An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes), we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure) as the affected core (A-core) of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs - chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, "de-centralizing" the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30-40% of 22q11DS patients develop.

jxSensor: a sensor network integration layer for JXTA

Nowadays, Wireless Sensor Networks (WSN) arealready a very important data source to obtain data about the environment. Thus, they are key to the creation of Cyber-Physical Systems (CPS). Given the popularity of P2P middlewares as ameans to efficiently process information and distribute services, being able to integrate them to WSN¿s is an interesting proposal. JXTA is a widely used P2P middleware that allows peers to easily exchange information, heavily relying on its main architectural highlight, the capability to organize peers with common interests into peer groups. However, right now, approaches to integrate WSNs to a JXTA network seldom take advantage of peer groups. For this reason, in this paper we present jxSensor, an integrationlayer for sensor motes which facilitates the deployment of CPS¿s under this architecture. This integration has been done taking into account JXTA¿s idiosyncrasies and proposing novel ideas,such as the Virtual Peer, a group of sensors that acts as a single entity within the peer group context.

Groups of services delivered by Brazilian branchless banking and respective network integration models

Over the last decade, Brazil has pioneered an innovative model of branchless banking, known as correspondent banking, involving distribution partnership between banks, several kinds of retailers and a variety of other participants, which have allowed an unprecedented growth in bank outreach and became a reference worldwide. However, despite the extensive number of studies recently developed focusing on Brazilian branchless banking, there exists a clear research gap in the literature. It is still necessary to identify the different business configurations involving network integration through which the branchless banking channel can be structured, as well as the way they relate to the range of bank services delivered. Given this gap, our objective is to investigate the relationship between network integration models and services delivered through the branchless banking channel. Based on twenty interviews with managers involved with the correspondent banking business and data collected on almost 300 correspondent locations, our research is developed in two steps. First, we created a qualitative taxonomy through which we identified three classes of network integration models. Second, we performed a cluster analysis to explain the groups of financial services that fit each model. By contextualizing correspondents' network integration processes through the lens of transaction costs economics, our results suggest that the more suited to deliver social-oriented, "pro-poor'' services the channel is, the more it is controlled by banks. This research offers contributions to managers and policy makers interested in understanding better how different correspondent banking configurations are related with specific portfolios of services. Researchers interested in the subject of branchless banking can also benefit from the taxonomy presented and the transaction costs analysis of this kind of banking channel, which has been adopted in a number of developing countries all over the world now. (C) 2011 Elsevier B.V. All rights reserved.

Integration of a regional GPS network within ITRF using precise point positioning

GPS precise point positioning (PPP) can provide high precision 3-D coordinates. Combined pseudorange and carrier phase observables, precise ephemeris and satellite clock corrections, together with data from dual frequency receivers, are the key factors for providing such levels of precision (few centimeters). In general, results obtained from PPP are referenced to an arbitrary reference frame, realized from a previous free network adjustment, in which satellite state vectors, station coordinates and other biases are estimated together. In order to obtain consistent results, the coordinates have to be transformed to the relevant reference frame and the appropriate daily transformation parameters must be available. Furthermore, the coordinates have to be mapped to a chosen reference epoch. If a velocity field is not available, an appropriated model, such as NNR-NUVEL-IA, has to be used. The quality of the results provided by this approach was evaluated using data from the Brazilian Network for Continuous Monitoring of the Global Positioning System (RBMC), which was processed using GIPSY-OASIS 11 software. The results obtained were compared to SIRGAS 1995.4 and ITRF2000, and reached precision better than 2cm. A description of the fundamentals of the PPP approach and its application in the integration of regional GPS networks with ITRF is the main purpose of this paper.

Development of machine learning methods for multi-modal biomarkers detection and integration

In medicine, innovation depends on a better knowledge of the human body mechanism, which represents a complex system of multi-scale constituents. Unraveling the complexity underneath diseases proves to be challenging. A deep understanding of the inner workings comes with dealing with many heterogeneous information. Exploring the molecular status and the organization of genes, proteins, metabolites provides insights on what is driving a disease, from aggressiveness to curability. Molecular constituents, however, are only the building blocks of the human body and cannot currently tell the whole story of diseases. This is why nowadays attention is growing towards the contemporary exploitation of multi-scale information. Holistic methods are then drawing interest to address the problem of integrating heterogeneous data. The heterogeneity may derive from the diversity across data types and from the diversity within diseases. Here, four studies conducted data integration using customly designed workflows that implement novel methods and views to tackle the heterogeneous characterization of diseases. The first study devoted to determine shared gene regulatory signatures for onco-hematology and it showed partial co-regulation across blood-related diseases. The second study focused on Acute Myeloid Leukemia and refined the unsupervised integration of genomic alterations, which turned out to better resemble clinical practice. In the third study, network integration for artherosclerosis demonstrated, as a proof of concept, the impact of network intelligibility when it comes to model heterogeneous data, which showed to accelerate the identification of new potential pharmaceutical targets. Lastly, the fourth study introduced a new method to integrate multiple data types in a unique latent heterogeneous-representation that facilitated the selection of important data types to predict the tumour stage of invasive ductal carcinoma. The results of these four studies laid the groundwork to ease the detection of new biomarkers ultimately beneficial to medical practice and to the ever-growing field of Personalized Medicine.

The evolution of controlled multitasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms

Eukaryotic phenotypic diversity arises from multitasking of a core proteome of limited size. Multitasking is routine in computers, as well as in other sophisticated information systems, and requires multiple inputs and outputs to control and integrate network activity. Higher eukaryotes have a mosaic gene structure with a dual output, mRNA (protein-coding) sequences and introns, which are released from the pre-mRNA by posttranscriptional processing. Introns have been enormously successful as a class of sequences and comprise up to 95% of the primary transcripts of protein-coding genes in mammals. In addition, many other transcripts (perhaps more than half) do not encode proteins at all, but appear both to be developmentally regulated and to have genetic function. We suggest that these RNAs (eRNAs) have evolved to function as endogenous network control molecules which enable direct gene-gene communication and multitasking of eukaryotic genomes. Analysis of a range of complex genetic phenomena in which RNA is involved or implicated, including co-suppression, transgene silencing, RNA interference, imprinting, methylation, and transvection, suggests that a higher-order regulatory system based on RNA signals operates in the higher eukaryotes and involves chromatin remodeling as well as other RNA-DNA, RNA-RNA, and RNA-protein interactions. The evolution of densely connected gene networks would be expected to result in a relatively stable core proteome due to the multiple reuse of components, implying,that cellular differentiation and phenotypic variation in the higher eukaryotes results primarily from variation in the control architecture. Thus, network integration and multitasking using trans-acting RNA molecules produced in parallel with protein-coding sequences may underpin both the evolution of developmentally sophisticated multicellular organisms and the rapid expansion of phenotypic complexity into uncontested environments such as those initiated in the Cambrian radiation and those seen after major extinction events.

Characterizing the connectome in schizophrenia with diffusion spectrum imaging.

Schizophrenia is a complex psychiatric disorder characterized by disabling symptoms and cognitive deficit. Recent neuroimaging findings suggest that large parts of the brain are affected by the disease, and that the capacity of functional integration between brain areas is decreased. In this study we questioned (i) which brain areas underlie the loss of network integration properties observed in the pathology, (ii) what is the topological role of the affected regions within the overall brain network and how this topological status might be altered in patients, and (iii) how white matter properties of tracts connecting affected regions may be disrupted. We acquired diffusion spectrum imaging (a technique sensitive to fiber crossing and slow diffusion compartment) data from 16 schizophrenia patients and 15 healthy controls, and investigated their weighted brain networks. The global connectivity analysis confirmed that patients present disrupted integration and segregation properties. The nodal analysis allowed identifying a distributed set of brain nodes affected in the pathology, including hubs and peripheral areas. To characterize the topological role of this affected core, we investigated the brain network shortest paths layout, and quantified the network damage after targeted attack toward the affected core. The centrality of the affected core was compromised in patients. Moreover the connectivity strength within the affected core, quantified with generalized fractional anisotropy and apparent diffusion coefficient, was altered in patients. Taken together, these findings suggest that the structural alterations and topological decentralization of the affected core might be major mechanisms underlying the schizophrenia dysconnectivity disorder. Hum Brain Mapp, 36:354-366, 2015. © 2014 Wiley Periodicals, Inc.

Intervention orthophonique et neurobiologie du cerveau : apports de la neuroimagerie à la prise en charge de l’aphasie chronique

L’aphasie est un trouble acquis du langage entraînant des problèmes de communication pouvant toucher la compréhension et/ou l’expression. Lorsque l’aphasie fait suite à un accident vasculaire cérébral, une régression des déficits communicatifs s'observe initialement, mais elle peut demeurer sévère pour certains et est considérée chronique après un an. Par ailleurs, l’aphasie peut aussi être observée dans l’aphasie progressive primaire, une maladie dégénérative affectant uniquement le langage dans les premières années. Un nombre grandissant d’études s’intéressent à l’impact de la thérapie dans l’aphasie chronique et ont démontré des améliorations langagières après plusieurs années. L’hémisphère gauche semble avoir un rôle crucial et est associé à de meilleures améliorations langagières, mais la compréhension des mécanismes de plasticité cérébrale est encore embryonnaire. Or, l’efficacité de la thérapie dans l’aphasie progressive primaire est peu étudiée. À l’aide de la résonance magnétique fonctionnelle, le but des présentes études consiste à examiner les mécanismes de plasticité cérébrale induits par la thérapie Semantic Feature Analysis auprès de dix personnes souffrant d’aphasie chronique et d’une personne souffrant d’aphasie progressive primaire. Les résultats suggèrent que le cerveau peut se réorganiser plusieurs années après une lésion cérébrale ainsi que dans une maladie dégénérative. Au niveau individuel, une meilleure amélioration langagière est associée au recrutement de l’hémisphère gauche ainsi qu’une concentration des activations. Les analyses de groupe mettent en évidence le recrutement du lobule pariétal inférieur gauche, alors que l’activation du gyrus précentral gauche prédit l’amélioration suite à la thérapie. D’autre part, les analyses de connectivité fonctionnelle ont permis d’identifier pour la première fois le réseau par défaut dans l’aphasie. Suite à la thérapie, l’intégration de ce réseau bien connu est comparable à celle des contrôles et les analyses de corrélation suggèrent que l’intégration du réseau par défaut a une valeur prédictive d’amélioration. Donc, les résultats de ces études appuient l’idée que l’hémisphère gauche a un rôle prépondérant dans la récupération de l’aphasie et fournissent des données probantes sur la neuroplasticité induite par une thérapie spécifique du langage dans l’aphasie. De plus, l’identification d’aires clés et de réseaux guideront de futures recherches afin d’éventuellement maximiser la récupération de l’aphasie et permettre de mieux prédire le pronostic.

Praxisrelevante Auswirkungen des Vorschlages für eine EU-Verordnung KOM/2000/7/final, 2000/0212(COD) des europäischen Parlaments und des Rates von der Kommission der Europäischen Gemeinschaften auf die Verkehrsplanung des öffentlichen Personennahverkehrs

Die Arbeit behandelt den Vorschlag für eine EU-Verordnung KOM/2000/7/final, 2000/0212(COD) des europäischen Parlaments und des Rates von der Kommission der Europäischen Gemeinschaften als Grundlage einer Marktöffnungsverordnung und welche Veränderungen sich dadurch in Deutschland einstellen werden. Ausschreibungen von Verkehrsleistungen werden zunehmen. Die Ausschreibungsarten werden sich in ländlichen Regionen von denen in Verkehrszentren unterscheiden. In der Region werden sich Bedarfslösungen stärker durchsetzen. Kürzungen von Verkehrsleistungen werden hier stärker ausfallen als in den Zentren und damit zu einem kleineren Leistungsvolumen führen. Aufgrund des geringen Leistungsumfangs gibt es weniger Interessenten. Bei Standardausschreibungen werden deshalb auch häufig die Varianten der beschränkten oder die freihändige Vergabe gewählt. Funktionale Ausschreibungen haben nur eine untergeordnete Bedeutung. In den Verkehrszentren sind die Lose größer und damit für viele Anbieter interessant. Die Verkehrszusatzleistungen sind zudem komplexer. Standardausschreibungen in öffentlicher Vergabeart werden sich hier vermutlich als Norm durchsetzen. Die VOL/A wird sicherlich ihre Bedeutung und ihren dafür notwendigen Regelungsumfang in Deutschland als deutsches oder als europäisches Recht behalten. Ob der empfehlende Charakter der DIN EN 13816 Norm „ÖPNV: Definition, Festlegung von Leistungszielen und Messung der Servicequalität“ erhalten werden kann und nicht als Steuerungselement zur Standardisierung im ÖPNV beitragen wird, ist dabei zu bezweifeln. Durch diese Wettbewerbspflicht wird der Aufgabenträger zum Besteller von Verkehrsleistungen. Damit geht die Verkehrsplanung in die Verantwortung des Aufgabenträgers über und gerät stärker in den Einflussbereich der Politik. Die strategisch abstrakte und die konkrete Verkehrsplanung wachsen für den Normfall der Standardausschreibung zusammen. Die Hoffnung auf eine bessere Netzintegration und eine Standardisierung des ÖPNV Angebots und der ÖPNV Qualität entsteht. Es entwickelt sich dadurch aber auch die Gefahr der Abhängigkeit des Nahverkehrsangebots von der derzeitigen Haushaltslage oder der Interessenlage der Politik. Kontinuität in Angebot und Qualität werden zu erklärten Planungszielen. Der Verkehrsplaner auf der Bestellerseite muss die Planung in Ausschreibungsunterlagen umsetzen. Dies erfordert erweiterte Kompetenzen in den Bereichen Betriebswirtschaft, Logistik, Jura, Informatik und Führungskompetenzen. Ausbildende Institutionen müssen darauf bereits im Vorfeld der Umsetzung reagieren. Durch die zeitliche Verzögerung der Umsetzung der Planung durch die Ausschreibungsschritte sind in der Verkehrsplanung längere Planungsvorlaufzeiten einzukalkulieren. Vorausschauender zu planen, wird dabei wichtiger. Auch eventuelle Fehler in der Planung sind nicht mehr so einfach zu korrigieren. Durch den gestiegenen Einsatz von Technologien in den Fahrzeugen besteht für den Verkehrsplaner dafür häufiger die Möglichkeit, Planungsänderungen auf ihre Wirksamkeit im Hinblick auf Attraktivität für den Fahrgast anhand von den ermittelten Fahrgastzahlen zu kontrollieren. Dasselbe gilt auch für Marketing- und Vertriebsmaßnahmen, wie für die Tarifpolitik. Die Zahlen stehen nicht nur für diese Rückkopplung zur Verfügung, sondern dienen auch als Planungsgrundlage für zukünftige Maßnahmen. Dem Planer stehen konkretere Zahlen für die Planung zur Verfügung. Ein Aspekt, der aufgrund der Sanktionsmaßnahmen bei Ausschreibungen an Bedeutung gewinnen wird, ist die Möglichkeit, Qualität von Verkehrsleistungen möglichst objektiv beurteilen zu können. Praxisrelevante Auswirkungen auf die Verkehrsplanung des öffentlichen Personennahverkehrs ergeben sich hauptsächlich durch die gestiegene Komplexität in der Planung selbst und den dadurch unverzichtbaren gewordenen Einsatz von Computerunterstützung. Die Umsetzung in Ausschreibungsunterlagen der Planung und die Kontrolle stellen neue Elemente im Aufgabenbereich des Verkehrsplaners dar und erfordern damit breiter ausgelegte Kernkompetenzen. Es werden mehr Verkehrsplaner mit breiterer Ausbildung benötigt werden. Diese Arbeit hat aufgezeigt, dass sich mit der Integration des Ausschreibungsgedankens in den Ablauf der Verkehrsplanung eine sprunghafte Entwicklung in der Planungstätigkeit ergeben wird. Aufgrund der in Zukunft steigenden Qualität und Quantität der Planungsgrundlagen und der ebenfalls gestiegenen Ansprüche an die Bewertungsparameter ergeben sich Veränderungen und neue Anforderungen auf diesem Gebiet, die in erster Linie für die Hochschulen und andere ausbildende Einrichtungen, aber auch für die Verkehrsplanung unterstützende Industrie.

Avaliação do cuidado na estratégia saúde da família em metrópoles do nordeste brasileiro

Objective: To evaluate the implementation of the Family Health Strategy (FHS) in Brazilian cities of the Northeast, expanding coverage, analyzing the progress, challenges and innovations. Methods: Multicentric Evaluation Research, Studies Baselines in urban centers, using as a case study method. Selected cases of Aracaju, being capital, advanced coverage with extended team, and Fortaleza, capital coverage incipient and minimal staff. In Fortaleza, purposive sample of 11 Units Primary (APS), 03 managers, 53 professionals and 109 users. In Aracaju, 09 units of APS, 02 managers, 36 professionals, and 90 users. Structured interviews for managers, and structured to professionals and users. Descriptive analysis focusing on the political and institutional dimensions, organization and comprehensive care. Results: There was consensus that the ESF is the preferred port users and acts as inducing changes in care. In the case of Fortaleza, the specificities were: care protocols and community activities aimed at chronic conditions (100%) , with greater participation of doctors and nurses (93%) ; conjunction with more complex services, but the teams reported difficulties with the examination center and experts, the long waits and poor access to local services were the main difficulties reported by users., As innovative practice, the therapeutic group of elderly caregivers mentioned by respondents; There was intersectoral initiatives and teams 87 % of users have participated in meetings about health problems. In the case of Aracaju, care protocols were directed to the lines of care and formulated locally, 85 % coverage of the population with FHS counterpart local financing; employees hired by public tender; 70 % of teams with expertise in public health center for continuing education acting; democratization in management; access technologies, welcoming and computerization in different integrated networks, and evaluation matrix. Conclusions: The ESF has promoted access to health care and inclusion of disadvantaged populations. Different perceptions and practices in the organization of care, with distinct trajectories of reorganization. In the case of Fortaleza, predominance of model programs valuing older, with evidence of advances in care practices and teamwork, but restricted to primary care practices and incipient in public policy perspective. In Aracaju, had network integration with technologies related to the family, in which the ESF is consolidated as public policy. It can be argued that the XII APS expanding coverage, exhibited efficacy, despite the challenges inherent to the different degrees of implementation

[strategies For Integration Of Health Care Practices And Sanitary Surveillance In The Context Of The Implementation Of Rede Cegonha - A Brazilian Mother And Infant Health Care Network].

Mother and infant mortality has been the scope of analysis throughout the history of public health in Brazil and various strategies to tackle the issue have been proposed to date. The Ministry of Health has been working on this and the Rede Cegonha strategy is the most recent policy in this context. Given the principle of comprehensive health care and the structure of the Unified Health System in care networks, it is necessary to ensure the integration of health care practices, among which are the sanitary surveillance actions (SSA). Considering that the integration of health care practices and SSA can contribute to reduce mother and infant mortality rates, this article is a result of qualitative research that analyzed the integration of these actions in four cities in the State of São Paulo/Brazil: Campinas, Indaiatuba, Jaguariúna and Santa Bárbara D'Oeste. The research was conducted through interviews with SSA and maternal health managers, and the data were evaluated using thematic analysis. The results converge with other studies, identifying the isolation of health care practices and SSA. The insertion of SSA in collectively-managed areas appears to be a potential strategy for health planning and implementation of actions in the context under scrutiny.

Processus intégratifs et gouvernance clinique dans la psychiatrie institutionnelle [Integration processes and clinical governance in the psychiatric network]

The Swiss Medical Insurance Act (LAMaL) requires the planning of psychiatric care. This necessitates a coordination between the Department of Public Health and the institutional governance. Given the difficulties to draw comparisons between a wide range of systems in a federal country, the Swiss Conference of the State Directors of Health (CDS) proposed as a first step that each canton present some of the key programs they had developed. In the canton Vaud, the implementation of mobile community treatment teams and of an early intervention program for psychosis was chosen. The main challenges faced were to go past traditional divides within the organisation of the Swiss Health system and to conciliate the requirements of public health with the needs of treating teams, in order to promote early intervention in mental health disorders.

Integration in project business : mechanisms for integrating customers and the project network during the life-cycle of industrial projects

This thesis focuses on integration in project business, i.e. how projectbased companies organize their product and process structures when they deliver industrial solutions to their customers. The customers that invest in these solutions run their businesses in different geographical, political and economical environments, which should be acknowledged by the supplier when providing solutions comprising of larger and more complex scopes than previously supplied to these customers. This means that the suppliers are increasing their supply range by taking over some of the activities in the value chain that have traditionally been handled by the customer. In order to be able to provide the functioning solutions, including more engineering hours, technical equipment and a wider project network, a change is needed in the mindset in order to be able to carry out and take the required responsibility that these new approaches bring. For the supplier it is important to be able to integrate technical products, systems and services, but the supplier also needs to have the capabilities to integrate the cross-functional organizations and departments in the project network, the knowledge and information between and within these organizations and departments, along with inputs from the customer into the product and process structures during the lifecycle of the project under development. Hence, the main objective of this thesis is to explore the challenges of integration that industrial projects meet, and based on that, to suggest a concept of how to manage integration in project business by making use of integration mechanisms. Integration is considered the essential process for accomplishing an industrial project, whereas the accomplishment of the industrial project is considered to be the result of the integration. The thesis consists of an extended summary and four papers, that are based on three studies in which integration mechanisms for value creation in industrial project networks and the management of integration in project business have been explored. The research is based on an inductive approach where in particular the design, commissioning and operations functions of industrial projects have been studied, addressing entire project life-cycles. The studies have been conducted in the shipbuilding and power generation industries where the scopes of supply consist of stand-alone equipment, equipment and engineering, and turnkey solutions. These industrial solutions include demanding efforts in engineering and organization. Addressing the calls for more studies on the evolving value chains of integrated solutions, mechanisms for inter- and intra-organizational integration and subsequent value creation in project networks have been explored. The research results in thirteen integration mechanisms and a typology for integration is proposed. Managing integration consists of integrating the project network (the supplier and the sub-suppliers) and the customer (the customer’s business purpose, operations environment and the end-user) into the project by making use of integration mechanisms. The findings bring new insight into research on industrial project business by proposing integration of technology and engineering related elements with elements related to customer oriented business performance in contemporary project environments. Thirteen mechanisms for combining products and the processes needed to deliver projects are described and categorized according to the impact that they have on the management of knowledge and information. These mechanisms directly relate to the performance of the supplier, and consequently to the functioning of the solution that the project provides. This thesis offers ways to promote integration of knowledge and information during the lifecycle of industrial projects, enhancing the development towards innovative solutions in project business.

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.