Asymmetries arising from the space-filling nature of vascular networks

Cardiovascular networks span the body by branching across many generations of vessels. The resulting structure delivers blood over long distances to supply all cells with oxygen via the relatively short-range process of diffusion at the capillary level. The structural features of the network that accomplish this density and ubiquity of capillaries are often called space-filling. There are multiple strategies to fill a space, but some strategies do not lead to biologically adaptive structures by requiring too much construction material or space, delivering resources too slowly, or using too much power to move blood through the system. We empirically measure the structure of real networks (18 humans and 1 mouse) and compare these observations with predictions of model networks that are space-filling and constrained by a few guiding biological principles. We devise a numerical method that enables the investigation of space-filling strategies and determination of which biological principles influence network structure. Optimization for only a single principle creates unrealistic networks that represent an extreme limit of the possible structures that could be observed in nature. We first study these extreme limits for two competing principles, minimal total material and minimal path lengths. We combine these two principles and enforce various thresholds for balance in the network hierarchy, which provides a novel approach that highlights the trade-offs faced by biological networks and yields predictions that better match our empirical data.Comment: 17 pages, 15 figure

A path-integral approach to Bayesian inference for inverse problems using the semiclassical approximation

We demonstrate how path integrals often used in problems of theoretical physics can be adapted to provide a machinery for performing Bayesian inference in function spaces. Such inference comes about naturally in the study of inverse problems of recovering continuous (infinite dimensional) coefficient functions from ordinary or partial differential equations (ODE, PDE), a problem which is typically ill-posed. Regularization of these problems using $L^2$ function spaces (Tikhonov regularization) is equivalent to Bayesian probabilistic inference, using a Gaussian prior. The Bayesian interpretation of inverse problem regularization is useful since it allows one to quantify and characterize error and degree of precision in the solution of inverse problems, as well as examine assumptions made in solving the problem -- namely whether the subjective choice of regularization is compatible with prior knowledge. Using path-integral formalism, Bayesian inference can be explored through various perturbative techniques, such as the semiclassical approximation, which we use in this manuscript. Perturbative path-integral approaches, while offering alternatives to computational approaches like Markov-Chain-Monte-Carlo (MCMC), also provide natural starting points for MCMC methods that can be used to refine approximations. In this manuscript, we illustrate a path-integral formulation for inverse problems and demonstrate it on an inverse problem in membrane biophysics as well as inverse problems in potential theories involving the Poisson equation.Comment: Fixed some spelling errors and the author affiliations. This is the version accepted for publication by J Stat Phy

The Energy of n Identical Bosons in a Finite Volume at O(L^{-7})

The volume dependence of the ground-state energy of n identical bosons with short-range interactions in a periodic spatial volume with sides of length L is calculated at order L^{-7} in the large volume expansion. This result will enable a refined determination of the pi^+ pi^+ pi^+ interaction from lattice QCD calculations.Comment: 3 page

Testing Foundations of Biological Scaling Theory Using Automated Measurements of Vascular Networks

Scientists have long sought to understand how vascular networks supply blood and oxygen to cells throughout the body. Recent work focuses on principles that constrain how vessel size changes through branching generations from the aorta to capillaries and uses scaling exponents to quantify these changes. Prominent scaling theories predict that combinations of these exponents explain how metabolic, growth, and other biological rates vary with body size. Nevertheless, direct measurements of individual vessel segments have been limited because existing techniques for measuring vasculature are invasive, time consuming, and technically difficult. We developed software that extracts the length, radius, and connectivity of in vivo vessels from contrast-enhanced 3D Magnetic Resonance Angiography. Using data from 20 human subjects, we calculated scaling exponents by four methods--two derived from local properties of branching junctions and two from whole-network properties. Although these methods are often used interchangeably in the literature, we do not find general agreement between these methods, particularly for vessel lengths. Measurements for length of vessels also diverge from theoretical values, but those for radius show stronger agreement. Our results demonstrate that vascular network models cannot ignore certain complexities of real vascular systems and indicate the need to discover new principles regarding vessel lengths

Out-of-pocket health expenditures in Australia: A semi-parametric analysis, CHERE Working Paper 2006/15

Out-of-pocket health expenditures in Australia are high in international comparisons and have been growing at a faster rate than most other health costs in recent years. This raises concerns about the extent to which out-of-pocket costs have constrained access to health services for low income households. Using data from the ABS Household Expenditure Survey 2003-04, we model the relationships between health expenditure shares and equivalised total expenditure for categories of out-of-pocket health expenditures and analyse the extent of protection given by concession cards. To allow for flexibility in the relationship we adopt a semi-parametric estimation technique following Yatchew (1997). We find mixed evidence for the protection health concession cards give against high out-of-pocket health expenditures. Despite higher levels of subsidy, households with concession cards have higher total health expenditure shares than other households. Surprisingly, the major drivers of the difference are not categories of expenditure where cards offer little or no protection, such as dental services and non-prescription medicines, but prescriptions costs, where concession cards guarantee a subsidy, and specialist consultations, where bulk billing rates would be expected to be higher for cardholders. This is the first detailed distributional analysis of household health expenditures in Australia.Out-of-pocket costs, international comparisons, Australia

Compounding Effects of Climate Warming and Antibiotic Resistance.

Bacteria have evolved diverse mechanisms to survive environments with antibiotics. Temperature is both a key factor that affects the survival of bacteria in the presence of antibiotics and an environmental trait that is drastically increasing due to climate change. Therefore, it is timely and important to understand links between temperature changes and selection of antibiotic resistance. This review examines these links by synthesizing results from laboratories, hospitals, and environmental studies. First, we describe the transient physiological responses to temperature that alter cellular behavior and lead to antibiotic tolerance and persistence. Second, we focus on the link between thermal stress and the evolution and maintenance of antibiotic resistance mutations. Finally, we explore how local and global changes in temperature are associated with increases in antibiotic resistance and its spread. We suggest that a multidisciplinary, multiscale approach is critical to fully understand how temperature changes are contributing to the antibiotic crisis

Catastrophic insurance: Impact of the Australian Medicare Safety Net on fees, service use and out-of-pocket costs, CHERE Working Paper 2006/9

Objectives: The Medicare Safety Net Policy was introduced in March 2004 to provide financial relief for those Australians who face high out-of-pocket (OOP) costs for outpatient medical services. This study evaluates the extent to which out-of-pocket costs have fallen since the introduction of the Safety Net and examines the impact of the policy on the level of service use, the amount of benefits paid by government and fees charged by medical providers. Methods: Regression modelling of time series data was used to examine whether there have been significant changes in levels of service use, fees charged and benefits paid for services provided by specialists in the two-year period following the introduction of the Safety Net. Four speciality fields were examined in this analysis: general specialists? consultations, obstetrics, pathology and diagnostic imaging. Results: The analysis indicates that the introduction of the Safety Net coincided with a substantial rise in public funding for Medicare services and a much smaller reduction in OOP costs. The policy has coincided with a small but significant change in the number of pathology and diagnostic imaging services used and in some specialty areas a substantial increase in the fees charged by providers. The net impact shows that for specialists? consultations every dollar spent on the Medicare Safety Net, $0.68 went towards higher fees and$0.32 went towards reducing OOP costs. The corresponding figures for diagnostic imaging were $0.74 and$0.26 respectively. Conclusions: The Safety Net was heralded by the government as a fundamental reform in Australia?s Medicare program. Whilst the Safety Net was introduced to help reduce out-of-pocket medical costs, this analysis shows that in its first two years of operation, there has been significant leakage of public funding towards higher provider fees. More research is needed using longer term data to assess the impact of the policy on patient and provider behaviour more widely, including examining the policy?s impact on those who did qualify for Safety Net and those who did not, as well as more disaggregated analysis of different Medicare services.Out-of-pocket costs; moral hazard; catastrophic insurance; health care financing; Australia