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. Trial registration: ClinicalTrials.gov identifier NCT01655706. Registered July 27, 2012.

Assessment of commercial network RTK user positioning performance over long inter-station distances

The paper provides an assessment of the performance of commercial Real Time Kinematic (RTK) systems over longer than recommended inter-station distances. The experiments were set up to test and analyse solutions from the i-MAX, MAX and VRS systems being operated with three triangle shaped network cells, each having an average inter-station distance of 69km, 118km and 166km. The performance characteristics appraised included initialization success rate, initialization time, RTK position accuracy and availability, ambiguity resolution risk and RTK integrity risk in order to provide a wider perspective of the performance of the testing systems. ----- ----- The results showed that the performances of all network RTK solutions assessed were affected by the increase in the inter-station distances to similar degrees. The MAX solution achieved the highest initialization success rate of 96.6% on average, albeit with a longer initialisation time. Two VRS approaches achieved lower initialization success rate of 80% over the large triangle. In terms of RTK positioning accuracy after successful initialisation, the results indicated a good agreement between the actual error growth in both horizontal and vertical components and the accuracy specified in the RMS and part per million (ppm) values by the manufacturers. ----- ----- Additionally, the VRS approaches performed better than the MAX and i-MAX when being tested under the standard triangle network with a mean inter-station distance of 69km. However as the inter-station distance increases, the network RTK software may fail to generate VRS correction and then may turn to operate in the nearest single-base RTK (or RAW) mode. The position uncertainty reached beyond 2 meters occasionally, showing that the RTK rover software was using an incorrect ambiguity fixed solution to estimate the rover position rather than automatically dropping back to using an ambiguity float solution. Results identified that the risk of incorrectly resolving ambiguities reached 18%, 20%, 13% and 25% for i-MAX, MAX, Leica VRS and Trimble VRS respectively when operating over the large triangle network. Additionally, the Coordinate Quality indicator values given by the Leica GX1230 GG rover receiver tended to be over-optimistic and not functioning well with the identification of incorrectly fixed integer ambiguity solutions. In summary, this independent assessment has identified some problems and failures that can occur in all of the systems tested, especially when being pushed beyond the recommended limits. While such failures are expected, they can offer useful insights into where users should be wary and how manufacturers might improve their products. The results also demonstrate that integrity monitoring of RTK solutions is indeed necessary for precision applications, thus deserving serious attention from researchers and system providers.

The determinants of corporate sustainability performance

This paper investigates the factors that drive high levels of corporate sustainability performance (CSP), as proxied by membership of the Dow Jones Sustainability World Index. Using a stakeholder framework, we examine the incentives for US firms to invest in sustainability principles and develop a number of hypotheses that relate CSP to firm-specific characteristics. Our results indicate that leading CSP firms are significantly larger, have higher levels of growth and a higher return on equity than conventional firms. Contrary to our predictions, leading CSP firms do not have greater free cash flows or lower leverage than other firms.

An analysis of the nature and effectiveness of corporate governance in smaller listed Australian companies

The objective of this thesis is to investigate the corporate governance attributes of smaller listed Australian firms. This study is motivated by evidence that these firms are associated with more regulatory concerns, the introduction of ASX Corporate Governance Recommendations in 2004, and a paucity of research to guide regulators and stakeholders of smaller firms. While there is an extensive body of literature examining the effectiveness of corporate governance, the literature principally focuses on larger companies, resulting in a deficiency in the understanding of the nature and effectiveness of corporate governance in smaller firms. Based on a review of agency theory literature, a theoretical model is developed that posits that agency costs are mitigated by internal governance mechanisms and transparency. The model includes external governance factors but in many smaller firms these factors are potentially absent, increasing the reliance on the internal governance mechanisms of the firm. Based on the model, the observed greater regulatory intervention in smaller companies may be due to sub-optimal internal governance practices. Accordingly, this study addresses four broad research questions (RQs). First, what is the extent and nature of the ASX Recommendations that have been adopted by smaller firms (RQ1)? Second, what firm characteristics explain differences in the recommendations adopted by smaller listed firms (RQ2), and third, what firm characteristics explain changes in the governance of smaller firms over time (RQ3)? Fourth, how effective are the corporate governance attributes of smaller firms (RQ4)? Six hypotheses are developed to address the RQs. The first two hypotheses explore the extent and nature of corporate governance, while the remaining hypotheses evaluate its effectiveness. A time-series, cross-sectional approach is used to evaluate the effectiveness of governance. Three models, based on individual governance attributes, an index of six items derived from the literature, and an index based on the full list of ASX Recommendations, are developed and tested using a sample of 298 smaller firms with annual observations over a five-year period (2002-2006) before and after the introduction of the ASX Recommendations in 2004. With respect to (RQ1) the results reveal that the overall adoption of the recommendations increased from 66 per cent in 2004 to 74 per cent in 2006. Interestingly, the adoption rate for recommendations regarding the structure of the board and formation of committees is significantly lower than the rates for other categories of recommendations. With respect to (RQ2) the results reveal that variations in rates of adoption are explained by key firm differences including, firm size, profitability, board size, audit quality, and ownership dispersion, while the results for (RQ3) were inconclusive. With respect to (RQ4), the results provide support for the association between better governance and superior accounting-based performance. In particular, the results highlight the importance of the independence of both the board and audit committee chairs, and of greater accounting-based expertise on the audit committee. In contrast, while there is little evidence that a majority independent board is associated with superior outcomes, there is evidence linking board independence with adverse audit opinion outcomes. These results suggest that board and chair independence are substitutes; in the presence of an independent chair a majority independent board may be an unnecessary and costly investment for smaller firms. The findings make several important contributions. First, the findings contribute to the literature by providing evidence on the extent, nature and effectiveness of governance in smaller firms. The findings also contribute to the policy debate regarding future development of Australia’s corporate governance code. The findings regarding board and chair independence, and audit committee characteristics, suggest that policy-makers could consider providing additional guidance for smaller companies. In general, the findings offer support for the “if not, why not?” approach of the ASX, rather than a prescriptive rules-based approach.

Microscale study of electrical characteristics of epoxy-multiwall carbon nanotube nanocomposites

Epoxy-multiwall carbon nanotube nanocomposite thin films were prepared by spin casting. High power air plasma was used to preferentially etch a coating of epoxy and expose the underlying carbon nanotube network. Scanning electron microscopy (SEM) examination revealed well distributed and spatially connected carbon nanotube network in both the longitudinal direction (plasma etched surface) and traverse direction (through-thickness fractured surface). Topographical examination and conductive mode imaging of the plasma etched surface using atomic force microscope (AFM) in the contact mode enabled direct imaging of topography and current maps of the embedded carbon nanotube network. Bundles consisting of at least three single carbon nanotubes form part of the percolating network observed under high resolution current maps. Predominantly non-ohmic response is obtained in this study; behaviour attributed to less than effective polymer material removal when using air plasma etching.

A longitudinal study of corporate earnings guidance in Australia’s continuous disclosure environment

Since the introduction of a statutory‐backed continuous disclosure regime (CDR) in 1994, regulatory reforms have significantly increased litigation risk in Australia for failure to disclose material information or for false and misleading disclosure. However, there is almost no empirical research on the impact of the reforms on corporate disclosure behaviour. Motivated by the absence of research and using management earnings forecasts (MEFs) as a disclosure proxy, this study examines (1) why managers issue earnings forecasts, (2) what firm‐specific factors influence MEF characteristics, and (3) how MEF behaviour changes as litigation risk increases. Based on theories in information economics, a theoretical framework for MEF behaviour is formulated which includes antecedent influencing factors related to firms‟ internal and external environments. Applying this framework, hypotheses are developed and tested using multivariate models and a large sample of hand-collected MEFs (7,213) issued by top 500 ASX-listed companies over the 1994 to 2008 period. The results reveal strong support for the hypotheses. First, MEFs are issued to reduce information asymmetry, litigation risk and signal superior performance. Second, firms with better financial performance, smaller earnings changes, and lower operating uncertainty provide better quality MEFs. Third, forecast frequency and quality (accuracy, timeliness and precision) noticeably improve as litigation risk increases. However, managers appear to be still reluctant to disclose earnings forecasts when there are large earnings changes, and an asymmetric treatment of news type continues to prevail (a good news bias). Thus, the findings generally provide support for the effectiveness of the CDR regulatory reforms in improving disclosure behaviour and will be valuable to market participants and corporate regulators in understanding the implications of management forecasting decisions and areas for further improvement.

A preliminary theory of dark network resilience

A crucial contemporary policy question for governments across the globe is how to cope with international crime and terrorist networks. Many such “dark” networks—that is, networks that operate covertly and illegally—display a remarkable level of resilience when faced with shocks and attacks. Based on an in-depth study of three cases (MK, the armed wing of the African National Congress in South Africa during apartheid; FARC, the Marxist guerrilla movement in Colombia; and the Liberation Tigers of Tamil Eelam, LTTE, in Sri Lanka), we present a set of propositions to outline how shocks impact dark network characteristics (resources and legitimacy) and networked capabilities (replacing actors, linkages, balancing integration and differentiation) and how these in turn affect a dark network's resilience over time. We discuss the implications of our findings for policymakers.

Resilience of a corrupt police network : the first and second jokes in Queensland

Resilient organised crime groups survive and prosper despite law enforcement activity, criminal competition and market forces. Corrupt police networks, like any other crime network, must contain resiliency characteristics if they are to continue operation and avoid being closed down through detection and arrest of their members. This paper examines the resilience of a large corrupt police network, namely The Joke which operated in the Australian state of Queensland for a number of decades. The paper uses social network analysis tools to determine the resilient characteristics of the network. This paper also assumes that these characteristics will be different to those of mainstream organised crime groups because the police network operates within an established policing agency rather than as an independent entity hiding within the broader community.

The subjective experience of negative symptoms : characteristics of emotional withdrawal

According to the diagnosis of schizophrenia in the DSM-IV-TR (American Psychiatric Association, 2000), negative symptoms are those personal characteristics that are thought to be reduced from normal functioning, while positive symptoms are aspects of functioning that exist as an excess or distortion of normal functioning. Negative symptoms are generally considered to be a core feature of people diagnosed with schizophrenia. However, negative symptoms are not always present in those diagnosed, and a diagnosis can be made with only negative or only positive symptoms, or with a combination of both. Negative symptoms include an observed loss of emotional expression (affective flattening), loss of motivation or self directedness (avolition), loss of speech (alogia), and also a loss of interests and pleasures (anhedonia). Positive symptoms include the perception of things that others do not perceive (hallucinations), and extraordinary explanations for ordinary events (delusions) (American Psychiatric Association, 2000). Both negative and positive symptoms are derived from watching the patient and thus do not consider the patient’s subjective experience. However, aspects of negative symptoms, such as observed affective flattening are highly contended. Within conventional psychiatry, the absence of emotional expression is assumed to coincide with an absence of emotional experience. Contrasting research findings suggests that patients who were observed to score low on displayed emotional expression, scored high on self ratings of emotional experience. Patients were also observed to be significantly lower on emotional expression when compared with others (Aghevli, Blanchard, & Horan, 2003; Selton, van der Bosch, & Sijben, 1998). It appears that there is little correlation between emotional experience and emotional expression in patients, and that observer ratings cannot help us to understand the subjective experience of the negative symptoms. This chapter will focus on research into the subjective experiences of negative symptoms. A framework for these experiences will be used from the qualitative research findings of the primary author (Le Lievre, 2010). In this study, the primary author found that subjective experiences of the negative symptoms belonged to one of the two phases of the illness experience; “transitioning into emotional shutdown” or “recovering from emotional shutdown”. This chapter will use the six themes from the phase of “transitioning into emotional shutdown”. This phase described the experience of turning the focus of attention away from the world and onto the self and the past, thus losing contact with the world and others (emotional shutdown). Transitioning into emotional shutdown involved; “not being acknowledged”, “relational confusion”, “not being expressive”, “reliving the past”, “detachment”, and “no sense of direction” (Le Lievre, 2010). Detail will be added to this framework of experience from other qualitative research in this area. We will now review the six themes that constitute a “transition into emotional shutdown” and corresponding previous research findings.

Characteristics of the Internet for Criminal Child Sexual Abuse by Online Groomers

This paper presents a number of characteristics of the Internet that makes it attractive to online groomers. Relevant Internet characteristics include disconnected personal communication, mediating technology, universality, network externalities, distribution channel, time moderator, low‐cost standard, electronic double, electronic double manipulation, information asymmetry, infinite virtual capacity, independence in time and space, cyberspace, and dynamic social network. Potential sex offenders join virtual communities, where they meet other persons who have the same interest. A virtual community provides an online meeting place where people with similar interests can communicate and find useful information. Communication between members may be via email, bulletin boards, online chat, web‐based conferencing or other computer‐based media.

Characteristics of police-reported road traffic crashes in Ethiopia over a six year period

Ethiopia has one of Africa’s fastest growing non-oil producing economies and an increasing level of motorisation (AfDB, OECD, UNDP, & UNECA, 2012). This rapidly increasing mobility has created some unique road safety concerns; however there is scant published information and related commentary (United Nations Economic Commission for Africa, 2009). The objective of this paper is to quantify police-reported traffic crashes in Ethiopia and characterise the existing state of road safety. Six years (July 2005 - June 2011) of police-reported crash data were analysed, consisting of 12,140 fatal and 29,454 injury crashes on the country’s road network. The 12,140 fatal crashes involved 1,070 drivers, 5,702 passengers, and 7,770 pedestrians, totalling 14,542 fatalities, an average of 1.2 road user fatalities per crash. An important and glaring trend that emerges is that more than half of the fatalities in Ethiopia involve pedestrians. The majority of the crashes occur during daytime hours, involve males, and involve persons in the 18-50 age group—Ethiopia’s active workforce. Crashes frequently occur in mid blocks or roadways. The predominant collision between motor vehicles and pedestrians was a rollover on a road tangent section. Failing to observe the priority of pedestrians and speeding were the major causes of crashes attributed by police. Trucks and minibus taxis were involved in the majority of crashes, while automobiles (small vehicles) were less involved in crashes relative to other vehicle types, partially because small vehicles tend to be driven fewer kilometres per annum. These data illustrate and justify a high priority to identify and implement effective programs, policies, and countermeasures focused on reducing pedestrian crashes.

Microstructure and electromagnetic characteristics of Ni nanoparticle film coated carbon microcoils

Carbon microcoils (CMCs) have been coated with a Ni nanoparticle film using an electroless plating process. The morphology, the elemental composition and the phases in the coating layer, complex permittivity and permeability of the CMCs and Ni-coated CMCs were, respectively, investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and microwave vector network analysis at room temperature. A homogeneous dispersion of Ni nanoparticles on the outer surface of the CMCs was obtained, with a mean particle size of ∼34.4 nm and the phosphorus content of about 8.5 wt%. When comparing the coated and uncoated CMC samples, the real (ε′) and imaginary (ε″) part of the complex permittivity as well as dielectric dissipation factor (tgδε = ε″/ε′) of the Ni-coated CMCs were much smaller, while the real (μ′) and imaginary (μ″) part of the complex permeability and the magnetic dissipation factor (t g σμ = μ″ / μ′) were larger. The enhanced microwave absorption of Ni-coated CMCs resulted from stronger dielectric and magnetic losses. In contrast, the microwave absorption of uncoated CMCs was mainly attributed to the dielectric rather than magnetic losses.

Measurement of transit network accessibility based on access stop choice behaviour

This research improved the measurement of public transport accessibility by capturing; travellers' behaviour; diversity of public transport mode; and the subjectivity of travellers' decision in the complex transport networks. The results of this research not only highlighted the importance of considering public transport network characteristics but also, revealed the impact of public transport diversity in the modelling of public transport accessibility. The research developed a hybrid discrete choice model with a nested logit structure to treat the correlation among the public transport mode choices and, a logit correction factor to rectify the correlation among the stop choices.

Cavitation erosion characteristics of poly(methyl methacrylate) in a rotating disk device

Experimental results pertaining to the initiation, dynamics and mechanism of cavitation erosion on poly(methyl methacrylate) specimens tested in a rotating disk device are described in detail. Erosion normally starts at the location nearest to the center of rotation (CR). As the exposure time to cavitation increases, additional erosion areas or sites appear away from the CR and secondary erosion (induced by eroded pits) spreads upstream and merges with the main pit. The microcracks increase in density towards the end of the incubation period and transform into macrocracks in most cases. A study of light optical photographs and scanning electron micrographs of the eroded area shows that material particles are removed from the network of cracks because of crack joining and pits indicate particle debris. Optical degradation (loss of transmittance) is observed to be greater on the back of the specimen than on the front.

Kinetics of copolyurethane network formation

Cure kinetics for the formation of copolyurethane networks of various compositions based on hydroxy-terminated polybutadiene(HTPB), poly(12-hydroxy stearic acid-co-TMP) ester polyol(PEP), and different isocyanates has been studied through viscosity build up during the cure reaction. The viscosity (N)-time (t) plots conform to the equation N = ae(bt), where a and b are empirical constants, dependent on the composition and the nature of the polyols and the isocyanates. The rate constants (b) for viscosity build up, evaluated from the slopes of dN/dt versus N plots at different temperatures, were found to vary significantly from 0.0073 to 0.25 min(-1); and the activation energies for gelation were found to be in the range 20 to 40 kJ mol(-1). The results have been interpreted in terms of the dependence of the rate constants on structural characteristics of the prepolymers. (C) 1997 John Wiley & Sons, Inc.