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This paper presents the empirical analysis of property values across a sample of 228 leaseholds and 79 Certificates of Possession (CP) on 34 First Nation Reserves. The property values were benchmarked against a sample of 338 fee simple property sales in 34 comparable non-Indigenous communities. The results were that leaseholds were discounted 17-75% (with a mean of 24%) and CPs were discounted 65-98% (with a mean of 88%). Data across 14 factors was used to analyze trends in property values. Three trends were noteworthy: (1) Leasehold values were higher in communities where the community housing score (estimate of the quality of housing) was higher; (2) CP values were higher in communities where the ratio of informality was lower (estimate of the proportion of properties held by formalized rights under the Indian Act); and (3) Property values were higher when Chief and Council remuneration was higher. The steep discounts observed here must spur research into the viability of existing land tenure/registration systems on First Nation Reserves and into the merits of new institutions to serve First Nations.

This paper presents the empirical analysis of property values across a sample of 228 leaseholds and 79 Certificates of Possession (CP) on 34 First Nation Reserves. The property values were benchmarked against a sample of 338 fee simple property sales in 34 comparable non-Indigenous communities. The results were that leaseholds were discounted 17-75% (with a mean of 24%) and CPs were discounted 65-98% (with a mean of 88%). Data across 14 factors was used to analyze trends in property values. Three trends were noteworthy: (1) Leasehold values were higher in communities where the community housing score (estimate of the quality of housing) was higher; (2) CP values were higher in communities where the ratio of informality was lower (estimate of the proportion of properties held by formalized rights under the Indian Act); and (3) Property values were higher when Chief and Council remuneration was higher. The steep discounts observed here must spur research into the viability of existing land tenure/registration systems on First Nation Reserves and into the merits of new institutions to serve First Nations.

The courts have consistently held that the process of erosion reduces the area of the riparian parcel, and that the water boundary is ambulatory. If, however, the parcel is not riparian when it is granted, what is its status upon the encroachment of water? Does the monumented boundary over which the water encroaches remain a fixed line defining one side of the parcel? The only Canadian case that deals with these questions, is the 1912 trial of Volcanic Oil and Gas Co. v. Chaplin. The trial principle that the monumented line is fixed and is not affected by the action of the water is not well understood, perhaps because Volcanic was successfully appealed on the basis of facts not being proved, or because there is a body of American case law opposed to Volcanic. More commonly followed is the doctrine of submergence, in which the non-riparian parcel continues to extend to the original boundary. The maxim of mutuality means that the parcel should not suffer through erosion if it cannot gain by accretion. This is not to say that lengthy submergence might not vest title to the submerged parcel with the owner of the bed. This principle of abandonment recognises that upland acquires the character of the bed after long submergence, and that upland proprietors are obligated to assert their rights to the land. A case study of lot 9, concession 4, Ennismore township shows the effects of a controlled lake level on a riparian parcel. If the encroachment of water is sudden and perceptible, and is caused by artificial means, then the water boundary remains in its original location, at a contour below the present-day water level. (Abstract shortened by UMI.)

In a randomized trial involving patients at high cardiovascular risk, the cholesteryl ester transfer protein inhibitor obicetrapib reduced low-density lipoprotein cholesterol levels by 29.9% at 84 days.

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes. The pathobiology of heart failure (HF) is incompletely understood. The authors identify 37 circulating proteins and 5 protein modules associated with HF risk, with several demonstrating causal effects on HF, risk factors, or cardiac dysfunction by Mendelian randomization analysis.

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011–2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91 × 10−45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development.

Abstract Rationale Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality, although the underlying mechanisms are not well understood. Objectives We aimed to determine whether more severe OSA, measured by the Respiratory Disturbance Index (RDI), is associated with subclinical myocardial injury and increased myocardial wall stress. Methods A total of 1,645 participants (62.5 ± 5.5 yr and 54% women) free of coronary heart disease and heart failure and participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies underwent overnight polysomnography and measurement of high-sensitivity troponin T (hs-TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Measurements and Main Results OSA severity was defined using conventional clinical categories: none (RDI ≤ 5), mild (RDI 5–15), moderate (RDI 15–30), and severe (RDI > 30). Hs-TnT, but not NT-proBNP, was associated with OSA after adjusting for 17 potential confounders (P = 0.02). Over a median of 12.4 (interquartile range, 11.6–13.1) years follow-up, hs-TnT was related to risk of death or incident heart failure in all OSA categories (P ≤ 0.05 in each category). Conclusions In middle-aged to older individuals, OSA severity is independently associated with higher levels of hs-TnT, suggesting that subclinical myocardial injury may play a role in the association between OSA and risk of heart failure. OSA was not associated with NT-proBNP levels after adjusting for multiple possible confounders.

We present a catalog of hard X-ray serendipitous sources detected in the first 80 months of observations by the Nuclear Spectroscopic Telescope Array (NuSTAR). The NuSTAR serendipitous survey 80 month (NSS80) catalog has an unprecedented ∼62 Ms of effective exposure time over 894 unique fields (a factor of 3 increase over the 40 month catalog, NSS40), with an areal coverage of ∼36 deg2, larger than all NuSTAR extragalactic surveys. NSS80 provides 1274 hard X-ray sources in the 3−24 keV band (822 new detections compared to the previous NSS40). Approximately 76% of the NuSTAR sources have lower-energy (<10 keV) X-ray counterparts from Chandra, XMM-Newton, and Swift-XRT. We have undertaken an extensive campaign of ground-based spectroscopic follow-up to obtain new source redshifts and classifications for 427 sources. Combining these with existing archival spectroscopy provides redshifts for 550 NSS80 sources, of which 547 are classified. The sample is primarily composed of active galactic nuclei (AGNs), detected over a large range in redshift (z = 0.012–3.43), but also includes 58 spectroscopically confirmed Galactic sources. In addition, five AGN–galaxy pairs, one dual AGN system, one BL Lac candidate, and a hotspot of 4C 74.26 (radio quasar) have been identified. The median rest-frame 10−40 keV luminosity and redshift of NSS80 are 〈L 10−40 keV〉 = 1.2 × 1044 erg s−1 and 〈z〉 = 0.56. We investigate the optical properties and construct composite optical spectra to search for subtle signatures not present in the individual spectra, finding an excess of redder BL AGNs compared to optical quasar surveys, predominantly due to the presence of the host galaxy and, at least in part, due to dust obscuration.

Assignment of values for natural ecological benefits and anthropocentric ecosystem services in riverine landscapes has been problematic because a firm scientific basis linking these to the river's physical structure has been absent. We highlight some inherent problems in this process and suggest possible solutions on the basis of the hydrogeomorphic classification of rivers. We suggest this link can be useful in fair asset trading (mitigation and offsets), selection of sites for rehabilitation, cost-benefit decisions on incremental steps in restoring ecological functions, and general protection of rivers.