Treatment of type 2 diabetes by free fatty acid receptor agonists

Dietary free fatty acids (FFAs), such as ω-3 fatty acids, regulate metabolic and anti-inflammatory processes, with many of these effects attributed to FFAs interacting with a family of G protein-coupled receptors. Selective synthetic ligands for Free Fatty Acid receptors (FFA1-4) have consequently been developed as potential treatments for type 2 diabetes (T2D). In particular, clinical studies show that Fasiglifam, an agonist of the long chain FFA receptor, FFA1, improved glycaemic control and reduced HbA1c levels in T2D patients, with a reduced risk of hypoglycemia. However, this ligand was removed from clinical trials due to potential liver toxicity and determining if this is a target or a ligand-specific feature is now of major importance. Pre-clinical studies also show that FFA4 agonism increases insulin sensitivity, induces weight loss and reduces inflammation and the metabolic and anti-inflammatory effects of short chain fatty acids (SCFAs) are linked with FFA2 and FFA3 activation. In this review, we therefore show that FFA receptor agonism is a potential clinical target for T2D treatment and discuss ongoing drug development programmes within industry and academia aimed at improving the safety and effectiveness of these potential treatments

Health Insurance Coverage in the Gulf Coast States after Affordable Care Act by Rural and Urban Area between 2009 and 2017

Background: Although health insurance coverage for adults in each of the Gulf Coast States and the rest of the country increased after implementing the Affordable Care Act, the coverage rates in the Gulf Coast region remained lower to rural residents, compared to those in the rest of the Nation. Purpose: This study aimed to update the changes of health insurance coverage in all states and the Gulf Coast states, confirm the significance of the health policy on insurance coverage by analyzing Louisiana, and examine the relationships between socio-demographic variables and rural/urban area by using interaction variables. Methods: This study used the American Community Survey, which is an annual survey of about three million U.S. households and collected social, demographic, and economic information, including health insurance coverage. Logistic regression was used to estimate the effects of the demographic and economic variables on health insurance coverage. Results: Florida and Texas increased health insurance coverage in the urban areas, while Alabama, Louisiana, and Mississippi present a more considerable increase in the rural area. However, Louisiana showed a significant increase in insurance coverage, rural areas in particular after joining the Medicaid expansion in 2016. A significant decrease in insurance coverage was found among young adults, African American, non-married, not in the labor force, and being poor for rural residents in Florida and Texas. In contrast, minorities in other races and unemployed decreased the likelihood of having insurance for rural residents in Alabama, Louisiana, and Mississippi. Discussion: Our examination of how socio-demographic variables interact with living in a rural area revealed a clear rural disadvantage pattern. The pattern, however, was varied between Florida and Texas and Alabama, Louisiana, and Mississippi. These findings have meaningful implications for the ongoing effort to reduce insurance coverage disparities in the Gulf Coast states and all Americans

A divisibility property of binomial coefficients viewed as an elementary sieve

The triangular array of binomial coefficients 012301111212131331… is said to have undergone a j-shift if the r-th row of the triangle is shifted rj units to the right (r=0,1,2,…). Mann and Shanks have proved that in a 2-shifted array a column number c>1 is prime if and only if every entry in the c-th column is divisible by its row number. Extensions of this result to j-shifted arrays where j>2 are considered in this paper. Moreover, an analog of the criterion of Mann and Shanks [2] is given which is valid for arbitrary arithmetic progressions

The effect of health insurance coverage and the doctor-patient relationship on health care utilization in high poverty neighborhoods

African Americans have higher rates of mortality than whites who are the same age and sex. We hypothesize that in low socioeconomic status neighborhoods, having health insurance coverage and a regular health care provider increases the likelihood of receiving diagnostic tests for cardiovascular disease and diabetes. We use data from a random two-stage cluster sample of 230 adults living in high poverty census tracts to examine the effects of insurance coverage and having a regular doctor on the likelihood receiving diagnostic tests for high cholesterol, high blood sugar, and blood pressure. We find that health insurance coverage increases the odds of having a regular health care provider (p \u3c 0.05) and of receiving the diagnostic tests (p \u3c 0.05). Having a regular doctor mediates the effect of insurance coverage on the likelihood of receiving the tests, especially when the participant can report the physician\u27s name

An efficient method for the anisotropic diffusion equation in magnetic fields

We solve the anisotropic diffusion equation in 2D, where the dominant direction of diffusion is defined by a vector field which does not conform to a Cartesian grid. Our method uses operator splitting to separate the diffusion perpendicular and parallel to the vector field. The slow time scale is solved using a provably stable finite difference formulation in the perpendicular to the vector field, and an integral operator for the diffusion parallel to it. Energy estimates are shown to for the continuous and semi-discrete cases. Numerical experiments are performed showing convergence of the method, and examples is given to demonstrate the capabilities of the method

Provably stable numerical method for the anisotropic diffusion equation in toroidally confined magnetic fields

We present a novel numerical method for solving the anisotropic diffusion equation in toroidally confined magnetic fields which is efficient, accurate and provably stable. The continuous problem is written in terms of a derivative operator for the perpendicular transport and a linear operator, obtained through field line tracing, for the parallel transport. We derive energy estimates of the solution of the continuous initial boundary value problem. A discrete formulation is presented using operator splitting in time with the summation by parts finite difference approximation of spatial derivatives for the perpendicular diffusion operator. Weak penalty procedures are derived for implementing both boundary conditions and parallel diffusion operator obtained by field line tracing. We prove that the fully-discrete approximation is unconditionally stable and asymptotic preserving. Discrete energy estimates are shown to match the continuous energy estimate given the correct choice of penalty parameters. Convergence tests are shown for the perpendicular operator by itself, and the ``NIMROD benchmark" problem is used as a manufactured solution to show the full scheme converges even in the case where the perpendicular diffusion is zero. Finally, we present a magnetic field with chaotic regions and islands and show the contours of the anisotropic diffusion equation reproduce key features in the field.Comment: 33 pages, 8 figure