Complexity and high-end computing in biology and medicine

Biomedical systems involve a large number of entities and intricate interactions between these. Their direct analysis is, therefore, difficult, and it is often necessary to rely on computational models. These models require significant resources and parallel computing solutions. These approaches are particularly suited, given parallel aspects in the nature of biomedical systems. Model hybridisation also permits the integration and simultaneous study of multiple aspects and scales of these systems, thus providing an efficient platform for multidisciplinary research.

High-performance computing for data analytics

One of the main challenges in data analytics is that discovering structures and patterns in complex datasets is a computer-intensive task. Recent advances in high-performance computing provide part of the solution. Multicore systems are now more affordable and more accessible. In this paper, we investigate how this can be used to develop more advanced methods for data analytics. We focus on two specific areas: model-driven analysis and data mining using optimisation techniques.

A Novel High Order Space-Time Spectral Method for the Time Fractional Fokker--Planck Equation

The fractional Fokker-Planck equation is an important physical model for simulating anomalous diffusions with external forces. Because of the non-local property of the fractional derivative an interesting problem is to explore high accuracy numerical methods for fractional differential equations. In this paper, a space-time spectral method is presented for the numerical solution of the time fractional Fokker-Planck initial-boundary value problem. The proposed method employs the Jacobi polynomials for the temporal discretization and Fourier-like basis functions for the spatial discretization. Due to the diagonalizable trait of the Fourier-like basis functions, this leads to a reduced representation of the inner product in the Galerkin analysis. We prove that the time fractional Fokker-Planck equation attains the same approximation order as the time fractional diffusion equation developed in [23] by using the present method. That indicates an exponential decay may be achieved if the exact solution is sufficiently smooth. Finally, some numerical results are given to demonstrate the high order accuracy and efficiency of the new numerical scheme. The results show that the errors of the numerical solutions obtained by the space-time spectral method decay exponentially.

The effect of feedback from pupil to teacher on assessment for leaning and visible learning: An ethnographic case study in a community school in England and the outcome in a state high school in Queensland, Australia

This study shows that there is positive regulatory effect of feedback from pupils to teachers on Assessment for Learning (AfL), classroom proactiveness, and on visible and progressive learning but not on behaviour. This research finding further articulates feedback from pupil to teacher as a paradigm shift from the classical paradigm of feedback from teacher to pupil. Here, the emphasis is geared towards pupils understanding of objectives built from previous knowledge. These are then feedback onto the teachers by the pupils in the form of discrete loops of cues and questions, where they are with their learning. This therefore enables them to move to the next level of understanding, and thus acquired independence, which in turn is reflected by their success in both formative and summative assessments. This study therefore shows that when feedback from pupil to teacher is used in combination with teacher to pupil feedback, AfL is ameliorated and hence, visible and accelerated learning occurs in a gender, nor subject non-dependent manner.

Product stability and sequestration mechanisms in Solanum tuberosum engineered to biosynthesize high value ketocarotenoids

To produce commercially valuable ketocarotenoids in Solanum tuberosum, the 4, 4′ β-oxygenase (crtW) and 3, 3′ β-hydroxylase (crtZ) genes from Brevundimonas spp. have been expressed in the plant host under constitutive transcriptional control. The CRTW and CRTZ enzymes are capable of modifying endogenous plant carotenoids to form a range of hydroxylated and ketolated derivatives. The host (cv. Désirée) produced significant levels of nonendogenous carotenoid products in all tissues, but at the apparent expense of the economically critical metabolite, starch. Carotenoid levels increased in both wild-type and transgenic tubers following cold storage; however, stability during heat processing varied between compounds. Subcellular fractionation of leaf tissues revealed the presence of ketocarotenoids in thylakoid membranes, but not predominantly in the photosynthetic complexes. A dramatic increase in the carotenoid content of plastoglobuli was determined. These findings were corroborated by microscopic analysis of chloroplasts. In tuber tissues, esterified carotenoids, representing 13% of the total pigment found in wild-type extracts, were sequestered in plastoglobuli. In the transgenic tubers, this proportion increased to 45%, with esterified nonendogenous carotenoids in place of endogenous compounds. Conversely, nonesterified carotenoids in both wild-type and transgenic tuber tissues were associated with amyloplast membranes and starch granules.

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment

Who struggles most in making a career choice and why? Findings from a cross-sectional survey of Australian high-school students

This paper reports findings from an empirical study examining the influence of student background and educational experiences on the development of career choice capability. Secondary school students attending years 9-12 (N = 706) in New South Wales, Australia, were invited to participate in an online survey that sought to examine factors influencing their readiness to make career choice. The survey included questions relating to student demographics, parental occupation, attitudes to school and to learning, career aspirations, and students’ knowledge of the further education or skills required to achieve their desired goal. We found no significant differences in the proportions of students who were ‘uncertain’ of their future career aspirations with respect to their individual characteristics such as age and gender. There were, however, significant differences in relation to students’ family background, and their perceptions associated with own academic abilities and self-efficacy.

School based experiences as contributors to career decision-making: Findings from a cross-sectional survey of high-school students

This paper is based on a study examining the impact of young people’s backgrounds and educational experiences on career choice capability with the aim of informing education policy. A total of 706 students from secondary schools (Years 9-12) in New South Wales, Australia took part in an online survey. This paper focuses on the differences found between groups on the basis of their educational experiences. Participants who were uncertain of their future career plans were more likely to attend non-selective, non-metropolitan schools and were more likely to hold negative attitudes towards school. Career ‘uncertain’ students were also less likely to be satisfied with the elective subjects offered at their school and reported less access to career education sessions. It is concluded that timely career information and guidance should be provided to students and their families in order to allow them to more meaningfully make use of the resources and opportunities available to them with a view toward converting these into real world benefits.