Genetic association of the KLK4 locus with risk of prostate cancer

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Multilevel determinants of breast cancer survival : association with geographic remoteness and area-level socioeconomic disadvantage

A major priority for cancer control agencies is to reduce geographical inequalities in cancer outcomes. While the poorer breast cancer survival among socioeconomically disadvantaged women is well established, few studies have looked at the independent contribution that area- and individual-level factors make to breast cancer survival. Here we examine relationships between geographic remoteness, area-level socioeconomic disadvantage and breast cancer survival after adjustment for patients’ socio- demographic characteristics and stage at diagnosis. Multilevel logistic regression and Markov chain Monte Carlo simulation were used to analyze 18 568 breast cancer cases extracted from the Queensland Cancer Registry for women aged 30 to 70 years diagnosed between 1997 and 2006 from 478 Statistical Local Areas in Queensland, Australia. Independent of individual-level factors, area-level disadvantage was associated with breast-cancer survival (p=0.032). Compared to women in the least disadvantaged quintile (Quintile 5), women diagnosed while resident in one of the remaining four quintiles had significantly worse survival (OR 1.23, 1.27, 1.30, 1.37 for Quintiles 4, 3, 2 and 1 respectively).) Geographic remoteness was not related to lower survival after multivariable adjustment. There was no evidence that the impact of area-level disadvantage varied by geographic remoteness. At the individual level, Indigenous status, blue collar occupations and advanced disease were important predictors of poorer survival. A woman’s survival after a diagnosis of breast cancer depends on the socio-economic characteristics of the area where she lives, independently of her individual-level characteristics. It is crucial that the underlying reasons for these inequalities be identified to appropriately target policies, resources and effective intervention strategies.

Three dimensional simulation of a parabolic trough concentrator thermal collector

Parabolic Trough Concentrators (PTC) are the most proven solar collectors for solar thermal power plants, and are suitable for concentrating photovoltaic (CPV) applications. PV cells are sensitive to spatial uniformity of incident light and the cell operating temperature. This requires the design of CPV-PTCs to be optimised both optically and thermally. Optical modelling can be performed using Monte Carlo Ray Tracing (MCRT), with conjugate heat transfer (CHT) modelling using the computational fluid dynamics (CFD) to analyse the overall designs. This paper develops and evaluates a CHT simulation for a concentrating solar thermal PTC collector. It uses the ray tracing work by Cheng et al. (2010) and thermal performance data for LS-2 parabolic trough used in the SEGS III-VII plants from Dudley et al. (1994). This is a preliminary step to developing models to compare heat transfer performances of faceted absorbers for concentrating photovoltaic (CPV) applications. Reasonable agreement between the simulation results and the experimental data confirms the reliability of the numerical model. The model explores different physical issues as well as computational issues for this particular kind of system modeling. The physical issues include the resultant non-uniformity of the boundary heat flux profile and the temperature profile around the tube, and uneven heating of the HTF. The numerical issues include, most importantly, the design of the computational domain/s, and the solution techniques of the turbulence quantities and the near-wall physics. This simulation confirmed that optical simulation and the computational CHT simulation of the collector can be accomplished independently.

A preconditioned Lanczos method for space-fractional reaction-diffusion equations on two-dimensional unstructured meshes

We consider a two-dimensional space-fractional reaction diffusion equation with a fractional Laplacian operator and homogeneous Neumann boundary conditions. The finite volume method is used with the matrix transfer technique of Ilić et al. (2006) to discretise in space, yielding a system of equations that requires the action of a matrix function to solve at each timestep. Rather than form this matrix function explicitly, we use Krylov subspace techniques to approximate the action of this matrix function. Specifically, we apply the Lanczos method, after a suitable transformation of the problem to recover symmetry. To improve the convergence of this method, we utilise a preconditioner that deflates the smallest eigenvalues from the spectrum. We demonstrate the efficiency of our approach for a fractional Fisher’s equation on the unit disk.

Power of QTL detection using association tests with family controls

The power of testing for a population-wide association between a biallelic quantitative trait locus and a linked biallelic marker locus is predicted both empirically and deterministically for several tests. The tests were based on the analysis of variance (ANOVA) and on a number of transmission disequilibrium tests (TDT). Deterministic power predictions made use of family information, and were functions of population parameters including linkage disequilibrium, allele frequencies, and recombination rate. Deterministic power predictions were very close to the empirical power from simulations in all scenarios considered in this study. The different TDTs had very similar power, intermediate between one-way and nested ANOVAs. One-way ANOVA was the only test that was not robust against spurious disequilibrium. Our general framework for predicting power deterministically can be used to predict power in other association tests. Deterministic power calculations are a powerful tool for researchers to plan and evaluate experiments and obviate the need for elaborate simulation studies.

The association between motivation in school physical education and self-reported physical activity during Finnish junior high school : a self-determination theory approach

The main purpose of this longitudinal study was to investigate the role of motivational climates, perceived competence and motivational regulations as antecedents of self-reported physical activity during junior high school years. The participants included 237 Finnish students (101 girls, 136 boys) that were 13 years old at the first stage of the study. Students completed the motivational climate and perceived competence questionnaires at Grade 7, motivation towards physical education questionnaire at Grade 8, and self-reported physical activity questionnaire at Grade 9. A path analysis revealed a path from task-involving motivational climate via perceived competence and intrinsic motivation to self-reported physical activity. Perceived competence and intrinsic motivation were statistically significant mediators between task-involving motivational climate and self-reported physical activity. This finding supports the four-stage causal sequence model of motivation.

A note on the ‘Linsanity’ of measuring the relative efficiency of National Basketball Association guards

This note examines the productive efficiency of 62 starting guards during the 2011/12 National Basketball Association (NBA) season. This period coincides with the phenomenal and largely unanticipated performance of New York Knicks’ starting point guard Jeremy Lin and the attendant public and media hype known as Linsanity. We employ a data envelopment analysis (DEA) approach that includes allowance for an undesirable output, here turnovers per game, with the desirable outputs of points, rebounds, assists, steals and blocks per game and an input of minutes per game. The results indicate that depending upon the specification, between 29% and 42% of NBA guards are fully efficient, including Jeremy Lin, with a mean inefficiency of 3.7% and 19.2%. However, while Jeremy Lin is technically efficient, he seldom serves as a benchmark for inefficient players, at least when compared with established players such as Chris Paul and Dwayne Wade. This suggests the uniqueness of Jeremy Lin's productive solution and may explain why his unique style of play, encompassing individual brilliance, unselfish play and team leadership, is of such broad public appeal.

Ureaplasma parvum multiple banded antigen (MBA) size variation - association with fetal inflammation in a sheep model (Published abstract)

Background: Ureaplasma species are the most prevalent isolates from women who deliver preterm. The MBA, a surface exposed lipoprotein, is a key virulence factor of ureaplasmas. We investigated MBA variation after chronic and acute intra-amniotic (IA) ureaplasma infections. Method: U. parvum serovar 3 (2x104 colony-forming-units) was injected IA into pregnant ewes at: 55 days gestation (d, term = 145d) (n=8); 117d (n=8) and 121d (n=8). Fetuses were delivered surgically (124d) and ureaplasmas cultured from amniotic fluid (AF), chorioamnion, fetal lung (FL) and umbilical cord were tested by western blot and PCR assays to demonstrate MBA and mba gene variation respectively. Tissue sections were sectioned and stained by haemotoxylin and eosin and inflammatory cell counts and pathology were reported (blinded to outcome). Results: Numerous MBA/mba variants were generated in vivo after chronic exposure to ureaplasma infection but after acute infection no variants (3d) or very few variants (7d) were generated. Identical MBA variants were detected within the AF and FL but different ureaplasma variants were detected within chorioamnion specimens. The severity of inflammation within chronically infected tissues varied between animals ranging from no inflammation to severe inflammation with/without fibrosis. Chorioamnion, FL and cord from the same animal demonstrated the same degree of inflammation. Conclusions: MBA/mba variation in vivo occurred after the initiation of the host immune response and we propose that ureaplasmas vary the MBA antigen to evade the host immune response. In some animals there was no inflammation despite colonisation with high numbers of ureaplasmas.

Summarization of association rules in multi-tier granule mining

It is a big challenge to find useful associations in databases for user specific needs. The essential issue is how to provide efficient methods for describing meaningful associations and pruning false discoveries or meaningless ones. One major obstacle is the overwhelmingly large volume of discovered patterns. This paper discusses an alternative approach called multi-tier granule mining to improve frequent association mining. Rather than using patterns, it uses granules to represent knowledge implicitly contained in databases. It also uses multi-tier structures and association mappings to represent association rules in terms of granules. Consequently, association rules can be quickly accessed and meaningless association rules can be justified according to the association mappings. Moreover, the proposed structure is also an precise compression of patterns which can restore the original supports. The experimental results shows that the proposed approach is promising.

Two novel numerical methods for solving the two-dimensional fractional Fitzhugh-Nagumo-monodomain model

Fractional mathematical models represent a new approach to modelling complex spatial problems in which there is heterogeneity at many spatial and temporal scales. In this paper, a two-dimensional fractional Fitzhugh-Nagumo-monodomain model with zero Dirichlet boundary conditions is considered. The model consists of a coupled space fractional diffusion equation (SFDE) and an ordinary differential equation. For the SFDE, we first consider the numerical solution of the Riesz fractional nonlinear reaction-diffusion model and compare it to the solution of a fractional in space nonlinear reaction-diffusion model. We present two novel numerical methods for the two-dimensional fractional Fitzhugh-Nagumo-monodomain model using the shifted Grunwald-Letnikov method and the matrix transform method, respectively. Finally, some numerical examples are given to exhibit the consistency of our computational solution methodologies. The numerical results demonstrate the effectiveness of the methods.

Changes in Knee Biomechanics After a Hip-Abductor Strengthening Protocol for Runners With Patellofemoral Pain Syndrome

Context: Very few authors have investigated the relationship between hip-abductor muscle strength and frontal-plane knee mechanics during running. Objective: To investigate this relationship using a 3-week hip-abductor muscle-strengthening program to identify changes in strength, pain, and biomechanics in runners with patellofemoral pain syndrome (PFPS). Design: Cohort study. Setting: University-based clinical research laboratory. Patients or Other Participants: Fifteen individuals (5 men, 10 women) with PFPS and 10 individuals without PFPS (4 men, 6 women) participated. Intervention(s): The patients with PFPS completed a 3-week hip-abductor strengthening protocol; control participants did not. Main Outcome Measure(s): The dependent variables of interest were maximal isometric hip-abductor muscle strength, 2-dimensional peak knee genu valgum angle, and stride-to-stride knee-joint variability. All measures were recorded at baseline and 3 weeks later. Between-groups differences were compared using repeated-measures analyses of variance. Results: At baseline, the PFPS group exhibited reduced strength, no difference in peak genu valgum angle, and increased stride-to-stride knee-joint variability compared with the control group. After the 3-week protocol, the PFPS group demonstrated increased strength, less pain, no change in peak genu valgum angle, and reduced stride-to-stride knee-joint variability compared with baseline. Conclusions: A 3-week hip-abductor muscle-strengthening protocol was effective in increasing muscle strength and decreasing pain and stride-to-stride knee-joint variability in individuals with PFPS. However, concomitant changes in peak knee genu valgum angle were not observed.

Non-contact ACL injuries : association with clegg soil impact test values for sports fields, soil moisture and prevailing weather

Introduction: There is a recognised relationship between dry weather conditions and increased risk of anterior cruciate ligament (ACL) injury. Previous studies have identified 28 day evaporation as an important weather-based predictor of non-contact ACL injuries in professional Australian Football League matches. The mechanism of non-contact injury to the ACL is believed to increased traction and impact forces between footwear and playing surface. Ground hardness and the amount and quality of grass are factors that would most likely influence this and are inturn, related to the soil moisture content and prevailing weather conditions. This paper explores the relationship between soil moisture content, preceding weather conditions and the Clegg Soil Impact Test (CSIT) which is an internationally recognised standard measure of ground hardness for sports fields. Methodology: The 2.25 kg Clegg Soil Impact Test and a pair of 12 cm soil moisture probes were used to measure ground hardness and percentage moisture content. Five football fields were surveyed at 13 prescribed sites just before seven football matches from October 2008 to January 2009 (an FC Women’s WLeague team). Weather conditions recorded at the nearest weather station were obtained from the Bureau of Meteorology website and total rainfall less evaporation was calculated for 7 and 28 days prior to each match. All non-contact injuries occurring during match play and their location on the field were recorded. Results/conclusions: Ground hardness varied between CSIT 5 and 17 (x10G) (8 is considered a good value for sports fields). Variations within fields were typically greatest in the centre and goal areas. Soil moisture ranged from 3 to 40% with some fields requiring twice the moisture content of others to maintain similar CSIT values. There was a non-linear, negative relationship for ground hardness versus moisture content and a linear relationship with weather (R2, of 0.30 and 0.34, respectively). Three non-contact ACL injuries occurred during the season. Two of these were associated with hard and variable ground conditions.

Hydrogen bonding in two ammonium salts of 5-sulfosalicylic acid : ammonium 3-carboxy-4-hydroxybenzenesulfonate monohydrate and triammonium 3-carboxy-4-hydroxybenzenesulfonate 3-carboxylato-4-hydroxybenzenesulfonate

The structures of two ammonium salts of 3-carboxy-4-hydroxybenzenesulfonic acid (5-sulfosalicylic acid, 5-SSA) have been determined at 200 K. In the 1:1 hydrated salt, ammonium 3-carboxy-4-hydroxybenzenesulfonate monohydrate, NH4+·C7H5O6S-·H2O, (I), the 5-SSA- monoanions give two types of head-to-tail laterally linked cyclic hydrogen-bonding associations, both with graph-set R44(20). The first involves both carboxylic acid O-HOwater and water O-HOsulfonate hydrogen bonds at one end, and ammonium N-HOsulfonate and N-HOcarboxy hydrogen bonds at the other. The second association is centrosymmetric, with end linkages through water O-HOsulfonate hydrogen bonds. These conjoined units form stacks down c and are extended into a three-dimensional framework structure through N-HO and water O-HO hydrogen bonds to sulfonate O-atom acceptors. Anhydrous triammonium 3-carboxy-4-hydroxybenzenesulfonate 3-carboxylato-4-hydroxybenzenesulfonate, 3NH4+·C7H4O6S2-·C7H5O6S-, (II), is unusual, having both dianionic 5-SSA2- and monoanionic 5-SSA- species. These are linked by a carboxylic acid O-HO hydrogen bond and, together with the three ammonium cations (two on general sites and the third comprising two independent half-cations lying on crystallographic twofold rotation axes), give a pseudo-centrosymmetric asymmetric unit. Cation-anion hydrogen bonding within this layered unit involves a cyclic R33(8) association which, together with extensive peripheral N-HO hydrogen bonding involving both sulfonate and carboxy/carboxylate acceptors, gives a three-dimensional framework structure. This work further demonstrates the utility of the 5-SSA- monoanion for the generation of stable hydrogen-bonded crystalline materials, and provides the structure of a dianionic 5-SSA2- species of which there are only a few examples in the crystallographic literature.

Proton-transfer compounds with 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (sulfamethazine): the structures and hydrogen-bonding in the salts with 5-nitrosalicylic acid and picric acid

The structures of the anhydrous proton-transfer compounds of the sulfa drug sulfamethazine with 5-nitrosalicylic acid and picric acid, namely 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2-hydroxy-5-nitrobenzoate, C12H15N4O2S(+)·C7H4NO4(-), (I), and 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2,4,6-trinitrophenolate, C12H15N4O2S(+)·C6H2N3O7(-), (II), respectively, have been determined. In the asymmetric unit of (I), there are two independent but conformationally similar cation-anion heterodimer pairs which are formed through duplex intermolecular N(+)-H...Ocarboxylate and N-H...Ocarboxylate hydrogen-bond pairs, giving a cyclic motif [graph set R2(2)(8)]. These heterodimers form separate and different non-associated substructures through aniline N-H...O hydrogen bonds, one one-dimensional, involving carboxylate O-atom acceptors, the other two-dimensional, involving both carboxylate and hydroxy O-atom acceptors. The overall two-dimensional structure is stabilized by π-π interactions between the pyrimidinium ring and the 5-nitrosalicylate ring in both heterodimers [minimum ring-centroid separation = 3.4580 (8) Å]. For picrate (II), the cation-anion interaction involves a slightly asymmetric chelating N-H...O R2(1)(6) hydrogen-bonding association with the phenolate O atom, together with peripheral conjoint R1(2)(6) interactions between the same N-H groups and O atoms of the ortho-related nitro groups. An inter-unit amine N-H...Osulfone hydrogen bond gives one-dimensional chains which extend along a and inter-associate through π-π interactions between the pyrimidinium rings [centroid-centroid separation = 3.4752 (9) Å]. The two structures reported here now bring to a total of four the crystallographically characterized examples of proton-transfer salts of sulfamethazine with strong organic acids.