Efficient simulation of unsaturated flow in heterogeneous soils using an exponential integrator

- Provided a practical variable-stepsize implementation of the exponential Euler method (EEM). - Introduced a new second-order variant of the scheme that enables the local error to be estimated at the cost of a single additional function evaluation. - New EEM implementation outperformed sophisticated implementations of the backward differentiation formulae (BDF) of order 2 and was competitive with BDF of order 5 for moderate to high tolerances.

Computationally Efficient Methods for MDL-Optimal Density Estimation and Data Clustering

The Minimum Description Length (MDL) principle is a general, well-founded theoretical formalization of statistical modeling. The most important notion of MDL is the stochastic complexity, which can be interpreted as the shortest description length of a given sample of data relative to a model class. The exact definition of the stochastic complexity has gone through several evolutionary steps. The latest instantation is based on the so-called Normalized Maximum Likelihood (NML) distribution which has been shown to possess several important theoretical properties. However, the applications of this modern version of the MDL have been quite rare because of computational complexity problems, i.e., for discrete data, the definition of NML involves an exponential sum, and in the case of continuous data, a multi-dimensional integral usually infeasible to evaluate or even approximate accurately. In this doctoral dissertation, we present mathematical techniques for computing NML efficiently for some model families involving discrete data. We also show how these techniques can be used to apply MDL in two practical applications: histogram density estimation and clustering of multi-dimensional data.

An exponential stability criterion for certain nonlinear systems

Improved sufficient conditions are derived for the exponential stability of a nonlinear time varying feedback system having a time invariant blockG in the forward path and a nonlinear time varying gain ϕ(.)k(t) in the feedback path. φ(.) being an odd monotone nondecreasing function. The resulting bound on is less restrictive than earlier criteria.

An exponential stability criterion for certain nonlinear systems

Improved sufficient conditions are derived for the exponential stability of a nonlinear time varying feedback system having a time invariant blockG in the forward path and a nonlinear time varying gain ϕ(.)k(t) in the feedback path. φ(.) being an odd monotone nondecreasing function. The resulting bound on $$\left( {{{\frac{{dk}}{{dt}}} \mathord{\left/ {\vphantom {{\frac{{dk}}{{dt}}} k}} \right. \kern-\nulldelimiterspace} k}} \right)$$ is less restrictive than earlier criteria.

Seeking continuity: Educational strategy in and for mobile ADF families

This report shares findings and insights from an interview study conducted in 2009, with 34 ADF families. These families were identified in the communities of primary schools in both state and Catholic systems with high ADF family enrolments in 3 towns across 2 states, with the assistance of the DCO and their embedded Defence School Transition Aides (DSTAs). In the interviews the parents were invited to describe their history of ADF relocations, and how they managed transitions for each member in terms of school choice, child care arrangements, spouse employment, and educational transitions. Parallel interviews were conducted with 12 teachers and 6 DSTAs across the identified schools to describe how schools cater for mobile ADF families flowing through their classes. Parents were invited to tell the story of their family’s sequence of moves and how each member made the transition, then reflect more generally on what advice they’d give other mobile families. Teachers were asked to describe how they respond to the mobile families in their school community, and to illustrate some of the issues and challenges from the institutional perspective. By offering perspectives from both parents and teachers, the report hopes to facilitate a dialogue between parties to address their common goal – promoting productive continuities in education for children in mobile families.

Entire Solutions of Hydrodynamical Equations with Exponential Dissipation

We consider a modification of the three-dimensional Navier-Stokes equations and other hydrodynamical evolution equations with space-periodic initial conditions in which the usual Laplacian of the dissipation operator is replaced by an operator whose Fourier symbol grows exponentially as e(vertical bar k vertical bar/kd) at high wavenumbers vertical bar k vertical bar. Using estimates in suitable classes of analytic functions, we show that the solutions with initially finite energy become immediately entire in the space variables and that the Fourier coefficients decay faster than e-(C(k/kd) ln(vertical bar k vertical bar/kd)) for any C < 1/(2 ln 2). The same result holds for the one-dimensional Burgers equation with exponential dissipation but can be improved: heuristic arguments and very precise simulations, analyzed by the method of asymptotic extrapolation of van der Hoeven, indicate that the leading-order asymptotics is precisely of the above form with C = C-* = 1/ ln 2. The same behavior with a universal constant C-* is conjectured for the Navier-Stokes equations with exponential dissipation in any space dimension. This universality prevents the strong growth of intermittency in the far dissipation range which is obtained for ordinary Navier-Stokes turbulence. Possible applications to improved spectral simulations are briefly discussed.

Decision-making in a death investigation: Emotions, families and the coroner

The role of the coroner in common law countries such as Australia, England, Canada and New Zealand is to preside over death investigations where there is uncertainty as to the manner of death, a need to identify the deceased, a death of unknown cause, or a violent or unnatural death. The vast majority of these deaths are not suspicious and thus require coroners to engage with grieving families who have been thrust into a legal process through the misfortune of a loved one's sudden or unexpected death. In this research, 10 experienced coroners discussed how they negotiated the grief and trauma evident in a death investigation. In doing so, they articulated two distinct ways in which legal officers engaged with emotions, which are also evident in the literature. The first engages the script of judicial dispassion, articulating a hierarchical relationship between reason and emotion, while the second introduces an ethic of care via the principles of therapeutic jurisprudence, and thus offers a challenge to the role of emotion in the personae of the professional judicial officer. By using Hochschild's work on the sociology of emotions, this article discusses the various ways in which coroners manage the emotion of a death investigation through emotion work. While emotional distance may be an understandable response by coroners to the grief and trauma experienced by families and directed at cleaner coronial decision-making, the article concludes that coroners may be better served by offering emotions such as sympathy, consideration and compassion directly to the family in those situations where families are struggling to accept, or are resistant to, coroners' decisions.

Looking at the other side: Families, public health and anti-vaccination

The choice to vaccinate or not to vaccinate a child is usually an ‘informed decision’, however, it is how this decision is informed which is of most importance. More frequently, families are turning to the Internet, in particular social media, as a data source to support their decisions. However, much of the online information may be unscientific or biased. While issues such as vaccination will always see dissenting voices, engaging with that ‘other side’ is difficult in the public policy debate which is informed by evidence based science. This chapter investigates the other side in light of the growing adoption and reliance on social media as a source of anti-vaccine information. The study adopts a qualitative approach to data collection and is based on a critical discourse analysis of online social media discourse. The findings demonstrate the valuable contribution this approach can make to public policy work in vaccination.

Assessment of Risk for Type 1 Diabetes in Children of Affected Families and in the General Population : Role of Immunological and Metabolic Markers

Background and aims. Type 1 diabetes (T1D), an autoimmune disease in which the insulin producing beta cells are gradually destroyed, is preceded by a prodromal phase characterized by appearance of diabetes-associated autoantibodies in circulation. Both the timing of the appearance of autoantibodies and their quality have been used in the prediction of T1D among first-degree relatives of diabetic patients (FDRs). So far, no general strategies for identifying individuals at increased disease risk in the general population have been established, although the majority of new cases originate in this population. The current work aimed at assessing the predictive role of diabetes-associated immunologic and metabolic risk factors in the general population, and comparing these factors with data obtained from studies on FDRs. Subjects and methods. Study subjects in the current work were subcohorts of participants of the Childhood Diabetes in Finland Study (DiMe; n=755), the Cardiovascular Risk in Young Finns Study (LASERI; n=3475), and the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP) Study subjects (n=7410). These children were observed for signs of beta-cell autoimmunity and progression to T1D, and the results obtained were compared between the FDRs and the general population cohorts. --- Results and conclusions. By combining HLA and autoantibody screening, T1D risks similar to those reported for autoantibody-positive FDRs are observed in the pediatric general population. Progression rate to T1D is high in genetically susceptible children with persistent multipositivity. Measurement of IAA affinity failed in stratifying the risk assessment in young IAA-positive children with HLA-conferred disease susceptibility, among whom affinity of IAA did not increase during the prediabetic period. Young age at seroconversion, increased weight-for-height, decreased early insulin response, and increased IAA and IA-2A levels predict T1D in young children with genetic disease susceptibility and signs of advanced beta-cell autoimmunity. Since the incidence of T1D continues to increase, efforts aimed at preventing T1D are important, and reliable disease prediction is needed both for intervention trials and for effective and safe preventive therapies in the future. Our observations confirmed that combined HLA-based screening and regular autoantibody measurements reveal similar disease risks in pediatric general population as those seen in prediabetic FDRs, and that risk assessment can be stratified further by studying glucose metabolism of prediabetic subjects. As these screening efforts are feasible in practice, the knowledge now obtained can be exploited while designing intervention trials aimed at secondary prevention of T1D.

Characterization of LRRTM and NGR gene families: Expression and functions

Some leucine-rich repeat (LRR) -containing membrane proteins are known regulators of neuronal growth and synapse formation. In this work I characterize two gene families encoding neuronal LRR membrane proteins, namely the LRRTM (leucine-rich repeat, transmembrane neuronal) and NGR (Nogo-66 receptor) families. I studied LRRTM and NGR family member's mRNA tissue distribution by RT-PCR and by in situ hybridization. Subcellular localization of LRRTM1 protein was studied in neurons and in non-neuronal cells. I discovered that LRRTM and NGR family mRNAs are predominantly expressed in the nervous system, and that each gene possesses a specific expression pattern. I also established that LRRTM and NGR family mRNAs are expressed by neurons, and not by glial cells. Within neurons, LRRTM1 protein is not transported to the plasma membrane; rather it localizes to endoplasmic reticulum. Nogo-A (RTN4), MAG, and OMgp are myelin-associated proteins that bind to NgR1 to limit axonal regeneration after central nervous system injury. To better understand the functions of NgR2 and NgR3, and to explore the possible redundancy in the signaling of myelin inhibitors of neurite growth, I mapped the interactions between NgR family and the known and candidate NgR1 ligands. I identified high-affinity interactions between RTN2-66, RTN3-66 and NgR1. I also demonstrate that Rtn3 mRNA is expressed in the same glial cell population of mouse spinal cord white matter as Nogo-A mRNA, and thus it could have a role in myelin inhibition of axonal growth. To understand how NgR1 interacts with multiple structurally divergent ligands, I aimed first to map in more detail the nature of Nogo-A:NgR1 interactions, and then to systematically map the binding sites of multiple myelin ligands in NgR1 by using a library of NgR1 expression constructs encoding proteins with one or multiple surface residues mutated to alanine. My analysis of the Nogo-A:NgR1 -interactions revealed a novel interaction site between the proteins, suggesting a trivalent Nogo-A:NgR1-interaction. Our analysis also defined a central binding region on the concave side of NgR1's LRR domain that is required for the binding of all known ligands, and a surrounding region critical for binding MAG and OMgp. To better understand the biological role of LRRTMs, I generated Lrrtm1 and Lrrtm3 knock out mice. I show here that reporter genes expressed from the targeted loci can be used for maping the neuronal connections of Lrrtm1 and Lrrtm3 expressing neurons in finer detail. With regard to LRRTM1's role in humans, we found a strong association between a 70 kb-spanning haplotype in the proposed promoter region of LRRTM1 gene and two possibly related phenotypes: left-handedness and schizophrenia. Interestingly, the responsible haplotype was linked to phenotypic variability only when paternally inherited. In summary, I identified two families of neuronal receptor-like proteins, and mapped their expression and certain protein-protein interactions. The identification of a central binding region in NgR1 shared by multiple ligands may facilitate the design and development of small molecule therapeutics blocking binding of all NgR1 ligands. Additionally, the genetic association data suggests that allelic variation upstream of LRRTM1 may play a role in the development of left-right brain asymmetry in humans. Lrrtm1 and Lrrtm3 knock out mice developed as a part of this study will likely be useful for schizophrenia and Alzheimer s disease research.

Affected sibling pairs with juvenile idiopathic arthritis : An immunogenetic study of the disease in multicase families

Genetic susceptibility to juvenile idiopathic arthritis (JIA) was studied in the genetically homogeneous Finnish population by collecting families with two or three patients affected by this disease from cases seen in the Rheumatism Foundation Hospital. The number of families ranged in different studies from 37 to 45 and the total number of patients with JIA, from among whom these cases were derived, was 2 000 to 2 300. Characteristics of the disease in affected siblings in Finland were compared with a population-based series and with a sibling series from the United States. A thorough clinical and ophthalmological examination was made of all affected patients belonging to sibpair series. Information on the occurrence of chronic rheumatic diseases in parents was collected by questionnaire and diagnoses were confirmed from hospital records. All patients, their parents and most of the healthy sibs were typed for human leukocyte antigen (HLA) alleles in loci A, C, B, DR and DQ. The HLA allele distribution of the cases was compared with corresponding data from Finnish bone marrow donors. The genetic component in JIA was found to be more significant than previously believed. A concordance rate of 25% for a disease with a population prevalence of 1 per 1000 implied a relative risk of 250 for a monozygotic (MZ) twin. An estimate for the sibling risk of an affected individual was about 15- to 20-fold. The disease was basically similar in familial and sporadic cases; the mean age at disease onset was however lower in familial cases, (4.8 years vs 7.4 years). Three sibpairs (3.4 expected) were concordant for the presence of asymptomatic uveitis. Uveitis would thus not appear to have any genetic component of its own, separate from the genetic basis of JIA. Four of the parents had JIA (0.2 cases expected), four had a type of rheumatoid factor-negative arthritis similar to that seen in juvenile patients but commencing in adulthood, and one had spondyloarthropathy (SPA). These findings provide additional support for the conception of a genetic predisposition to JIA and suggest the existence of a new disease entity, JIA of adult onset. Both the linkage analysis of the affected sibpairs and the association analysis of nuclear families provided overwhelming evidence of a major contribution of HLA to the genetic susceptibility to JIA. The association analysis in the Finnish population confirmed that the most significant associations prevailed for DRB1*0801, DQB1*0402, as expected from previous observations, and indicated the independent role of Cw*0401.