et Athabasca. Toutefois, les utilisateurs des terres autochtones comprennent mieux les mécanismes locaux par lesquels les inondations se répercutent sur les rats musqués, tandis qu’ils demeurent mal compris par la science occidentale. Les peuples autochtones continuent de considérer le rat musqué comme un indicateur de la santé écologique et culturelle du delta des rivières de la Paix et Athabasca. Cette étude fait ressortir la valeur d’un suivi écologique constant qui tient compte des connaissances autochtones

INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial

Background: The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn's disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. Methods: Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. Results: Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. Conclusions: Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel

Electrophysiological correlates of attention networks in childhood and early adulthood

Attention has been related to functions of alerting, orienting, and executive control, which are associated with distinct brain networks. This study aimed at understanding the neural mechanisms underlying the development of attention functions during childhood. A total of 46 healthy 4–13-year-old children and 15 adults performed an adapted version of the Attention Network Task (ANT) while brain activation was registered with a high-density EEG system. Performance of the ANT revealed changes in the efficiency of attention networks across ages. While no differences were observed on the alerting score, both orienting and executive attention scores showed a more protracted developmental curve. Further, age-related differences in brain activity were mostly observed in early ERP components. Young children had poorer early processing of warning cues compared to 10–13-year-olds and adults, as shown by an immature auditory-evoked potential complex elicited by warning tones. Also, 4–6-year-olds exhibited a poorer processing of orienting cues as indexed by lack of modulation of the N1. Finally, flanker congruency produced earlier modulation of ERPs amplitude with age. Flanker congruency effects were delayed and more anteriorly distributed for young children, compared to adults who showed a clear modulation of the N2 in fronto-parietal channels. Additionally, interactions among attention networks were examined. Both alerting and orienting conditions modulated the effectiveness of conflict processing by the executive attention network. The Orienting×Executive networks interactions was only observed after about age 7. Results are informative of the neural correlates of the development of attention networks in childhood

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.  METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country).  RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.  CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms