Combining genome-wide association mapping and transcriptional networks to identify novel genes controlling glucosinolates in Arabidopsis thaliana.

BackgroundGenome-wide association (GWA) is gaining popularity as a means to study the architecture of complex quantitative traits, partially due to the improvement of high-throughput low-cost genotyping and phenotyping technologies. Glucosinolate (GSL) secondary metabolites within Arabidopsis spp. can serve as a model system to understand the genomic architecture of adaptive quantitative traits. GSL are key anti-herbivory defenses that impart adaptive advantages within field trials. While little is known about how variation in the external or internal environment of an organism may influence the efficiency of GWA, GSL variation is known to be highly dependent upon the external stresses and developmental processes of the plant lending it to be an excellent model for studying conditional GWA.Methodology/principal findingsTo understand how development and environment can influence GWA, we conducted a study using 96 Arabidopsis thaliana accessions, >40 GSL phenotypes across three conditions (one developmental comparison and one environmental comparison) and ∼230,000 SNPs. Developmental stage had dramatic effects on the outcome of GWA, with each stage identifying different loci associated with GSL traits. Further, while the molecular bases of numerous quantitative trait loci (QTL) controlling GSL traits have been identified, there is currently no estimate of how many additional genes may control natural variation in these traits. We developed a novel co-expression network approach to prioritize the thousands of GWA candidates and successfully validated a large number of these genes as influencing GSL accumulation within A. thaliana using single gene isogenic lines.Conclusions/significanceTogether, these results suggest that complex traits imparting environmentally contingent adaptive advantages are likely influenced by up to thousands of loci that are sensitive to fluctuations in the environment or developmental state of the organism. Additionally, while GWA is highly conditional upon genetics, the use of additional genomic information can rapidly identify causal loci en masse

Linkage disequilibrium compared between five populations of domestic sheep

<p>Abstract</p> <p>Background</p> <p>The success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x^2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino × Border Leicester), along with an inbred Australian Merino museum flock were analysed.</p> <p>Results</p> <p>Short range LD (0 – 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x^2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino × Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 – 2.5 centimorgans, depending on the population used.</p> <p>Conclusion</p> <p>Sheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x^2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.</p

The influence of genetic variation in gene expression

Variations in gene expression have long been hypothesised to be the major cause of individual differences. An initial focus of this research thesis is to elucidate the genetic regulatory architecture of gene expression. Expression quantitative trait locus (eQTL) mapping analyses have been performed on expression levels of over 22,000 mRNAs from three tissues of a panel of recombinant inbred mice. These analyses are "single-locus" where "linkage" (i.e. significant correlation) between an expression trait and a putative eQTL is considered independently of other loci. Major conclusions from these analyses are: 1. Gene expression is mainly influenced by genetic (sequence) variations that act in trans rather than in cis; 2. Subsets of genes are controlled by master regulators that influence multiple genes; 3. Gene expression is a polygenic trait with multiple regulators. Single-locus mapping analyses are not designed for detecting multiple regulators of gene expression, and so observation of multiple-linkages (i.e. one expression trait mapped to multiple eQTLs) formed the basis of the second objective of this research project: to investigate the relationship between multiple-linkages and genotype pattern-association. A locus-pair is said to have associated genotype patterns if they have similar inheritance pattern across a panel of individuals, and these are attributed to one of fours sources: 1. linkage disequilibrium between loci located on the same chromosome; 2. non-syntenic association; 3. random association; 4. un-associated. To understand the validity of multiple-linkages observed in single-locus mapping studies, a newly developed method, bqtl.twolocus, is applied to confirm two-locus effects for a total of 898 out of 1,233 multiple-linkages identified from the three studies mentioned above as well as from seven publicly available eQTL-mapping studies. Combining these results with information of genotype pattern-association, a subset of 478 multiple-linkages has been deduced for which there is high confidence to be real

Helping Students to Build Multicultural and Multidisciplinary Competences: A Pilot of Challenge-Based Collaborative Learning on a Digital Gamified Platform

Global issues such as poverty, hunger, and environmental problems are inextricable and cannot be solved comprehensively by homogeneous groups. With the advance of technology, collaborations with peoples at different geographical locations can be achieved effectively. Higher education in the 21st Century must therefore facilitate students to learn how to eclectically connect their creativity and problem-solving skills with technology, and most importantly to work with heterogeneous groups to solve complex global issues.This paper will elaborate on a pilot study of a project in Hong Kong, titled the CCGame Project, which aims to heighten students’ multicultural and multidisciplinary competences by deploying gamified learning and challenge-based learning. Team-based, self-guided learning is the core of the challenge-based learning approach. To preserve students’ interest in learning and accomplishing the tasks for the team, cloud-based learning platforms have been deployed. In the pilot, the online learning platform collected data for analysis of individual and team behaviour. The pilot demonstrated that students could work in a diverse team to complete a challenge. Evidence-based results supported with data analytics will be presented and the project’s plan of work will also be elucidated in this paper

Enhancing Student Learning with Podcasting, a Newly Emergent Social Technology

The complement between pull and push learning modes is believed to be contributable to enriching students\u27 learning experiences. Podcasting, a push technology, can be used to push teaching materials to the students\u27 handheld devices, allowing them to study without any geographical and temporal constraints. The students can then revise the materials according to their own preferences. This explicit push technology together with students\u27 implicit pull motivation can encourage the students to learn in a more efficient way. As the students have the autonomy to choose their preferred media to access learning materials, it is believed to be able to increase students\u27 satisfaction in the learning process. We implemented this idea in one of the courses taught in a university in Hong Kong. The encouraging findings confirmed with our belief that podcasting can help students to learn better by increasing their learning satisfaction

Three-Dimensional Photography and Computer Modeling as a Reconstructive Surgical Training Tool

BACKGROUND: Reconstructive surgery operations are often complex, staged, and have a steep learning curve. As a vocational training requiring thorough three-dimensional (3D) understanding of reconstructive techniques, the use of 3D photography and computer modeling can accelerate this learning for surgical trainees. OBJECTIVES: The authors illustrate the benefits of introducing a streamlined reconstructive pathway that integrates 3D photography and computer modeling, to create a learning database for use by trainees and patients alike, to improve learning and comprehension. METHODS: A computer database of 3D photographs and associated computer models was developed for 35 patients undergoing reconstructive facial surgery at the Royal Free Hospital, London, UK. This was used as a training and teaching tool for 20 surgical trainees, with an MCQ questionnaire assessing knowledge and a Likert scale questionnaire assessing satisfaction with the understanding of core reconstructive techniques, given before and after teaching sessions. Data were analyzed using the Mann-Whitney U test for trainee knowledge and Wilcoxon rank sum test for trainee satisfaction. RESULTS: Trainee (n = 20) knowledge showed a statistically significant improvement, P < .01, as did trainee satisfaction, P < .05, after a teaching session using 3D photography and computer models for facial reconstruction. CONCLUSIONS: Three-dimensional photography and computer modeling are useful teaching and training tools for reconstructive facial surgery. The authors advocate the implementation of an integrated pathway for patients with facial defects to include 3D photography and computer modeling wherever possible, to develop internal databases for training trainees as well as patients. This algorithm can be extrapolated to other aspects of reconstructive surgery

Patient-Reported Outcome Measures in a Facial Reconstruction Case Series Following the Implementation of an Integrated Craniofacial Multidisciplinary Team Clinic, Three-Dimensional Photography, and Computer Modeling

BACKGROUND: Facial reconstruction surgery is often a complex and staged process, leading to lengthy reconstructive journeys for patients. The integration of a clinical pathway can give patients a clearer understanding of what to expect at each stage of their reconstructive journey. OBJECTIVES: The authors demonstrate how the incorporation of multidisciplinary team clinics, three-dimensional (3D) photography, and 3D modeling into an integrated pathway can streamline the process for patients undergoing facial reconstructive surgeries and aid their understanding of their surgeries. METHODS: A novel clinical pathway was developed for patients undergoing facial reconstructive surgery at a tertiary reconstructive unit in London. A case series was collated of 35 patients who had been through the integrated pathway. Patient-reported outcome measures (PROMs) were assessed using FACE-Q scales, Global Aesthetic Improvement Scale, Self-Perception of Age score, and Ordinal Rank change in facial aesthetic appearance, determined subjectively and objectively. Statistical analysis was performed to calculate mean averages for each scale and PROM. RESULTS: High patient satisfaction with overall facial appearance, aging appearance, and the decision-making process was demonstrated. The average perceived improvement in age-related facial appearance was -7.7 years postreconstruction compared with prereconstruction. The Ordinal Rank improvement on facial aesthetic appearance showed considerable improvement, both subjectively and objectively. CONCLUSIONS: The authors advocate the implementation of an integrated clinical pathway for facial reconstruction, with positive impacts observed in terms of patient satisfaction and objective assessments of facial appearance. Similar principles can be extrapolated to other aspects of reconstructive surgery

On the evaluation of the safety aspects of nanomaterials in medical devices – a regulatory perspective

Nanotechnology is widely used in many aspects of the design and manufacture of medical devices. To date, many of these new medical devices, referred to as nano medical devices, have been submitted to health authorities for premarket regulatory review. There are ongoing discussions between medical device manufacturers and regulatory authorities regarding the standards and methods required for the evaluation process. Taking into consideration aspects including nano-toxicology and biocompatibility, the clinical effects of nanotechnology and risk management, there are issues yet to be resolved. In this article, we will discuss nano medical device safety from the regulatory control point of view

Humor Therapy: Relieving Chronic Pain and Enhancing Happiness for Older Adults

The present study examined the effectiveness of a humor therapy program in relieving chronic pain, enhancing happiness and life satisfaction, and reducing loneliness among older persons with chronic pain. It was a quasiexperimental pretest-posttest controlled design. Older persons in a nursing home were invited to join an 8-week humor therapy program (experimental group), while those in another nursing home were treated as a control group and were not offered the program. There were 36 older people in the experimental group and 34 in the control group. Upon completion of the humor therapy program, there were significant decreases in pain and perception of loneliness, and significant increases in happiness and life satisfaction for the experimental group, but not for the control group. The use of humor therapy appears to be an effective nonpharmacological intervention. Nurses and other healthcare professionals could incorporate humor in caring for their patients

Patient Priorities Concerning Treatment Decisions for Advanced Neuroendocrine Tumors Identified by Discrete Choice Experiments.

BACKGROUND Patients with advanced neuroendocrine tumors (NETs) have multiple treatment options. Ideally, treatment decisions are shared between physician and patient; however, previous studies suggest that oncologists and patients place different value on treatment attributes such as adverse event (AE) rates. High-quality information on NET patient treatment preferences may facilitate patient-centered decision making by helping clinicians understand patient priorities. METHODS This study used 2 discrete choice experiments (DCE) to elicit preferences of NET patients regarding advanced midgut and pancreatic NET (pNET) treatments. The DCEs used the "potentially all pairwise rankings of all possible alternatives" (PAPRIKA) method. The primary objective was to determine relative utility rankings for treatment attributes, including progression-free survival (PFS), treatment modality, and AE rates. Ranking of attribute profiles matching specific treatments was also determined. Levels for treatment attributes were obtained from randomized clinical trial data of NET treatments. RESULTS One hundred and 10 participants completed the midgut NET DCE, and 132 completed the pNET DCE. Longer PFS was the highest ranked treatment attribute in 64.5% of participants in the midgut NET DCE, and in 59% in the pNET DCE. Approximately, 40% of participants in both scenarios prioritized lower AE rates or less invasive treatment modalities over PFS. Ranking of treatment profiles in the midgut NET scenario identified 60.9% of participants favoring peptide receptor radionuclide therapy (PRRT), and 30.0% somatostatin analogue dose escalation. CONCLUSION NET patients have heterogeneous priorities when choosing between treatment options based on the results of 2 independent DCEs. These results highlight the importance of shared decision making for NET patients