Long Overdue: A Reappraisal of Section 121 of the Constitution Act, 1867

This article offers a new interpretation of s. 121 of the Constitution Act, 1867. The author re-evaluates the traditional interpretation of s. 121, found in Gold Seal Limited v. The Attorney General of the Province of Alberta. That interpretation limited the application of s. 121 to prohibiting interprovincial customs duties but nothing else. The author analyzes s. 121 using a purposive approach. After reviewing the provision\u27s wording, legislative history, legislative context and its place within the scheme of the Act, the article concludes that a purposive and progressive interpretation leads to a more robust role for s. 121. Thus interpreted, s. 121 would prohibit any impediment to the free flow of goods across Canada and the imposition of any obligation on the movement of Canadian goods that in its essence is related to a provincial boundary, subject to regulation of subsidiary features. The author also analyzes Gold Seal and other s. 121 jurisprudence. He contends that the Supreme Court\u27s interpretation of s. 121 in Gold Seal is inconsistent with the modern purposive approach to constitutional interpretation and resulted from expediency

What do older people do when sitting and why? Implications for decreasing sedentary behaviour

Background and Objectives: Sitting less can reduce older adults’ risk of ill health and disability. Effective sedentary behavior interventions require greater understanding of what older adults do when sitting (and not sitting), and why. This study compares the types, context, and role of sitting activities in the daily lives of older men and women who sit more or less than average. Research Design and Methods: Semistructured interviews with 44 older men and women of different ages, socioeconomic status, and objectively measured sedentary behavior were analyzed using social practice theory to explore the multifactorial, inter-relational influences on their sedentary behavior. Thematic frameworks facilitated between-group comparisons. Results: Older adults described many different leisure time, household, transport, and occupational sitting and non-sitting activities. Leisure-time sitting in the home (e.g., watching TV) was most common, but many non-sitting activities, including “pottering” doing household chores, also took place at home. Other people and access to leisure facilities were associated with lower sedentary behavior. The distinction between being busy/not busy was more important to most participants than sitting/not sitting, and informed their judgments about high-value “purposeful” (social, cognitively active, restorative) sitting and low-value “passive” sitting. Declining physical function contributed to temporal sitting patterns that did not vary much from day-to-day. Discussion and Implications: Sitting is associated with cognitive, social, and/or restorative benefits, embedded within older adults’ daily routines, and therefore difficult to change. Useful strategies include supporting older adults to engage with other people and local facilities outside the home, and break up periods of passive sitting at home

Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls

Recurrent rearrangements of chromosome 1q21.1 that occur via non-allelic homologous recombination have been associated with variable phenotypes exhibiting incomplete penetrance, including congenital heart disease (CHD). However, the gene or genes within the ∼1 Mb critical region responsible for each of the associated phenotypes remains unknown. We examined the 1q21.1 locus in 948 patients with tetralogy of Fallot (TOF), 1488 patients with other forms of CHD and 6760 ethnically matched controls using single nucleotide polymorphism genotyping arrays (Illumina 660W and Affymetrix 6.0) and multiplex ligation-dependent probe amplification. We found that duplication of 1q21.1 was more common in cases of TOF than in controls [odds ratio (OR) 30.9, 95% confidence interval (CI) 8.9-107.6); P = 2.2 × 10−7], but deletion was not. In contrast, deletion of 1q21.1 was more common in cases of non-TOF CHD than in controls [OR 5.5 (95% CI 1.4-22.0); P = 0.04] while duplication was not. We also detected rare (n = 3) 100-200 kb duplications within the critical region of 1q21.1 in cases of TOF. These small duplications encompassed a single gene in common, GJA5, and were enriched in cases of TOF in comparison to controls [OR = 10.7 (95% CI 1.8-64.3), P = 0.01]. These findings show that duplication and deletion at chromosome 1q21.1 exhibit a degree of phenotypic specificity in CHD, and implicate GJA5 as the gene responsible for the CHD phenotypes observed with copy number imbalances at this locu

Phenotype-specific effect of chromosome 1q21.1 rearrangements and GJA5 duplications in 2436 congenital heart disease patients and 6760 controls

Recurrent rearrangements of chromosome 1q21.1 that occur via non-allelic homologous recombination have been associated with variable phenotypes exhibiting incomplete penetrance, including congenital heart disease (CHD). However, the gene or genes within the ∼1 Mb critical region responsible for each of the associated phenotypes remains unknown. We examined the 1q21.1 locus in 948 patients with tetralogy of Fallot (TOF), 1488 patients with other forms of CHD and 6760 ethnically matched controls using single nucleotide polymorphism genotyping arrays (Illumina 660W and Affymetrix 6.0) and multiplex ligation-dependent probe amplification. We found that duplication of 1q21.1 was more common in cases of TOF than in controls [odds ratio (OR) 30.9, 95% confidence interval (CI) 8.9–107.6); P = 2.2 × 10−7], but deletion was not. In contrast, deletion of 1q21.1 was more common in cases of non-TOF CHD than in controls [OR 5.5 (95% CI 1.4–22.0); P = 0.04] while duplication was not. We also detected rare (n = 3) 100–200 kb duplications within the critical region of 1q21.1 in cases of TOF. These small duplications encompassed a single gene in common, GJA5, and were enriched in cases of TOF in comparison to controls [OR = 10.7 (95% CI 1.8–64.3), P = 0.01]. These findings show that duplication and deletion at chromosome 1q21.1 exhibit a degree of phenotypic specificity in CHD, and implicate GJA5 as the gene responsible for the CHD phenotypes observed with copy number imbalances at this locus

Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine

Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10−7) and replicated convincingly (P = 3.9 × 10−5) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10−11 in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10−7) and replicated convincingly (P = 1.2 × 10−5) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10−11 in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TO

Primary irritant and delayed-contact hypersensitivity reactions to the freshwater cyanobacterium Cylindrospermopsis raciborskii and its associated toxin cylindrospermopsin

BACKGROUND: Freshwater cyanobacteria are common inhabitants of recreational waterbodies throughout the world; some cyanobacteria can dominate the phytoplankton and form blooms, many of which are toxic. Numerous reports in the literature describe pruritic skin rashes after recreational or occupational exposure to cyanobacteria, but there has been little research conducted on the cutaneous effects of cyanobacteria. Using the mouse ear swelling test (MEST), we sought to determine whether three toxin-producing cyanobacteria isolates and the purified cyanotoxin cylindrospermopsin produced delayed-contact hypersensitivity reactions. METHODS: Between 8 and 10 female Balb/c mice in each experiment had test material applied to depilated abdominal skin during the induction phase and 10 or 11 control mice had vehicle only applied to abdominal skin. For challenge (day 10) and rechallenge (day 17), test material was applied to a randomly-allocated test ear; vehicle was applied to the other ear as a control. Ear thickness in anaesthetised mice was measured with a micrometer gauge at 24 and 48 hours after challenge and rechallenge. Ear swelling greater than 20% in one or more test mice is considered a positive response. Histopathology examination of ear tissues was conducted by independent examiners. RESULTS: Purified cylindrospermopsin (2 of 9 test mice vs. 0 of 5 control mice; p = 0.51) and the cylindrospermopsin-producing cyanobacterium C. raciborskii (8 of 10 test mice vs. 0 of 10 control mice; p = 0.001) were both shown to produce hypersensitivity reactions. Irritant reactions were seen on abdominal skin at induction. Two other toxic cyanobacteria (Microcystis aeruginosa and Anabaena circinalis) did not generate any responses using this model. Histopathology examinations to determine positive and negative reactions in ear tissues showed excellent agreement beyond chance between both examiners (κ = 0.83). CONCLUSION: The irritant properties and cutaneous sensitising potential of cylindrospermopsin indicate that these toxicological endpoints should be considered by public health advisors and reservoir managers when setting guidelines for recreational exposure to cyanobacteria

Inclusive and differential cross-section measurements of t\bartZ production in pp collisions at √s=13 TeV with the ATLAS detector, including EFT and spin-correlation interpretations

Measurements of both the inclusive and differential production cross sections of a top-quark-top-antiquark pair in association with a Z boson (tt¯Z) are presented. Final states with two, three or four isolated leptons (electrons or muons) are targeted. The measurements use the data recorded by the ATLAS detector in pp collisions at s√=13 TeV at the Large Hadron Collider during the years 2015-2018, corresponding to an integrated luminosity of 140 fb−1. The inclusive cross section is measured to be σtt¯Z=0.86±0.04 (stat.)±0.04 (syst.) pb and found to be in agreement with the most advanced Standard Model predictions. The differential measurements are presented as a function of a number of observables that probe the kinematics of the tt¯Z system. Both the absolute and normalised differential cross-section measurements are performed at particle level and parton level for specific fiducial volumes, and are compared with NLO+NNLL theoretical predictions. The results are interpreted in the framework of Standard Model effective field theory and used to set limits on a large number of dimension-6 operators involving the top quark. The first measurement of spin correlations in tt¯Z events is presented: the results are in agreement with the Standard Model expectations, and the null hypothesis of no spin correlations is disfavoured with a significance of 1.8 standard deviations

Observation of quantum entanglement in top-quark pairs using the ATLAS detector

We report the highest-energy observation of entanglement, in top−antitop quark events produced at the Large Hadron Collider, using a proton−proton collision data set with a center-of-mass energy of s√=13 TeV and an integrated luminosity of 140 fb−1 recorded with the ATLAS experiment. Spin entanglement is detected from the measurement of a single observable D, inferred from the angle between the charged leptons in their parent top- and antitop-quark rest frames. The observable is measured in a narrow interval around the top−antitop quark production threshold, where the entanglement detection is expected to be significant. It is reported in a fiducial phase space defined with stable particles to minimize the uncertainties that stem from limitations of the Monte Carlo event generators and the parton shower model in modelling top-quark pair production. The entanglement marker is measured to be D=−0.547±0.002 (stat.)±0.021 (syst.) for 340<mtt¯<380 GeV. The observed result is more than five standard deviations from a scenario without entanglement and hence constitutes both the first observation of entanglement in a pair of quarks and the highest-energy observation of entanglement to date

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection