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Conventionally, regression discontinuity analysis contrasts a univariate regression's limits as its independent variable, "R," approaches a cut point, "c," from either side. Alternative methods target the average treatment effect in a small region around "c," at the cost of an assumption that treatment assignment, I[R

Over the last century, northwestern Canada experienced some of the highest rates of tropospheric warming globally, which caused glaciers in the region to rapidly retreat. Our study seeks to extend the record of glacier fluctuations and assess climate drivers prior to the instrumental record in the Mackenzie and Selwyn mountains of northwestern Canada. We collected 27 10 Be surface exposure ages across nine cirque and valley glacier moraines to constrain the timing of their emplacement. Cirque and valley glaciers in this region reached their greatest Holocene extents in the latter half of the Little Ice Age (1600–1850 CE). Four erratic boulders, 10–250 m distal from late Holocene moraines, yielded 10 Be exposure ages of 10.9–11.6 ka, demonstrating that by ca. 11 ka, alpine glaciers were no more extensive than during the last several hundred years. Estimated temperature change obtained through reconstruction of equilibrium line altitudes shows that since ca. 1850 CE, mean annual temperatures have risen 0.2–2.3 ∘ C. We use our glacier chronology and the Open Global Glacier Model (OGGM) to estimate that from 1000 CE, glaciers in this region reached a maximum total volume of 34–38 km 3 between 1765 and 1855 CE and had lost nearly half their ice volume by 2019 CE. OGGM was unable to produce modeled glacier lengths that match the timing or magnitude of the maximum glacier extent indicated by the 10 Be chronology. However, when applied to the entire Mackenzie and Selwyn mountain region, past millennium OGGM simulations using the Max Planck Institute Earth System Model (MPI-ESM) and the Community Climate System Model 4 (CCSM4) yield late Holocene glacier volume change temporally consistent with our moraine and remote sensing record, while the Meteorological Research Institute Earth System Model 2 (MRI-ESM2) and the Model for Interdisciplinary Research on Climate (MIROC) fail to produce modeled glacier change consistent with our glacier chronology. Finally, OGGM forced by future climate projections under varying greenhouse gas emission scenarios predicts 85 % to over 97 % glacier volume loss by the end of the 21st century. The loss of glaciers from this region will have profound impacts on local ecosystems and communities that rely on meltwater from glacierized catchments. [ABSTRACT FROM AUTHOR]

In advanced non-small cell lung cancer (NSCLC), patients with actionable genomic alterations may derive additional clinical benefit from targeted treatment compared to cytotoxic chemotherapy. Current guidelines recommend extensive testing with next generation sequencing (NGS) panels. We investigated the impact of using a targeted NGS panel (TruSight Tumor 15, Illumina) as reflex testing for NSCLC samples at a single institution. Molecular analysis examined 15 genes for hotspot mutation variants, including AKT1, BRAF, EGFR, ERBB2, FOXL2, GNA11, GNAQ, KIT, KRAS, MET, NRAS, PDGFRA, PIK3CA, RET and TP53 genes. Between February 2017 and October 2020, 1460 samples from 1395 patients were analyzed. 1201 patients (86.1%) had at least one variant identified, most frequently TP53 (47.5%), KRAS (32.2%) or EGFR (24.2%). Among these, 994 patients (71.3%) had clinically relevant variants eligible for treatment with approved therapies or clinical trial enrollment. The incremental cost of NGS beyond single gene testing (EGFR, ALK) was CAD $233 per case. Reflex upfront NGS identified at least one actionable variant in more than 70% of patients with NSCLC, with minimal increase in testing cost. Implementation of NGS panels remains essential as treatment paradigms continue to evolve. [ABSTRACT FROM AUTHOR]

Background: Despite decades of research, our understanding of Alzheimer's disease (AD) etiology remains incomplete. In recent years, appreciation has grown for potential roles for the microbiota in shaping neurological health.Objective: This study aimed to examine associations between the microbiota and AD in a human cross-sectional cohort.Methods: Forty-five AD patients and 54 matched controls were recruited in Vancouver, Canada. Fecal and oral samples underwent 16S microbiota sequencing. A wide array of demographic and clinical data were collected. Differences between participant groups were assessed, and associations between microbes and clinical variables were examined within the AD population.Results: The gut microbiota of AD patients displayed lower diversity relative to controls, although taxonomic differences were sparse. In contrast, the AD oral microbiota displayed higher diversity, with several taxonomic differences relative to controls, including a lower abundance of the families Streptococcaceae and Actinomycetaceae, and a higher abundance of Weeksellaceae, among others. The periodontitis-associated oral microbe Porphyromonas gingivalis was 5 times more prevalent among patients. No significant associations between gut or oral microbes and cognition were detected, but several correlations existed between microbes and mood disorders and BMI among patients, including a strong positive correlation between Alphaproteobacteria and depression score.Conclusion: The gut microbiota of AD patients was not overtly different from controls, although it displayed lower diversity, an overall marker of microbiota health. The oral microbiota did display marked differences. Cognition was not associated with a microbial signature, but other relevant AD factors including mood and BMI did demonstrate an association. [ABSTRACT FROM AUTHOR]

The Canadian Wildlife Service (CWS) requires reliable estimates of the harvest of migratory game birds, including waterfowl, to effectively manage populations of these hunted species. The National Harvest Survey is an annual survey of hunters who purchase Canada's mandatory migratory game bird hunting permit, integrating information from a survey of hunting activity with information from a separate survey of species composition in the harvest. We used these survey data to estimate the number of birds harvested for each species and hunting activity metrics (e.g., number of active hunters, days spent hunting). The analytical methods used to generate these estimates have not changed since the survey was first designed in the early 1970s. We describe a new hierarchical Bayesian integrated model, which replaces the series of ratio estimators that comprised the old model. We are using this new model to generate estimates for migratory bird harvests as of the 2019–2020 hunting season, and to generate updated estimates for all earlier years. The hierarchical Bayesian model uses over‐dispersed Poisson distributions to model mean hunter activity and harvest (zero‐inflated Poisson and zero‐truncated Poisson, respectively). It also includes multinomial distributions to model some key components (e.g., variation in harvest across periods of the hunting season, the species composition of the harvest within each of those periods, the age and sex composition in the harvests of a given species). We estimated the parameters of the Poisson and the multinomial distributions for each year as random effects using first‐difference time‐series. This time‐series component allows the model to share information across years and reduces the sensitivity of the estimates to annual sampling noise. The new model estimates are generally very similar to those from the old model, particularly for the species that occur most commonly in the harvest, so the results do not suggest any major changes to harvest management decisions and regulations. Estimates for all species from the new model are more precise and less susceptible to annual sampling error, particularly for species that occur less commonly in the harvest (e.g., sea ducks, other species of conservation concern). This new model, with its hierarchical Bayesian framework, will also facilitate future improvements and elaborations, allowing the incorporation of prior information from the rich literature and knowledge in game bird management and biology. [ABSTRACT FROM AUTHOR]

Individual variation in the age of pubertal onset is linked to physical and mental health, yet the factors underlying this variation are poorly understood. Life history theory predicts that individuals at higher risk of mortality due to extrinsic causes such as infectious disease should sexually mature and reproduce earlier, whereas those at lower risk can delay puberty and continue to invest resources in somatic growth. We examined relationships between a genetic predictor of infectious disease resistance, heterozygosity of the major histocompatibility complex (MHC), referred to as the human leukocyte antigen (HLA) gene in humans, and self-reported pubertal timing. In a combined sample of men from Canada (n = 137) and the United States (n = 43), MHC heterozygosity predicted later self-reported pubertal development. These findings suggest a genetic trade-off between immunocompetence and sexual maturation in human males. [ABSTRACT FROM AUTHOR]

Copyright of Avian Diseases is the property of American Association of Avian Pathologists, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We focus on the personal networks of members of an anti-environmentalism countermovement in a small town in Canada (Port Alberni, B.C.) that mobilized against the environmental movement. Drawing primarily from social survey data, we investigate the effects of network-based mobilization processes, and contending-movement ties (ties to the environmental movement), on level of participation in the countermovement. We add to the literature on networks and social movements, and movement-countermovement dynamics by 1) comparing network processes amongst a counter movement with those amongst a corresponding social movement, and 2) comparing personal network structures and mobilization processes between countermovement members and the general public. We find a similar pattern of network-based micromobilization processes amongst movement and countermovement participant networks. We find both similarities, and key differences between the counter movement and the general public in terms of activism and social network ties. Theoretical predictions have suggested that individuals who have ties to opposing groups will moderate their participation in a social movement. However, in this study of a community countermovement organization in a small town in Canada that mobilized against the provincial environmental movement we find that the number of contending movement ties (the range of ties to environmental organizations) held by individuals in the countermovement has a significant positive association with countermovement activism, and is the strongest statistical predictor of countermovement activism. Drawing upon both theory and substantive information we discuss the implications of this novel finding. [ABSTRACT FROM AUTHOR]

In this article we analyze how media coverage for environmental actors (individual environmental activists and environmental movement organizations) is associated with their perceived policy influence in Canadian climate change policy networks. We conceptualize media coverage as the total number of media mentions an actor received in Canada's two main national newspapers--the Globe and Mail and National Post. We conceptualize perceived policy influence as the total number of times an actor was nominated by other actors in a policy network as being perceived to be influential in domestic climate change policy making in Canada. Literature from the field of social movements, agenda setting, and policy networks suggests that environmental actors who garner more media coverage should be perceived as more influential in policy networks than actors who garner less coverage. We assess support for this main hypothesis in two ways. First, we analyze how actor attributes (such as the type of actor) are associated with the amount of media coverage an actor receives. Second, we evaluate whether being an environmental actor shapes the association between media coverage and perceived policy influence. We find a negative association between media coverage and perceived policy influence for individual activists, but not for environmental movement organizations. This case raises fundamental theoretical questions about the nature of relations between media and policy spheres, and the efficacy of media for signaling and mobilizing policy influence. [ABSTRACT FROM AUTHOR]

Two separate and distinct diamictite-rich units occur in the mixed carbonate-siliciclastic Polarisbreen Group, which comprises the top kilometer of >7 km of Neoproterozoic strata in the northeast of the Svalbard archipelago. The platformal succession accumulated on the windward, tropical to subtropical margin of Laurentia. The older Petrovbreen Member is a thin glacimarine diamictite that lacks a cap carbonate. It contains locally derived clasts and overlies a regional karstic disconformity that was directly preceded by a large (>10‰) negative δ13C anomaly in the underlying shallow-marine carbonates. This anomaly is homologous to anomalies in Australia, Canada and Namibia that precede the Marinoan glaciation. The younger and thicker Wilsonbreen Formation comprises terrestrial ice-contact deposits. It contains abundant extrabasinal clasts and is draped by a transgressive cap dolostone 3–18 m thick. The cap dolostone is replete with sedimentary features strongly associated with post-Marinoan caps globally, and its isotopic profile is virtually identical to that of other Marinoan cap dolostones. From the inter-regional perspective, the two diamictite-rich units in the Polarisbreen Group should represent the first and final phases of the Marinoan glaciation. Above the Petrovbreen diamictite are ∼200 m of finely laminated, dark olive-coloured rhythmites (MacDonaldryggen Member) interpreted here to represent suspension deposits beneath shorefast, multi-annual sea ice (sikussak). Above the suspension deposits and below the Wilsonbreen diamictites is a <30-m-thick regressive sequence (Slangen Member) composed of dolomite grainstone and evaporitic supratidal microbialaminite. We interpret this sabkha-like lagoonal sequence as an oasis deposit that precipitated when local marine ice melted away under greenhouse forcing, but while the tropical ocean remained covered due to inflow of sea glaciers from higher latitudes. It appears that the Polarisbreen Group presents an unusually complete record of the Marinoan snowball glaciation. [ABSTRACT FROM AUTHOR]

Discusses the treatment of goods and services tax (GST) claims under Canada's principal insolvency statutes considered by the Ontario Superior Court of Justice in the case of Ottawa Senators Hockey Club Corp. filed on December 19, 2003. Provision on GST under the Excise Tax Act; Argument questioning the differential treatment of GST obligations; Other cases that form the basis of the court's ruling.

Examines the patterns of home-range size and habitat selection of American marten in southeastern Labrador, a region of extensive and pristine forests. Availability of habitat types with their use; Variation in home-range size at two scales; Association between marten and dense-canopy coniferous forests.

BACKGROUND: Between-country variation in health care resource use and its impact on outcomes in acute care settings have been challenging to disentangle from illness severity by using administrative data. METHODS: We conducted a preplanned analysis employing patient-level emergency department (ED) data from children enrolled in 2 previously conducted clinical trials. Participants aged 3 to <48 months with <72 hours of gastroenteritis were recruited in pediatric EDs in the United States (N = 10 sites; 588 participants) and Canada (N = 6 sites; 827 participants). The primary outcome was an unscheduled health care provider visit within 7 days; the secondary outcomes were intravenous fluid administration and hospitalization at or within 7 days of the index visit. RESULTS: In adjusted analysis, unscheduled revisits within 7 days did not differ (adjusted odds ratio [aOR]: 0.72; 95% confidence interval (CI): 0.50 to 1.02). At the index ED visit, although participants in Canada were assessed as being more dehydrated, intravenous fluids were administered more frequently in the United States (aOR: 4.6; 95% CI: 2.9 to 7.1). Intravenous fluid administration rates did not differ after enrollment (aOR: 1.4; 95% CI: 0.7 to 2.8; US cohort with Canadian as referent). Overall, intravenous rehydration was higher in the United States (aOR: 3.8; 95% CI: 2.5 to 5.7). Although hospitalization rates during the 7 days after enrollment (aOR: 1.1; 95% CI: 0.4 to 2.6) did not differ, hospitalization at the index visit was more common in the United States (3.9% vs 2.3%; aOR: 3.2; 95% CI: 1.6 to 6.8). CONCLUSIONS: Among children with gastroenteritis and similar disease severity, revisit rates were similar in our 2 study cohorts, despite lower rates of intravenous rehydration and hospitalization in Canadian-based EDs. [ABSTRACT FROM AUTHOR]

The vision of Chandler (Chan) S. Robbins for a continental-scale omnibus survey of breeding birds led to the development of the North American Breeding Bird Survey (BBS). Chan was uniquely suited to develop the BBS. His position as a government scientist had given him experience with designing and Implementing continental-scale surveys, his research background made him an effective advocate of the need for a survey to monitor pesticide effects on birds, and his prominence In the birding community gave him connections to Infrastructure--a network of qualified volunteer birders who could conduct roadside surveys with standardized point counts. Having started In the eastern United States and the Atlantic provinces of Canada In 1966, the BBS now provides population change Information for ~546 species In the continental United States and Canada, and recently Initiated routes In Mexico promise to greatly expand the areas and species covered by the survey. Although survey protocols have remained unchanged for 50 years, the BBS remains relevant In a changing world. Several papers that follow In this Special Section of The Condor: Ornithological Advances review how the BBS has been applied to conservation assessments, especially In combination with other large-scale survey data. A critical feature of the BBS program Is an active research program Into field and analytical methods to enhance the quality of the count data and to control for factors that Influence detectability. Papers In the Special Section also present advances In BBS analyses that Improve the utility of this expanding and sometimes controversial survey. In this Perspective, we Introduce the Special Section by reviewing the history of the BBS, describing current analyses, and providing summary trend results for all species, highlighting 3 groups of conservation concern: grassland-breeding birds, arldland-breedlng birds, and aerial Insectivorous birds. [ABSTRACT FROM AUTHOR]

The North American Breeding Bird Survey (BBS) was established in 1966 in response to a lack of quantitative data on changes in the populations of many bird species at a continental scale, especially songbirds. The BBS now provides the most reliable regional and continental trends and annual indices of abundance available for >500 bird species. This paper reviews some of the ways in which BBS data have contributed to bird conservation in North America over the past 50 yr, and highlights future program enhancement opportunities. BBS data have contributed to the listing of species under the Canadian Species at Risk Act and, in a few cases, have informed species assessments under the U.S. Endangered Species Act. By raising awareness of population changes, the BBS has helped to motivate bird conservation efforts through the creation of Partners in Flight. BBS data have been used to determine priority species and locations for conservation action at regional and national scales through Bird Conservation Region strategies and Joint Ventures. Data from the BBS have provided the quantitative foundation for North American State of the Birds reports, and have informed the public with regard to environmental health through multiple indicators, such as the Canadian Environmental Sustainability Indicators and the U.S. Environmental Protection Agency's Report on the Environment. BBS data have been analyzed with other data (e.g., environmental, land cover, and demographic) to evaluate potential drivers of population change, which have then informed conservation actions. In a few cases, BBS data have contributed to the evaluation of management actions, including informing the management of Mourning Doves (Zenaida macroura}, Wood Ducks (Aix sponsa}, and Golden Eagles (Aquila chrysaetos}. Improving geographic coverage in northern Canada and in Mexico, improving the analytical approaches required to integrate data from other sources and to address variation in detectability, and completing the database, by adding historical bird data at each point count location and pinpointing the current point count locations would further enhance the survey's value. [ABSTRACT FROM AUTHOR]

[Display omitted] An international sampling study yielded 69 samples of extended-release prescription pharmaceuticals for legal sale in the U.S. Samples included 29 lots of innovator and 40 lots of generic solid oral extended-release drugs manufactured at 16 different facilities and containing 6 different active ingredients. Dosage unit uniformity and dissolution were tested for each lot. All samples met the relevant testing criteria for dosage unit uniformity and dissolution. There were no indications that manufacturer or region impacted a product's acceptability for use by patients. The variability of attributes was used to calculate a process performance index (Ppk) for each facility. Higher Ppk values suggest less variability relative to specification limits. Only two manufacturers fell below a 4-sigma manufacturing benchmark Ppk of 1.33 for dosage unit uniformity: a European manufacturer of a brand drug and an Asian manufacturer of a generic drug. Conversely, all but four manufacturers fell below a 4-sigma benchmark for the minimum Ppk across their product's dissolution timepoints: generic drug manufacturers in India (two), the U.S., and Canada. Compared to the immediate-release products of a previous study, Ppks were generally lower for extended-release products. A retrospective analysis found that manufacturers performing below median Ppks submitted more Field Alert Reports after the end of the sampling period. [ABSTRACT FROM AUTHOR]

Abstract: In some basalt flows of the 1.1-billion-year-old Keweenawan Rift exposed at Mamainse Point, Ontario, there is a magnetic phase that holds a remanence antiparallel to the populations of magnetite and hematite that are typical of flows in the succession. The paleomagnetic and geological context of this component demonstrates that it is not a chemical overprint whose remanence is attributable to a subsequently reversed geomagnetic field, but that the component is a self-reversal of the primary magnetization. Here we use rock magnetic experiments and Mössbauer spectroscopy to show that this phase occurs in the most oxidized flows and is held by a fine-grained population of hematite that acquired its self-reversed remanence through interactions with a phase of lower blocking temperature. We propose that this self-reversed hematite is a manifestation of the self-reversal phenomena that has been observed to occur experimentally during the transformation of maghemite to hematite and that has been attributed to negative exchange coupling across the crystal lattices. We suggest that hematite formed in association with iron-silicates in the basalt flows carries a remanence reflective of the field in which it formed, but that martite (hematite pseudomorphed after magnetite) which formed through the progressive oxidation of magnetite to maghemite with subsequent inversion to hematite carries the self-reversed remanence. This study marks the second time that a naturally occurring self-reversed magnetization has been attributed to this mechanism and marks the oldest reported instance of any type of self-reversed remanence. The martite that forms through this process has the ability to retain a record of the negative exchange coupling from the time of its formation for hundreds of millions of years. [Copyright &y& Elsevier]

Glacial deposits of Sturtian and Marinoan age occur in the well-studied Neoproterozoic successions of northern Namibia, South Australia, and northwestern Canada. In all three regions, the Marinoan glaciation is presaged by a large negative δ13C anomaly, and the cap carbonates to both glacial units share a suite of unique sedimentological, stratigraphic, and geochemical features. These global chronostratigraphic markers are the bases of a new correlation scheme for the Neoproterozoic that corroborates radiometric data that indicate that there were three glacial epochs between ca. 750 and 580 Ma. Intraregional correlation of Neoproterozoic successions in the present-day North Atlantic region suggests that glacial diamictite pairs in the Polarisbreen Group in northeastern Svalbard and the Tillite Group in eastern Greenland were deposited during the Marinoan glaciation, whereas the younger of a pair of glacials (Mortensnes Formation) in the Vestertana Group of northern Norway was deposited during the third (Gaskiers) Neoproterozoic glaciation. Gaskiers-aged glacial deposits are neither globally distributed nor overlain by a widespread cap carbonate but are associated with an extremely negative δ13C anomaly. The chronology developed here provides the framework for a new, high-resolution model carbon-isotope record for the Neoproterozoic comprising new δ13C (carbonate) data from Svalbard (Akademikerbreen Group) and Namibia (Otavi Group) and data in the literature from Svalbard, Namibia, and Oman. A new U-Pb zircon age of 760 ± 1 Ma from an ash bed in the Ombombo Subgroup in Namibia provides the oldest direct time-calibration point in the compilation, but the time scale of this preliminary δ13C record remains poorly constrained. [ABSTRACT FROM AUTHOR]

The Neoproterozoic was an era of great environmental and biological change, but a paucity of direct and precise age constraints on strata from this time has prevented the complete integration of these records. We present four high-precision U-Pb ages for Neoproterozoic rocks in northwestern Canada that constrain large perturbations in the carbon cycle, a major diversification and depletion in the microfossil record, and the onset of the Sturtian glaciation. A volcanic tuff interbedded with Sturtian glacial deposits, dated at 716.5 million years ago, is synchronous with the age of the Franklin large igneous province and paleomagnetic poles that pin Laurentia to an equatorial position. Ice was therefore grounded below sea level at very low paleolatitudes, which implies that the Sturtian glaciation was global in extent. [ABSTRACT FROM AUTHOR]

Agriculture is one the main drivers of bird decline in both Europe and North America. While it is clear that agricultural practices and changes in the rural landscape directly and indirectly affect bird communities, we still do not know the extent to which these impacts might change across broad spatial and temporal scales. To address this question, we combined information on agricultural activities with occurrence and abundance of 358 bird species across five time periods spanning 20 years in Canada. As a proxy for agricultural impact, we used a combined index that included different agricultural metrics, such as cropland and tillage area and area treated with pesticides. We found that agriculture impact was negatively associated with bird diversity and evenness across all 20 years studied, but these associations seemed to vary by region. We found good support for an overall negative association between agriculture impact and bird diversity and evenness in the Eastern and Atlantic regions but weaker associations in the Prairies and Pacific. These findings suggest that agricultural activities result in bird communities that are less diverse and disproportionately benefit certain species. The spatial variation in the impact of agriculture on bird diversity and evenness we observed is likely a result of regional differences in the native vegetation, the type of crops and commodities produced, the historical context of agriculture, as well as the native bird community and the extent of their association with open habitat. Thus, our work provides support for the idea that the on-going agricultural impact on bird communities, while largely negative, is not uniform, and can vary across broad geographic regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: It is unknown if probiotics exert pathogen-specific effects in children with diarrhea secondary to acute gastroenteritis., Methods: Analysis of patient-level data from 2 multicenter randomized, placebo controlled trials conducted in pediatric emergency departments in Canada and the United States. Participants were 3-48 months with >3 diarrheal episodes in the preceding 24 hours and were symptomatic for <72 hours and <7 days in the Canadian and US studies, respectively. Participants received either placebo or a probiotic preparation (Canada-Lactobacillus rhamnosus R0011/Lactobacillus helveticus R0052; US-L. rhamnosus GG). The primary outcome was post-intervention moderate-to-severe disease (ie, ≥9 on the Modified Vesikari Scale [MVS] score)., Results: Pathogens were identified in specimens from 59.3% of children (928/1565). No pathogen groups were less likely to experience an MVS score ≥9 based on treatment allocation (test for interaction = 0.35). No differences between groups were identified for adenovirus (adjusted relative risk [aRR]: 1.42; 95% confidence interval [CI]: .62, 3.23), norovirus (aRR: 0.98; 95% CI: .56, 1.74), rotavirus (aRR: 0.86; 95% CI: .43, 1.71) or bacteria (aRR: 1.19; 95% CI: .41, 3.43). At pathogen-group and among individual pathogens there were no differences in diarrhea duration or the total number of diarrheal stools between treatment groups, regardless of intervention allocation or among probiotic sub-groups. Among adenovirus-infected children, those administered the L. rhamnosus R0011/L. helveticus R0052 product experienced fewer diarrheal episodes (aRR: 0.65; 95% CI: .47, .90)., Conclusions: Neither probiotic product resulted in less severe disease compared to placebo across a range of the most common etiologic pathogens. The preponderance of evidence does not support the notion that there are pathogen specific benefits associated with probiotic use in children with acute gastroenteritis., Clinical Trials Registration: NCT01773967 and NCT01853124., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Many have examined the desirability and mate competition tactics of adults higher on psychopathy using cross-sectional data, but few have studied the longitudinal associations between the lower-order factors of psychopathy (e.g., primary and secondary psychopathy) with indices of mating behavior in adolescents. More work is also needed to unravel how psychopathic youth outcompete rivals for mates. Delinquency has long been associated with dating and sexual behavior in adolescents, which may help to explain the competitive success of youth higher in psychopathic traits in vying for mates. We used cross-lagged panel modeling with three waves of data from a randomly drawn sample of 514 Canadian adolescents who provided annual self-reports of primary and secondary psychopathy, delinquency, and dating involvement from Grades 10 to 12 (15-18 years of age). Constructs were temporally stable. Secondary psychopathy and delinquency had positive within-time correlations with current dating status in Grade 10. A cross-lagged pathway from delinquency to dating involvement was supported from Grade 10 to 11, which replicated from Grade 11 to 12. However, this effect was specific to boys and not girls. An indirect effect also emerged whereby secondary psychopathy in Grade 10 increased the likelihood of being in a dating relationship in Grade 12 via heightened delinquency in Grade 11.

Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all advanced stage non-squamous NSCLC patients be also tested for ROS1 gene rearrangements. Several studies have suggested that ROS1 immunohistochemistry (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung cancers, with assays showing high sensitivity but moderate to high specificity. A break apart fluorescence in situ hybridization (FISH) test is then used to confirm the presence of ROS1 gene rearrangement. The goal of Canadian ROS1 (CROS) study was to harmonize ROS1 laboratory developed testing (LDT) by using IHC and FISH assays to detect ROS1 rearranged lung cancers across Canadian pathology laboratories. Cell lines expressing different levels of ROS1 (high, low, none) were used to calibrate IHC protocols after which participating laboratories ran the calibrated protocols on a reference set of 24 NSCLC cases (9 ROS1 rearranged tumors and 15 ROS1 non-rearranged tumors as determined by FISH). Results were compared using a centralized readout. The stained slides were evaluated for the cellular localization of staining, intensity of staining, the presence of staining in non-tumor cells, the presence of non-specific staining (e.g. necrosis, extracellular mater, other) and the percent positive cells. H-score was also determined for each tumor. Analytical sensitivity and specificity harmonization was achieved by using low limit of detection (LOD) as either any positivity in the U118 cell line or H-score of 200 with the HCC78 cell line. An overall diagnostic sensitivity and specificity of up to 100% and 99% respectively was achieved for ROS1 IHC testing (relative to FISH) using an adjusted H-score readout on the reference cases. This study confirms that LDT ROS1 IHC assays can be highly sensitive and specific for detection of ROS1 rearrangements in NSCLC. As NSCLC can demonstrate ROS1 IHC positivity in FISH-negative cases, the degree of the specificity of the IHC assay, especially in highly sensitive protocols, is mostly dependent on the readout cut-off threshold. As ROS1 IHC is a screening assay for a rare rearrangements in NSCLC, we recommend adjustment of the readout threshold in order to balance specificity, rather than decreasing the overall analytical and diagnostic sensitivity of the protocols., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

ROS1 rearrangements are identified in 1-2% of lung adenocarcinoma cases, and reflex testing is guideline-recommended. We developed a decision model for population-based ROS1 testing from a Canadian public healthcare perspective to determine the strategy that optimized detection of true-positive (TP) cases while minimizing costs and turnaround time (TAT). Eight diagnostic strategies were compared, including reflex single gene testing via immunohistochemistry (IHC) screening, fluorescence in-situ hybridization (FISH), next-generation sequencing (NGS), and biomarker-informed ( EGFR/ALK/KRAS wildtype) testing initiated by pathologists and clinician-initiated strategies. Reflex IHC screening with FISH confirmation of positive cases yielded the best results for TAT, TP detection rate, and cost. IHC screening saved CAD 1,000,000 versus reflex FISH testing. NGS was the costliest reflex strategy. Biomarker-informed testing was cost-efficient but delayed TAT. Clinician-initiated testing was the least costly but resulted in long TAT and missed TP cases, highlighting the importance of reflex testing. Thus, reflex IHC screening for ROS1 with FISH confirmation provides a cost-efficient strategy with short TAT and maximizes the number of TP cases detected.

Importance: Despite guidelines endorsing oral rehydration therapy, intravenous fluids are commonly administered to children with acute gastroenteritis in high-income countries., Objective: To identify factors associated with intravenous fluid administration and hospitalization in children with acute gastroenteritis., Design, Setting, and Participants: This study is a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) probiotic trials. Participants include children aged 3 to 48 months with 3 or more watery stools in 24 hours between November 5, 2013, and April 7, 2017, for the PERC study and July 8, 2014, and June 23, 2017, for the PECARN Study. Children were from 16 pediatric emergency departments throughout Canada (6) and the US (10). Data were analyzed from November 2, 2018, to March 16, 2021., Exposures: Sex, age, preceding health care visit, distance between home and hospital, country (US vs Canada), frequency and duration of vomiting and diarrhea, presence of fever, Clinical Dehydration Scale score, oral ondansetron followed by oral rehydration therapy, and infectious agent., Main Outcomes and Measures: Intravenous fluid administration and hospitalization., Results: This secondary analysis of 2 randomized clinical trials included 1846 children (mean [SD] age, 19.1 [11.4] months; 1007 boys [54.6%]), of whom 534 of 1846 (28.9%) received oral ondansetron, 240 of 1846 (13.0%) received intravenous rehydration, and 67 of 1846 (3.6%) were hospitalized. The following were independently associated with intravenous rehydration: higher Clinical Dehydration Scale score (mild to moderate vs none, odds ratio [OR], 8.73; 95% CI, 5.81-13.13; and severe vs none, OR, 34.15; 95% CI, 13.45-86.73); country (US vs Canada, OR, 6.76; 95% CI, 3.15-14.49); prior health care visit with intravenous fluids (OR, 4.55; 95% CI, 1.32-15.72); and frequency of vomiting (per 5 episodes, OR, 1.66; 95% CI, 1.39-1.99). The following were independently associated with hospitalization: higher Clinical Dehydration Scale score (mild to moderate vs none, OR, 11.10; 95% CI, 5.05-24.38; and severe vs none, OR, 23.55; 95% CI, 7.09-78.25) and country (US vs Canada, OR, 3.37; 95% CI, 1.36-8.40). Oral ondansetron was associated with reduced odds of intravenous rehydration (OR, 0.21; 95% CI, 0.13-0.32) and hospitalization (OR, 0.44; 95% CI, 0.21-0.89)., Conclusions and Relevance: Intravenous rehydration and hospitalization were associated with clinical evidence of dehydration and lack of an oral ondansetron-supported oral rehydration period. Strategies focusing on oral ondansetron administration followed by oral rehydration therapy in children with dehydration may reduce the reliance on intravenous rehydration and hospitalization., Trial Registration: ClinicalTrials.gov Identifiers: NCT01853124 (PERC) and NCT01773967 (PECARN).

Background: The presence of anaplastic lymphoma kinase (ALK) rearrangement predicts response to ALK tyrosine kinase inhibitor (TKI) therapy. Fluorescence in situ hybridization (FISH) was the initial reference standard to detect ALK rearrangement, but immunohistochemistry (IHC) using D5F3 has gained acceptance as an alternative diagnostic method. ALK IHC assays using other ALK antibodies have also been used as screening methods, but data supporting their utility as diagnostic tests have not been widely reported., Methods: Data from reflexive clinical ALK IHC test using the 5A4 clone concurrent with epidermal growth factor receptor (EGFR) mutation testing were analyzed. ALK IHC results were reported as negative (-), equivocal, or positive (+), with equivocal or positive staining validated by FISH break-apart probe testing. Treatment outcomes were reviewed for ALK IHC+ patients., Results: Between 2012 and 2015, 146 (2.5%) cases were reported as ALK IHC+, 188 (3.2%) were reported as equivocal, and 5624 (94.4%) were reported as ALK IHC-. Of the ALK IHC+ cases, 131/143(91.6%) were ALK FISH+. Excluding 6 cases in which FISH was inconclusive or not performed, the positive predictive value was 95.6%, and the negative predictive value was 100%. Most specimens (n = 5352 [89.6%]) were also successfully tested for EGFR. Clinical responses to ALK TKIs were noted in 49 ALK IHC+ patients, with a median progression-free survival of 9.9 months., Conclusions: ALK 5A4 IHC can serve as a robust diagnostic test for ALK-rearranged lung cancer and is associated with treatment response and survival. Optimized tissue allocation resulted in high success rates of combined reflex EGFR and ALK testing., (© 2019 American Cancer Society.)

Species extinctions have defined the global biodiversity crisis, but extinction begins with loss in abundance of individuals that can result in compositional and functional changes of ecosystems. Using multiple and independent monitoring networks, we report population losses across much of the North American avifauna over 48 years, including once-common species and from most biomes. Integration of range-wide population trajectories and size estimates indicates a net loss approaching 3 billion birds, or 29% of 1970 abundance. A continent-wide weather radar network also reveals a similarly steep decline in biomass passage of migrating birds over a recent 10-year period. This loss of bird abundance signals an urgent need to address threats to avert future avifaunal collapse and associated loss of ecosystem integrity, function, and services., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Importance: Pediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes., Objective: To evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer., Design, Setting, and Participants: This cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials. RNA sequencing (RNA-Seq) data were obtained from the following 4 clinical sites and analyzed at UCSC: British Columbia Children's Hospital (n = 31), Lucile Packard Children's Hospital at Stanford University (n = 80), CHOC Children's Hospital and Hyundai Cancer Institute (n = 46), and the Pacific Pediatric Neuro-Oncology Consortium (n = 24). The study dates were January 1, 2016, to March 22, 2017., Exposures: Participants underwent tumor RNA-Seq profiling as part of 4 separate clinical trials at partner hospitals. The UCSC either downloaded RNA-Seq data from a partner institution for analysis in the cloud or provided a Docker pipeline that performed the same analysis at a partner institution. The UCSC then compared each participant's tumor RNA-Seq profile with more than 11 000 uniformly analyzed tumor profiles from pediatric and young adult patients with cancer, downloaded from public data repositories. These comparisons were used to identify genes and pathways that are significantly overexpressed in each patient's tumor. Results of the UCSC analysis were presented to clinical partners., Main Outcomes and Measures: Feasibility of a third-party institution (UCSC Treehouse Childhood Cancer Initiative) to obtain tumor RNA-Seq data from patients, conduct comparative analysis, and present analysis results to clinicians; and proportion of patients for whom comparative tumor gene expression analysis provided useful clinical and biological information., Results: Among 144 samples from children and young adults (median age at diagnosis, 9 years; range, 0-26 years; 72 of 118 [61.0%] male [26 patients sex unknown]) with a relapsed, refractory, or rare cancer treated on precision medicine protocols, RNA-Seq-derived gene expression was potentially useful for 99 of 144 samples (68.8%) compared with DNA mutation information that was potentially useful for only 34 of 74 samples (45.9%)., Conclusions and Relevance: This study's findings suggest that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into the clinical genomic interpretation framework for difficult-to-treat pediatric and young adult patients with cancer. The study also highlights for the first time to date the potential clinical utility of harmonized publicly available genomic data sets.

Background and Objectives: Management practices for acute appendicitis are changing. In cases of nonoperative treatment, the risk of missed or delayed diagnosis of malignancy should be considered. We aimed to identify predictors associated with appendiceal cancer diagnosis after appendectomy for acute appendicitis., Materials and Methods: This retrospective cohort study was performed using the National Surgical Quality Improvement Program (NSQIP) appendectomy-targeted data set from 2016 to 2017. A total of 21 069 patients with imaging-confirmed or imaging indeterminate appendicitis who underwent appendectomy were included. Logistic regression was used to identify predictors of cancer diagnosis., Results: Increasing age had an increasing monotonic relationship with the odds of pathologic cancer diagnosis after appendectomy (age 50-59 odds ratio [OR], 2.08, 95% confidence interval [CI], 1.28-3.39, P = .003; age 60-69 OR, 2.89, 95% CI, 1.72-4.83, P < .001; age 70-79 OR, 3.85, 95% CI, 2.08-7.12, P < .001; age >80 OR, 5.32, 95% CI, 2.38-11.9, P < .001). Other significant predictors included obesity, morbid obesity, normal preoperative white blood cell count, and imaging indeterminate for appendicitis., Conclusions: When counseling patients regarding operative vs nonoperative treatment options for management of acute appendicitis, the rising risk of a delayed or missed cancer diagnosis with increasing age must be discussed., (© 2019 Wiley Periodicals, Inc.)

Climate change will have profound and unanticipated effects on species distributions. The pace and nature of this change is largely unstudied, especially for the most diverse elements of terrestrial communities--the arthropods--here we have only limited knowledge concerning the taxonomy and the ecology of these groups. Because Arctic ecosystems have already experienced significant increases in temperature over the past half century, shifts in community structure may already be in progress. Here we utilise collections of a particularly hyperdiverse insect group--parasitoid wasps (Hymenoptera; Braconidae; Microgastrinae)--at Churchill, Manitoba, Canada in the early and mid-twentieth century to compare the composition of the contemporary community to that present 50-70 years ago. Morphological and DNA barcoding results revealed the presence of 79 species of microgastrine wasps in collections from Churchill, but we estimate that 20% of the local fauna awaits detection. Species composition and diversity between the two time periods differ significantly; species that were most common in historic collections were not found in contemporary collections and vice versa. Using barcodes we compared these collections to others from across North America; contemporary Churchill species are most affiliated with more south-western collections, while historic collections were more affiliated with eastern collections. The past five decades has clearly seen a dramatic change of species composition within the area studied coincident with rising temperature.