POTENTIAL HEALTHCARE SAVINGS FROM PLANT STEROL ENRICHED FOODS IN CANADA

Increased consumption of foods containing plant sterols has the potential to reduce the incidence of coronary heart disease (CHD) and thus reduce costs associated with treating that disease in a significant way. This paper reports the results of an investigation of the potential monetary benefits of allowing foods enriched with plant sterols to be marketed in Canada. The objective of this research was to estimate the annual savings that would accrue to Canada’s single-payer publicly funded health care system if plant sterols were approved for use. If foods containing plant sterols are consumed at a sufficient rate, a reduction in CHD should follow. This research employs a variation of traditional cost-of-illness analysis entailing four steps: (i) estimation of a “success rate” (proportion of persons who would consume plant sterols at the necessary rate); (ii) presumption of blood cholesterol reduction due to plant sterol consumption; (iii) assumption of reduction in CHD that follows from blood cholesterol reduction; (iv) calculation of cost savings associated with reduced incidence of CHD. Calculations were carried out for four scenarios: ideal, optimistic, pessimistic, and very pessimistic. It was estimated that between $38 million (very pessimistic scenario) and$2.45 billion (ideal scenario) could be saved annually by Canada’s health care system with plant sterol enriched food products being made available for sale.coronary heart disease, cost of illness analysis, health care costs, success rate, Agricultural and Food Policy, Consumer/Household Economics, Demand and Price Analysis, Food Consumption/Nutrition/Food Safety, Food Security and Poverty, Health Economics and Policy, I18,

P-Wave Charmonium Production in B-Meson Decays

We calculate the decay rates of $B$ mesons into P-wave charmonium states using new factorization formulas that are valid to leading order in the relative velocity of the charmed quark and antiquark and to all orders in the running coupling constant of QCD. We express the production rates for all four P states in terms of two nonperturbative parameters, the derivative of the wavefunction at the origin and another parameter related to the probability for a charmed-quark-antiquark pair in a color-octet S-wave state to radiate a soft gluon and form a P-wave bound state. Using existing data on $B$ meson decays into $\chi_{c1}$ to estimate the color-octet parameter, we find that the color-octet mechanism may account for a significant fraction of the $\chi_{c1}$ production rate and that $B$ mesons should decay into $\chi_{c2}$ at a similar rate.Comment: 14 page

Economic valuation of the potential health benefits from foods enriched with plant sterols in Canada

Background: Increased consumption of foods containing plant sterols has the potential to reduce the incidence of coronary heart disease (CHD) and thus reduce costs associated with treating that disease in a significant way. This paper reports the results of an investigation of the potential monetary benefits of allowing foods enriched with plant sterols to be marketed in Canada. Objective: The objective of this research was to estimate the annual savings that would accrue to Canada's single-payer publicly funded health care system if plant sterols were approved for use. If foods containing plant sterols are consumed at a sufficient rate, a reduction in CHD should follow. Given the significant costs associated with CHD, approval of plant sterols in Canada has important public policy implications. Design: This research employs a variation of traditional cost-of-illness analysis entailing four steps: (1) estimation of a ‘success rate’ (proportion of persons who would consume plant sterols at the necessary rate); (2) presumption of blood cholesterol reduction due to plant sterol consumption; (3) assumption of reduction in CHD that follows from blood cholesterol reduction; and (4) calculation of cost savings associated with reduced incidence of CHD. Results: Calculations were carried out for four scenarios: ideal, optimistic, pessimistic, and very pessimistic. It was estimated that between $38 million (very pessimistic scenario) and $2.45 billion (ideal scenario) could be saved annually by Canada's health care system with plant sterol-enriched food products being made available for sale. Conclusion: Significant expenditure reductions within Canada's publicly funded health care system could be realized with plant sterols approved for sale. Reduced CHD resulting from lower blood cholesterol levels would lessen the financial burden of disease in Canada

CNTN4 modulates neural elongation through interplay with APP

The neuronal cell adhesion molecule contactin-4 (CNTN4) is genetically associated with autism spectrum disorder (ASD) and other psychiatric disorders. Cntn4-deficient mouse models have previously shown that CNTN4 plays important roles in axon guidance and synaptic plasticity in the hippocampus. However, the pathogenesis and functional role of CNTN4 in the cortex has not yet been investigated. Our study found a reduction in cortical thickness in the motor cortex of Cntn4 -/- mice, but cortical cell migration and differentiation were unaffected. Significant morphological changes were observed in neurons in the M1 region of the motor cortex, indicating that CNTN4 is also involved in the morphology and spine density of neurons in the motor cortex. Furthermore, mass spectrometry analysis identified an interaction partner for CNTN4, confirming an interaction between CNTN4 and amyloid-precursor protein (APP). Knockout human cells for CNTN4 and/or APP revealed a relationship between CNTN4 and APP. This study demonstrates that CNTN4 contributes to cortical development and that binding and interplay with APP controls neural elongation. This is an important finding for understanding the physiological function of APP, a key protein for Alzheimer's disease. The binding between CNTN4 and APP, which is involved in neurodevelopment, is essential for healthy nerve outgrowth

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

SJS/TEN 2019: From Science to Translation

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

The British Army, information management and the First World War revolution in military affairs

Information Management (IM) – the systematic ordering, processing and channelling of information within organisations – forms a critical component of modern military command and control systems. As a subject of scholarly enquiry, however, the history of military IM has been relatively poorly served. Employing new and under-utilised archival sources, this article takes the British Expeditionary Force (BEF) of the First World War as its case study and assesses the extent to which its IM system contributed to the emergence of the modern battlefield in 1918. It argues that the demands of fighting a modern war resulted in a general, but not universal, improvement in the BEF’s IM techniques, which in turn laid the groundwork, albeit in embryonic form, for the IM systems of modern armies. KEY WORDS: British Army, Information Management, First World War, Revolution in Military Affairs, Adaptatio

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Intermittent PI3Ko inhibition sustains anti-tumor immunity and curbs irAEs

YesPhosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1–3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity