Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Evidence of reciprocal connections between the dorsal raphe nucleus and the retina in the monkey Cebus apella

Possible connections between the retina and the raphe nuclei were investigated in the monkey Cebus apella by intraocular injection of cholera toxin B subunit (CTb). CTb-positive fibers were seen in the lateral region of the dorsal raphe nucleus (DR) on the side contralateral to the injection, and a few labeled perikarya were observed in the lateral portion of the DR on the ipsilateral side. Our findings suggest that direct and reciprocal connections between the retina and DR may exist in Cebus apella. These connections might be part of an important pathway through which the light/dark cycle influences the Activity and/or functional status of raphe neurons, with potential effects on a broad set of neural and behavioral circuits. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Road and Traffic Signs Recognition using Vector Machines

Intelligent Transportation System (ITS) is a system that builds a safe, effective and integrated transportation environment based on advanced technologies. Road signs detection and recognition is an important part of ITS, which offer ways to collect the real time traffic data for processing at a central facility.This project is to implement a road sign recognition model based on AI and image analysis technologies, which applies a machine learning method, Support Vector Machines, to recognize road signs. We focus on recognizing seven categories of road sign shapes and five categories of speed limit signs. Two kinds of features, binary image and Zernike moments, are used for representing the data to the SVM for training and test. We compared and analyzed the performances of SVM recognition model using different features and different kernels. Moreover, the performances using different recognition models, SVM and Fuzzy ARTMAP, are observed.

Exercise, diet and skeletal muscle gene expression

Skeletal muscle, as a consequence of its mass and great capacity for altered metabolism, has a major impact on whole-body metabolic homeostasis and is capable of remarkable adaptation in response to various physiological stimuli, including exercise and dietary intervention. Exercise-induced increases in skeletal muscle mRNA levels of a number of genes have been reported, due to transcriptional activation and/or increased mRNA stability. The cellular adaptations to exercise training appear to be due to the cumulative effects of transient increases in gene transcription after repeated exercise bouts. The relative importance of transcriptional (mRNA synthesis) and translational (mRNA stability or translational efficiency) mechanisms for the training-induced increases in skeletal muscle protein abundance remains to be fully elucidated. Dietary manipulation, and the associated alterations in nutrient availability and hormone levels, can also modify skeletal muscle gene expression, although fewer studies have been reported. A major challenge is to understand how exercise and diet exert their effects on gene and protein expression in skeletal muscle. In relation to exercise, potential stimuli include stretch and muscle tension, the pattern of motor nerve activity and the resultant calcium transients, the energy charge of the cell and substrate availability, oxygen tension and circulating hormones. These are detected by various cellular signaling mechanisms, acting on a range of downstream targets and a wide range of putative transcription factors. A key goal in the years ahead is to identify how alterations at the level of gene expression are coupled to the changes in skeletal muscle phenotype. It is clear that gene expression, although representing a specific site of regulation, is only one step in a complex cascade from the initial stimulus to the final phenotypic adaptation and integrated physiological response.

Planning, delivery and evaluation of information literacy training for engineering and technology students

Information literacy has become an important skill for undergraduate students due to societal changes that have seen information become a valuable commodity, the need for graduates to become lifelong learners, and the recognition that information literacy is an underpinning generic skill for effective learning in higher education. This paper describes a sequence of activities and technologies designed to help students learn and practice information literacy skills. These activities have been purposefully designed and integrated into a first-year engineering and technology study unit as a core syllabus element. A formal evaluation of aspects of these activities was planned and undertaken in semester one 2003.

Information literacy for a sustainable career in engineering and technology

Information literacy has become an important skill for undergraduate students due to societal changes that have seen information become a valuable commodity, the need for graduates to become lifelong learners to remain effective across their working lives, and the recognition by many stakeholders that information literacy is an underpinning generic skill for effective learning in higher education. Important elements in the design and delivery of information literacy training include the collaborative process between library and academic staff, the need to link generic information literacy skills into the specific discipline context of the students, and catering for a wide diversity in the student body including off-campus students. This paper describes a sequence of activities designed to help students learn and practice information literacy skills that have been purposefully designed and integrated into a first-year engineering and technology study unit as a core element of the unit syllabus.

Towards a renewable adaptive recyclable and environmental architecture

Research in pursuit of an effective response to the demands for a sustainable architecture has lead towards the conception of a Renewable, Adaptive, Recyclable and Environmental (R.A.R.E.) building typology. The term R.A.R.E. expresses issues that have assumed central importance in the current architectural debate. This paper establishes the principles of the typology, drawing on the contents and pedagogical methods applied in a building technology academic course, at fourth year level. The R.A.R.E methodology is presented to and explored by students in the search for a definition of an innovative architecture, which is both progressive and sustainable. The unit is structured into eight subjects: Sustainable Site & Climate Analysis; Flexible & Adaptive Structural Systems; Renewable & Environmental Building Materials; Modular Building Systems; Innovative Building Envelope Systems; Renewable & Non-conventional Energy Systems; Innovative Heating, Ventilation & Air Conditioning Systems; Water Collection & Storage Systems. Through a holistic and integrated approach, the unit presents a comprehensive overview of these ‘Sustainable Building Categories’, so that the students can produce a guide towards the design requirements of a Renewable, Adaptive, Recyclable and Environmental (R.A.R.E.) Architecture.

So what do customer value propositions and strategic planning have to do with teaching and learning?

Within most universities there are central areas that assist with teaching and learning and, in the case of universities offering programs through distance education or flexible learning, there are also units that develop and or manufacture course material. As budget constraints squeeze universities and, with a plethora of choices in online and integrated learning, the usefulness of centralised learning resource units can be called into question. To ensure these units remain vital and can justify their budgets to their parent organisations they need to demonstrate delivery of customer value. What do faculty staff value from a central unit? What irritates students about their course materials? What are the most important services from the point of view of a head of school? This paper outlines the process followed by Learning Services at Deakin University to discover its customers’ value model. Customer value propositions and the removal of what irritates the customer are then used to drive strategic planning, service offerings and continuous process improvement.

Internet and competitive advantage in Australian professional sport organisations

The electronic revolution has proven to be a powerful stimulus for change in business practice. As a business tool however, the Internet must endure the same scrutiny under which other business activities are placed. If the use of the Internet in business is a sound strategy, then it must contribute toward competitive advantage. The sport business industry has not been isolated from the vagaries of Internet applications. Moreover, as the industry has become more competitive, forcing sporting organisations towards unprecedented levels of accountability and business practice, the Internet has been increasingly seen as a potential 'holy grail' for sport organisations struggling for revenue (Stewart & Smith, 1999). This research is a response to these pressures. It seeks to identify Internet based opportunities for competitive advantage, and to provide strategies and recommendations for the successful use of the Internet in Australian professional sport organisations. In realising this objective, a newly developed and integrated Business Activity Model has been constructed. The model assists in the identification of specific Internet based competitive advantage strategies, and provides a theoretical framework for this research. The Business Activity Model conceptualises, for the first time, the relationships between the value chain, constituents of electronically enabled competitive advantage, and the Internet. With Australia's limited group of fully professional sports capable of sustaining the human resources and budgets necessary to implement comprehensive e-commerce strategies, the organisations selected to participate in this research represent the pinnacle of Australian professional sport clubs. Specifically, the 55 clubs competing in the Australian Football League (A.F.L.), National Basketball League (N.B.L.), National Rugby League (N.R.L.), and National Soccer League (N.S.L.) constituted the research sample and population. In concert with the 87% participation rate, sampling approached a census. A telephone-administered survey, based primarily on the rigorously tested instrument developed by Sethi and King (1994), was employed for data collection. This research employs a comprehensive set of descriptive statistics, and is bolstered by a confirmatory and an exploratory factor analysis, undertaken on one component of the data. The outcome of this research was the identification of seven practical recommendations for Australian professional sport organisations seeking to improve competitive advantage via the Internet. These recommendations were based on an inventory of the 'gaps' between the strategies proposed by the literature, and the practices of the sample, and relate to both overall Internet strategy, and specific web site applications. The development of the new Business Activity Model and the identification of key online strategy themes support and complement these recommendations. An examination of variations in the practices of participating organisations, and some comparisons against United States sporting organisations, also provides depth and context to the findings. This research provides a platform for sport managers to effectively harness the potential of the Internet, through their web sites in particular, and realise significant competitive advantages. The Business Activity Model provides managers in all industries with a tool for the detection and understanding of potential elements of competitive advantage, and incorporates all activities critical to business in the new digital economy. Seven practical recommendations for improved online performance based on identified competitive advantage and strategies fulfils the primary objective of this research. E-commerce continues to grow at astronomical rates, and with the Internet poised to become the life-blood of 21st century sporting organisations, these recommendations will assist managers in their ongoing search for competitive advantage.

Structured development of an asynchronous forth processor using trace theory

This thesis examines the use of a structured design methodology in the design of asynchronous circuits so that high level constructs can be specified purely in terms of signal exchanges and without the intrusion of lower level concepts. Trace theory is used to specify a multi-processor Forth machine at a high level then part of the design is further elaborated using trace theory operations to (insure that the behaviours of the lower level constructs will combine to give the high level specified behaviour without locking or other hazards. A novel form of threaded language to take advantage of the machine architecture is developed. At suitable points the design is tested by simulation. The stack element which is designed is reduced to an electric circuit which is itself tested by simulation to verify the design.

Older adults' neuromuscular adaptations to resistence training and effects on challenging gait tasks

Community locomotion is threatened when older individuals are required to negotiate obstacles, which place considerable stress on the musculoskeletal system. The vulnerability of older adults during challenging locomotor tasks is further compromised by age-related strength decline and muscle atrophy. The first study in this investigation determined the relationship between the major muscle groups of the lower body and challenging locomotor tasks commonly found in the community environment of older adults. Twenty-nine females and sixteen males aged between 62 and 88 years old (68.2 ±6.5) were tested for the maximal voluntary contraction (MVC) strength of the knee extensors and 1-RM for the hip extensors, flexors, adductors, abductors, knee extensors and flexors and ankle plantar flexors. Temporal measurements of an obstacle course comprising four gait tasks set at three challenging levels were taken. The relationship between strength and the obstacle course dependent measures was explored using linear regression models. Significant associations (p≤0.05) between all the strength measures and the gait performances were found. The correlation values between strength and obstructed gait (r = 0.356-0.554) and the percentage of the variance explained by strength (R2 = 13%-31%), increased as a function of the challenging levels, especially for the stepping over and on and off conditions. While the difficulty of community older adults to negotiate obstacles cannot be attributed to a single causal pathway, the findings of the first study showed that strength is a critical requirement. That the magnitude of the association increased as a function of the challenging levels, suggests that interventions aimed at improving strength would potentially be effective in helping community older adults to negotiate environmental gait challenges. In view of the findings of the first study, a second investigation determined the effectiveness of a progressive resistance-training program on obstructed gait tasks measured under specific laboratory conditions and on an obstacle course mimicking a number of environmental challenges. The time courses of strength gains and neuromuscular mechanisms underpinning the exercise-induced strength improvements in community-dwelling older adults were also investigated. The obstructed gait conditions included stepping over an obstacle, on and off a raised surface, across an obstacle and foot targeting. Forty-three community-living adults with a mean age of 68 years (control =14 and experimental=29) completed a 24-week progressive resistance training program designed to improve strength and induce hypertrophy in the major muscles of the lower body. Specific laboratory gait kinetics and kinematics and temporal measures taken on the obstacle course were measured. Lean tissue mass and muscle activation of the lower body muscle groups were assessed. The MVC strength of the knee extensors and 1-RM of the hip extension, hip flexion, knee extension, knee flexion and ankle plantar flexion were measured. A 25% increase on the MVC of the knee extensors (p≤0.05) was reported in the training group. Gains ranging between 197% and 285% were recorded for the 1-RM exercises in the trained subjects with significant improvements found throughout the study (p≤0.05). The exercise-induced strength gains were mediated by hypertrophic and neural factors as shown by 8.7% and 27.7% increases (p≤0.05) in lean tissue mass and integrated electromyographic activity, respectively. Strength gains were accompanied by increases in crossing velocity, stride length and reductions in stride duration, stance and swing time for all gait tasks except for the foot targeting condition. Specific kinematic variables associated with safe obstacle traverse such as vertical obstacle heel clearance, limb flexion, horizontal foot placements prior to and at post obstacle crossing and landing velocities resulted in an improved crossing strategy in the experimental subjects. Significant increases in the vertical and anterior-posterior ground reaction forces accompanied the changes in the gait variables. While further long-term prospective studies of falls rates would be needed to confirm the benefits of lower limb enhanced strength, the findings of the present study provide conclusive evidence of significant improvements to gait efficiency associated with a systematic resistance-training program. It appears, however, that enhanced lower body strength has limited effects on gait tasks involving a dynamic balance component. In addition, due to the larger strength-induced increases in voluntary activation of the leg muscle compared to relatively smaller gains in lean tissue mass, neural adaptations appear to play a greater contributing role in explaining strength gains during the current resistance training protocol.

Community of practice and the wider organisation : a multi-faceted KM framework

A conceptual knowledge management (KM) framework was developed and tested. The social bond combined with the expertise of a Community of Practice (CoP) constitutes a bottom-up aproach to KM, at the same time influencing top-down KM efforts by managers. A successful feedback loop between CoP and Management assists in establishing a collaborative and integrated top-down/bottom-up KM strategy.

Growing community : the impact of the Stephanie Alexander kitchen garden program on the social and learning environment in primary schools

This article presents results from a mixed-method evaluation of a structured cooking and gardening program in Australian primary schools, focusing on program impacts on the social and learning environment of the school. In particular, we address the Stephanie Alexander Kitchen Garden Program objective of providing a pleasurable experience that has a positive impact on student engagement, social connections, and confidence within and beyond the school gates. Primary evidence for the research question came from qualitative data collected from students, parents, teachers, volunteers, school principals, and specialist staff through interviews, focus groups, and participant observations. This was supported by analyses of quantitative data on child quality of life, cooperative behaviors, teacher perceptions of the school environment, and school-level educational outcome and absenteeism data. Results showed that some of the program attributes valued most highly by study participants included increased student engagement and confidence, opportunities for experiential and integrated learning, teamwork, building social skills, and connections and links between schools and their communities. In this analysis, quantitative findings failed to support findings from the primary analysis. Limitations as well as benefits of a mixed-methods approach to evaluation of complex community interventions are discussed.

Tuneable optical waveguide based on dielectrophoresis and microfluidics

In this work, an array of dielectrophoretic curved microelectrodes patterned in a microfluidic channel and integrated with a multimode rib polymeric waveguide is demonstrated. The microfluidic channel is infiltrated with suspended silica (SiO2) and tungsten trioxide (WO3) nanoparticles. The optofluidic system is found to be sensitive and responds not only to the infiltration of nanoparticle suspensions in the microfluidic channel, but also to the magnitude and frequencies of dielectrophoretic forces applied on the nanoparticles. The nanoparticles can be uniformly concentrated or repelled from the region between the curved microelectrode tips forming either a dense stream of flowing nanoparticles or a region void of nanoparticles in the evanescent sensitive region of the polymeric waveguide. The concentration and repulsion of nanoparticles from this region creates a refractive index gradient in the upper cladding of the polymeric waveguide. These conditions made it possible for light to either remain guided or be scattered as a function of dielectrophoretic settings applied on the nanoparticles. The results demonstrate that we successfully developed a novel tuneable polymeric waveguide based on dielectrophoretic assembly of nanoparticles suspended in fluids.

Targeting and measuring housing problems in developing countries through urban texture analysis

Latin-american countries passed from predominantely rural to predominantely urban within few decades. The level of urbanisation in Brazil progressed from 36% in 1950, 50% in 1970, and scalating to 85% in 2005. This rapid transformation resulted in many social problems, as cities were not able to provide appropriate housing and infrastructure for the growing population. As a response, the Brazilian Ministry for Cities, in 2005, created the National System for Social Housing, with the goal to establish guidelines in the Federal level, and build capacity and fund social housing projects in the State and Local levels. This paper presents a research developed in Gramado city, Brazil, as part of the Local Social Housing Plan process, with the goal to produce innovative tools to help social housing planning and management. It proposes and test a methodology to locate and characterise/rank housing defficiencies across the city combining GIS and fractal geometry analysis. Fractal measurements, such as fractal dimension and lacunarity, are able to differentiate urban morphology, and integrated to infrastructure and socio-economical spatial indicators, they can be used to estimate housing problems and help to target, classify and schedule actions to improve housing in cities and regions. Gramado city was divided in a grid with 1,000 cells. For each cell, the following indicators were measured: average income of households, % of roads length which are paved (as a proxy for availability of infrastructures as water and sewage), fractal dimension and lacunarity of the dwellings spatial distribution. A statistical model combining those measurements was produced using a sample of 10% of the cells divided in five housing standards (from high income/low density dwellings to slum's dwellings). The estimation of the location and level of social housing deficiencies in the whole region using the model, compared to the real situation, achived high correlations. Simple and based on easily accessible and inexpensive data, the method also helped to overcome limitations of lack of information and fragmented knowledge of the area related to housing conditions by local professionals.