Clinical data warehousing : a business analytics approach for managing health data

Heterogeneous health data is a critical issue when managing health information for quality decision making processes. In this paper we examine the efficient aggregation of lifestyle information through a data warehousing architecture lens. We present a proof of concept for a clinical data warehouse architecture that enables evidence based decision making processes by integrating and organising disparate data silos in support of healthcare services improvement paradigms.

Long-range stereo visual odometry for unmanned aerial vehicles

This thesis explored the utility of long-range stereo visual odometry for application on Unmanned Aerial Vehicles. Novel parameterisations and initialisation routines were developed for the long-range case of stereo visual odometry and new optimisation techniques were implemented to improve the robustness of visual odometry in this difficult scenario. In doing so, the applications of stereo visual odometry were expanded and shown to perform adequately in situations that were previously unworkable.

Characterization and Mapping of Patterned Ground in the Saginaw Lowlands, Michigan: Possible Evidence for Late-Wisconsin Permafrost

We identified, mapped, and characterized a widespread area (gt;1,020 km2) of patterned ground in the Saginaw Lowlands of Michigan, a wet, flat plain composed of waterlain tills, lacustrine deposits, or both. The polygonal patterned ground is interpreted as a possible relict permafrost feature, formed in the Late Wisconsin when this area was proximal to the Laurentide ice sheet. Cold-air drainage off the ice sheet might have pooled in the Saginaw Lowlands, which sloped toward the ice margin, possibly creating widespread but short-lived permafrost on this glacial lake plain. The majority of the polygons occur between the Glacial Lake Warren strandline (~14.8 cal. ka) and the shoreline of Glacial Lake Elkton (~14.3 cal. ka), providing a relative age bracket for the patterned ground. Most of the polygons formed in dense, wet, silt loam soils on flat-lying sites and take the form of reticulate nets with polygon long axes of 150 to 160 m and short axes of 60 to 90 m. Interpolygon swales, often shown as dark curvilinears on aerial photographs, are typically slightly lower than are the polygon centers they bound. Some portions of these interpolygon swales are infilled with gravel-free, sandy loam sediments. The subtle morphology and sedimentological characteristics of the patterned ground in the Saginaw Lowlands suggest that thermokarst erosion, rather than ice-wedge replacement, was the dominant geomorphic process associated with the degradation of the Late-Wisconsin permafrost in the study area and, therefore, was primarily responsible for the soil patterns seen there today.

Natural free convection in porous media: First field documentation in groundwater

Natural free convection is a process of great importance in disciplines from hydrology to meteorology, oceanography, planetary sciences, and economic geology, and for applications in carbon sequestration and nuclear waste disposal. It has been studied for over a century - but almost exclusively in theoretical and laboratory settings, Despite its importance, conclusive primary evidence of free convection in porous media does not currently exist in a natural field setting. Here, we present recent electrical resistivity measurements from a sabkha aquifer near Abu Dhabi, United Arab Emirates, where large density inversions exist. The geophysical images from this site provide, for the first time, compelling field evidence of fingering associated with natural free convection in groundwater.

Accelerating junior-secondary mathematics

Unfortunately, in Australia there is a prevalence of mathematically underperforming junior-secondary students in low-socioeconomic status schools. This requires targeted intervention to develop the affected students’ requisite understanding in preparation for post-compulsory study and employment and, ultimately, to increase their life chances. To address this, the ongoing action research project presented in this paper is developing a curriculum of accelerated learning, informed by a lineage of cognitivist-based structural sequence theory building activity (e.g., Cooper & Warren, 2011). The project’s conceptual framework features three pillars: the vertically structured sequencing of concepts; pedagogy grounded in students’ reality and culture; and professional learning to support teachers’ implementation of the curriculum (Cooper, Nutchey, & Grant, 2013). Quantitative and qualitative data informs the ongoing refinement of the theory, the curriculum, and the teacher support.

Protein loaded mesoporous silica spheres as a controlled delivery platform

Background The adsorption of bovine serum albumin (BSA) onto mesoporous silica spheres (MPS) synthesized from silica colloids was studied employing real time in situ measurements. The stabilities of the BSA at different pH values, their isoelectric points and zeta potentials were determined in order to probe the interactions between the protein and the mesoporous silica. Results The pore size of MPS was designed for protein, and this, coupled with an in depth understanding of the physico-chemical characteristics of the protein and MPS has yielded a better binding capacity and delivery profile. The adsorption isotherm at pH 4.2 fitted the Langmuir model and displayed the highest adsorption capacity (71.43 mg mL-1 MPS). Furthermore, the delivery rates of BSA from the MPS under physiological conditions were shown to be dependent on the ionic strength of the buffer and protein loading concentration. Conclusion Economics and scale-up considerations of mesoporous material synthesized via destabilization of colloids by electrolyte indicate the scaleability and commercial viability of this technology as a delivery platform for biopharmaceutical applications.

Secret Millionares Club

Secret Millionaires Club is an animated series of 26 webisodes featuring Warren Buffett (CEO and largest shareholder of Berkshire Hathaway) as a secret mentor to a group of kids who learn practical life lessons during fun-filled adventures in business.

Implementation of National Rental Affordability Scheme in Queensland

In 2008 the Australian government introduced the National Rental Affordability Scheme (NRAS) to increase the supply of affordable rental in Australia. This Federal Government initiative was progressively rolled out through four different rounds over the years with fifth round to be announced some time in 2014. Although the scheme has been successful evident there have been numerous setbacks experienced. This paper focuses on understanding lessons learnt from the performance of the scheme to make recommendations for future government initiatives. This evaluation is based on the combination of document analysis, government officers as well as approved NRAS participants operating throughout Queensland. The most significant challenges for the NRAS participants is the involvement of three levels government which cause delays in the scheme approval process.

Mutations in the gene encoding IFT dynein complex component WDR34 cause jeune asphyxiating thoracic dystrophy

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Parenting and the behavior problems of young children with an intellectual disability: Concurrent and longitudinal relationships in a population-based study

We examined parenting behaviors, and their association with concurrent and later child behavior problems. Children with an intellectual disability (ID) were identified from a UK birth cohort (N  =  516 at age 5). Compared to parents of children without an ID, parents of children with an ID used discipline less frequently, but reported a more negative relationship with their child. Among children with an ID, discipline, and home atmosphere had no long-term association with behavior problems, whereas relationship quality did: closer relationships were associated with fewer concurrent and later child behavior problems. Increased parent-child conflict was associated with greater concurrent and later behavior problems. Parenting programs in ID could target parent-child relationship quality as a potential mediator of behavioral improvements in children.

Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer

Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10-5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10-4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10-9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense. © 2012 Nature America, Inc. All rights reserved.

A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1

To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.