Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families : evidence for common founders and independent mutations

Germ-line mutations in CDKN2A have been shown to predispose to cutaneous malignant melanoma. We have identified 2 new melanoma kindreds which carry a duplication of a 24bp repeat present in the 5' region of CDKN2A previously identified in melanoma families from Australia and the United States. This mutation has now been reported in 5 melanoma families from 3 continents: Europe, North America, and Australasia. The M53I mutation in exon 2 of CDKN2A has also been documented in 5 melanoma families from Australia and North America. The aim of this study was to determine whether the occurrence of the mutations in these families from geographically diverse populations represented mutation hotspots within CDKN2A or were due to common ancestors. Haplotypes of 11 microsatellite markers flanking CDKN2A were constructed in 5 families carrying the M53I mutation and 5 families carrying the 24bp duplication. There were some differences in the segregating haplotypes due primarily to recombinations and mutations within the short tandem-repeat markers; however, the data provide evidence to indicate that there were at least 3 independent 24bp duplication events and possibly only 1 original M53I mutation. This is the first study to date which indicates common founders in melanoma families from different continents.

Stochastic modelling of T cell homeostasis for two competing clonotypes via the master equation

Stochastic models for competing clonotypes of T cells by multivariate, continuous-time, discrete state, Markov processes have been proposed in the literature by Stirk, Molina-París and van den Berg (2008). A stochastic modelling framework is important because of rare events associated with small populations of some critical cell types. Usually, computational methods for these problems employ a trajectory-based approach, based on Monte Carlo simulation. This is partly because the complementary, probability density function (PDF) approaches can be expensive but here we describe some efficient PDF approaches by directly solving the governing equations, known as the Master Equation. These computations are made very efficient through an approximation of the state space by the Finite State Projection and through the use of Krylov subspace methods when evolving the matrix exponential. These computational methods allow us to explore the evolution of the PDFs associated with these stochastic models, and bimodal distributions arise in some parameter regimes. Time-dependent propensities naturally arise in immunological processes due to, for example, age-dependent effects. Incorporating time-dependent propensities into the framework of the Master Equation significantly complicates the corresponding computational methods but here we describe an efficient approach via Magnus formulas. Although this contribution focuses on the example of competing clonotypes, the general principles are relevant to multivariate Markov processes and provide fundamental techniques for computational immunology.

Novel numerical methods for time-space fractional reaction diffusion equations in two dimensions

We consider time-space fractional reaction diffusion equations in two dimensions. This equation is obtained from the standard reaction diffusion equation by replacing the first order time derivative with the Caputo fractional derivative, and the second order space derivatives with the fractional Laplacian. Using the matrix transfer technique proposed by Ilic, Liu, Turner and Anh [Fract. Calc. Appl. Anal., 9:333--349, 2006] and the numerical solution strategy used by Yang, Turner, Liu, and Ilic [SIAM J. Scientific Computing, 33:1159--1180, 2011], the solution of the time-space fractional reaction diffusion equations in two dimensions can be written in terms of a matrix function vector product $f(A)b$ at each time step, where $A$ is an approximate matrix representation of the standard Laplacian. We use the finite volume method over unstructured triangular meshes to generate the matrix $A$, which is therefore non-symmetric. However, the standard Lanczos method for approximating $f(A)b$ requires that $A$ is symmetric. We propose a simple and novel transformation in which the standard Lanczos method is still applicable to find $f(A)b$, despite the loss of symmetry. Numerical results are presented to verify the accuracy and efficiency of our newly proposed numerical solution strategy.

Influence of internal fixator stiffness on murine fracture healing : two types of fracture healing lead to two distinct cellular events and FGF-2 expressions

This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.

Post-operative CT assessment of interbody fusion two years after thoracoscopic scoliosis surgery

The relationship between radiologic union and clinical outcome in thoracoscopic scoliosis surgery is not clear, as apparent non-union of a spinal fusion does not always correspond to a poor clinical result. The aim of this study was to evaluate CT fusion rates 24 months after thoracoscopic anterior scoliosis surgery, and to explore the relationship between fusion scores and; (i) rod diameter, (ii) graft type, (iii) fusion level, (iv) occurrence of post-operative implant failure, and (v) lateral position of the fusion mass in the intervertebral disc space. We propose that moderate fusion scores on the Sucato scale secure successful clinical outcomes in thoracoscopic scoliosis surgery.

Postoperative low dose CT assessment of interbody fusion two years after thoracoscopic scoliosis surgery

The relationship between radiologic union and clinical outcomes in thoracoscopic scoliosis surgery is not clear, as apparent non-union of a spinal fusion does not always correspond to a poor clinical result. The aim of this study was to evaluate for the first time the interbody fusion rates using low dose CT scans at minimum 24 months after thoracoscopic scoliosis surgery, and to explore the relationship between fusion scores and; (i) rod diameter, (ii) graft type, (iii) fusion level, (iv) implant failure, and (v) lateral position in the disc space. The study found that moderate fusion scores on the Sucato scale secure successful clinical outcomes in thoracoscopic scoliosis surgery.

An examination of the predictors of blood donors' intentions to donate during two phases of an avian influenza outbreak

BACKGROUND: Data from prior health scares suggest that an avian influenza outbreak will impact on people’s intention to donate blood; however research exploring this is scarce. Using an augmented theory of planned behavior (TPB), incorporating threat perceptions alongside the rational decision-making components of the TPB, the current study sought to identify predictors of blood donors’ intentions to donate during two phases of an avian influenza outbreak. STUDY DESIGN AND METHODS: Blood donors (N = 172) completed an on-line survey assessing the standard TPB predictors as well as measures of threat perceptions from the health belief model (HBM; i.e., perceived susceptibility and severity). Path analyses examined the utility of the augmented TPB to predict donors’ intentions to donate during a low- and high-risk phase of an avian influenza outbreak. RESULTS: In both phases, the model provided a good fit to the data explaining 69% (low risk) and 72% (high risk) of the variance in intentions. Attitude, subjective norm, and perceived susceptibility significantly predicted donor intentions in both phases. Within the low-risk phase, gender was an additional significant predictor of intention, while in the high-risk phase, perceived behavioral control was significantly related to intentions. CONCLUSION: An augmented TPB model can be used to predict donors’ intentions to donate blood in a low-risk and a high-risk phase of an outbreak of avian influenza. As such, the results provide important insights into donors’ decision-making that can be used by blood agencies to maintain the blood supply in the context of an avian influenza outbreak.

Underwater emissions from a two-stroke outboard engine : a comparison between an EAL and an equivalent mineral lubricant

The emissions to water from a 1.9 kW two-stroke outboard engine were investigated in the laboratory and in the field, with the primary objective being to characterise and quantify the pollutants that remain within the water column. The emission rates of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) were determined for the engine when using a mineral and an equivalent environmentally adapted lubricant (EAL). A comparison of the emission rates was conducted between the results from the fresh and sea water tests. The results showed that there was little difference in the emission rates of these pollutants when either of the lubricants was used in both the fresh and sea water. A further set of tests were done to find out the effect on pH of water due to the underwater emissions and these tests were done using both mineral and environmentally adapted lubricant. The results showed that the type of lubricant does not have any effect on the change in pH of the water.

Phase two of the National Credit Reforms : examining the regulation of payday lenders

This study seeks to analyse the adequacy of the current regulation of the payday lending industry in Australia, and consider whether there is a need for additional regulation to protect consumers of these services. The report examines the different regulatory approaches adopted in comparable OECD countries, and reviews alternative models for payday regulation, in particular, the role played by responsible lending. The study also examines the consumer protection mechanisms now in existence in Australia in the National Consumer Credit Protection Act 2009 (Cth) (NCCP) and the National Credit Code (NCC) contained in Schedule 1 of that Act and in the Australian Securities and Investments Commission Act 2001 (Cth).

Post-operative CT assessment of interbody fusion two years after thoracoscopic scoliosis surgery

The relationship between radiologic union and clinical outcome in thoracoscopic scoliosis surgery is not clear, as apparent non-union of a spinal fusion does not always correspond to a poor clinical result. The aim of this study was to evaluate CT fusion rates 2yrs after thoracoscopic surgery, and to explore the relationship between fusion scores and rod diameter, graft type, fusion level, implant failure, and lateral position in the disc space. This study suggests that moderate fusion scores secure successful clinical outcomes in thoracoscopic scoliosis surgery.

Flow regime transition criteria for two-phase flow at reduced gravity conditions

Flow regime transition criteria are of practical importance for two-phase flow analyses at reduced gravity conditions. Here, flow regime transition criteria which take the friction pressure loss effect into account were studied in detail. Criteria at reduced gravity conditions were developed by extending an existing model with various experimental datasets taken at microgravity conditions showed satisfactory agreement. Sample computations of the model were performed at various gravity conditions, such as 0.196, 1.62, 3.71, and 9.81 m/s2 corresponding to micro-gravity and lunar, Martian and Earth surface gravity, respectively. It was found that the effect of gravity on bubbly-slug and slug-annular (churn) transitions in a two-phase flow system was more pronounced at low liquid flow conditions, whereas the gravity effect could be ignored at high mixture volumetric flux conditions. While for the annular flow transitions due to flow reversal and onset of dropset entrainment, higher superficial gas velocity was obtained at higher gravity level.

The social orders of family mealtime

This study examined the everyday practices of families within the context of family mealtime to investigate how members accomplished mealtime interactions. Using an ethnomethodological approach, conversation analysis and membership categorization analysis, the study investigated the interactional resources that family members used to assemble their social orders moment by moment during family mealtimes. While there is interest in mealtimes within educational policy, health research and the media, there remain few studies that provide fine-grained detail about how members produce the social activity of having a family meal. Findings from this study contribute empirical understandings about families and family mealtime. Two families with children aged 2 to 10 years were observed as they accomplished their everyday mealtime activities. Data collection took place in the family homes where family members video recorded their naturally occurring mealtimes. Each family was provided with a video camera for a one-month period and they decided which mealtimes they recorded, a method that afforded participants greater agency in the data collection process and made available to the analyst a window into the unfolding of the everyday lives of the families. A total of 14 mealtimes across the two families were recorded, capturing 347 minutes of mealtime interactions. Selected episodes from the data corpus, which includes centralised breakfast and dinnertime episodes, were transcribed using the Jeffersonian system. Three data chapters examine extended sequences of family talk at mealtimes, to show the interactional resources used by members during mealtime interactions. The first data chapter explores multiparty talk to show how the uniqueness of the occasion of having a meal influences turn design. It investigates the ways in which members accomplish two-party talk within a multiparty setting, showing how one child "tells" a funny story to accomplish the drawing together of his brothers as an audience. As well, this chapter identifies the interactional resources used by the mother to cohort her children to accomplish the choralling of grace. The second data chapter draws on sequential and categorical analysis to show how members are mapped to a locally produced membership category. The chapter shows how the mapping of members into particular categories is consequential for social order; for example, aligning members who belong to the membership category "had haircuts" and keeping out those who "did not have haircuts". Additional interactional resources such as echoing, used here to refer to the use of exactly the same words, similar prosody and physical action, and increasing physical closeness, are identified as important to the unfolding talk particularly as a way of accomplishing alignment between the grandmother and grand-daughter. The third and final data analysis chapter examines topical talk during family mealtimes. It explicates how members introduce topics of talk with an orientation to their co-participant and the way in which the take up of a topic is influenced both by the sequential environment in which it is introduced and the sensitivity of the topic. Together, these three data chapters show aspects of how family members participated in family mealtimes. The study contributes four substantive themes that emerged during the analytic process and, as such, the themes reflect what the members were observed to be doing. The first theme identified how family knowledge was relevant and consequential for initiating and sustaining interaction during mealtime with, for example, members buying into the talk of other members or being requested to help out with knowledge about a shared experience. Knowledge about members and their activities was evident with the design of questions evidencing an orientation to coparticipant’s knowledge. The second theme found how members used topic as a resource for social interaction. The third theme concerned the way in which members utilised membership categories for producing and making sense of social action. The fourth theme, evident across all episodes selected for analysis, showed how children’s competence is an ongoing interactional accomplishment as they manipulated interactional resources to manage their participation in family mealtime. The way in which children initiated interactions challenges previous understandings about children’s restricted rights as conversationalists. As well as making a theoretical contribution, the study offers methodological insight by working with families as research participants. The study shows the procedures involved as the study moved from one where the researcher undertook the decisions about what to videorecord to offering this decision making to the families, who chose when and what to videorecord of their mealtime practices. Evident also are the ways in which participants orient both to the video-camera and to the absent researcher. For the duration of the mealtime the video-camera was positioned by the adults as out of bounds to the children; however, it was offered as a "treat" to view after the mealtime was recorded. While situated within family mealtimes and reporting on the experiences of two families, this study illuminates how mealtimes are not just about food and eating; they are social. The study showed the constant and complex work of establishing and maintaining social orders and the rich array of interactional resources that members draw on during family mealtimes. The family’s interactions involved members contributing to building the social orders of family mealtime. With mealtimes occurring in institutional settings involving young children, such as long day care centres and kindergartens, the findings of this study may help educators working with young children to see the rich interactional opportunities mealtimes afford children, the interactional competence that children demonstrate during mealtimes, and the important role/s that adults may assume as co-participants in interactions with children within institutional settings.