Philippe Finet
email: phfinet@ch-alencon.fr

Olivier Dameron

B Gibaud

R Lebouquin Jeannes

R Le Bouquin Jeannès

1. Introduction:

The number of patients suffering from one or more non-communicable diseases increases with the aging of the population [START_REF] Finet | Review of current telemedicine applications for chronic diseases. Toward a more integrated system?[END_REF]. Non-communicable chronic diseases were responsible for 36 of the 57 million deaths worldwide in 2008 [START_REF]Global Status Report on Non communicable Diseases[END_REF]. There are several complications associated with chronic diseases. For example, diabetes slows wound healing and increases the risk of infection [START_REF] Shakya | Hyperglycemia-Induced Changes in Hyaluronan Contribute to Impaired Skin Wound Healing in Diabetes: Review and Perspective[END_REF]. In Basse Normandie, France, there are around 20,000 patients with complex wounds [START_REF] Blanchère | The latest developments in telemedicine applied to wound care[END_REF]. Complex chronic wounds increase re-admission rate in hospitals (15 days per patient per year at the Caen University Hospital between 2008 and 2012) [START_REF] Rees | The effects of TeleWound management on use of service and financial outcomes[END_REF] and require repeated transportations for people with low independence. In this context, telemedicine can contribute to reduce hospital consultations and transport [START_REF] Ong | Telemedicine and wound care[END_REF]. Telemedicine facilitates patient follow-up outside hospital [START_REF] Kitsiou | Systematic reviews and metaanalyses of home telemonitoring interventions for patients with chronic diseases: a critical assessment of their methodological quality[END_REF]. Telemedicine applications can help reducing healthcare costs while maintaining healthcare quality [START_REF] Kitsiou | Systematic reviews and metaanalyses of home telemonitoring interventions for patients with chronic diseases: a critical assessment of their methodological quality[END_REF].

This situation has led the Basse-Normandie and Languedoc-Roussillon regions to implement the Domoplaie telemedicine project [START_REF] Blanchère | The latest developments in telemedicine applied to wound care[END_REF]. Its goal was to develop a wound care system with tele-expertise, teleconsultation and tele-assistance for home care patients in order to reduce both transportations and hospital stays. This application supports collaboration between the general practitioner, the private duty nurse and the hospital staff.

In the current implementation, a specific Electronic Healthcare Record supports medical data exchange between the healthcare professionals. However, interoperability between this system and the various partners' information systems remains limited. This study focuses on the Domoplaie implementation in Basse-Normandie in the context of TELAP [telemedicine network applied to wound care].

We propose a new implementation of medical data exchange based on Health Level 7 (HL7) Clinical Document Architecture (CDA) and on implementation guidelines from the Integrating the Healthcare Enterprise (IHE) Cross-Enterprise Document Sharing (XDS) profile facilitating interoperation between the various information systems.

In this contribution, we first describe the Domoplaie telemedicine application and analyse its current constraints and limitations, with a particular focus on interoperability. In a second step, we propose a solution which makes it possible to obtain interoperability of clinical data when including a patient in the TELAP network.

Description of Domoplaie:

2.1. Steps of the coordinated healthcare circuit: Domoplaie covers all the stages of the coordinated healthcare circuit [START_REF] Blanchère | The latest developments in telemedicine applied to wound care[END_REF]. The main Domoplaie users are then general practitioners, private duty nurses, hospital staff and specialists [START_REF] Blanchère | The latest developments in telemedicine applied to wound care[END_REF]. The first stage is to conduct an initial complete medical examination of the patient chronic wound. It can be performed either by a general practitioner or a specialist. Then, an inclusion request is completed with the patient's data as well as the result of medical examinations. Currently, this inclusion request has to be faxed or sent by e-mail to the TELAP coordination. The patient's data contained in this document need to be manually recorded in the Electronic Healthcare Record by the TELAP staff. Next, a first teleconsultation session between the hospital staff, the private duty nurse and the patient must be planned by the TELAP coordination. The aim of the teleconsultation is to obtain a second opinion from a remote specialist (dermatologist or diabetologist) so that patient transport is not required. During the videoconference, the specialist can examine pictures sent by the nurse.

At the end of the teleconsultation session, a report is sent to Domoplaie partners (e.g. general practitioner) through secure messaging. Additional teleconsultation sessions can be planned if needed until the patient's recovery.

System components:

The various system components incorporate three technology types (see Fig. 1): Patient's data are stored in a specific Electronic Healthcare Record. Teleconsultation sessions are supported by a videoconferencing system available at three expert sites in Basse-Normandie (Alençon Hospital diabetes department, Caen University Hospital dermatology department and Cherbourg Hospital dermatology department). The private duty nurse is equipped with a smartphone or a tablet [START_REF] Blanchère | The latest developments in telemedicine applied to wound care[END_REF] to take pictures or videos of wounds at the patient's home.

Lack of interoperability in Domoplaie:

The first difficulty concerns the inclusion request. This document is initially recorded by the general practitioner who can either fax it or send it as a PDF file. In both cases, the TELAP staff is then required to enter data manually for patient data registration into the Domoplaie Electronic Healthcare Record. The second difficulty is the lack of interoperability between Domoplaie and the information systems of the healthcare facilities

Relevance of health level 7 clinical document architecture and integrating the healthcare enterprise cross-enterprise document sharing profile for managing chronic wounds in a telemedicine context

Fig1 : Domoplaie application (clinical care centres, hospitals, etc.). The only way for TELAP to communicate with healthcare facilities is to send PDF files by secure messaging. At the receiver end, these documents cannot be easily integrated into the information system.

Proposed new implementation:

Improved data exchange should allow, on the one hand, a single data entry during inclusion request, and, on the other hand, interoperable representation of clinical documents. For Domoplaie, the coordinated healthcare circuit requires two types of interoperable clinical documents (the first one for the inclusion request, the second one for the teleconsultation session reports). This new implementation must also take into account an architecture supporting the sharing of these documents between the heterogeneous information systems of the various partners.

3.1. Functional and technical requirements: Clinical documents named "inclusion request" are required to initiate the process. The header of these documents must include the patient's identification, the contact details of medical practitioners and nurses, and the addresses of the facilities involved in the coordinated healthcare circuit. The document bodies must contain results from laboratory analysis, ultrasound and imaging examinations. They should provide the results of the wound initial assessment. These documents must be interoperable with software from healthcare facilities. They must contain coded and structured data, which can be integrated in the healthcare facilities' databases. They must also be easily read by humans. These documents should be accessible by Domoplaie users and TELAP staff. They can be archived on the same server as electronic health records.

Inclusion Request: A computerised data entry form for the patient inclusion request is a technical solution for removing redundant manual data entry. It must be a simple form which can be on a website, that is easily accessible to all Domoplaie users (like with a regional web portal). For each field in the form, data entered by general practitioners or private duty nurses are added to the inclusion request created for each patient's first medical examination.

Teleconsultation session reports: To share the teleconsultation reports, the development of a second model of interoperable clinical documents is proposed. There is no structured model of the teleconsultation session report yet. The content of these documents varies depending on the medical examination performed during the teleconsultation session. Patients and health professionals' identification and teleconsultation dates are currently the only structured information fields. However, the reports may contain pictures, values in the form of trends or tables and other results of medical examinations as plain text.

Digital document repository: To share the inclusion requests and the teleconsultation reports with the entire Domoplaie community, a digital document repository is needed. This system must facilitate clinical documents archiving and reading. This document repository can be located at a healthcare data host.

Standard data exchange procedures and formats:

To share clinical documents between Domoplaie users, the use of international standards such as HL7 CDA [START_REF] Dolin | The HL7 Clinical Document Architecture[END_REF] is an interesting option. A CDA document is a complete information object, which can include text, pictures, sound and other contents. It can either be sent within a message or exist independently [START_REF] Dolin | The HL7 Clinical Document Architecture[END_REF]. As for the implementation of a digital document repository, we propose to use the IHE XDS profile [9] which facilitates the registration, distribution and access to medical documents across healthcare facilities.

HL7 CDA: CDA [10] is a new approach based on XML for structuring and exchanging medical data within and between healthcare facilities. CDA documents, which contain a header and a body, are defined with three levels of architecture corresponding to three different levels of interoperability [START_REF] Dolin | The HL7 Clinical Document Architecture[END_REF]. For level 1, the clinical document body can be unstructured. It can contain something other than XML language (e.g. PDF file). With this level, the structured CDA headers allow to differentiate the types of documents. For level 2, The CDA document may include several different sections that contain human readable narrative forms or codified structures for an automatic processing. Compared with level 2, CDA level 3 provides additional specified constraints at the entry level within a section. With this level, the body text sections include codified entries to recover external data. Today, the CDA exists in two main versions: the CDA release 1 (CDA R1) that mainly focuses on the structured header [START_REF] Ferranti | The Clinical Document Architecture and the Continuity of Care Record: A Critical Analysis[END_REF], and the CDA release 2 (CDA R2) [START_REF] Ferranti | The Clinical Document Architecture and the Continuity of Care Record: A Critical Analysis[END_REF] that includes structured elements in both the document header and the document body. The latter may contain health encoded data that can be easily integrated into data bases of healthcare facilities.

IHE XDS profile: For the creation of a digital document repository, IHE proposed the XDS profile [START_REF] Duftschmid | The EHR-ARCHE project: Satisfying clinical information needs in a Shared Electronic Health Record System based on IHE XDS and Archetypes[END_REF], which comes from the IHE IT Infrastructure Technical Framework (ITI TF). This profile describes appropriate sharing of medical information It specifies the transactions supporting the registration, distribution and access to shared between healthcare facilities. These documents may contain any type of clinical information. They may include, for example, simple text, formatted text (e.g., HL7 CDA Release 1), images (e.g., DICOM) or structured and vocabulary coded clinical information (e.g., CDA Release 2). With the IHE XDS profile, sending and receiving clinical documents can be achieved with standard communication protocols as HTTP or HTTPS. This information flow is managed through one or more document repositories and one document registry which must be precisely defined.

CDA document implementation:

The implementation of a CDA document requires to select an existing model that contains templates and rules sets [START_REF]HL7 Implementation Guide: S&I Framework Transitions of Care Companion Guide to Consolidated-CDA for Meaningful Use Stage 2, Release 1 -US Realm[END_REF]. The Implementation Guides for CDA [START_REF]HL7 Implementation Guide: S&I Framework Transitions of Care Companion Guide to Consolidated-CDA for Meaningful Use Stage 2, Release 1 -US Realm[END_REF] contain templates that address specific uses. They can represent professional recommendations, or national clinical practice guidelines.

Template definition: Templates are designed to create standardised clinical documents that are specifically intended to support clinical workflows in various use cases. A CDA template can be a document template that defines rules for an entire CDA document, or a header template, section template, or entry template covering a relevant portion of the overall CDA document.

Implementation of Domoplaie CDA documents: Our goal was to find CDA document templates suited to the inclusion request or the teleconsultation reports. Because of the national context of the Domoplaie project, the document templates were retrieved from the ASIP web site under the "Health Information Systems Interoperability Framework (HIS-IF)" heading [START_REF]Synthèse médicale-Volet de Synthèse Médicale (VSM) élaboré à partir du modèle métier de synthèse médical[END_REF]. As for the inclusion request document, a template matched our needs. The name and the Object Identifier (OID) of this document template were respectively "Volet de la Synthèse Médicale" and (1.2.250.1.213.1.1.1.3.1) [START_REF]Synthèse médicale-Volet de Synthèse Médicale (VSM) élaboré à partir du modèle métier de synthèse médical[END_REF]. The version of CDA used for this technical model document was CDA R2. As a result, Domoplaie CDA documents have potentially codified structures in the header and in the body of the document for an automatic processing. In contrast, there is no need for structured data for the teleconsultation report body. The use of the same model for both types of Domoplaie documents allows us to have a common codified header. This makes it easier to identify documents.

Creation of a data entry form and CDA documents:

At first, it was necessary to create Domoplaie CDA documents. For this purpose, we chose a tool developed by the ART-DECOR expert group [START_REF] Heitmann | ART-DECOR: a tool bridging the chasm between clinicians and health IT[END_REF]. After creating the CDA documents, this tool also allows to check their structures and their XML contents (generation of schematrons) [START_REF] Heitmann | ART-DECOR: 'An open-source tool bridging the chasm between clinicians and health IT[END_REF]. Creating CDA documents with ART-DECOR involves three steps [START_REF] Heitmann | ART-DECOR: 'An open-source tool bridging the chasm between clinicians and health IT[END_REF]. The first step is the identification of the CDA document project team including the name of the author and the version of the document (required in HL7 CDA). In the second step, it is necessary, particularly for the document named "Inclusion request", to describe the concepts which correspond to different analyzed items and datatypes in data set sections of these documents (according to the document template selected previously). For the inclusion request and the teleconsultation session reports, the document's header must contain at least the following concepts: patient information, contact details of primary physician, private duty nurse and other participants, document creation date and author identification. For the inclusion request, the concepts described in the document body are wound examination, associated pathology and past illness and wound healing factor. In a third step, we have to define the considered scenarios which correspond to the use cases. At this level, we are able to determine two different transactions (the communication of the inclusion request and the communication of the teleconsultation session report). The terminology section of this tool includes the used nomenclatures (e.g. LOINC and SNOMED) and the related value set definitions. This section is also the place where the different templates are defined.

Finally, the combination of data sets, value sets and defined templates allows us to produce an XML file entitled "Retrieve Transaction". We converted the XML file into an HTML data entry form using an XSLT stylesheet. This form can then be accessed by means of any Internet browser (see Fig. 2 for a simple example of a XLST transformation).

Creation of document repository:

For the creation of this repository, the concept is to use Domoplaie's current infrastructure. As shown in Fig. 3, this document sharing management system can be built with the XDS profile functional architecture. The Document Repository can be installed on the secure database server on the local host. A regional website can keep a register of CDA documents (patient identification is managed by the TELAP staff) [START_REF] Blanchère | The latest developments in telemedicine applied to wound care[END_REF]. In this case, (i) the general practitioners fill the Web form, (ii) the CDA document is automatically generated and (iii) it is made accessible by the Domoplaie users, on the regional Internet site. After their establishment, all CDA documents can be stored on the healthcare data host. Domoplaie users can retrieve them through the regional web-portal. For all transactions described in Fig. 3, the CDA documents can be exchanged over the HTTPS secure data transfer protocol [START_REF] Yong | A Prototype Model Using Clinical Document Architecture (CDA) with a Japanese Local Standard: Designing and Implementing a Referral Letter system[END_REF].

Discussion:

The key to success of this project relies in selecting an appropriate modeling tool for CDA document creation. This tool should consider both qualitative and quantitative data from Domoplaie documents. At the same time, it should be flexible enough to integrate essential non-structured data concerning the medical examination of the patient's chronic wounds. Among the most commonly used CDA tools, MDHT, ART-DECOR and TRIFOLIA are the main candidates supporting the generation of various elements (e.g. creation of templates, documentation, XML instance, test tools, etc.) [START_REF] Boufahja | Modelbased Analysis of HL7 CDA R2 Conformance and Requirements Coverage[END_REF]. ART-DECOR is the most widely used in Europe. It is a web-based application that records HL7 and other reusable templates and value sets. The benefits of this tool are first to allow schematron validation, and, second, to enable integration of unstructured section in CDA document. This is important for the teleconsultation reports. With this tool, a document can combine unstructured and structured sections. Thus, this tool allows to easily create both types of Domoplaie information regarding patient identity, the document type and the document identification. With the XDS profile, to group together documents pertaining to the same patient, a unique patient identification is required [START_REF] Kitsiou | Systematic reviews and metaanalyses of home telemonitoring interventions for patients with chronic diseases: a critical assessment of their methodological quality[END_REF]. The identifier is called the XDS Affinity Domain Patient Identifier (XAD-PID) linked to a local patient ID. The XAD-PID is assigned to all documents contained in a XDS Document Registry. It conveniently supports grouping the CDA documents pertaining to the same person. With the HL7 CDA R2 standard, it is possible to retrieve the patient identity and the document identification from the CDA document headers. With the XDS profile, the document repository registers this document information. So, the documents of interest for the care of one patient may be easily found by the Domoplaie users. The CDA documents are stored in the repository with an address allocated by the registry. This system allows telemedicine application users to retrieve any specific examination report from one patient from the repository.

We have now demonstrated that ART-DECOR is a suitable modeling tool for Domoplaie. It enables an implementation of a technical solution which allows the capture, the recording and the distribution of the CDA documents of telemedicine applications. This technical solution may be an interesting option for many telemedicine applications. The only parameter which varies according to telemedicine applications is the selection of document templates depending on the content of shared information.

Fig3. CDA Domoplaie document repository

Conclusion:

The lack of interoperability in Domoplaie has led us to propose a technical solution which facilitates communications between healthcare professionals of the coordinated healthcare circuit. The implementation of CDA documents avoids redundant data entries and simplifies the exchange of patient information. The ART-DECOR tool gives us the opportunity to implement a comprehensive system that will manage the creation, registration and distribution of clinical documents exchanged in telemedicine applications. With ART-DECOR, it is easy to integrate all structured and unstructured data which are contained in inclusion request documents.

The technical solution presented in this contribution is suitable for improving interoperability within any telemedicine application and any document sharing system in a healthcare facility or network. The next steps will consist in deploying both CDA documents as well as the XDS-compliant actors within the Domoplaie infrastructure.

Acknowledgments:

The Domoplaie project is supported by the European Regional Development Fund (ERDF) and the Regional public health agencies (ARS) of Basse-Normandie and Languedoc-Roussillon. We would like to thank Dr Jean Pierre Blanchère, President of TELAP, for his willingness to take part in this study and Eric Poiseau (INRIA) for his assistance in the choice of CDA implementation tools.

Fig. 2 :

 2 Fig. 2: First sampleXML file entitled ″Retrieve Transaction″ with corresponding data entry form using an XLT stylesheet


Eimad Shotar

Alexis Guédon

Nader Sourour

Federico Di

Joseph Gabrieli

Aurélien Nouet

Jacques Chiras

Superficial Middle Cerebral Vein Connection to the Cavernous Sinus is Not Infrequent in Brain Arteriovenous Malformations: an Argument Against Their Congenital Origin?

Keywords: anatomy, arteriovenous malformations, congenital origin, postnatal development, superficial middle cerebral vein, connection Anteroposterior CS: Cavernous Sinus LCS: Laterocavernous Sinus PCS: Paracavernous Sinus PP: Pterygoid Plexus SMCV: Superficial Middle Cerebral Vein SPS: Superior Petrosal Sinus

PURPOSE:

The aim of this study was to test the hypothesis that the superficial middle cerebral vein (SMCV) is frequently absent or fails to connect with the cavernous sinus (CS) in presence of brain AVMs, a frequently reported argument for the congenital origin of brain AVMs.

METHODS:

The SMCV was retrospectively compared between patients with a brain AVM and a control group. The presence or absence of the SMCV, its direct or indirect connection to the CS and its termination in a laterocavernous sinus (LCS), paracavernous sinus (PCS) or directly in the CS was studied on digital subtraction angiography.

RESULTS: 125 left or right side carotid angiograms from 70 patients with a brain AVM were compared to 125 angiograms from 74 controls. The SMCV was present in 88 (70.4%) cases in the brain AVM group and 96 (76.8%) cases in controls (p= 0.25).

The SMCV was connected directly or indirectly to the CS in 65 (52%) cases in the brain AVM group and 65 (52%) cases in controls (p= 1). When comparing the subgroup of carotid angiograms ipsilateral to a supratentorial AVM, no statistically significant difference was found with controls. In 3/6 cases in which a SMCV drained an AVM, the vein terminated directly or indirectly in the CS. CONCLUSIONS: No difference of SMCV presence and direct or indirect connection to the CS was found between patients with AVM and a control group. SMCV anatomy does not support the congenital origin of brain AVMs.

Introduction

AVMs are rare vascular malformations characterized by an abnormal connection between arteries and veins through a network of tangled and tortuous vessels: the so-called nidus. Brain AVMs have an annual detection rate of roughly 1 per 100 000 in prospective population-based studies [START_REF] Al-Shahi | Prospective, populationbased detection of intracranial vascular malformations in adults: the Scottish Intracranial Vascular Malformation Study (SIVMS)[END_REF][START_REF] Stapf | The New York Islands AVM Study: design, study progress, and initial results[END_REF] and are a leading cause of stroke in young adults [START_REF] Stapf | The New York Islands AVM Study: design, study progress, and initial results[END_REF].

Brain AVMs have been thought to be congenital in nature [3,[START_REF] Friedlander | Clinical practice. Arteriovenous malformations of the brain[END_REF]. In 1996, Mullan et al. hypothesized that brain AVMs were possibly formed in utero during the 40 to 80 mm stage [START_REF] Mullan | Embryological basis of some aspects of cerebral vascular fistulas and malformations[END_REF]. They stated that the frequent absence or anomaly of the middle cerebral vein and its failure to communicate with the cavernous sinus in the presence of both cerebral venous malformations and AVMs are linked to the late development of that vein and to its even later connection to the cavernous sinus [START_REF] Mullan | Embryological basis of some aspects of cerebral vascular fistulas and malformations[END_REF]. As the connection of the superficial middle cerebral vein (SMCV) with the cavernous sinus (CS) is thought to be postnatal [START_REF] Padget | The cranial venous system in man in reference to development, adult configuration, and relation to the arteries[END_REF], failure of the SMCV to connect with the CS in presence of a brain AVM could be an argument for their congenital nature. This reminds of vein of Galen aneurysmal malformations. Indeed, vein of Galen aneurysmal malformations are true congenital vascular arteriovenous shunts with a persistent median prosencephalic vein and are associated with failure of the deep venous system to reach adult configuration [START_REF] Lasjaunias | Deep venous drainage in great cerebral vein (vein of Galen) absence and malformations[END_REF].

Several recent observations contradict the long-held dogma that brain AVMs are congenital lesions. Antenatal ultrasound and MRI have dramatically increased prenatal detection of fetal malformations, among which vein of Galen aneurysmal malformations and dural sinus malformations [START_REF] Roccatagliata | Pediatric intracranial arteriovenous shunts: a global overview[END_REF]. However, prenatal detection of pial arteriovenous shunts remains exceedingly rare and to date, only cases of non-nidal fetal pial arteriovenous fistulas have been reported [START_REF] Auyeung | Prenatal diagnosis of unusual fetal pial arteriovenous malformation. A case report[END_REF][START_REF] Garel | Pial arteriovenous fistulas: dilemmas in prenatal diagnosis, counseling and postnatal treatment. Report of three cases[END_REF][START_REF] Köroğlu | Prenatal diagnosis of intracranial pial arteriovenous fistula and endovascular treatment during the neonatal period[END_REF][START_REF] Paladini | Prenatal ultrasound diagnosis of cerebral arteriovenous fistula[END_REF]. Only 20% of brain AVMs are revealed during childhood, raising the question of why most brain AVMs clinically manifest during adulthood if they are congenital and present from birth [START_REF] Rocco | Cerebral arteriovenous malformations in children[END_REF]. Several reports of de novo brain AVMs have been documented on serial angiographies and MRIs, demonstrating the potential for postnatal onset [START_REF] Yeo | Pediatric de novo cerebral AVM: report of two cases and review of literature[END_REF]. Finally, experimental studies have shown de novo brain AVM development to be possible after Eng or Alk1 deletion and angiogenic stimulation in adult mice [START_REF] Chen | De novo cerebrovascular malformation in the adult mouse after endothelial Alk1 deletion and angiogenic stimulation[END_REF][START_REF] Choi | Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia[END_REF].

Although having been published about 20 years ago, the original report by Mullan et al. [START_REF] Mullan | Embryological basis of some aspects of cerebral vascular fistulas and malformations[END_REF] has never been contradicted and continues to be regularly cited as an argument for the congenital origin of brain AVM [3, [START_REF] Morales-Valero | Are parenchymal AVMs congenital lesions?[END_REF][START_REF] Murphy | Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels[END_REF][START_REF] Zhuge | Notch4 is activated in endothelial and smooth muscle cells in human brain arteriovenous malformations[END_REF]. The aim of our study was to test Mullan's statement that the SMCV is frequently absent or fails to connect with the CS in presence of brain AVM.

Methods

Study population

A retrospective review of medical records of patients with brain AVM managed at our institution was undertaken. A list of consecutive patients with a diagnosis of ruptured or unruptured brain AVM on DSA was generated by searching discharge databases of interventional neuroradiology, neurosurgery, neurosurgical intensive care and neurology departments. We screened adult patients with DSA performed from

DSA and image analysis

All patients underwent DSA using a standard femoral approach under local or general anesthesia in a biplane angiography suite (Axiom Artis, Siemens, Erlangen, Germany). Images were acquired at a frame rate of two or six images per second.

Unilateral or bilateral carotid studies were generated with venous phase in anteroposterior (AP) and lateral projections in all patients. Oblique projections were generated in most patients. The imaging studies were independently reviewed by a junior (ES or AG) and a senior (FC) interventional neuroradiologist blinded to the clinical data of the patient. The following data were recorded by both readers: presence or absence of a SMCV, duplicated SMCV, direct or indirect (through a laterocavernous sinus [LCS] or paracavernous sinus [PCS]) connection of the SMCV to the CS, presence of a brain AVM ipsilateral to the SMCV and drainage of the brain AVM into the SMCV. The termination of the SMCV into a LCS, PCS or directly into the CS and the drainage of the LCS or PCS into the CS, pterygoid plexus (PP), superior petrosal sinus (SPS) or tentorial sinus were recorded as previously described [START_REF] Gailloud | Angiographic anatomy of the laterocavernous sinus[END_REF]. Discrepancies were settled by joint discussion by the two readers. For patients with a bAVM, we have chosen, when DSAs were available, to include both side (i.e.: ipsilateral and contralateral to the bAVM) in the group "bAVM" since venous outflows are interrelated and an abnormality of one part will often influence the evolution of others [START_REF] Lasjaunias | Chapter 7: Intracranial Venous System[END_REF]. We also compared the subgroup of carotid angiograms ipsilateral to supratentorial brain AVMs with control group DSAs.

In order to better understand the close spatial relationship between the different vascular structures studied, fusion images were generated. These images for the figures were generated using an open-source software (GIMP, version 2.8, available at http://www.gimp.org/). The grey scale of one of the two images to be superimposed was inverted. Transparency was modified until both images were adequately visible. When fusing images of different phases (arterial and venous) of a single carotid angiogram in the same patient, no manipulation for registration was necessary. For fusing of different angiograms (right and left sides) of a single patient, the superior sagittal sinus, transverse sinuses and sigmoid sinuses were used as references for accurate registration.

Statistical analysis

All statistical analyses were performed using a commercially available software package (Stata, StataCorp, Texas, USA). All variables were considered independent.

Categorical data are presented as proportions and continuous variables are presented as mean ± standard deviations. The interobserver reliability for determining the SMCV anatomy on DSA was assessed by calculation of κ values.

The κ values were categorized as previously reported [START_REF] Landis | The measurement of observer agreement for categorical data[END_REF] : κ=0.41 to 0.6, 0.61 to 0.8, and 0.81 to 1 indicate moderate, good, and excellent agreement between observers, respectively. A κ=1 indicates total agreement between observers.

Comparisons of the brain AVM and control groups were performed on a merged data set after discrepancies were settled by joint discussion by the two readers. The demographic and radiological characteristics were compared between patients with a brain AVM and controls by using Chi-squared test, Fisher's exact test, and student t test as appropriate. A p<0.05 was considered statistically significant. A Bonferroni's correction was applied for subgroup analysis (3 types of SMCV's connection to the CS) with an adjusted statistical significance threshold of p<0.016 (0.05/3=0.016). In a second analysis, radiological characteristics were compared between angiograms with an ipsilateral supratentorial brain AVM and controls.

Ethical statement

Neither approval of the institutional review board nor patient informed consent are required by the ethics committee of our institution for retrospective analyses of patients' records and imaging data.

Results

One hundred and fifty patients with a total of 275 right or left side carotid angiograms were screened for this study. SMCV's anatomy was deemed not interpretable in 25 angiograms (motion artifacts in 13 cases, venous phase not available in 8, inadequate subtraction in 3 and vasospasm in 1 case) and were thus excluded (leading to exclusion of 6 patients, either because bilateral angiograms were deemed not interpretable in 5 patients or because the only available angiogram was deemed not interpretable for 1 patient). Seventy patients with 125 angiograms (55 patients with bilateral angiograms, 10 patients with only right sided angiograms and 5 patients with only left sided angiograms) were included for analysis in the brain AVM group.

Seventy-four patients with 125 angiograms (51 patients with bilateral angiograms, 14 patients with only right sided angiograms and 9 patients with only left sided angiograms only) were included in the control group. Mean age was 41±15 years (51% males) in the brain AVM group and 50±13 years (30% males) in the control group (Table 1).

All angiograms were analyzed by two of the study authors. For determining whether the SMCV was present or absent, and when present if it was connected directly or indirectly to the CS, the inter-rater agreement was good (κ = 0.71; 95% CI = 0.64 to 0.79). For determining whether the SMCV was present or absent, and, when present, its mode of termination into a LCS, PCS or directly into the CS, the inter-rater agreement was moderate (κ = 0.59; 95% CI = 0.51 to 0.66).

All variants of the SMCV termination were observed, including absence of SMCV (Fig. 1), direct termination of the SMCV in the CS (Fig. 2), termination in a LCS (Fig. 2) and termination in a PCS (Fig. 3). There was no difference in terms of presence or absence of the SMCV between the brain AVM and control groups (Table 1). Moreover, when present, the SMCV direct or indirect (through a LCS or PCS) connection to the CS was not significantly different between the two groups. No difference was observed regarding SMCV termination into a LCS or directly into the CS between the brain AVM and the control group (Table 1). However, the SMCV terminated into a PCS less frequently in the brain AVM group than in the control group (p-value=0.02) but this difference was no longer statistically significant when applying a Bonferroni's correction (0.05/3=0.016).

In a second analysis, all carotid angiograms ipsilateral to supratentorial brain AVMs (53 patients with 53 angiograms) were compared to the control group (74 patients with 125 left and/or right side angiograms) (Table 2). No statistically significant difference was found in terms of SMCV anatomy between the two groups.

In 6 out of 70 patients, a brain AVM was found to be drained completely or partly through a SMCV. In 2 cases, the SMCV directly terminated in the CS (Fig. 4). In 1 case, the SMCV terminated in a LCS that drained in the CS and PP. In 2 cases, the SMCV terminated in a PCS that drained in the SPS Finally, in 1 case, the SMCV terminated in a LCS that drained only in the SPS. Thus, in 3 out of 6 cases (50%), a SMCV draining a brain AVM terminated directly or indirectly in the CS.

Hemorrhagic presentation is a potential source of bias as it may obscure the SMCV. Therefore, we sought to compare SMCV anatomy between patients with and without hemorrhagic presentation. In the AVM group, the SMCV was found to be present in 67/96 (69.8%) sides in patients with a hemorrhagic presentation (54/70 patients, 77.1%) and in 21/29 (72.4%) sides in patients without hemorrhagic presentation (16/70 patients, 22.9%) (p-value=0.97). When present, the SMCV connected directly or indirectly to the CS in 48/96 (50%) sides in the ruptured brain AVM group and in 17/29 (58.6%) sides in the non-ruptured brain AVM group (p-value=0.55). In the control group, the SMCV was found to be present in 54/74 (73%) sides in patients with hemorrhagic presentation (45/74 patients, 60.8%) and 42/51 (82.4%) sides in patients without hemorrhagic presentation (29/74 patients, 39.2%) (p-value=0.31).

When present, the SMCV connected directly or indirect to the CS in 36/74 (48.6%) sides in the control group with hemorrhagic presentation and 29/51 (56.9%) sides in the control group without hemorrhagic presentation (p-value=0.47).

Discussion

A SMCV draining a brain AVM and terminating in the CS has previously been reported [START_REF] Davidson | The embryologic basis for the anatomy of the cerebral vasculature related to arteriovenous malformations[END_REF]. However, our work is, to the best of our knowledge, the first systematic study of the SMCV anatomy in a group of patients with brain AVMs compared to a control group.

The SMCV is a supratentorial cerebral vein coursing along the lateral sulcus and connected caudally to the superior anastomotic vein of Trolard and/or to the inferior anastomotic vein of Labbé. Its cranial termination has long been assimilated to the sphenoid portion of the sphenoparietal sinus of Breschet. This notion has been challenged by San Millan Ruίz et al., who have shown that the so called sphenoparietal sinus corresponds to the artificial combination of two venous structures: a dural sinus coursing under the lesser sphenoid wing and the parietal portion of the anterior branches of the middle meningeal veins [START_REF] Millán Ruíz | The sphenoparietal sinus of breschet: does it exist? An anatomic study[END_REF]. They have further shown that the sinus of the lesser sphenoid wing was connected laterally to the anterior branch of the middle meningeal veins and medially to the cavernous sinus, but never to the SMCV [START_REF] Millán Ruíz | The sphenoparietal sinus of breschet: does it exist? An anatomic study[END_REF]. In another study, San Millan Ruίz et al. have also demonstrated the existence of a venous structure within the two dural layers forming the lateral wall of the cavernous sinus which they termed the LCS [START_REF] San Millán Ruiz | Laterocavernous sinus[END_REF]. According to these authors, the termination of the SMCV can follow three distinct patterns: 1) direct termination into the anterosuperior aspect of the CS; 2) termination within the lateral wall of the CS in what is called a LCS; or 3) following a lateral trajectory within the dural floor of the middle cranial fossa, taking the name of PCS [START_REF] Gailloud | Angiographic anatomy of the laterocavernous sinus[END_REF][START_REF] San Millán Ruiz | Laterocavernous sinus[END_REF]. The LCS can have three distinct draining patterns: 1) towards the ipsilateral transverse sinus via the SPS; 2) towards the PP through middle cranial fossa foramina; or 3) towards the posterior aspect of the CS, all of which can be angiographically demonstrated [START_REF] Gailloud | Angiographic anatomy of the laterocavernous sinus[END_REF]. The drainage pathways towards the SPS and the PP are similar to the drainage patterns described for the PCS as sphenopetrous and sphenobasal sinuses, respectively [START_REF] Gailloud | Angiographic anatomy of the laterocavernous sinus[END_REF]. Gailloud et al. have found the SMCV to be absent in 19% of the cases. When present, they found the SMCV terminating directly in the CS in 20% of cases, in a PCS in 39% of cases and in a LCS in 22% of cases [START_REF] Gailloud | Angiographic anatomy of the laterocavernous sinus[END_REF]. Compared to these previous results, we found a larger proportion of SMCV terminating in a LCS (24.8% in the control group and 30% in the overall population) and a smaller proportion terminating directly in the CS (17.6% in the control group and 15.6% in the overall population) and in a PCS (34.4% in the control group and 28% in the overall population).

Age and sex ratio were different in the brain AVM and control groups. This was to be expected given that brain AVMs are usually discovered at a younger age and, contrary to brain AVM, intracranial aneurysms are more frequent in women than in men [START_REF] Stapf | The New York Islands AVM Study: design, study progress, and initial results[END_REF][START_REF] Wiebers | Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment[END_REF]. To the best of our knowledge, SMCV anatomy does not vary at adult age or between men and women. However, we found no report in the literature specifically directing this issue. Moreover, hemorrhagic presentation was more frequent in the brain AVM group as compared to the control group, which is related to specificity of patient referral in the study center. We have not shown any statistically significant difference between patients with a brain AVM and those from the control group regarding absence or presence of the SMCV. Furthermore, no difference was found regarding the proportion of direct and indirect connection of the SMCV to the CS. This result contradicts previous reports and consequently the hypothesis that brain AVMs have a congenital origin [START_REF] Mullan | Embryological basis of some aspects of cerebral vascular fistulas and malformations[END_REF][START_REF] Mullan | Reflections upon the nature and management of intracranial and intraspinal vascular malformations and fistulae[END_REF].

As indicated above, recent observations contradict the congenital origin of brain AVMs, stressing the need for new models to explain brain AVM development. New insight into pathogenesis of this disease has been provided by animal models based on deletion of Eng or Alk1 genes, implicated in hereditary hemorrhagic telangiectasia type 1 and 2, respectively. Most strikingly, deletion of these genes in adult mice, in combination with local "Vascular Endothelial Growth Factor" stimulation, leads to brain AVM development [START_REF] Chen | De novo cerebrovascular malformation in the adult mouse after endothelial Alk1 deletion and angiogenic stimulation[END_REF][START_REF] Choi | Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia[END_REF][START_REF] Walker | Arteriovenous malformation in the adult mouse brain resembling the human disease[END_REF]. These works have lead to propose the « response-to-injury » paradigm to explain brain AVMs' pathogenesis [START_REF] Kim | Brain arteriovenous malformation pathogenesis: a response-to-injury paradigm[END_REF]. In this model, brain AVMs are considered an exuberant dysplastic response of a vulnerable vascular segment to an pro-angiogenic stimulus. Vulnerability may be genetic or anatomic. The inciting event might be mechanical, ischemic, a somatic second hit mutation or any other phenomenon stimulating angiogenesis. To date, this model represents the most satisfactory explanation to brain AVMs' pathogenesis.

Furthermore, the « response-to-injury » paradigm does not necessarily regard brain AVMs as congenital lesions. Indeed, vulnerability, whether anatomical or genetic, may be prenatal while onset of the brain AVM following injury may be postnatal.

Limitations:

Several limitations undermine the results of our study including retrospective design, small sample size and referral bias influencing demographic and clinical characteristics of the patient cohort [START_REF] Hofmeister | Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation[END_REF]. The control group was not composed of healthy individuals but instead patients managed for intracranial aneurysms. It has been reported that venous hypertension may be implicated in aneurysm rupture [START_REF] Lee | Intracranial venous hemodynamics and rupture of cerebral aneurysm[END_REF].

However, contrary to perimesencephalic nonaneurysmal hemorrhage [START_REF] Van Der Schaaf | Venous drainage in perimesencephalic hemorrhage[END_REF], there is, to the best of our knowledge, no evidence of venous anatomical variations in patients harboring intracranial aneurysms. Moreover, since the advent of non-invasive brain imaging modalities, DSA is usually reserved to patients with known neurovascular disease, limiting the possibility to constitute a control group of healthy individuals.

Hemorrhage is a potential source of bias by obscuring the SMCV. However, no statistically significant difference was found between patients with and without hemorrhagic presentation, either in the brain AVM group or the control group. The study was not restricted to brain AVM draining in the SMCV. This would have required a much larger brain AVM cohort, difficult to assemble given the low prevalence of brain AVMs. However, Mullan et al. [START_REF] Mullan | Embryological basis of some aspects of cerebral vascular fistulas and malformations[END_REF] do not restrict their observation to this subset of patients and instead describe frequent absence of SMCV and failure to connect to the CS in the general setting of brain AVM. Moreover, in 3 out of 6 cases in which the AVM drained via the SMCV in our study population, the vein terminated directly or indirectly in the CS. While this study does suggest that the theory implicating the absence of a SMCV or the lack of connection to the cavernous sinus is probably not associated with brain AVM development, it does not necessarily follow that other differences in venous anatomy might not point to a congenital origin.

Further work comparing general venous anatomy between brain AVM patients and controls is needed to clarify this point. Finally, the result of this study does not directly contradict the congenital origin of brain AVM but instead only challenge a frequently reported argument for congenital origin [3,[START_REF] Morales-Valero | Are parenchymal AVMs congenital lesions?[END_REF][START_REF] Murphy | Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels[END_REF][START_REF] Zhuge | Notch4 is activated in endothelial and smooth muscle cells in human brain arteriovenous malformations[END_REF].

Conclusions

We did not find any difference in terms of presence of a SMCV and connection to the CS between patients with a brain AVM and a control group. SMCV anatomy does not support the congenital origin of brain AVM.

Figure captions

September 1 ,

 1 2007, to December 31, 2014. Patients previously treated for their brain AVM were excluded. The control group was composed of patients admitted at the same Institution for ruptured or unruptured intracranial aneurysms from January 1, 2014, to December 31, 2014. Age, gender and past history of brain AVM or aneurysm rupture were recorded.

Fig. 1 DSAFig. 2 DSAFig. 4 DSA

 124 Fig.1

Fig. 1

 1 Fig. 1

Fig. 2 29Fig. 3

 23 Fig. 2

Fig. 4

 4 Fig. 4

Table 1 .

 1 Comparison of SMCV's anatomy in patients with a brain AVM and controls total number of sides analyzed for each group; numbers in brackets are percentagesThe p-values are for comparison of the brain AVM and control groups.

				Overall	Brain AVM group
						Control group (74
				population (144	(70 patients;
						patients;	p-value
				patients; n=	n= 125)
						n= 125)
				250)
	Mean age +/-standard
				45 ±15	41 ± 15	50 ± 13	<10 -4 ‡
	deviation (years)
	Male sex (%)		58 (40)	36 (51)	22 (30)	0.007
	Hemorrhagic presentation
				99 (68.7)	54 (77.1)	45 (60.8)	0.03
	(%)
	SMCV present (%)		184 (73.6)	88 (70.4)	96 (76.8)	0.25
	Multiple SMCV (%)		50 (20)	21 (16.8)	29 (23.2)	0.20
	Direct	or	indirect			1
	connection of the SMCV	130 (52)	65 (52)	65 (52)
	to the CS (%)
	SMCV terminating into a
				75 (30)	44 (35.2)	31 (24.8)	0.07
	LCS (%)
	Drainage of the
				68 (90.6)	40 (90.9)	28 (90.3)	1*
	LCS in the CS (%)
	Drainage of the
	LCS in the SPS or	8 (10.6)	7 (15.9)	1 (3.2)	0.12*
	tentorial sinus (%)
	Drainage of the
				35 (46.6)	21 (47.7)	14 (45.1)	0.82
	LCS in the PP (%)

*: Fisher's Exact Test ‡ : Student's t-test Abbreviations: Cavernous Sinus (CS) ; Laterocavernous Sinus (LCS) ; Paracavernous Sinus (PCS) ; Pterygoid Plexus (PP) ; Superficial Middle Cerebral Vein (SMCV)

Table 2 .

 2 Comparison of SMCV's anatomy in patients with an ipsilateral supratentorial brain AVM and controls

				Brain AVM group (53	Control group (74	p-value
				patients; n= 53)	patients; n= 125)
	Right-Side (%)		27 (50.9)	65 (52)	0.89
	Left-Side (%)		26 (49.0)	60 (48)	0.89
	Mean	age	+/-	38 ± 13	50 ± 13	<10 -4 ‡
	standard	deviation
	(years)
	Male sex (%)		28 (53)	22 (30)	0.008
	Hemorrhagic		40 (75.5)	45 (60.8)	0.08
	presentation (%)
	SMCV present (%)		38 (71.6)	96 (76.8)	0.47
	Multiple SMCV (%)	10 (18.8)	29 (23.2)	0.52
	Direct or indirect	26 (49.0)	65 (52)	0.71
	connection of the
	SMCV to the CS (%)
	SMCV	terminating	17 (32.0)	31 (24.8)	0.31
	into a LCS (%)
	Drainage	of	15 (88.2)	28 (90.3)	1*
	the LCS in the
	CS (%)
	Drainage	of	2 (11.7)	1 (3.2)	0.28*
	the LCS in the
	SPS	or
	tentorial sinus
	(%)
	Drainage	of	9 (52.9)	14 (45.1)	0.60
	the LCS in the
	PP (%)
	SMCV	terminating	15 (28.3)	43 (34.4)	0.42
	into a PCS (%)
	Drainage	of	6 (40)	16 (37.2)	0.84
	the PCS in the
	CS (%)
	Drainage	of	5 (33.3)	16 (37.2)	0.78
	the PCS in the
	SPS	or
	tentorial sinus

Conflict of Interest

We declare that we have no conflict of interest.


Aegats

Isabelle Laplace
email: isabelle.laplace@enac.fr

Chantal Latgé-Roucolle
email: chantal.latge-roucolle@enac.fr

Ion Buzdugan
email: ionbuzdugan92@yahoo.com

AEGATS2016_paper Id

Keywords: Air transport, aircraft innovation, aircraft size, airlines, competitive strategies

The objective of this empirical paper is to analyze the impact of an innovation in air transport system on airlines competitive behavior. We consider as innovation, the use of an aircraft with a significant higher capacity: the Airbus 380. Does the use of the A380 by an airline on a particular route give incentives to competitors to introduce as well this type on aircraft on the same route? To answer this question we use some econometric methods to estimate the impact of the introduction of the A380 by an airline, on the probability that airline's competitors will follow up the innovation. Controlling for others factors which might impact the choice of innovation, we show that the use of the A380 by an airline on a route gives incentives to competitors to introduce it as well.

INTRODUCTION

Launching on the market some aircraft with innovative technologies is always a challenge for aircraft manufacturers since this new product has to appeal to airlines. The challenge is all the more important that the innovative aircraft involves differences in the operating process. This is in particular the case for the Airbus 380 whose dimension is bigger than anything previously produced for a civil aircraft and for which new transportation methods were needed.

The decision to operate an innovative and different aircraft is driven by the competitive advantage that airlines might identify once the innovation has been adopted. But what are its impacts on competitors' strategies?

The objective of this empirical paper is to provide answers to this question. We consider as innovation the introduction of an aircraft with a significant higher capacity: the Airbus 380. We tend to answer the question: does the use of the A380 by an airline on a particular route give incentives to competitors to introduce as well this type of aircraft on the same route?

We use some econometric methods to estimate the impact of the introduction of the A380 by an airline, on the probability that airline's competitor will follow up the innovation.

We implement the analysis on an oligopoly market, Frankfurt -New York JFK route, for the period of time January 1st 2006 to December 31th 2015. We estimate the model using the adapted econometric model: a Conditional Fixed Effects Logistic model.

In the following second part we summarize the economic literature related to aircraft capacity on the air transport market. Then, we describe the market we focus on. In the fourth part we explain the econometric model and the variables of interest. In the last part we present the results of our analysis.

2.

RELEVANT LITERATURE Among all the aircraft characteristics, aircraft size may be the one which has the biggest impact on the whole aviation industry. Airlines choose the size of the aircraft in their fleet in order to provide the most adapted air transport capacity to fulfill demand while facing competition. Airport planers need to know the size of the aircraft they receive from both technical (runways, gates etc.) and practical (congestion) points of view. Policy makers use the predicted aircraft size for planning expensive infrastructure investments and future traffic control regulation.

In order to accommodate their air transport capacity to existent and future demand, airlines may use two levers: aircraft size and service frequency. Both variables play a central role in their profitability (by the load factor) and strategic (competition) decisions.

Keeping high load factors while offering high frequency service, moves airlines towards the use of smaller aircraft. In 2006, according to Givoni and Rietvel (2009), "at many of the world's largest airports there were fewer than 100 passengers per air transport movement despite growing congestion and delays". [START_REF] Givoni | Airline's choice of Aircraft Size -Explanations and Implications[END_REF] investigate and explain this phenomenon. They associate this choice with the benefits of high frequency service, the competitive environment in which airlines operate and the way airport capacity is allocated and priced. By a regression analysis of over 500 routes in the US, Europe and Asia they provide empirical evidence that the choice of aircraft size is mainly influenced by route and airport characteristics. They estimate that the aircraft size depends on market size with an elasticity of 0.35, indicating that carriers give priority to increases in frequency.

From the supply point of view it is important to know how the total cost (capital cost & operating cost) is affected by the aircraft size. [START_REF] Wei | Cost Economics of Aircraft Size[END_REF] have estimated a trans-log cost function for aircraft operating costs and confirmed the existence of economies of size and stage length. They found a positive relationship between the aircraft optimal size and the stage length. They also find that the scale properties of the cost function are changed considerably if pilot unit cost is treated as endogenous, since it is positively correlated with aircraft size. Consequently, pilot wage structure is particularly responsible for airlines choice of smaller jets on short-haul markets. [START_REF] Wei | Impact of aircraft size and seat availability on airlines demand and market share in duopoly markets[END_REF] have also investigated how size together with service frequency affects the total demand and the market share in a nonstop duopoly market. Using a nested logit model they confirmed previous findings of an S-curve effect -an increase in service frequency over a certain level translates in a more than proportional increase in market share. Increasing service frequency give higher returns in market share than increasing aircraft size. Therefore they argued that airlines have an economic incentive to use smaller than optimal aircrafts, since for the same capacity provided in the market, an increase in frequency can attract more passengers. Another important result is that they don't observe from their data a passenger preference for larger aircraft which can be inferred from such reasons as aircraft amenity, comfort and safety, by contrast. Only the number of available seats matters.

The size of aircraft is determined by a number of factors, among them the route characteristics and the market size. On the markets they operate, airlines face a trade-off between size of aircraft and frequency of the operations. The factors which impact the choice of aircraft impact as well the frequency of flights. As a result it is difficult to split the direct effect of frequency on aircraft choice and the indirect effect through other factors.

We decide to simplify the analysis focusing on the choice of aircraft with frequency remaining constant. Our objective is to determine the direct effect of several factors, such as the size of the market, the characteristics of route…, on the probability to choice a particular aircraft size. We select a route where the frequencies remain constant while the size of the aircraft evolves during the period of observation. A higher aircraft size corresponds to the choice of the A380. We interpret this choice as an innovative technological choice. Then, to answer the question of incentives to follow one's innovation, the behavior of competitors in terms of innovation is introduced as a factor which impacts the choice of using the innovative technology.

THE FRAPORT -JOHN F. KENNEDY MARKET

We focus on the Fraport-John F. Kennedy market. The FRA-JFK route is an oligopoly market with three competitors: Lufthansa, Singapore Airlines and Delta Airline. Lufthansa and Singapore Airlines have introduced recently the A380 for their operations. The introduction of A380 is observed at different period of time. This route is a good candidate for the analysis of the impact between competitors of the use of A380. Moreover the frequency supplied by the different airlines on the route remain constant, whatever the choice of aircraft.

The main source of our data is the OAG database. The OAG schedule analyzer is a product from the Official Airline Guidea British business company providing aviation information and analytical services. It contains worldwide data on capacity reports from 693 active carriers and 3413 active airports. We access data on the time period 2005 to 2015. We supplement the information on capacities with socio-economic data from World Bank, IMF, U.S. Energy Information Administration websites, air transport data from ENAC Air Transport Database, and ENAC BADA Eurocontrol calculation model for the aircraft fuel consumption data.

We observe monthly capacities supplied by the three airlines from January 1 st 2005 to January 1 st 2015. This corresponds to 109 monthly observations for each company, and there are no missing values in the data set.

The demand on the route is increasing as stressed by 0. The evolution of air traffic demand on the route is consistent with the worldwide evolution of air traffic: +5% yearly on average according to several sources in particular IATA 1 . Moreover, the evolution of the number of passengers exhibits a positive trend in each airport during the period of analysis. The regional GDP, traditionally considered as a driver of local demand, also increases in departure and arrival airports. The evolution of capacities during the period of observation is presented in Figure 2.

In terms of total capacities supplied, Lufthansa dominates the market during the full period 2005-2015, with an average of 22150 monthly seats when Singapore and Delta airlines supply respectively on average 11820 and 6218 monthly seats. Lufthansa introduces first the A380 on February 2011, but the A380 use is not regular. The A380 has been used from February to October in 2011, from May to October in 2012 and from April to October In 2014. The strategy implemented by Singapore Airline is different: once the A380 is introduced on the route, on January 2012, it remains in use, except during the short period January to March 2013. Note that, Delta never uses A380 on this route.

Finally, the evolution of market shares in terms of seats on the route seems disconnected to the intensity of use of the A380 (see Figure 3). When an airline introduces the A380 or when it intensifies its use, this doesn't lead to an increase on its market share in terms of posted capacity on the route.

MODEL

To test the likelihood that competitors on a route follow the innovation adopted by one another, we use a condition fixed effect logistic regression model. This model is consistent with panel data as the ones we have. In particular the endogenous variable, i.e. the use of A380, is observed several times for two among the three airlines and the control variables, i.e. the factors which might impact the use of A380, change across time.

The data are monthly observed. The endogenous variable of the model is a dummy variable which takes value 1 if the airline uses the A380 during a month of the period of analysis, and 0 otherwise.

The logit model will estimate the probability for an airline to use an A380, given that she was using it the month before, and given that competitors use it or not. Among all others factors which influence the probability to innovate the competitor's use of innovation is of the main interest.

The own use of A380 is included as the lagged ratio of A380 use: number of seats supplied with the A380 with respect to the total number of seats during the month before the current period. We expect a positive relation between the use of the innovation during the current period of time and its use during the previous period.

The impact of competitors' use of innovation is also measured through the ratio of A380 use. The effect is the main effect that we want to estimate.

A positive sign would correspond to positive incentives of following the innovation; a negative sign to negative incentives; finally a nonsignificance of the impact could be interpreted as an absence of relationship between the use of innovation by the competitors on the route.

Additional factors which might impact the probability to use the innovation are included into the regression. These factors are related to the market power of the firm on the route, the evolution of demand, as well as some cost factors.

Regarding the market power on the route, we have tested the usual index of concentration, HHI, as well as the market share, expressed in available seats, of the main competitor. Due to lack of variability in the HHI, we kept the market share of the main competitor has the indicator of market power.

There are several ways to measure the evolution of demand on the market. Population and GDP are traditionally considered as the main drivers of the air transport demand. We observe the regional GDP on a yearly basis for the two regions of Frankfurt and New-York and we will test this impact on the model. We expect a positive impact of the level of GDP on the probability to use the A380.

The observed demand on the route is the perfect candidate to measure the impact of the traffic evolution on the probability to use the innovation.

We use the lagged traffic as we suspect that airlines react with a time gap to a potential traffic increase. As for GDP we suspect the impact of the lagged-traffic to be positive on the probability to use the innovation.

We don't have any a priori argument in favor of one or the other control for demand and we propose two different specifications of the model with one or the other variable.

Finally we introduce into the model the price of fuel, assuming that it impacts the probability to use the A380. Because of its large size, the A380 is designed to minimize seat costs in both fuel and CO2. 2 The share of fuel cost in cost of operations keeps increasing and as reached the level of 29% on average in 2014.

3 This is due to the constant increase in fuel price. As a consequence the increase in price of fuel might be an additional incentive to use greener aircraft such as the A380.

We introduce in our model the price of fuel, in 2015 constant prices, and expect a positive relationship with the probability to use the A380.

The variables used into the model are described in Table 1.

Variable code Variable description

Competitor A380-ratio

Competitor monthly seats supplied with A380, as percentage of its total seats

Own lagged A380-ratio

Own monthly seats supplied with A380, as percentage of its total seats

Competitor Market Share

Competitor market share in terms of capacity supplied

Fuel Price

Fuel price in constant $2015

Lagged route traffic

One year lagged annual traffic on FRA-JFK route

Departure GDP GDP of departure country in 2015

Table 1.

Variables of the model

Because Delta doesn't use the A380 during the period of observation, it is automatically excluded from the analyses and the two remaining groups correspond to Lufthansa and Singapore Airline.

The estimation is implemented on the monthly observation of the two airlines from January 2005 up to December 2014. This leads to a 218 sample size.

MAIN RESULTS

We built two specifications in order to test the different proxies for the demand. Moreover we implement two versions by specification using or not the variable Own-lagged-A380-ratio.

The robustness of the model is confirmed by the similarity of the results obtained with the two specifications (see Table 2 andTable 3).

We find a positive and statistically significant impact for the variable Own-lagged-A380-ratio (model 1.2 and 2.2). When an airline already uses the A380 during the previous period, this increases its probability to use it at the current period. As expected the impact of using the innovation during the previous period increases the probability to keep on using it during the current period.

Whatever the specification, there is a positive and statistically significant relationship between the intensity of use of the A380 by a competitor and the probability to use the innovation. This is the main result of our model: it is likely that competitors on a route follow the innovation adopted by one of them.

When the market share of the competitor on the route increases the model estimates a statistically significant negative impact on the probability to use the innovation. If the market share is interpreted as the market power on the route, the highest market power of the competitors, the lowest incentives to innovate.

If the price of the fuel increases, the model suggests an increase in the probability to use the A380. This is consistent with the characteristic of the A380 to exhibit a lowest cost of fuel per passenger.

Finally the demand is measured by the laggedtraffic on the route (Models 1.1 and 1.2), or by the level of GDP on departure airport (Models 2.1 and 2.2). When the demand increases on the route, the probability to innovate using the A380 increases as well. The impact is statistically significant in the models without the own-lagged-A380-ratio and non-significant into the models which include this variable. The use of an A380 during the previous period impacts more the probability to use the A380 during the current period than the increase of demand on the market.

Exogenous variables

Model

CONCLUSION

The objective of this empirical paper is to analyze the impact of an innovation in air transport system on airlines competitive behavior. We consider as innovation, the use of an aircraft with a significant higher capacity: the Airbus 380. Does it give incentives to competitors to introduce as well this type on aircraft on the same route?

To answer these questions we use econometric methods to estimate the impact of the introduction of the A380 by an airline, on the probability that airline's competitor will follow up the innovation. We implement the analysis for an oligopoly market, Frankfurt -New-York JFK route, for the period of time January 1st 2005 to December 31th 2015. The three competitors on that route are Lufthansa, Delta airlines and Singapore Airlines. Lufthansa introduces first the A380 on that route, but the A380 use is not regular. The strategy implemented by Singapore Airline is different: once the A380 has been introduced on the route, it remains in use, except during a short period of time.

We estimate a Conditional Fixed Effects Logistic model. Two specifications of the model are tested with different control for the demand on the route. The robustness of the model is confirmed by the similarity of the results obtained with the two specifications.

We find that the introduction of the A380 by a company has a positive impact on the probability of its introduction in its rival's operational fleet: the higher is the intensity of the A380 use, the higher is the probability to introduce the A380. We find that the fuel price has a positive effect on the probability to use an A380. This result is consistent with decreasing cost per passenger when the capacity of the aircraft increases. Finally, the higher the level of GDP in the country, the higher the probability to use an A380.

The empirical results show the incentives to innovate given by an innovative airline, when introducing a new aircraft without changing the frequency of operations on its route. An extension of this analysis will be to consider the case where the introduction of the new bigger aircraft leads the innovative airline to reduce its flight frequency level. The model would then have to consider this additional strategic choice linked to the use of the new aircraft when estimating the impact on competitors' strategies.

Such extended model, applied on a panel of routes on which the A380 has been operated, will then help to go further in the analysis and to estimate environmental impacts of this innovative aircraft. More precisely, besides pollution reduction linked to the aircraft technological performance, environmental benefits can also be obtained by changes in airlines' operations when adopting this new aircraft. The larger size of the A380 associated to a reduction in flight frequencies reduce the fuel consumption per seatkilometer and by the way the carbon dioxide emissions. The impacts would be all the more important that other airlines in competition on the same long-haul routes could also use larger aircraft and decrease their flight frequencies.

One important result of the extended econometric model would then be to estimate to what extend the introduction of the A380 innovative aircraft can help reducing air transport environmental impacts.

  Figure 1.Evolution in number of passengers on the route

Figure 2 .

 2 Figure 2. Supplied capacity on the Fraport -J.F. Kennedy market

  Figure 3.Market share and ratio of A380 use

1.1 Model 1.2

				Airline fixed effect	yes	yes
				Statistics of the model
				LR chi2 (dl)	104.6 (15)	183.43 (16)
				Prob > chi2	0.000	0.000
				Log likelihood	-67.4103	-27.991
				Note: Std.Err. in parenthesis; *** 1% significance; ** 5%
				significance; * 10% significance
				Table 2.	Results of estimation Model 1.1
				and 1.2
				Exogenous	Model 2.1	Model 2.2
				variables
				Competitor A380-	0.044***	0.023*
				ratio	(0.011)	(0.014)
				Own lagged	0.092***
				A380-ratio	(0.023)
				Competitor	-0.597***	-0.288*
				Market Share	(0.120)	(0.178)
				Fuel Price	0.006**	0.002
				(0.003)	(0.005)
				Departure GDP	5.27E-06**	3.99E-06
				(2.08E-06)	(3.29E-06)
				Monthly fixed	yes	yes
				effect
				Airline fixed	yes	yes
				effect
				Statistics of the model
				LR chi2 (dl)	91.15 (15)	142.28
				Prob > chi2	0.000	0.000
				Log likelihood	-47.9789	-22.0371
				Note: Std.Err. in parenthesis; *** 1% significance; ** 5%
				significance; * 10% significance
				Table 3.	Result of estimation Model 2.1
				and 2.2
	Competitor A380-ratio	0.030*** (0.008)	0.021* (0.012)
	Own lagged A380-		0.106***	6.
	ratio		(0.024)
	Competitor Market	-0.394***	-0.219*
	Share	(0.077)	(0.128)
	Fuel Price	0.005***	0.004
		(0.002)	(0.003)
	Lagged route traffic 0.00004***	4.22E-06
		(0.00001)	(0.0000184)
	Monthly fixed	yes	yes
	effect

Source : IATA, World Air Transport Statistics