Efficient parameter sensitivity computation for spatially extended reaction networks

Reaction-diffusion models are widely used to study spatially-extended chemical reaction systems. In order to understand how the dynamics of a reaction-diffusion model are affected by changes in its input parameters, efficient methods for computing parametric sensitivities are required. In this work, we focus on stochastic models of spatially-extended chemical reaction systems that involve partitioning the computational domain into voxels. Parametric sensitivities are often calculated using Monte Carlo techniques that are typically computationally expensive; however, variance reduction techniques can decrease the number of Monte Carlo simulations required. By exploiting the characteristic dynamics of spatially-extended reaction networks, we are able to adapt existing finite difference schemes to robustly estimate parametric sensitivities in a spatially-extended network. We show that algorithmic performance depends on the dynamics of the given network and the choice of summary statistics. We then describe a hybrid technique that dynamically chooses the most appropriate simulation method for the network of interest. Our method is tested for functionality and accuracy in a range of different scenarios

Synoptic climatology of northwest flow snowfall in the southern Appalachians

Snowfall in association with low-level winds out of the northwest is a common occurrence at higher elevations and along windward slopes in the Southern Appalachian Mountains. These northwest flow snow (NWFS) events typically have low temperatures and considerable blowing and drifting snow. Due to the high degree of spatial variability of snowfall and limited ability of numerical models to predict these events, forecasting NWFS remains a challenge. This dissertation analyzes the synoptic climatology of NWFS events in the Southern Appalachians for the period 1950 to 2000. Hourly observations from first-order stations, daily snowfall data from cooperative observer stations, and National Center for Environmental Prediction (NCEP) reanalysis data are utilized to identify NWFS events, defined here as snow events with 850 hPa northwest flow (270 to 360 degrees) at the hour of greatest snow extent. Atmospheric fields of temperature, wind, moisture, and associated variables are analyzed for heavy and light snowfalls separately by calculating composite field values and constructing composite plots of the synoptic patterns. The NOAA Hysplit Trajectory Tool is used to calculate 72-hour antecedent upstream air trajectories, and composite trajectories are mapped in a geographic information system (GIS). The sample of events in the trajectory analysis is limited to those with synoptic-scale subsidence, a frequent occurrence with NWFS. Analyses of vertical soundings are coupled with NCEP data to iv determine the synoptic characteristics associated with different air trajectories. Results indicate that NWFS accounts for as much as 56 percent of mean annual snowfall along the higher elevation windward slopes. Heavy NWFS events are tied to higher values of synopticscale ascent and relative humidity in the lower troposphere, as well as lower 500 hPa heights and longer event durations. Additionally, upstream air trajectories with a Great Lakes connection have higher composite mean areal and maximum point snowfall totals along the higher elevation windward slopes than other northwest trajectories. Little Great Lakes influence is noted at lower elevations and on leeward slopes

Multiple housing problems: a view through the housing niche lens

Online 5 October 2016This paper presents an alternative view on the patterning of housing problems – across populations and within people. The conceptualization of housing problems through a ‘housing niche’ lens allows the cumulative influence of multiple housing vulnerabilities to be better visualized and understood. Using a large, representative sample of the Australian population, the analysis describes and models patterns of multiple housing problems, the characteristics of the population at risk, and reflects on the implications for how policy might better understand and respond to multiple housing problems.Emma Baker, Laurence Leste

Extending the multi-level method for the simulation of stochastic biological systems

The multi-level method for discrete state systems, first introduced by Anderson and Higham [Multiscale Model. Simul. 10:146--179, 2012], is a highly efficient simulation technique that can be used to elucidate statistical characteristics of biochemical reaction networks. A single point estimator is produced in a cost-effective manner by combining a number of estimators of differing accuracy in a telescoping sum, and, as such, the method has the potential to revolutionise the field of stochastic simulation. The first term in the sum is calculated using an approximate simulation algorithm, and can be calculated quickly but is of significant bias. Subsequent terms successively correct this bias by combining estimators from approximate stochastic simulations algorithms of increasing accuracy, until a desired level of accuracy is reached. In this paper we present several refinements of the multi-level method which render it easier to understand and implement, and also more efficient. Given the substantial and complex nature of the multi-level method, the first part of this work (Sections 2 - 5) is written as a tutorial, with the aim of providing a practical guide to its use. The second part (Sections 6 - 8) takes on a form akin to a research article, thereby providing the means for a deft implementation of the technique, and concludes with a discussion of a number of open problems.Comment: 38 page

Is Housing a Health Insult?

In seeking to understand the relationship between housing and health, research attention is often focussed on separate components of people?s whole housing ?bundles?. We propose in this paper that such conceptual and methodological abstraction of elements of the housing and health relationship limits our ability to understand the scale of the accumulated effect of housing on health and thereby contributes to the under-recognition of adequate housing as a social policy tool and powerful health intervention. In this paper, we propose and describe an index to capture the means by which housing bundles influence health. We conceptualise the index as reflecting accumulated housing ?insults to health??an Index of Housing Insults (IHI). We apply the index to a sample of 1000 low-income households in Australia. The analysis shows a graded association between housing insults and health on all outcome measures. Further, after controlling for possible confounders, the IHI is shown to provide additional predictive power to the explanation of levels of mental health, general health and clinical depression beyond more traditional proxy measures. Overall, this paper reinforces the need to look not just at separate housing components but to embrace a broader understanding of the relationship between housing and health

Hyperinsulinism Caused by Paternal-Specific Inheritance of a Recessive Mutation in the Sulfonylurea-Receptor Gene

Neonatal hyperinsulinism (HI) is a genetic disorder of pancreatic b-cells characterized by failure to suppress insulin secretion in the presence of hypoglycemia, resulting in brain damage or death if not adequately treated. Germline mutations in four genes have been associated with HI. Some patients have focal regions of b-cell proliferation (focal HI). Seventy HI probands in whom at least one S U R - 1 mutation was identified were studied. Clinical data from patients with two S U R - 1 mutant alleles were compared with those from patients with single paternally inherited mutations. Thirtyseven probands were homozygous or compound heterozygous for S U R - 1 mutations. In 33 probands, only a single mutation was identified, and in 31, the parental origin of the proband could be determined; in 29, the mutation was on the paternal allele (P \u3c 0.0002). For three of these, pancreatic tissue was available and showed focal b-cell hyperplasia. DNA extracted from the focal lesion and adjacent normal pancreas revealed loss of the maternal chromosome 11p15, resulting in reduction to homozygosity for the S U R - 1 mutation within the focal lesion only. Using the Tdt-mediated dUTP nick end labeling (TUNEL) reaction, apoptotic b-cells were identified exclusively within the focal region. At diagnosis, disease severity was similar in patients with paternally inherited mutations and those with two mutations. For patients who did not undergo surgery, those with only paternal mutations entered clinical remission within 16 ± 6.2 months, compared with 48 ± 23 months for those with two S U R - 1 mutations (P = 0.001). In conclusion, we identified a novel mechanism to explain the pathophysiology of focal HI and provide evidence to suggest that this entity may be self-limiting, since affected b-cells undergo apoptosis