Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

A new open-pit multi-stage mine production timetabling model for drilling, blasting and excavating operations

This paper proposes a new multi-resource multi-stage mine production timetabling problem for optimising the open-pit drilling, blasting and excavating operations under equipment capacity constraints. The flow process is analysed based on the real-life data from an Australian iron ore mine site. The objective of the model is to maximise the throughput and minimise the total idle times of equipment at each stage. The following comprehensive mining attributes and constraints are considered: types of equipment; operating capacities of equipment; ready times of equipment; speeds of equipment; block-sequence-dependent movement times; equipment-assignment-dependent operational times; etc. The model also provides the availability and usage of equipment units at multiple operational stages such as drilling, blasting and excavating stages. The problem is formulated by mixed integer programming and solved by ILOG-CPLEX optimiser. The proposed model is validated with extensive computational experiments to improve mine production efficiency at the operational level.

Agreement between physiotherapists rating scapular posture in multiple planes in patients with neck pain: Reliability study

Objective Evaluation of scapular posture is an integral component of the clinical assessment of painful neck disorders. The aim of this study was to evaluate agreement between therapist judgements of scapula posture in multiple biomechanical planes in individuals with neck pain. Design Inter-therapist reliability study. Setting Research laboratory. Participants Fifteen participants with chronic neck pain. Main outcome measures Four physiotherapists recorded ratings of scapular orientation (relative to the thorax) in five different scapula postural planes (plane of scapula, sagittal plane, transverse plane, horizontal plane, and vertical plane) under four test conditions (at rest, and during three isometric shoulder conditions) in all participants. Inter-therapist reliability was expressed using both generalized and paired kappa coefficient. Results Following adjustment for expected agreement and the high prevalence of neutral ratings (81%), on average both the generalised kappa (0.37) as well as Cohen's Kappa for the two therapist pairs (0.45 and 0.42) demonstrated only slight to moderate inter-therapist reliability. Conclusions The findings suggest that ratings of scapular posture in individuals with neck pain by visual inspection has only slight to moderate reliability and should only be used in conjunction with other clinical tests when judging scapula function in these patients.

Multiple alignment and sorting of peptides derived from phage-displayed random peptide libraries with polyclonal sera allows discrimination of relevant phagotopes

Biopanning of phage-displayed random peptide libraries is a powerful technique for identifying peptides that mimic epitopes (mimotopes) for monoclonal antibodies (mAbs). However, peptides derived using polyclonal antisera may represent epitopes for a diverse range of antibodies. Hence following screening of phage libraries with polyclonal antisera, including autoimmune disease sera, a procedure is required to distinguish relevant from irrelevant phagotopes. We therefore applied the multiple sequence alignment algorithm PILEUP together with a matrix for scoring amino acid substitutions based on physicochemical properties to generate guide trees depicting relatedness of selected peptides. A random heptapeptide library was biopanned nine times using no selecting antibodies, immunoglobulin G (IgG) from sera of subjects with autoimmune diseases (primary biliary cirrhosis (PBC) and type 1 diabetes) and three murine ascites fluids that contained mAbs to overlapping epitope(s) on the Ross River Virus envelope protein 2. Peptides randomly sampled from the library were distributed throughout the guide tree of the total set of peptides whilst many of the peptides derived in the absence of selecting antibody aligned to a single cluster. Moreover peptides selected by different sources of IgG aligned to separate clusters, each with a different amino acid motif. These alignments were validated by testing all of the 53 phagotopes derived using IgG from PBC sera for reactivity by capture ELISA with antibodies affinity purified on the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major autoantigen in PBC: only those phagotopes that aligned to PBC-associated clusters were reactive. Hence the multiple sequence alignment procedure discriminates relevant from irrelevant phagotopes and thus a major difficulty with biopanning phage-displayed random peptide libraries with polyclonal antibodies is surmounted.

Predictors of physical activity in colorectal cancer survivors after participation in a telephone-delivered multiple health behavior change intervention

Purpose: Physical activity improves the health outcomes of colorectal cancer (CRC) survivors, yet few are exercising at levels known to yield health benefits. Baseline demographic, clinical, behavioral, and psychosocial predictors of physical activity at 12 months were investigated in CRC survivors. Methods: Participants were CRC survivors (n = 410) who completed a 12-month multiple health behavior change intervention trial (CanChange). The outcome variable was 12 month sufficient physical activity (≥150 min of moderate–vigorous physical activity/week). Baseline predictors included demographics and clinical variables, health behaviors, and psychosocial variables. Results: Multivariate linear regression revealed that baseline sufficient physical activity (p < 0.001), unemployment (p = 0.004), private health insurance (p = 0.040), higher cancer-specific quality of life (p = 0.031) and higher post-traumatic growth (p = 0.008) were independent predictors of sufficient physical activity at 12 months. The model explained 28.6 % of the variance. Conclusions: Assessment of demographics, health behaviors, and psychosocial functioning following a diagnosis of CRC may help to develop effective physical activity programs.

A randomized controlled trial of a multiple health behavior change intervention delivered to colorectal cancer survivors: Effects on sedentary behavior

BACKGROUND Sedentary behavior may independently contribute to morbidity and mortality among survivors of colorectal cancer. In the current study, the authors assessed whether a telephone-delivered multiple health behavior change intervention had an effect on the sedentary behavior of recently diagnosed colorectal cancer survivors. METHODS A total of 410 participants were recruited through the Queensland Cancer Registry and randomized to the health coaching (intervention) or usual-care (control) group. Eleven health coaching sessions addressing multiple health behaviors, including sedentary behavior, were delivered over a period of 6 months. Data were collected at baseline (before randomization), at 6 months, and at 12 months via a telephone interview. RESULTS At 12 months, there was a significant decrease noted in the hours per day of sedentary time in both the health coaching (−1.21; 95% confidence interval [95% CI], −1.71 to −0.70) and usual-care groups (−0.55; 95% CI, −1.06 to −0.05), but the between-group difference was not found to be statistically significant (−0.65; 95% CI, −1.37 to 0.06 [P = .07]). In stratified subgroup analyses, the multiple health behavior change intervention was found to have a significant effect on total sedentary time (hours/day) at 12 months in survivors of colorectal cancer who were aged > 60 years (−0.90; 95% CI, −1.80 to −0.01 [P = .05]), male (−1.33; 95% CI, −2.44 to −0.21 [P = .02]), and nonobese (−1.10; 95% CI, −1.96 to −0.25; [P = .01]). CONCLUSIONS Incorporating simple messages about limiting sedentary behaviors into a multiple health behavior change intervention was found to have modest effects on sedentary behavior. A sedentary behavior-specific intervention strategy may be required to achieve substantial changes in sedentary behavior among colorectal cancer survivors

Combining transcriptome assemblies from multiple de novo assemblers in the allo-tetraploid plant Nicotiana benthamiana

Background Nicotiana benthamiana is an allo-tetraploid plant, which can be challenging for de novo transcriptome assemblies due to homeologous and duplicated gene copies. Transcripts generated from such genes can be distinct yet highly similar in sequence, with markedly differing expression levels. This can lead to unassembled, partially assembled or mis-assembled contigs. Due to the different properties of de novo assemblers, no one assembler with any one given parameter space can re-assemble all possible transcripts from a transcriptome. Results In an effort to maximise the diversity and completeness of de novo assembled transcripts, we utilised four de novo transcriptome assemblers, TransAbyss, Trinity, SOAPdenovo-Trans, and Oases, using a range of k-mer sizes and different input RNA-seq read counts. We complemented the parameter space biologically by using RNA from 10 plant tissues. We then combined the output of all assemblies into a large super-set of sequences. Using a method from the EvidentialGene pipeline, the combined assembly was reduced from 9.9 million de novo assembled transcripts to about 235,000 of which about 50,000 were classified as primary. Metrics such as average bit-scores, feature response curves and the ability to distinguish paralogous or homeologous transcripts, indicated that the EvidentialGene processed assembly was of high quality. Of 35 RNA silencing gene transcripts, 34 were identified as assembled to full length, whereas in a previous assembly using only one assembler, 9 of these were partially assembled. Conclusions To achieve a high quality transcriptome, it is advantageous to implement and combine the output from as many different de novo assemblers as possible. We have in essence taking the ‘best’ output from each assembler while minimising sequence redundancy. We have also shown that simultaneous assessment of a variety of metrics, not just focused on contig length, is necessary to gauge the quality of assemblies.

Multiple primary cancers associated with Merkel cell carcinoma in Queensland, Australia, 1982-2011

The relatively high incidence of Merkel cell carcinoma (MCC) in Queensland provides a valuable opportunity to examine links with other cancers. A retrospective cohort study was performed using data from the Queensland Cancer Registry. Standardized incidence ratios (SIRs) were used to approximate the relative risk of being diagnosed with another primary cancer either following or prior to MCC. Patients with an eligible first primary MCC (n=787) had more than double the expected number of subsequent primary cancers (SIR=2.19, 95% confidence interval (CI)=1.84–2.60; P<0.001). Conversely, people who were initially diagnosed with cancers other than MCC were about two and a half times more likely to have a subsequent primary MCC (n=244) compared with the general population (SIR=2.69, 95% CI=2.36–3.05; P<0.001). Significantly increased bi-directional relative risks were found for melanoma, lip cancer, head and neck cancer, lung cancer, myelodysplastic diseases, and cancer with unknown primary site. In addition, risks were elevated for female breast cancer and kidney cancer following a first primary MCC, and for subsequent MCCs following first primary colorectal cancer, prostate cancer, non-Hodgkin lymphoma, or lymphoid leukemia. These results suggest that several shared pathways are likely for MCC and other cancers, including immunosuppression, UV radiation, and genetics.

Tracking the patient journey by combining multiple hospital database systems

With new national targets for patient flow in public hospitals designed to increase efficiencies in patient care and resource use, better knowledge of events affecting length of stay will support improved bed management and scheduling of procedures. This paper presents a case study involving the integration of material from each of three databases in operation at one tertiary hospital and demonstrates it is possible to follow patient journeys from admission to discharge. What is known about this topic? At present, patient data at one Queensland tertiary hospital are assembled in three information systems: (1) the Hospital Based Corporate Information System (HBCIS), which tracks patients from in-patient admission to discharge; (2) the Emergency Department Information System (EDIS) containing patient data from presentation to departure from the emergency department; and (3) Operation Room Management Information System (ORMIS), which records surgical operations. What does this paper add? This paper describes how a new enquiry tool may be used to link the three hospital information systems for studying the hospital journey through different wards and/or operating theatres for both individual and groups of patients. What are the implications for practitioners? An understanding of the patients’ journeys provides better insight into patient flow and provides the tool for research relating to access block, as well as optimising the use of physical and human resources.

Programming: Reading, writing and reversing

In this paper, we look at the concept of reversibility, that is, negating opposites, counterbalances, and actions that can be reversed. Piaget identified reversibility as an indicator of the ability to reason at a concrete operational level. We investigate to what degree novice programmers manifest the ability to work with this concept of reversibility by providing them with a small piece of code and then asking them to write code that undoes the effect of that code. On testing entire cohorts of students in their first year of learning to program, we found an overwhelming majority of them could not cope with such a concept. We then conducted think aloud studies of novices where we observed them working on this task and analyzed their contrasting abilities to deal with it. The results of this study demonstrate the need for better understanding our students' reasoning abilities, and a teaching model aimed at that level of reality.

Linear programming for large-scale Markov decision problems

We consider the problem of controlling a Markov decision process (MDP) with a large state space, so as to minimize average cost. Since it is intractable to compete with the optimal policy for large scale problems, we pursue the more modest goal of competing with a low-dimensional family of policies. We use the dual linear programming formulation of the MDP average cost problem, in which the variable is a stationary distribution over state-action pairs, and we consider a neighborhood of a low-dimensional subset of the set of stationary distributions (defined in terms of state-action features) as the comparison class. We propose a technique based on stochastic convex optimization and give bounds that show that the performance of our algorithm approaches the best achievable by any policy in the comparison class. Most importantly, this result depends on the size of the comparison class, but not on the size of the state space. Preliminary experiments show the effectiveness of the proposed algorithm in a queuing application.

Effects of a multiple health behavior change intervention for colorectal cancer survivors on psychosocial outcomes and quality of life: A randomized controlled trial

Background Multiple health behavior change can ameliorate adverse effects of cancer. Purpose The purpose of this study was to determine the effects of a multiple health behavior change intervention (CanChange) for colorectal cancer survivors on psychosocial outcomes and quality of life. Methods A total of 410 colorectal cancer survivors were randomized to a 6-month telephone-based health coaching intervention (11 sessions using acceptance and commitment therapy strategies focusing on physical activity, weight management, diet, alcohol, and smoking) or usual care. Posttraumatic growth, spirituality, acceptance, mindfulness, distress, and quality of life were assessed at baseline, 6 and 12 months. Results Significant intervention effects were observed for posttraumatic growth at 6 (7.5, p < 0.001) and 12 months (4.1, p = 0.033), spirituality at 6 months (1.8, p = 0.011), acceptance at 6 months (0.2, p = 0.005), and quality of life at 6 (0.8, p = 0.049) and 12 months (0.9, p = 0.037). Conclusions The intervention improved psychosocial outcomes and quality of life (physical well-being) at 6 months with most effects still present at 12 months. (Trial Registration Number: ACTRN12608000399392).

Increasing autonomy transparency through capability communication in multiple heterogeneous UAV management

Interest in the area of collaborative Unmanned Aerial Vehicles (UAVs) in a Multi-Agent System is growing to compliment the strengths and weaknesses of the human-machine relationship. To achieve effective management of multiple heterogeneous UAVs, the status model of the agents must be communicated to each other. This paper presents the effects on operator Cognitive Workload (CW), Situation Awareness (SA), trust and performance by increasing the autonomy capability transparency through text-based communication of the UAVs to the human agents. The results revealed a reduction in CW, increase in SA, increase in the Competence, Predictability and Reliability dimensions of trust, and the operator performance.

Do motor vehicle crashes arise from single or multiple unique risk processes? An inquiry into crash causes and modelling

Crashes at any particular transport network location consist of a chain of events arising from a multitude of potential causes and/or contributing factors whose nature is likely to reflect geometric characteristics of the road, spatial effects of the surrounding environment, and human behavioural factors. It is postulated that these potential contributing factors do not arise from the same underlying risk process, and thus should be explicitly modelled and understood. The state of the practice in road safety network management applies a safety performance function that represents a single risk process to explain crash variability across network sites. This study aims to elucidate the importance of differentiating among various underlying risk processes contributing to the observed crash count at any particular network location. To demonstrate the principle of this theoretical and corresponding methodological approach, the study explores engineering (e.g. segment length, speed limit) and unobserved spatial factors (e.g. climatic factors, presence of schools) as two explicit sources of crash contributing factors. A Bayesian Latent Class (BLC) analysis is used to explore these two sources and to incorporate prior information about their contribution to crash occurrence. The methodology is applied to the state controlled roads in Queensland, Australia and the results are compared with the traditional Negative Binomial (NB) model. A comparison of goodness of fit measures indicates that the model with a double risk process outperforms the single risk process NB model, and thus indicating the need for further research to capture all the three crash generation processes into the SPFs.

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.