Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript

Abstract Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P = 3.9 × 10−22). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P = 1.9 × 10−34). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk.

Abundance of introduced species at home predicts abundance away in herbaceous communities

Many ecosystems worldwide are dominated by introduced plant species, leading to loss of biodiversity and ecosystem function. A common but rarely tested assumption is that these plants are more abundant in introduced vs. native communities, because ecological or evolutionary-based shifts in populations underlie invasion success. Here, data for 26 herbaceous species at 39 sites, within eight countries, revealed that species abundances were similar at native (home) and introduced (away) sites – grass species were generally abundant home and away, while forbs were low in abundance, but more abundant at home. Sites with six or more of these species had similar community abundance hierarchies, suggesting that suites of introduced species are assembling similarly on different continents. Overall, we found that substantial changes to populations are not necessarily a pre-condition for invasion success and that increases in species abundance are unusual. Instead, abundance at home predicts abundance away, a potentially useful additional criterion for biosecurity programmes.

Human proximal tubule epithelial cells modulate autologous dendritic cell function

Background We have previously demonstrated that human kidney proximal tubule epithelial cells (PTEC) are able to modulate autologous T and B lymphocyte responses. It is well established that dendritic cells (DC) are responsible for the initiation and direction of adaptive immune responses and that these cells occur in the renal interstitium in close apposition to PTEC under inflammatory disease settings. However, there is no information regarding the interaction of PTEC with DC in an autologous human context. Methods Human monocytes were differentiated into monocyte-derived DC (MoDC) in the absence or presence of primary autologous activated PTEC and matured with polyinosinic:polycytidylic acid [poly(I:C)], while purified, pre-formed myeloid blood DC (CD1c+ BDC) were cultured with autologous activated PTEC in the absence or presence of poly(I:C) stimulation. DC responses were monitored by surface antigen expression, cytokine secretion, antigen uptake capacity and allogeneic T-cell-stimulatory ability. Results The presence of autologous activated PTEC inhibited the differentiation of monocytes to MoDC. Furthermore, MoDC differentiated in the presence of PTEC displayed an immature surface phenotype, efficient phagocytic capacity and, upon poly(I:C) stimulation, secreted low levels of pro-inflammatory cytokine interleukin (IL)-12p70, high levels of anti-inflammatory cytokine IL-10 and induced weak Th1 responses. Similarly, pre-formed CD1c+ BDC matured in the presence of PTEC exhibited an immature tolerogenic surface phenotype, strong endocytic and phagocytic ability and stimulated significantly attenuated T-cell proliferative responses. Conclusions Our data suggest that activated PTEC regulate human autologous immunity via complex interactions with DC. The ability of PTEC to modulate autologous DC function has important implications for the dampening of pro-inflammatory immune responses within the tubulointerstitium in renal injuries. Further dissection of the mechanisms of PTEC modulation of autologous immune responses may offer targets for therapeutic intervention in renal medicine.

Impact and energy absorption of road safety barriers by coupled SPH/FEM

Road safety barriers are used to minimise the severity of road accidents and protect lives and property. There are several types of barrier in use today. This paper reports the initial phase of research carried out to study the impact response of portable water-filled barrier (PWFB) which has the potential to absorb impact energy and hence provide crash mitigation under low to moderate speeds. Current research on the impact and energy absorption capacity of water-filled road safety barriers is limited due to the complexity of fluid-structure interaction under dynamic impact. In this paper, a novel fluid-structure interaction method is developed based on the combination of Smooth Particle Hydrodynamics (SPH) and Finite Element Method (FEM). The sloshing phenomenon of water inside a PWFB is investigated to explore the energy absorption capacity of water under dynamic impact. It was found that water plays an important role in energy absorption. The coupling analysis developed in this paper will provide a platform to further the research in optimising the behaviour of the PWFB. The effect of the amount of water on its energy absorption capacity is investigated and the results have practical applications in the design of PWFBs.

Designing a self-service technology to increase self-efficacy and maintain breastfeeding

Despite the significant health benefits attributed to breastfeeding, rates in countries, such as Australia, continue to remain static or to decline. Typically, the tangible support offered for women to support breastfeeding behaviours takes the form of face-to-face advice from health professionals, peer counselling via not-for-profit organizations such as the ABA, and provision of information through websites, pamphlets, and books. Prior research indicates that face-to-face support is more effective than telephone contact (Britton, McCormic, Renfrew, Wade, & King, 2009). Given the increasing costs associated with the provision of personalized face-to-face professional support and the need for some women to maximize privacy, discretion, and judgment-free consultations, there is a gap that could be filled by the use of m-technologies such as text messaging and other social media. The research team developed MumBubConnect; a two-way SMS system which combined the personalized aspects of face-to-face contact but maintained levels of privacy. The use of SMS was immediate, portable, and overcame many of the barriers associated with embarrassment. An Page 205 of 312 online survey of 130 breastfeeding mothers indicated that MumBubConnect facilitated the seeking of social support using m-technology, increased self-efficacy and maintained the desire behaviour.

Water-based exercise for patients with chronic arm lymphedema : a randomized controlled pilot trial

Objective: To evaluate the feasibility and effect of a water-based exercise (WBE) program on lymphedema status and shoulder range of motion (ROM) among women with breast cancer related lymphedema. Design: Single-blinded, randomized controlled pilot trial. Twenty-nine eligible breast cancer survivors (median 10 years after surgery) with arm lymphedema (median 21% inter limb difference) were included and randomized into intervention (n= 15) or control (n=14). Twenty-five participants completed the study. The intervention was at least twice weekly WBE for 8 weeks; supervised initially but performed independently during the study period. Outcomes of interest were feasibility as measured by retention and adherence, lymphedema status as measured by optoelectronic perometry, bioimpedance spectroscopy and tissue dielectric constant, and shoulder range of motion (ROM) as measured by goniometer. Results: Four participants were not measured at post-intervention and were not included in the analysis (retention). Four participants in the intervention group did not perform the minimum WBE criteria set (adherence). No effect was found on lymphedema status. Compared to the control group, median ROM change for flexion was 6 (1-10) degrees (p<0.001) and 6 (0-15.5) degrees (p=0,07) for external rotation. Clinically relevant increase in the intervention group was found for 36% in flexion (p≤0.05) and (57%) in external rotation (p≤0.05) compared to controls. Conclusions: This study shows WBE is feasible for breast cancer survivors with arm lymphedema and that shoulder ROM can be improved years after cancer treatment has been completed.

Orthogonality defect and reduced search-space size for solving integer least-squares problems

In the context of ambiguity resolution (AR) of Global Navigation Satellite Systems (GNSS), decorrelation among entries of an ambiguity vector, integer ambiguity search and ambiguity validations are three standard procedures for solving integer least-squares problems. This paper contributes to AR issues from three aspects. Firstly, the orthogonality defect is introduced as a new measure of the performance of ambiguity decorrelation methods, and compared with the decorrelation number and with the condition number which are currently used as the judging criterion to measure the correlation of ambiguity variance-covariance matrix. Numerically, the orthogonality defect demonstrates slightly better performance as a measure of the correlation between decorrelation impact and computational efficiency than the condition number measure. Secondly, the paper examines the relationship of the decorrelation number, the condition number, the orthogonality defect and the size of the ambiguity search space with the ambiguity search candidates and search nodes. The size of the ambiguity search space can be properly estimated if the ambiguity matrix is decorrelated well, which is shown to be a significant parameter in the ambiguity search progress. Thirdly, a new ambiguity resolution scheme is proposed to improve ambiguity search efficiency through the control of the size of the ambiguity search space. The new AR scheme combines the LAMBDA search and validation procedures together, which results in a much smaller size of the search space and higher computational efficiency while retaining the same AR validation outcomes. In fact, the new scheme can deal with the case there are only one candidate, while the existing search methods require at least two candidates. If there are more than one candidate, the new scheme turns to the usual ratio-test procedure. Experimental results indicate that this combined method can indeed improve ambiguity search efficiency for both the single constellation and dual constellations respectively, showing the potential for processing high dimension integer parameters in multi-GNSS environment.

The use of computerised simulators for training of transthoracic and transoesophageal echocardiography. The future of echocardiographic training?

Echocardiography is the commonest form of non-invasive cardiac imaging and is fundamental to patient management. However, due to its methodology, it is also operator dependent. There are well defined pathways in training and ongoing accreditation to achieve and maintain competency. To satisfy these requirements, significant time has to be dedicated to scanning patients, often in the time pressured clinical environment. Alternative, computer based training methods are being considered to augment echocardiographic training. Numerous advances in technology have resulted in the development of interactive programmes and simulators to teach trainees the skills to perform particular procedures, including transthoracic and transoesophageal echocardiography. 82 sonographers and TOE proceduralists utilised an echocardiographic simulator and assessed its utility using defined criteria. 40 trainee sonographers assessed the simulator and were taught how to obtain an apical 2 chamber (A2C) view and image the superior vena cava (SVC). 100% and 88% found the simulator useful in obtaining the SVC or A2C view respectively. All users found it easy to use and the majority found it helped with image acquisition and interpretation. 42 attendees of a TOE training day utilising the simulator assessed the simulator with 100% finding it easy to use, as well as the augmented reality graphics benefiting image acquisition. 90% felt that it was realistic. This study revealed that both trainee sonographers and TOE proceduralists found the simulation process was realistic, helped in image acquisition and improved assessment of spatial relationships. Echocardiographic simulators may play an important role in the future training of echocardiographic skills.

Development of a food frequency questionnaire for Sri Lankan adults

Abstract (provisional) Background Food Frequency Questionnaires (FFQs) are commonly used in epidemiologic studies to assess long-term nutritional exposure. Because of wide variations in dietary habits in different countries, a FFQ must be developed to suit the specific population. Sri Lanka is undergoing nutritional transition and diet-related chronic diseases are emerging as an important health problem. Currently, no FFQ has been developed for Sri Lankan adults. In this study, we developed a FFQ to assess the regular dietary intake of Sri Lankan adults. Methods A nationally representative sample of 600 adults was selected by a multi-stage random cluster sampling technique and dietary intake was assessed by random 24-h dietary recall. Nutrient analysis of the FFQ required the selection of foods, development of recipes and application of these to cooked foods to develop a nutrient database. We constructed a comprehensive food list with the units of measurement. A stepwise regression method was used to identify foods contributing to a cumulative 90% of variance to total energy and macronutrients. In addition, a series of photographs were included. Results We obtained dietary data from 482 participants and 312 different food items were recorded. Nutritionists grouped similar food items which resulted in a total of 178 items. After performing step-wise multiple regression, 93 foods explained 90% of the variance for total energy intake, carbohydrates, protein, total fat and dietary fibre. Finally, 90 food items and 12 photographs were selected. Conclusion We developed a FFQ and the related nutrient composition database for Sri Lankan adults. Culturally specific dietary tools are central to capturing the role of diet in risk for chronic disease in Sri Lanka. The next step will involve the verification of FFQ reproducibility and validity.

Rate of torque and electromyographic development during anticipated eccentric contraction is lower in previously strained hamstrings

Background: Hamstring strain injuries are prevalent in sport and re-injury rates have been high for many years. Whilst much focus has centred on the impact of previous hamstring strain injury on maximal eccentric strength, high rates of torque development is also of interest, given the important role of the hamstrings during the terminal swing phase of running. The impact of prior strain injury on myoelectrical activity of the hamstrings during tasks requiring high rates of torque development has received little attention. Purpose: To determine if recreational athletes with a history of unilateral hamstring strain injury, who have returned to training and competition, will exhibit lower levels of myoelectrical activity during eccentric contraction, rate of torque development and impulse 30, 50 and 100ms after the onset of myoelectrical activity or torque development in the previously injured limb compared to the uninjured limb. Study design: Case-control study Methods: Twenty-six recreational athletes were recruited. Of these, 13 athletes had a history of unilateral hamstring strain injury (all confined to biceps femoris long head) and 13 had no history of hamstring strain injury. Following familiarisation, all athletes undertook isokinetic dynamometry testing and surface electromyography assessment of the biceps femoris long head and medial hamstrings during eccentric contractions at -60 and -1800.s-1. Results: In the injured limb of the injured group, compared to the contralateral uninjured limb rate of torque development and impulse was lower during -600.s-1 eccentric contractions at 50 (RTD, injured limb = 312.27 ± 191.78Nm.s-1 vs. uninjured limb = 518.54 ± 172.81Nm.s-1, p=0.008; IMP, injured limb = 0.73 ± 0.30 Nm.s vs. uninjured limb = 0.97 ± 0.23 Nm.s, p=0.005) and 100ms (RTD, injured limb = 280.03 ± 131.42Nm.s-1 vs. uninjured limb = 460.54.54 ± 152.94Nm.s-1,p=0.001; IMP, injured limb = 2.15 ± 0.89 Nm.s vs. uninjured limb = 3.07 ± 0.63 Nm.s, p<0.001) after the onset of contraction. Biceps femoris long head muscle activation was lower at 100ms at both contraction speeds (-600.s-1, normalised iEMG activity (x1000), injured limb = 26.25 ± 10.11 vs. uninjured limb 33.57 ± 8.29, p=0.009; -1800.s-1, normalised iEMG activity (x1000), injured limb = 31.16 ± 10.01 vs. uninjured limb 39.64 ± 8.36, p=0.009). Medial hamstring activation did not differ between limbs in the injured group. Comparisons in the uninjured group showed no significant between limbs difference for any variables. Conclusion: Previously injured hamstrings displayed lower rate of torque development and impulse during slow maximal eccentric contraction compared to the contralateral uninjured limb. Lower myoelectrical activity was confined to the biceps femoris long head. Regardless of whether these deficits are the cause of or the result of injury, these findings could have important implications for hamstring strain injury and re-injury. Particularly, given the importance of high levels of muscle activity to bring about specific muscular adaptations, lower levels of myoelectrical activity may limit the adaptive response to rehabilitation interventions and suggest greater attention be given to neural function of the knee flexors following hamstring strain injury.

Automatic particle picking of biological molecules imaged by electron microscopy

One of the next great challenges of cell biology is the determination of the enormous number of protein structures encoded in genomes. In recent years, advances in electron cryo-microscopy and high-resolution single particle analysis have developed to the point where they now provide a methodology for high resolution structure determination. Using this approach, images of randomly oriented single particles are aligned computationally to reconstruct 3-D structures of proteins and even whole viruses. One of the limiting factors in obtaining high-resolution reconstructions is obtaining a large enough representative dataset ($>100,000$ particles). Traditionally particles have been manually picked which is an extremely labour intensive process. The problem is made especially difficult by the low signal-to-noise ratio of the images. This paper describes the development of automatic particle picking software, which has been tested with both negatively stained and cryo-electron micrographs. This algorithm has been shown to be capable of selecting most of the particles, with few false positives. Further work will involve extending the software to detect differently shaped and oriented particles.

Tracing moments

The interactive art system +-NOW captures moments in the past and present for dreamy, reflective play. It is composed of sand, imagery and interaction. This paper traces the creative process from initial landscape studies to museum installation in 2008. Key design concepts discussed include the origin and use of sand and emergence.