A review of modern computational algorithms for Bayesian optimal design

Bayesian experimental design is a fast growing area of research with many real-world applications. As computational power has increased over the years, so has the development of simulation-based design methods, which involve a number of algorithms, such as Markov chain Monte Carlo, sequential Monte Carlo and approximate Bayes methods, facilitating more complex design problems to be solved. The Bayesian framework provides a unified approach for incorporating prior information and/or uncertainties regarding the statistical model with a utility function which describes the experimental aims. In this paper, we provide a general overview on the concepts involved in Bayesian experimental design, and focus on describing some of the more commonly used Bayesian utility functions and methods for their estimation, as well as a number of algorithms that are used to search over the design space to find the Bayesian optimal design. We also discuss other computational strategies for further research in Bayesian optimal design.

5-HT(2B) receptors are required for serotonin-selective antidepressant actions

The therapeutic effects induced by serotonin-selective reuptake inhibitor (SSRI) antidepressants are initially triggered by blocking the serotonin transporter and rely on long-term adaptations of pre- and post-synaptic receptors. We show here that long-term behavioral and neurogenic SSRI effects are abolished after either genetic or pharmacological inactivation of 5-HT(2B) receptors. Conversely, direct agonist stimulation of 5-HT(2B) receptors induces an SSRI-like response in behavioral and neurogenic assays. Moreover, the observation that (i) this receptor is expressed by raphe serotonergic neurons, (ii) the SSRI-induced increase in hippocampal extracellular serotonin concentration is strongly reduced in the absence of functional 5-HT(2B) receptors and (iii) a selective 5-HT(2B) agonist mimics SSRI responses, supports a positive regulation of serotonergic neurons by 5-HT(2B) receptors. The 5-HT(2B) receptor appears, therefore, to positively modulate serotonergic activity and to be required for the therapeutic actions of SSRIs. Consequently, the 5-HT(2B) receptor should be considered as a new tractable target in the combat against depression.

The SOLO Taxonomy as a means of shaping and assessing learning in higher education

This paper is a discussion of the use of the SOLO (Structure of Observed Learning Outcomes) Taxonomy (Biggs & Collis, 1982, 1989; Biggs, 1991, 1992a, 1992b; Boulton‐Lewis, 1992, 1994) as a means of developing and assessing higher order thinking in Higher Education. It includes a summary of the research into its use to date as an instrument to find out what students know and believe about their own learning, to assess entering knowledge in a discipline, to present examples of structural organization of knowledge in a discipline, to provide models of levels of desired learning outcomes, and in particular to assess learning outcomes. A proposal is made for further research.

Agent-based modelling of aircraft boarding methods

We implemented six different boarding strategies (Wilma, Steffen, Reverse Pyramid, Random, Blocks and By letter) in order to investigate boarding times for Boeing 777 and Airbus 380 aircraft. We also introduce three new boarding methods to find the optimum boarding strategy. Our models explicitly simulate the behaviour of groups of people travelling together and we explicitly simulate the timing to store their luggage as part of the boarding process. Results from the simulation demonstrates the Reverse Pyramid method is the best boarding method for Boeing 777, and the Steffen method is the best boarding method for Airbus 380. For the new suggested boarding methods, aisle first boarding method is the best boarding strategy for Boeing 777 and row arrangement method is the best boarding strategy for Airbus 380. Overall best boarding strategy is aisle first boarding method for Boeing 777 and Steffen method for Airbus 380.

Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic MARKers (LANDMark): Baseline findings

Purpose:Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods:The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results:396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions:The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.

Can larger cemented femoral components reduce periprosthetic fractures?

Introduction The risk for late periprosthetic fractures is higher in patients treated for a neck of femur fracture compared to those treated for osteoarthritis. It has been hypothesised that osteopenia and consequent decreased stiffness of the proximal femur are responsible for this. We investigated if a femoral component with a bigger body would increase the torque to failure in a biaxially loaded composite sawbone model. Method A biomechanical composite sawbone model was used. Two different body sizes (Exeter 44-1 vs 44-4) of a polished tapered cemented stem were implanted by an experienced surgeon, in 7 sawbones each and loaded at 40 deg/s internal rotation until failure. Torque to fracture and fracture energy were measured using a biaxial materials testing device (Instron 8874). Data are non-parametric and tested with Mann-Whitney U-test. Results The mean torque load to fracture was 154.1 NM (SD 4.4) for the 44-1 stem and 229 NM (SD10.9) for the 44-4 stem (p = 0.01). The mean fracture energy was 9.6 J (SD1.2) for the 44-1 stem and 17.2 J (SD2.0) for the 44-4 stem (p = 0.14). Conclusion the use of a large body polished tapered cemented stem for neck of femur fractures increases the torque to failure in a biomechanical model and therefore is likely to reduce late periprosthetic fracture risk in this vulnerable cohort.

The role of resilience and mTBI as predictors of postconcussional disorder symptomatology

Objective Resilience is 1 of several factors that are thought to contribute to outcome following mild traumatic brain injury (mTBI). This study explored the predictors of the postconcussional syndrome (PCS) symptoms that can occur following mTBI. We hypothesized that a reported recent mTBI and lower psychological resilience would predict worse reported PCS symptomatology. Method 233 participants completed the Neurobehavioral Symptom Inventory (NSI) and the Brief Resilience Scale (BRS). Three NSI scores were used to define PCS symptomatology. A total of 35 participants reported an mTBI (as operationally defined by the World Health Organization) that was sustained between 1 and 6 months prior to their participation (positive mTBI history); the remainder reported having never had an mTBI. Results Regression analyses revealed that a positive reported recent mTBI history and lower psychological resilience were significant independent predictors of reported PCS symptomatology. These results were found for the 3 PCS scores from the NSI, including using a stringent caseness criterion, p < .05. Demographic variables (age and gender) were not related to outcome, with the exception of education in some analyses. Conclusion The results demonstrate that: (a) both perceived psychological resilience and mTBI history play a role in whether or not PCS symptoms are experienced, even when demographic variables are considered, and; (b) of these 2 variables, lower perceived psychological resilience was the strongest predictor of PCS-like symptomatology.

Spatial mapping of proteoglycan content in articular cartilage using near-infrared (NIR) spectroscopy

Diagnosis of articular cartilage pathology in the early disease stages using current clinical diagnostic imaging modalities is challenging, particularly because there is often no visible change in the tissue surface and matrix content, such as proteoglycans (PG). In this study, we propose the use of near infrared (NIR) spectroscopy to spatially map PG content in articular cartilage. The relationship between NIR spectra and reference data (PG content) obtained from histology of normal and artificially induced PG-depleted cartilage samples was investigated using principal component (PC) and partial least squares (PLS) regression analyses. Significant correlation was obtained between both data (R2 = 91.40%, p<0.0001). The resulting correlation was used to predict PG content from spectra acquired from whole joint sample, this was then employed to spatially map this component of cartilage across the intact sample. We conclude that NIR spectroscopy is a feasible tool for evaluating cartilage contents and mapping their distribution across mammalian joint

Therapeutic options for metastatic castration resistant prostate cancer : has the situation improved?

Limited treatment options for Castration Resistant Prostate Cancer (CRPC) still remain a major challenge. Despite therapeutic advances, most patients with malignant PCa have a poor prognosis. Since the year 2000, we have rapidly expanded our understanding of the molecular mechanisms underlying CRPC and this has led to an unprecedented number of new drug approvals within a short span of time. Recently, four new agents namely Abiraterone Acetate, Enzalutamide, Cabazitaxel, and Radium-223 have been shown to be effective in the post-chemotherapy setting in CRPC. The continued dependency of CRPC on androgen synthesis has seen the development of a number of new anti-androgen therapies, with abiraterone acetate and Enzalutamide being the most promising discoveries. Immunotherapeutic approaches have also found their niche in PCa with Sipuleucel-T shown to be effective in minimally asymptomatic CRPC. Research focussed on bone-targeting therapies has witnessed the arrival of promising new drugs with Denosumab and Radium-223 displaying improved survival of patients with CRPC. This review briefly discusses the findings and limitations from ongoing and completed clinical trials of novel treatments and regimens. In addition, potential mechanisms of therapy resistance and future challenges are discussed.

Hosting an asylum seeker in Australia: A nationwide exploratory study

In recent years, there has been a rise in the number of people seeking asylum in Australia, resulting in over-crowded detention centres in various parts of the country. Appropriate management and assistance of asylum seekers has been an issue of major socio-political concern. In mid-2012, the Australian ruling government introduced a ‘first of its kind’ community placement initiative, which involved relocating low-risk asylum seekers from detention centres to homes of those Australian families who volunteered for this program. The present study investigated host families’ motivations for volunteering into this scheme and their resulting experiences. Twenty-four men and women from all over Australia were interviewed in person or over the telephone. Consistent with theoretical frameworks of altruism, acculturation, and intergroup contact, thematic analysis indicated participants’ interest in diversity/humanitarian issues were major factors that motivated them to host asylum seekers. Language and cultural barriers were reported as challenges, but generally, participants found the experience positive and rewarding. The initiative was regarded as an excellent avenue of learning about new cultures. The hosts played a strong role in promoting the English language proficiency and intercultural settlement of the asylum seekers. The scheme was considered as one way of diffusing fear/biases against asylum seekers prevalent amongst the Australian community at-large. Participants also provided suggestions to improve the scheme.

Considerations for a social and geographical framework for agent-based epidemics

Understanding the dynamics of disease spread is of crucial importance, in contexts such as estimating load on medical services to risk assessment and intervention policies against large-scale epidemic outbreaks. However, most of the information is available after the spread itself, and preemptive assessment is far from trivial. Here, we investigate the use of agent-based simulations to model such outbreaks in a stylised urban environment. For most diseases, infection of a new individual may occur from casual contact in crowds as well as from repeated interactions with social partners such as work colleagues or family members. Our model therefore accounts for these two phenomena.Presented in this paper is the initial framework for such a model, detailing implementation of geographical features and generation of social structures. Preliminary results are a promising step towards large-scale simulations and evaluation of potential intervention policies.

Embracing humanity in the face of death: Why do existential concerns moderate ingroup humanization?

People humanize their ingroup to address existential concerns about their mortality, but the reasons why they do so remain ambiguous. One explanation is that people humanize their ingroup to bolster their social identity in the face of their mortality. Alternatively, people might be motivated to see their ingroup as more uniquely human (UH) to distance themselves from their corporeal “animal” nature. These explanations were tested in Australia, where social identity is tied less to UH and more to human nature (HN) which does not distinguish humans from animals. Australians attributed more HN traits to the ingroup when mortality was salient, while the attribution of UH traits remained unchanged. This indicates that the mortality-buffering function of ingroup humanization lies in reinforcing the humanness of our social identity, rather than just distancing ourselves from our animal nature. Implications for (de)humanization in intergroup relations are discussed.