Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci

Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

pi-conjugation and conformation in a semiconducting polymer: small angle x-ray scattering study

Small angle x-ray scattering (SAXS) in a poly[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV) solution has shown the important role of pi-electron conjugation in controlling the chain conformation and assembly. By increasing the extent of conjugation from 30 to 100%, the persistence length (l(p)) increases from 20 to 66 angstrom. Moreover, a pronounced second peak in the pair distribution function has been observed in a fully conjugated chain, at larger length scales. This feature indicates that the chain segments tend to self-assemble as the conjugation along the chain increases. Xylene enhances the rigidity of the PPV backbone to yield extended structures, while tetrahydrofuran solvates the side groups to form compact coils in which the lp is much shorter.

Structural mobility and transformations in globular proteins

Although globular proteins are endowed with well defined three-dimensional structures, they exhibit substantial mobility within the framework of the given threedimensional structure. The different types of mobility found in proteins by and large correspond to the different levels of organisational hierarchy in protein architecture. They are of considerable structural and functional significance, and can be broadly classified into(a) thermal and conformational fluctuations, (b) segmental mobility, (c) interdomain mobility and (d) intersubunit mobility. Protein crystallographic studies has provided a wealth of information on all of them. The temperature factors derived from X-ray diffraction studies provide a measure of atomic displacements caused by thermal and conformational fluctuations. The variation of displacement along the polypeptide chain have provided functionally significant information on the flexibility of different regions of the molecule in proteins such as myoglobin, lysozyme and prealbumin. Segmental mobility often involves the movement of a region or a segment of a molecule with respect to the rest, as in the transition between the apo and the holo structures of lactate dehydrogenase. It may also involve rigidification of a disordered region of the molecule as in the activation of the zymogens of serine proteases. Transitions between the apo and the holo structures of alcohol dehydrogenase,and between the free and the sugar bound forms of hexokinase, are good examples of interdomain mobility caused by hinge-bending. The capability of different domains to move semi-independently contributes greatly to the versatility of immunoglobulin molecules. Interdomain mobility in citrate synthase appears to be more complex and its study has led to an alternative description of domain closure. The classical and the most thoroughly studied case of intersubunit mobility is that in haemoglobin. The stereochemical mechanism of the action of this allosteric protein clearly brings out the functional subtilities that could be achieved through intersubunit movements. In addition to ligand binding and activation,environmental changes also often cause structural transformations. The reversible transformation between 2 Zn insulin and 4 Zn insulin is caused by changes in the ionic strength of the medium. Adenylate Kinase provides a good example for functionally significant reversible conformational transitions induced by variation in pH. Available evidences indicate that reversible structural transformations in proteins could also be caused by changes in the aqueous environment, including those in the amount of water surrounding protein molecules.

Efficient designs for sampling and subsampling in fisheries research based on ranked sets

Sampling strategies are developed based on the idea of ranked set sampling (RSS) to increase efficiency and therefore to reduce the cost of sampling in fishery research. The RSS incorporates information on concomitant variables that are correlated with the variable of interest in the selection of samples. For example, estimating a monitoring survey abundance index would be more efficient if the sampling sites were selected based on the information from previous surveys or catch rates of the fishery. We use two practical fishery examples to demonstrate the approach: site selection for a fishery-independent monitoring survey in the Australian northern prawn fishery (NPF) and fish age prediction by simple linear regression modelling a short-lived tropical clupeoid. The relative efficiencies of the new designs were derived analytically and compared with the traditional simple random sampling (SRS). Optimal sampling schemes were measured by different optimality criteria. For the NPF monitoring survey, the efficiency in terms of variance or mean squared errors of the estimated mean abundance index ranged from 114 to 199% compared with the SRS. In the case of a fish ageing study for Tenualosa ilisha in Bangladesh, the efficiency of age prediction from fish body weight reached 140%.

Improving Knowledge and Practices in Mango Supply Chains

Mangoes consigned to domestic markets suffered from fruit quality problems from 1997 to 2000. A high incidence of disease breakdown and green-ripe fruit resulted in loss of confidence by marketers, and reduced profits for everyone from grower to retailer. The ‘Better Mangoes’ project was initiated to identify where, and why quality was being lost, and to use this information to improve the knowledge and practices of supply chain businesses.

Molecular discrimination of Perna (Mollusca: Bivalvia) species using the polymerase chain reaction and species-specific mitochondrial primers

This work was prompted by the need to be able to identify the invasive mussel species, Perna viridis, in tropical Australian seas using techniques that do not rely solely on morphology. DNA-based molecular methods utilizing a polymerase chain reaction (PCR) approach were developed to distinguish unambiguously between the three species in the genus Perna. Target regions were portions of two mitochondrial genes, cox1 and nad4, and the intergenic spacer between these that occurs in at least two Perna species. Based on interspecific sequence comparisons of the nad4 gene, a conserved primer has been designed that can act as a forward primer in PCRs for any Perna species. Four reverse primers have also been designed, based on nad4 and intergenic spacer sequences, which yield species-specific products of different lengths when paired with the conserved forward primer. A further pair of primers has been designed that will amplify part of the cox1 gene of any Perna species, and possibly other molluscs, as a positive control to demonstrate that the PCR is working.

Improving knowledge and practices in fresh produce chains

A successful supply chain must delivery the right product, value and satisfaction to the end customer, and profitability for its participants. Critical to getting the product right is the practices used to produce and maintain product quality through the supply chain from production to sale to the end customer. This paper describes the approach used by a R&D team to add value to supply chains through improving knowledge and practices. The desired outcome is better produce quality for consumers and more control and less wastage for chain participants. The team worked with specific supply chains to identify areas for improvement and to develop, test and implement improved practices. The knowledge gained was communicated to the industry to gain wider adoption of results. Three conditions were identified as critical for practice change - motivation, knowledge, and capacity for change. For improvement in practices to occur, a business must be motivated and have the knowledge and capacity to improve. Two case studies of working with Australian supply chains (mango and melons) are presented to illustrate our participatory methodology. A key activity is monitoring produce quality and handling practices and conditions to demonstrate to participants the points where quality deterioration occurs in the supply chain. This participatory approach is successful because working with supply chain participants generates knowledge and solutions to real problems. It enables the participants to observe the effect of handling practices and conditions on produce quality, gain knowledge and assess the benefits of improvements. Where existing knowledge is not present, research is conducted to fill the knowledge gaps. IV International Conference on Managing Quality in Chains - The Integrated View on Fruits and Vegetables Quality

Evaluation of Charges for Power Transmission and Losses in Bilateral Power Contracts

The paper presents a method for transmission loss charge allocation in deregulated power systems based on Relative Electrical Distance (RED) concept. Based on RED between the generator and load nodes and the predefined bilateral power contracts, charge evaluation is carried out. Generally through some power exchange mechanism a set of bilateral contracts are determined that facilitate bilateral agreements between the generation and distribution entities. In this paper the possible charges incurred in meeting loads like generation charge, transmission charge and charge due to losses are evaluated. Case studies have been carried out on a few practical equivalent systems. Due to space limitation results for a sample 5 bus system are presented considering ideal load/generation power contracts and deviated load/generation power contracts. Extensive numerical testing indicates that the proposed allocation scheme produces loss allocations that are appropriate and that behave in a physically reasonable manner.

Destination image: identifying baseline perceptions of Brazil, Argentina and Chile in the nascent Australian long haul travel market

While the popularity of destination image research has increased exponentially in the literature, there has been relatively little published about perceptions held by international consumers of destinations in South America. The purpose of this paper is to report the findings of a research project that aimed to identify the baseline market perceptions of Brazil, Argentina and Chile amongst Australian residents, at the time of the emergence of this long haul market. Of interest was the extent to which Australians differentiate the three distinct countries versus perceiving the continent as a gestalt. These baseline perceptions enable the effectiveness of future marketing communications in Australia by the three national tourism offices to be monitored over time. Importance-Performance Analysis (IPA) is used as a practical analytical tool to guide decision makers. In terms of operationalising destination image, a key research finding was the very high ratio or participants using the ‘Don’t know’ (DK) option for each destination performance scale item. This finding has practical implications for the destination marketers, as well as for researchers engaged in destination image research in long haul and/or emerging markets.

Net radiation dynamics: performance of 20 daily net radiation models as related to model structure and intricacy in two climates.

We compared daily net radiation (Rn) estimates from 19 methods with the ASCE-EWRI Rn estimates in two climates: Clay Center, Nebraska (sub-humid) and Davis, California (semi-arid) for the calendar year. The performances of all 20 methods, including the ASCE-EWRI Rn method, were then evaluated against Rn data measured over a non-stressed maize canopy during two growing seasons in 2005 and 2006 at Clay Center. Methods differ in terms of inputs, structure, and equation intricacy. Most methods differ in estimating the cloudiness factor, emissivity (e), and calculating net longwave radiation (Rnl). All methods use albedo (a) of 0.23 for a reference grass/alfalfa surface. When comparing the performance of all 20 Rn methods with measured Rn, we hypothesized that the a values for grass/alfalfa and non-stressed maize canopy were similar enough to only cause minor differences in Rn and grass- and alfalfa-reference evapotranspiration (ETo and ETr) estimates. The measured seasonal average a for the maize canopy was 0.19 in both years. Using a = 0.19 instead of a = 0.23 resulted in 6% overestimation of Rn. Using a = 0.19 instead of a = 0.23 for ETo and ETr estimations, the 6% difference in Rn translated to only 4% and 3% differences in ETo and ETr, respectively, supporting the validity of our hypothesis. Most methods had good correlations with the ASCE-EWRI Rn (r2 > 0.95). The root mean square difference (RMSD) was less than 2 MJ m-2 d-1 between 12 methods and the ASCE-EWRI Rn at Clay Center and between 14 methods and the ASCE-EWRI Rn at Davis. The performance of some methods showed variations between the two climates. In general, r2 values were higher for the semi-arid climate than for the sub-humid climate. Methods that use dynamic e as a function of mean air temperature performed better in both climates than those that calculate e using actual vapor pressure. The ASCE-EWRI-estimated Rn values had one of the best agreements with the measured Rn (r2 = 0.93, RMSD = 1.44 MJ m-2 d-1), and estimates were within 7% of the measured Rn. The Rn estimates from six methods, including the ASCE-EWRI, were not significantly different from measured Rn. Most methods underestimated measured Rn by 6% to 23%. Some of the differences between measured and estimated Rn were attributed to the poor estimation of Rnl. We conducted sensitivity analyses to evaluate the effect of Rnl on Rn, ETo, and ETr. The Rnl effect on Rn was linear and strong, but its effect on ETo and ETr was subsidiary. Results suggest that the Rn data measured over green vegetation (e.g., irrigated maize canopy) can be an alternative Rn data source for ET estimations when measured Rn data over the reference surface are not available. In the absence of measured Rn, another alternative would be using one of the Rn models that we analyzed when all the input variables are not available to solve the ASCE-EWRI Rn equation. Our results can be used to provide practical information on which method to select based on data availability for reliable estimates of daily Rn in climates similar to Clay Center and Davis.

A framework for optimising capital investment and operations in livestock logistics

Despite the longevity, scale and importance of northern Australia's beef industry, recent disruptions to external markets have demonstrated a degree of vulnerability to shocks in the supply chain. Matching the industry's long-evident resilience to climatic variability with resilience to changes in markets and supply chains requires careful planning. One component of this is how investments in infrastructure will need to be planned to facilitate adaptive responses to market changes. This paper provides an outline of a modelling framework that links strategic and operational dynamic models of logistics along the supply chain from the property to the abattoir or port. A novelty of the methodology is that it takes into account the high granularity of individual livestock transport vehicle movements and the ability to scale up to an almost complete view of logistics costs across the entire beef industry of northern Australia. The paper illustrates how the methodology could be used to examine the effects of changes in logistics infrastructure on efficiency and costs using examples from the states of Northern Territory, Western Australia and Queensland.

Leadership and creativity in higher education

Leadership and creativity have received increasing attention from researchers in the field of higher education; however, empirical studies investigating these topics simultaneously are rare. In this study, the authors examined relationships between PhD students' perceptions of their advising professors' passive-avoidant, transactional, and transformational leadership behaviors and professors' ratings of their students' work-related creativity. Data were provided by 71 dyads of professors and PhD students. Consistent with expectations based on the leadership literature on followers' identification with their leaders, results showed that students' perceptions of professors' transformational leadership positively predicted professors' ratings of their students' creativity above and beyond students' perceptions of professors' passive-avoidant and transactional leadership. Contrary to expectations, students' perceptions of professors' passive-avoidant and transactional leadership did not significantly predict professors' ratings of students' creativity. Implications for future research on leadership and creativity as well as tentative practical applications of the findings in higher education settings are discussed.

Ionic Liquids and Microwaves in Promotion of Organic Synthesis : Friedel-Crafts reaction, deuterolabelling and O-Demethylation

The use of ionic liquids in chemical research has gained considerable interest and activity in recent years. Due to their unique and varied physicochemical properties, in comparison to molecular solvents, the potential applications for ionic liquids are enormous. The use of microwave irradiation, as a powerful dielectric heating technique, in synthetic organic chemistry has been known since 1986. Since then, it has gained significant recognition for its research and application in both academia and industry. The use of either ionic liquids or microwave irradiation in synthetic organic chemistry has been known to afford improved, alternative or complimentary selectivities, in comparison to traditional processes. In this study, the use of ionic liquids as solvents, co-solvents and catalytic media was explored in Friedel-Crafts, deuterolabelling and O-demethylation reactions. Alternative methods for the production of a variety of aromatic ketones using the Friedel-Crafts acylation methodology were investigated using ionic liquid catalyst or ionic liquid acidic additive systems. The disclosed methods, i.e. metal bistriflamides and chloroindate ionic liquids systems, possessed good catalytic activity in the synthesis of typical benzophenones. These catalytic systems were also recyclable. Microwave irradiation was found to be useful in the synthesis of various polyhydroxydeoxybenzoins and arylpropanones as synthetic precursors to naturally occurring or potentially bioactive compounds. Under optimized condition, the reaction occurred in only four minutes using systems such as [bmim][NTf2]/HNTf2 and [bmim][BF4]/BF3·OEt2. Naturally occurring polyphenols, such as isoflavones, can possess various types of biological or pharmacological activity. In particular, some are noted for their beneficial effects on human health. Isotopically labelled analogues of polyphenols are valuable as analytical standards in the quantification of these compounds from biological matrices. A new strategy for deuterolabelling of polyphenols was developed using ionic liquids as co-solvents and 35% DCl/D2O, as a cheap deuterium source, under microwave irradiation. Under these conditions, perdeuterated compounds were achieved in short reaction times, in high isotopic purity and in excellent yields. An O-demethylation reaction was developed, using an ionic liquid reaction medium with BBr3 for the deprotection of a variety methyl protected polyphenolic compounds, such as isoflavons and lignans. This deprotection procedure was found to be very practical as the reaction occurred under mild reaction conditions and in short reaction times. The isolation and purification steps were particularly straightforward and high yielding, in comparison to traditional methods.

Precipitation-induced runoff and leaching from milled peat mining mires by peat types : a comparative method for estimating the loading of water bodies during peat pruduction

Precipitation-induced runoff and leaching from milled peat mining mires by peat types: a comparative method for estimating the loading of water bodies during peat production. This research project in environmental geology has arisen out of an observed need to be able to predict more accurately the loading of watercourses with detrimental organic substances and nutrients from already existing and planned peat production areas, since the authorities capacity for insisting on such predictions covering the whole duration of peat production in connection with evaluations of environmental impact is at present highly limited. National and international decisions regarding monitoring of the condition of watercourses and their improvement and restoration require more sophisticated evaluation methods in order to be able to forecast watercourse loading and its environmental impacts at the stage of land-use planning and preparations for peat production.The present project thus set out from the premise that it would be possible on the basis of existing mire and peat data properties to construct estimates for the typical loading from production mires over the whole duration of their exploitation. Finland has some 10 million hectares of peatland, accounting for almost a third of its total area. Macroclimatic conditions have varied in the course of the Holocene growth and development of this peatland, and with them the habitats of the peat-forming plants. Temperatures and moisture conditions have played a significant role in determining the dominant species of mire plants growing there at any particular time, the resulting mire types and the accumulation and deposition of plant remains to form the peat. The above climatic, environmental and mire development factors, together with ditching, have contributed, and continue to contribute, to the existence of peat horizons that differ in their physical and chemical properties, leading to differences in material transport between peatlands in a natural state and mires that have been ditched or prepared for forestry and peat production. Watercourse loading from the ditching of mires or their use for peat production can have detrimental effects on river and lake environments and their recreational use, especially where oxygen-consuming organic solids and soluble organic substances and nutrients are concerned. It has not previously been possible, however, to estimate in advance the watercourse loading likely to arise from ditching and peat production on the basis of the characteristics of the peat in a mire, although earlier observations have indicated that watercourse loading from peat production can vary greatly and it has been suggested that differences in peat properties may be of significance in this. Sprinkling is used here in combination with simulations of conditions in a milled peat production area to determine the influence of the physical and chemical properties of milled peats in production mires on surface runoff into the drainage ditches and the concentrations of material in the runoff water. Sprinkling and extraction experiments were carried out on 25 samples of milled Carex (C) and Sphagnum (S) peat of humification grades H 2.5 8.5 with moisture content in the range 23.4 89% on commencement of the first sprinkling, which was followed by a second sprinkling 24 hours later. The water retention capacity of the peat was best, and surface runoff lowest, with Sphagnum and Carex peat samples of humification grades H 2.5 6 in the moisture content class 56 75%. On account of the hydrophobicity of dry peat, runoff increased in a fairly regular manner with drying of the sample from 55% to 24 30%. Runoff from the samples with an original moisture content over 55% increased by 63% in the second round of sprinkling relative to the first, as they had practically reached saturation point on the first occasion, while those with an original moisture content below 55% retained their high runoff in the second round, due to continued hydrophobicity. The well-humified samples (H 6.5 8.5) with a moisture content over 80% showed a low water retention capacity and high runoff in both rounds of sprinkling. Loading of the runoff water with suspended solids, total phosphorus and total nitrogen, and also the chemical oxygen demand (CODMn O2), varied greatly in the sprinkling experiment, depending on the peat type and degree of humification, but concentrations of the same substances in the two sprinklings were closely or moderately closely correlated and these correlations were significant. The concentrations of suspended solids in the runoff water observed in the simulations of a peat production area and the direct surface runoff from it into the drainage ditch system in response to rain (sprinkling intensity 1.27 mm/min) varied c. 60-fold between the degrees of humification in the case of the Carex peats and c. 150-fold for the Sphagnum peats, while chemical oxygen demand varied c. 30-fold and c. 50-fold, respectively, total phosphorus c. 60-fold and c. 66-fold, total nitrogen c. 65-fold and c. 195-fold and ammonium nitrogen c. 90-fold and c. 30-fold. The increases in concentrations in the runoff water were very closely correlated with increases in humification of the peat. The correlations of the concentrations measured in extraction experiments (48 h) with peat type and degree of humification corresponded to those observed in the sprinkler experiments. The resulting figures for the surface runoff from a peat production area into the drainage ditches simulated by means of sprinkling and material concentrations in the runoff water were combined with statistics on the mean extent of daily rainfall (0 67 mm) during the frost-free period of the year (May October) over an observation period of 30 years to yield typical annual loading figures (kg/ha) for suspended solids (SS), chemical oxygen demand of organic matter (CODmn O2), total phosphorus (tot. P) and total nitrogen (tot. N) entering the ditches with respect to milled Carex (C) and Sphagnum (S) peats of humification grades H 2.5 8.5. In order to calculate the loading of drainage ditches from a milled peat production mire with the aid of these annual comparative values (in kg/ha), information is required on the properties of the intended production mire and its peat. Once data are available on the area of the mire, its peat depth, peat types and their degrees of humification, dry matter content, calorific value and corresponding energy content, it is possible to produce mutually comparable estimates for individual mires with respect to the annual loading of the drainage ditch system and the surrounding watercourse for the whole service life of the production area, the duration of this service life, determinations of energy content and the amount of loading per unit of energy generated (kg/MWh). In the 8 mires in the Köyhäjoki basin, Central Ostrobothnia, taken as an example, the loading of suspended solids (SS) in the drainage ditch networks calculated on the basis of the typical values obtained here and existing mire and peat data and expressed per unit of energy generated varied between the mires and horizons in the range 0.9 16.5 kg/MWh. One of the aims of this work was to develop means of making better use of existing mire and peat data and the results of corings and other field investigations. In this respect combination of the typical loading values (kg/ha) obtained here for S, SC, CS and C peats and the various degrees of humification (H 2.5 8.5) with the above mire and peat data by means of a computer program for the acquisition and handling of such data would enable all the information currently available and that deposited in the system in the future to be used for defining watercourse loading estimates for mires and comparing them with the corresponding estimates of energy content. The intention behind this work has been to respond to the challenge facing the energy generation industry to find larger peat production areas that exert less loading on the environment and to that facing the environmental authorities to improve the means available for estimating watercourse loading from peat production and its environmental impacts in advance. The results conform well to the initial hypothesis and to the goals laid down for the research and should enable watercourse loading from existing and planned peat production to be evaluated better in the future and the resulting impacts to be taken into account when planning land use and energy generation. The advance loading information available in this way would be of value in the selection of individual peat production areas, the planning of their exploitation, the introduction of water protection measures and the planning of loading inspections, in order to achieve controlled peat production that pays due attention to environmental considerations.

On linear order and computation : The expressiveness of interactive computations on linear orders and computations indexed by ordinals

We solve the Dynamic Ehrenfeucht-Fra\"iss\'e Game on linear orders for both players, yielding a normal form for quantifier-rank equivalence classes of linear orders in first-order logic, infinitary logic, and generalized-infinitary logics with linearly ordered clocks. We show that Scott Sentences can be manipulated quickly, classified into local information, and consistency can be decided effectively in the length of the Scott Sentence. We describe a finite set of linked automata moving continuously on a linear order. Running them on ordinals, we compute the ordinal truth predicate and compute truth in the constructible universe of set-theory. Among the corollaries are a study of semi-models as efficient database of both model-theoretic and formulaic information, and a new proof of the atomicity of the Boolean algebra of sentences consistent with the theory of linear order -- i.e., that the finitely axiomatized theories of linear order are dense.