The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international data-sharing consortium focused on enabling advances in precision oncology through the gathering and sharing of tumor genetic sequencing data linked with clinical data. The project’s history, operational structure, lessons learned, and institutional perspectives on participation in the data-sharing consortium are reviewed. Individuals involved with the inception and execution of AACR Project GENIE from each member institution described their experiences and lessons learned. The consortium was conceived in January 2014 and publicly released its first data set in January 2017, which consisted of 18,804 samples from 18,324 patients contributed by the eight founding institutions. Commitment and contributions from many individuals at AACR and the member institutions were crucial to the consortium’s success. These individuals filled leadership, project management, informatics, data curation, contracts, ethics, and security roles. Many lessons were learned during the first 3 years of the consortium, including on how to gather, harmonize, and share data; how to make decisions and foster collaboration; and how to set the stage for continued participation and expansion of the consortium. We hope that the lessons shared here will assist new GENIE members as well as others who embark on the journey of forming a genomic data–sharing consortium. With that work in mind, this review highlights some of the practical and administrative aspects of starting and running the GENIE consortium from the perspectives of AACR and the initial eight member institutions. We hope that the lessons shared here will assist new GENIE members and others who embark on the journey of forming a genomic data–sharing consortium.The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international genomic data–sharing consortium focused on enabling advances in the understanding and treatment of cancer. The consortium’s first data release was on January 5, 2017, and an article that explored the scientific rationale for the project, the data standardization process, the landscape of the first publicly released data set, and future challenges was published.2 On the basis of this article and his experiences as AACR president and Global Alliance for Genomics and Health steering committee member and with the clinical sequencing program at Memorial Sloan Kettering Cancer Center, Charles L. Sawyers, MD, proposed the concept for AACR Project GENIE. He championed the premise that no single institution would be able to sequence a sufficient number of patients to improve clinical decision making in all tumor types, particularly in rare cancers and for rare variants in common cancers, and that the solution was to pool data from multiple institutions and share it publicly. In June 2014, AACR convened a think tank to gauge interest and begin to define the structure of what would become AACR Project GENIE ; Institut Gustave Roussy ; Netherlands Cancer Institute , on behalf of the Center for Personalized Cancer Treatment ; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center ; Memorial Sloan Kettering Cancer Center ; Princess Margaret Cancer Centre, University Health Network ; The University of Texas MD Anderson Cancer Center ; and Vanderbilt-Ingram Cancer Center .AACR Project GENIE is executed through a coordinating center that comprised a director, clinical data manager, project manager, and program coordinator. The coordinating center staff is crucial to ensuring that the project is fully operational. Eight founding data-contributing institutions were chosen to provide a manageable number of institutions that could provide sufficient data to answer a clinical question within 2 years. Of note, these institutions had ongoing CLIA/ISO –certified clinical sequencing programs in 2014 as well as expertise in the clinical and bioinformatics challenges of converting clinical data into knowledge. Furthermore, the founding institutions expressed a willingness to share clinical cancer genomic data and longitudinal outcomes and had institutional support to do so. A requirement of membership in the GENIE consortium is that each institution contributes at least 500 genomic records annually. The genomic data are accompanied by a minimum set of required clinical data elements. All institutions signed a master participation agreement and data use agreement before data submission. All institutions are required to protect and maintain patient privacy, which generally was done through existing consent for sharing deidentified data, specific consents for sharing specifically to GENIE, or a waiver of consent from the local institutional review board (IRB).AACR Project GENIE is led by a steering committee that comprises a senior representative from each contributing institution, the AACR chief executive officer, the current AACR president, one representative from the AACR Science Policy and Regulatory Affairs Subcommittee of the Science Policy and Government Affairs Committee, and one representative from the Clinical and Translational Cancer Research Committee . The steThree subcommittees report to the steering committee. The operations subcommittee prioritizes overall project efforts and ensures that all clinical projects and other project workflows run on schedule or that contingencies have been implemented. The participation subcommittee evaluates requests for new participating institutions and collaborations and ensures ongoing compliance of existing participants. The data use and publications subcommittee reviews concept proposals, manuscripts, and abstracts to minimize conflict with regard to research topics and authorship.More subcommittees can be added; for example, a business development subcommittee is being created. In addition, a pediatric subcommittee has been partially established to provide guidance to the steering committee on pediatric oncology and to serve as a liaison between GENIE and the pediatric oncology community.3 quality, quantity, and submission deadlines. Both groups report to the operations subcommittee. Examples of temporary working groups are the data analysis working group, which helped to clean and analyze the first data set for public release and for incorporation into the manuscript, and the manuscript working group, which wrote the manuscript and shepherded it through internal and external review.In addition to the more formal subcommittees, working groups achieve specific tasks. A permanent clinical data working group identifies and defines the routinely collected clinical data elements. In addition, a data standards working group defines and ensures compliance with data formats,One of the primary sources of project funding is sponsored studies. Participation in clinical studies is strongly encouraged when feasible but is not a requirement for consortium membership. Such studies are executed through ad hoc working groups that comprise study co-principal investigators (PIs), site PIs, site leaders, data abstractors, and statistical services. Statistical services usually reside within one of the co-PIs’ home institutions. We discovered that central overall project management of each sponsored study is essential to timely delivery of project milestones. Member institutions have faced a few unanticipated challenges, such as the need to understand and comply with confidentiality agreements between clinical trial sponsors and the individual institutions.Communication has been essential to the GENIE consortium’s success, and meetings are a critical communication vehicle. The steering committee and other groups previously described meet regularly through Web conferencing. Twice a year, the steering committee and individuals from each participating institution meet at an in-person summit to discuss progress and plans. In addition to the operational and scientific value of these approximately 40-person meetings, the summits help to strengthen the consortium through shared activities and meals, and they encourage the generation of new ideas and formation of new collaborations. In addition to the summits, ad hoc in-person meetings occasionally are required. One example was the data “hackathon” where a group assembled to finalize the data and begin the manuscript. The early meetings focused on building the infrastructure and operational procedures necessary for GENIE to function. Now that the project is more mature, we recently engaged in a facilitated strategic planning session in July 2017 to chart the project’s future. One of the lessons learned is that there is never enough time to adequately discuss scientific questions at in-person summits, and participation is limited to a small number of attendees from each institution. To address this issue, we may institute a scientific symposium.4 Any unresolved issues or follow-up questions were handled on an applicant-by-applicant basis. Finalists were then given instructions to complete a sample data upload to identify potential issues in interacting with the project data platforms. The criteria for new sites are the same as for the founding institutions and are described in Participating Institutions and listed in Appendix After the first public data release, an open call for new sites was broadly publicized, including direct communication with each institution that had inquired about joining. The application process was handled through an online survey that opened March 8, 2017, and closed May 1, 2017. Any institution that began an application before the close date or requested an extension was granted an extension to May 15, 2017. The survey results were reviewed by the participation subcommittee by using criteria published on the GENIE Web site.www.synapse.org) provides data versioning and provenance and serves as the primary data hub for the consortium.5 For sponsored studies, clinical data are collected and staged by using the open-source Research Electronic Data Capture (REDCap) system6 (www.project-redcap.org); these data are subsequently imported into Synapse. All data are pushed into cBioPortal8  for data visualization and analysis; data also can be directly exported from both Synapse and REDCap for analysis in other platforms. In addition, each technology permits multiple levels of access control so that public, consortium, and sponsor access to the appropriate data sets is easily managed on all platforms; data access is centrally managed by Sage Bionetworks.Several open-source technologies allow GENIE to share and analyze data safely and securely both internally and externally . The SynAll genomic data are mapped to ref 37 (hg19). Note that the Genomic Data Commons (GDC) uses GRCh38, and we likely need to begin to transition GENIE in this direction. The consortium only shares variant calls and not raw data, which was one of the early agreements that facilitated data sharing. For each gene panel, a browser extensible data (BED) file is provided, which is a list of all the genomic features that a particular test sequences. Each site defines a workflow file that links information about the sequencing assay to the BED file. The BED and workflow files may not be straightforward to obtain if an institution uses outside vendors for its sequencing and if these file types are not included in the data use agreements between institutions and vendors.cis , adherence to variant call format, normalization of gene symbols, and the need to develop a germline filter for tumor-only sequencing.1 The filter removes as many private or noncommon single-nucleotide polymorphisms as possible. Although the filter is effective, we could not be sure that all risk of patient reidentification was removed; thus, we implemented terms of use that must be reviewed and endorsed before users can access data.After the initial data were available to the consortium, an ad hoc working group analyzed the initial data freeze for the manuscript and first public release. As part of this exercise, a few initial issues were identified, including mutations in 3 and this is summarized in Currently, only CLIA/ISO-certified data are eligible for submission to GENIE. The guidelines for sequencing varied somewhat between institutions,3 Now that the consortium is well established, it is conducting feasibility analyses to add more clinical data elements. Our most important near-term additions are slated to be age at death, age at last follow-up, and institutionally administered cancer-directed therapeutics, with others to follow.The consortium took a pragmatic approach to getting started and began with a limited set of clinical data elements that was informative but easily extracted in a short period.A great variability exists among the institutions with respect to the ability to pull data automatically versus through manual chart review for the minimum clinical data elements. Among those institutions that required chart review, considerable differences existed with respect to dedicated resources for curation. Even among institutions with more automated extraction and thorough clinical annotation of all institutional patients, there was a general underestimation of the time required to deliver data because of field mapping issues, retrieval of missing data, recoding of pathologic diagnosis to the project ontology, and so forth.Sponsored studies generally require manual extraction of additional data elements from the electronic health record of the local institutions. One half of the consortium is able to share limited protected health information (PHI)—dates, specifically—for purposes of sponsored studies, whereas the remaining one half cannot. As a result, copies of study-specific data dictionaries are implemented in local instances of REDCap hosted behind the firewalls of institutions that cannot share limited PHI. After data collection, the data are deidentified for export to Synapse. The remaining sites collect data in a centralized REDCap instance held by Sage Bionetworks. PHI is deidentified before delivery to study sponsors. As the project continues to mature, the consortium aims to automate extraction of more clinical data elements.9 Our interactions with GDC were straightforward, and because of the submission it has already received from Foundation Medicine, GDC is prepared to accept a subset of clinical data and to help with mapping. The most difficult aspect of the submission was the database of genotype phenotype registration.The consortium is deeply committed to open science and data sharing as long as patient privacy is protected. To this end, terms of access have been implemented that require steering committee approval of any data redistribution, which is predicated on the ability of the receiving platform to implement the same terms of access that GENIE has implemented. To date, five requests for redistribution have been received and granted. As good global citizens, the consortium has deposited its first data release, version 1.0.1, in the National Cancer Institute GDC.Several tiers of data access are built into the master participation agreement. After GENIE is fully operationalized, institutions will have sole access to their own data for 6 months from the date of the sequencing report. Then, on a twice-yearly basis, genomic and clinical data will be deposited for all samples sequenced 6 months ago. Consortium members will have access to the data for 6 months, after which the data will be released to the public. For the first public data release, GENIE members waived their consortium-only access.TP53, KRAS, and PIK3CA, respectively, with CDKN2A and CDKN2B deletions and CCND1 amplification representing the most common copy number alterations. The three most common cancers are non–small-cell lung cancer, breast cancer, and colorectal cancer, respectively, with lung adenocarcinoma, invasive ductal carcinoma, and colon adenocarcinoma comprising the most common cancer subtypes  as the primary point of contact between the GENIE coordinating center and other internal stakeholders reported this as an effective way of managing the consortium relationship.One of the primary lessons shared by the participating institutions was the need for an institutional champion. Being a part of the consortium requires a commitment of financial and institutional resources, including personnel, and executive leadership must be supportive of the endeavor if it is to succeed. Each institution ultimately must be committed to sharing broad clinical data beyond the basic elements. Furthermore, a well-organized institutional team is required to ensure that milestones are met.When thinking about participation in a data-sharing consortium, institutions should consider the ability of their electronic health record to structure data so that automated data extraction is possible. Institutions can take stock of their processes and map these against the core processes of the data-sharing consortium and address any gaps. The dedication of resources to create systems to automate or structure essential data elements early will save time and resources later and make sharing data multiple times a year easier. Even so, each institution needs to dedicate resources to do the technical work of data manipulation for integration into the target. Many institutions were surprised by the resource requirements and initially under-resourced the project.Institutions receive partial compensation from AACR to cover expenses incurred as a result of their participation in the consortium and use a combination of existing operational funds, small grants, and philanthropy to cover remaining costs. The Netherlands Cancer Institute and MD Anderson Cancer Center have additional funding from the Dutch Ministry of Health and Dutch Cancer Society and the Khalifa Institute for Personalized Cancer Therapy, respectively. An in-depth accounting of the actual costs of membership has yet to be undertaken; however, direct costs of sequencing range from several to tens of millions of US dollars in addition to significant donations of uncompensated personnel time.With respect to ethical, legal, and social implications of the project, exchange of best practices with regard to IRB waivers and informed consent documents may aid members and potential members to get their own ethical, legal, and social implication issues resolved in advance. Numerous ethical, legal, and logistic challenges are associated with international data transfer. One of these concerned the invalidation by the European Court of Justice of the safe harbor procedure for exchange of personal data in 2015, which means that alternative procedures had to be implemented to allow the European partners to continue their participation in GENIE. Furthermore, the consortium encountered intellectual property issues related to clinical trial–associated data, such as disclosure of treatment with investigational agents. Discussion and consideration of these hurdles early and a consensus on data elements to be collected and how to handle potential intellectual property and PHI concerns are important. Overall, institutions were pleasantly surprised at how willing all were to work together and share data.At the time of the inception of AACR Project GENIE in 2014, few mature cancer data consortia existed. Since, several have emerged with variance in focus and approach. AACR Project GENIE is distinguished from these in several notable ways. First, AACR Project GENIE is focused on cancers where tumors have already undergone a minimum depth of somatic sequencing, whereas several other consortia include all patients with cancer from an institution . This focus has several advantages. At its inception, this more limited population for data sharing lowered the barrier to entry for many institutions who were not comfortable about sharing all their cancer data, and it significantly lowered the operational costs of the GENIE project because tumor sequencing as part of clinical care had already occurred as a condition of patient eligibility. Other consortia provide sequencing services as part of their program, some as commercial sequencing vendors  and others as part of the benefits of membership . Although these consortia incur the additional costs of sequencing, they have the advantage of having a single sequencing platform over which to evaluate their population. Because the members of the GENIE consortium use various sequencing platforms, data normalization is required, and analyses must take into account variance in breadth of sequencing across patients. However, because sequencing data are structured and there was high concordance of data definitions and standards, data normalization was achieved relatively rapidly and at low cost. This focus resulted in the rapid generation of a highly valuable population of molecularly characterized cancer cases for discovery, even with the current limited depth of clinical annotation.12 Consortium members believe that the data will have a far greater impact on the cancer community if made publically available. Furthermore, AACR believes strongly that all AACR members should have access to these data, which is achieved through public release. However, public release of data requires additional safeguards for patient privacy, especially when genetics data are included. Given that most of the GENIE members’ next-generation sequencing panels tested tumor tissue only and not tumor-normal pairs, special processing was required to remove potential germline alterations in somatic tumor calls to decrease the risk of reidentification in the public data set. We hope that GENIE’s approach to public release of data will serve as a model to other consortia.AACR Project GENIE has a strong commitment to public release of consortium data, which distinguishes it from all other non–federally funded cancer data consortia, and is reinforced by the Beau Biden Cancer Moonshot.In conclusion, the AACR Project GENIE member institutions are excited to share their first public data release and look forward to continued participation in the consortium. Several lessons were learned related to creating and sustaining a data-sharing consortium, which are described here; Appendix


In the field of oncology research, next-generation sequencing has contributed significantly to the discovery of DNA mutations associated with diagnosis and prognosis. It also aids in the development of targeted therapies to specific mutations and the rise of personalized medicine. As part of molecular diagnostics in cancer patients, analysis by next-generation sequencing is becoming part of routine clinical practice. The introduction of this complex technology in a healthcare system comes with multiple challenges and requires a clear action plan. Such an action plan, as outlined in this paper, was developed in Belgium and includes steps in ensuring the quality and indications of NGS testing, installing data registration and tackling ethical issues. A final step is to perform a pilot study to control the access, quality, harmonization and expertise in DNA testing. This action plan can serve as a guide for similar initiatives by other countries to facilitate NGS implementation in clinical practice. BRAFV600E mutation . Lev. Lev8]. Application of NGS in clinical laboratories, as any other analysis, requires external quality assessment. In first instance, it was considered important to estimate the baseline performance of the clinical labs for their adequate manner of using NGS in their routine diagnostics within a benchmarking trial. The performance of NGS testing need to be evaluated on different aspects and sequentially with first, using samples from well-characterized genomic DNA from tumor cell lines to assess the quality of NGS analysis on determining the presence or absence of somatic variants and their allele frequencies. Secondly, extending these assessments to the pre-analytical conditions and to clinical interpretation, using FFPE or blood samples as start material and theoretical case studies for interpretation assessments. Consultation with all concerned parties is recommended for the development of the evaluation procedures. This action is performed together with a department of Sciensano, the department Quality of laboratories. In a final phase, it is essential to establish a national EQA program to monitor the quality of NGS testing in clinical practice and to propose corrective actions where needed.NGS analysis goes along with the generation of large amounts of data and the management of such information can represent an important added value for quality, outcome analysis and reimbursement reallocation as well as for clinical and public health research. The purpose of this action is to develop the technical platform for the central collection and storage of NGS data generated by licensed and accredited labs. In Belgium, this part of the NGS implementation is governed by the Healthdata.be services at Sciensano. The Healthdata.be service has a technical platform as part of the implementation of the e-Health 2013–2018 Action Plan of Belgium. Healthdata.be looks after the daily management and maintenance of this new technological tool, the objective of which is to bring all the data that is now stored in multiple health registers into a single Internet-based platform. Consequently, our platform contributes substantially to the provision of an infrastructural system dedicated to research and monitoring in Belgium. Irrespective of the topic, the data is recorded in Healthdata.be in a uniform and secure manner. This action requires the development of a data registration format and IT solutions for NGS data transfer to the Healthdata.be platform through the eHealth infrastructure. Also, an automatic link with the national Cancer Registry is being established. The ultimate goal is that NGS data are collected together with additional test results into a molecular registry improving accessibility of data for clinical research as well as facilitating evaluation and decision making for policy makers.NGS is becoming more accessible for clinical labs but is also accompanied with various challenges. It is therefore necessary to provide education and training on the use of NGS. Defining the concrete needs in NGS education and training is done in concert with the healthcare sector, more specifically the College of Oncology, the College of Genetics, the Commission of Clinical Biology and the Commission of anatomic pathology. It is clear that different aspects can be covered including technical, legal and ethical aspects, as well as clinical applications and new evolutions towards third-generation long-range DNA sequencing, whole genome/exome sequencing, RNA sequencing, etc. The formats that can be used for post academic training and education are symposia, workshops, webinars and online courses. A first initiative was taken by the Molecular Pathology Working Group, where a two-day course was offered to residents in pathology. Participating on this course is now mandatory for all residents in pathology.It is generally recognized that with the use of NGS technology in clinical practice, new legal and ethical points of attention emerge . BesidesNGS implementation into the clinical routine diagnostics is a complex new intervention and will benefit from a transition period where the introduction of NGS testing itself is monitored. A real life pilot study can be put in place for this purpose through conventions of participating labs/hospitals with the reimbursement agency. At the end of this real life pilot study, an assessment will be made on the effectiveness of NGS in molecular diagnostics in oncology and hemato-oncology, including how this multi-testing approach can be positioned in the current reimbursement system, taking into account clinical utility, alternatives, therapeutic and societal need, quality and costs. The pilot phase will also allow to evaluate how a molecular data registration system can be best organized to allow documentation of test results and their use for later applications in quality control, output analysis and public health research.Optimal use of NGS demands investments in infrastructure and technology, in trained laboratory staff and in IT; affecting not only the logistics of the laboratory but potentially also that of the whole hospital setting. An additional challenge for optimal NGS-implementation in a hospital-setting, aside from the logistics, includes providing adequate genomic oncology training to clinicians, pathologists and geneticists to facilitate the dissemination of genomic knowledge fit-for-purpose for patient management. In regions with multiple testing laboratories and hospitals, all with different practices on the implementation of these genomic tools in their daily practice and thus potentially with different impact on patient care, the establishment of a network-infrastructure between those hospitals will most probably be beneficial. Establishing infrastructures for these purposes requires a huge collaborative effort between all the stakeholders involved, namely oncologists, pathologists, organ-specific specialists, geneticists, patients and general practitioners, as well as healthcare system representatives from the Government in order to align medical genomic-driven practice with health care policy. It may therefore be considered beneficial for patient care to organize the testing, data analysis and interpretation within such a network infrastructure.The development of regional NGS-network infrastructures should be supported by a thorough documentation of all quality-measures needed to establish optimal genomic-driven patient care. This includes documentation of the needed expertise of laboratory staff, documentation on how to ensure optimal interpretation of NGS-variants for daily practice, documentation on how to aim for optimal inclusion of patients in clinical trials, etc.….The additional benefits of network-infrastructures for optimal NGS-use are 1°) to expand and link to existing national genomic medicine implementation initiatives; 2°) to develop new collaborative projects in diverse settings and populations within a region or between regions; 3°) to contribute in a more efficient way to evidence based use of genomic information for clinical care; 4°) to define, share and disseminate the best practices of genomic medicine implementation, diffusion and sustainability in diverse settings within a region and 5°) to more efficiently contribute to the development of a nationwide database containing specific genomic information in various histological types of cancer.Precision medicine has offered new opportunities in cancer care with biomarker testing playing a major contributive role in this process. As a consequence, targeted NGS is gradually introduced in molecular diagnostics in daily practice. It offers the advantage to obtain more information with less material, thereby replacing sequential biomarker testing. NGS raises a number of challenges concerning standardization, sample quality, use of different platforms, variant interpretation, reporting, data storage, reimbursement, and ethics. A roadmap outlining a number of actions to tackle these challenges is described in this paper. The actions include the development of guidelines and criteria for NGS by experts, quality assessments for NGS testing, installation of data registration, NGS education and training. Finally these actions need to be implemented in a real life pilot study that includes the formation of NGS networks. In Belgium, this roadmap is running and resulted in technical guidelines for NGS , in a doIn conclusion, this action plan can serve as a guide for similar initiatives by other countries to facilitate the implementation of NGS in clinical practice in oncology and hemato-oncology.


Driving behavior is the main basis for evaluating the performance of an unmanned vehicle. In simulation tests of unmanned vehicles, in order for simulation results to be approximated to the actual results as much as possible, model of driving behaviors must be able to exhibit actual motion of unmanned vehicles. We propose an automatic approach of simulating dynamic driving behaviors of vehicles in traffic scene represented by image sequences. The spatial topological attributes and appearance attributes of virtual vehicles are computed separately according to the constraint of geometric consistency of sparse 3D space organized by image sequence. To achieve this goal, we need to solve three main problems: Registration of vehicle in a 3D space of road environment, vehicle’s image observed from corresponding viewpoint in the road scene, and consistency of the vehicle and the road environment. After the proposed method was embedded in a scene browser, a typical traffic scene including the intersections was chosen for a virtual vehicle to execute the driving tasks of lane change, overtaking, slowing down and stop, right turn, and U-turn. The experimental results show that different driving behaviors of vehicles in typical traffic scene can be exhibited smoothly and realistically. Our method can also be used for generating simulation data of traffic scenes that are difficult to collect. Evaluation of the intelligence level and comprehensive performance of unmanned vehicles turns to ontology and phenomenology. According to Turing , a systeDriving behavior is the main basis for evaluating the performance of unmanned vehicles. Testing the driving behaviors of unmanned vehicles is an important means of giving scientific and just evaluation of the research quality of key technologies such as environment perception, control, and decision . UnmanneThe most authoritative way to test and verify unmanned vehicles is by testing on the real road. For this purpose, competitions are held all over the world, such as DARPA-Urban Challenge in the US and the Future Challenge in China. However, this kind of test method is faced with difficulties such as limitation of test site, unrepeatable test condition, time-consuming, and high-cost procedure. Additionally, the actual testing environment may not be accessible, or may only be accessible at certain times while the simulated environment is always available . TherefoFaced with these limitations, we try to explore ways to realistically simulate and exhibit typical driving behaviors of vehicles with real data of traffic environment in simulation test of unmanned vehicles, as shown in However, there are quite a few challenges for us to achieve this goal. One is the modeling of virtual vehicles. For “traditional” computer graphics, recent advances in material modeling and global illumination have facilitated the synthesis of realistic and detailed imagery. But it needs painstaking work for the actual visual world, which is very complicated. Each object to be rendered requires lots of work to give surface properties and detailed geometry. Though we can use many image-based approaches to build the model, the data is not acquired straightforward and the methods are not suitable for our relatively large and moving vehicles. Another one is the spatial topology relationship between the virtual vehicles and the road environment. The scene for testing the unmanned vehicles is an image sequence containing spatial topology information. Virtual vehicles have spatial topology attributes, i.e., virtual vehicles should be consistent with reference scene in both appearance and spatial topology relationship.Encouragingly, we have proposed a simple and effective approach which can exhibit typical dynamic driving behaviors smoothly and realistically.As part of our work on parallel testing of vehicle intelligence , we propThere are three critical elements for us to solve our task:Typical Traffic Scene: Unmanned vehicles should be tested in a typical traffic environment including static, dynamic, and uncertain factors such as urban roads, highways, and rural roads. We analyze test tasks and scoring criteria of DARPA-Urban Challenge and the Future Challenge. Then, a typical traffic scene including the intersections is chosen for virtual vehicles to execute the driving tasks of lane change, overtaking, slowing down and stop, right turn, and U-Turn.3D Road Environment Representation: Road scene simulation and modeling based on vehicle sensors are currently an important research topic in the field of intelligent transportation systems  records coordinates of three vertexes.Sequences of boundary points are connected to adjoint triangle meshes which form the road surface.Moving road boundary points through the Y axis, we obtain other two sequences of boundary points. The boundary walls in corridor model can be rendered using these two sequences.The road geometric space based on corridor model shown in  can be iThe 3D road geometric space is used to restrict the motion range of traffic elements to be in the operating area. Irrlicht engine provides three methods of collision detection respectively based on ellipsoidal bounding box, triangle, and octree. We choose triangle collision detection to achieve our goal. The scene manager builds a triangle picker to judge whether the ray intersects with the plane of triangle mesh. Then, the triangle picker binds to the scene node waiting for collision detection. For example, when the vehicle moving in the road geometric space collides with the boundary, collision response animator controls the vehicle to response to the collision, so that the vehicle keeps moving on the road surface. eC is the coordinates in real world, ENUC is the coordinates in ENU coordinate system, R is the rotation matrix, S is the scaling matrix, and T is the translation matrix.The perception data of road environment is the data captured by the vehicle sensors, including road scene videos, location information captured by GPS, and pose information from inertial navigation, etc. When existed road scene videos are used for augmentation, no new real-time data is available from the road scene. Thus, we transform the coordinate system of existed perception data to the coordinate system of virtual road space to avoid frequent coordinate transformation between the real world and virtual world. The virtual world uses ENU coordinate system. The transformation relationship can be expressed asAfter the transformation and registration, virtual camera is one-to-one correspondence to real camera. In the virtual road scene, virtual camera moves through the path of the real camera. Each recorded viewpoint has corresponding road scene image. Then, the virtual vehicle is synthesized to the road scene image, shown in γ1 and γ2. The index is organized in the form of hash table to achieve quick load of vehicle images.Since the acquisition of vehicle image in all viewpoints is unavailable, we discretely capture the image of unmanned vehicle at different viewpoints, as shown in However, the images we captured are not enough. When the virtual vehicle moves to different angles, the vehicle image switches abruptly. To solve this problem, we need more vehicle images in other viewpoints. For the vehicle images that have not been captured, we generate them by view interpolation  and the We design a miniature scene to verify the reasonability and accuracy of our approach. This is because the advantages of using miniature scene are more controllable than large scene. Besides, most of the current research does not deal with comparisons between real-world images and synthesized scenes. The miniature scene can provide us quantitative data to evaluate the approaches. The coordinates, orientation, and size computed by real location data would be compared with those that are obtained directly from the real image. If these two types of data can match well, then the approach is effective.As shown in An image, the new location coordinate and orientation of the car model were recorded after the car model had been moved to a new place. Thus, we collect 60 groups of images and location data. The location data is used by our approach to compute relevant parameters. For the purpose of further verification of our method, we embed the algorithm in a scene browser and choose a typical traffic scene including the intersections for virtual vehicle to execute the driving tasks of lane change, overtaking, slowing down and stop, right turn, and U-turn.Our experiments were undertaken on a computer with an Intel i5 processor @3.33 GHz and with 16 GB Memory). The experimental data was mostly taken from the TSD-max dataset , which wThe traffic image sequences are formed by frames of videos captured from real road environment. The fame rate of the video is 24 fps. When we collect the videos of real road environment, we get the GPS data at the same time. However, GPS data only record the ground and lacks the height information. The height of viewpoint is manually measured. In our experiment, the height of viewpoint is 1.8 m. The height of virtual vehicle’s center related to the type of vehicle. Thus, GPS data and height data provide the coordinates of virtual vehicle’s center and that of viewpoint corresponding to each image. Applying the algorithm and method mentioned in In this paper, we propose a simple and effective approach of simulating dynamic driving behaviors in the traffic scene organized by image sequences collected from real road environment. In order to obtain the geometric consistency of 3D vehicle model and road environment, we use GPS data to accomplish the registration, obtaining vehicle pose and scale transformation. A logical model named as “corridor model” is defined to restrict the motion range of virtual vehicles. The experimental results verify good performance of our method on simulation of dynamic driving behaviors in typical traffic scenes.For further work, we will build a more complete simulation system with the function of editing traffic scene freely and easy to use. For example, light and weather condition impacts the performance of visual task for unmanned vehicles. Some detectors based on machine learning, such as CNN-based detectors, highly rely on data augmentation techniques to stimulate performance; training detectors with both day and night images are necessary so as to make them more general. In future, we will generate image data in different light and weather condition via generative adversarial networks for varied scenes.


Background: Many individuals with autism spectrum disorder (ASD) engage in problem behavior, presenting significant challenges for those providing care and services for this population. Psychophysiological measures of arousal, such as electrodermal activity (EDA), may provide an early indication of subsequent problem behavior. However, variability in EDA patterns associated with behaviors may limit this predictive ability.Methods: EDA data was sampled from eight individuals with severe ASD in a naturalistic setting, while participating in educational programming in a school setting at a residential facility for severely affected individuals with developmental disabilities, to examine variability in EDA patterns.Results: An anticipatory rise in EDA only occurred 60% of the time prior to the problem behavior. Additionally, EDA after a problem behavior returned to median baseline levels only 45% of the time.Conclusions: Heterogeneity of EDA responses in those with the most severe forms of ASD will be an important consideration in future studies utilizing psychophysiological tools such as EDA to anticipate problem behavior, including the need for monitoring of return to baseline after problem behaviors. Incorporation of this consideration may lead to greater reliability of these approaches to help anticipate and manage problem behaviors. Autism spectrum disorder (ASD) is a neurodevelopmental condition that is characterized by persistent deficits in social communication and restricted, repetitive patterns of behavior that occur early in development . ResearcAmong those with ASD, high levels of stress may manifest as problem behaviour . AdditioA great amount of heterogeneity exists in ASD, which can complicate research efforts when examining data at the group level. As such, identification of subtypes within ASD may lead to more effective treatments , 16. PsyThe present study first examined the feasibility of collecting EDA data from individuals with severe ASD in a naturalistic setting, while participating in skill acquisition in a school setting at a residential facility for severely affected individuals with developmental disabilities. The lab school at The Center for Discovery (TCFD) utilizes discreetly mounted video cameras and microphones in classrooms to collect behavioral data, while students wear physiological data collection sensors to gain a better understanding of the physiological correlates associated with learning and behavior in individuals with ASD. As such, we wished to examine the feasibility of examining psychophysiological variables in individuals with severe ASD as they are related to problem behavior. The beginning and end of problem behaviors were identified through video recordings and were confirmed by trained staff at TCFD. The associated EDA  was monitored prior to the occurrence of the initial problem behaviors as well as immediately after the cessation of the problem behavior, to examine individual variability in this particular psychophysiological variable as it related to problem behavior.th Edition for students with verbal abilities (nd Edition (CTONI-2) for those who were non-verbal  were examined see , a 70-itbilities , or the n-verbal . IQ scorn-verbal  score. AThe study was approved by the Institutional Review Board at TCFD. All data were collected from students with ASD enrolled at the TCFD, located in Hurleyville, NY. Due to the severity of the patient population, consent was provided by the parent/legal guardian, and assent was also obtained for those with the capacity to respond after explanation through an explicit social story. The data were processed and analyzed at the University of Missouri, which was approved by the Health Sciences Institutional Review Board through a reliance agreement with TCFD. Research staff at TCFD recorded problem behavior and EDA data for the eight students over 1 year in the lab school setting at TCFD.Monitoring was done while students were engaged in a classroom-based behavior intervention plan, where interventions were targeting specific behaviors. Occurrences of each problem behavior were noted by educational and residential staff trained to document these behaviors, as part of the standard procedure. The onset and offset of the each problem behavior was notated in Noldus The Observer XT software . The resulting onset and offset of problem behaviors were then used as endpoints for the EDA analysis.For the EDA analysis, only the first occurrence of a problem behavior was analyzed per session. This was implemented to prevent the occurrence of additive effects of previous problem behaviors on EDA, which may confound the results. Thus, if a participant engaged in problem behavior at 10 min into a session, then EDA analyses were only carried out on that problem behavior, and subsequent problem behaviors during the session were not analyzed. Overall behavioral profile for each student was also tracked, as documented by staff, for all behaviors at any point during the session , with a sampling rate of 32Hz, which was placed with Ag/AgCl dry electrodes, for extended use, to the wrist of the non-dominant hand. If the student would not tolerate a wrist-worn sensor, then the sensor was applied to the student’s ankle . Once thFrequencies of BIP and EDA associated with the behaviors were reported overall for each student. Incidence of anticipatory rise prior to behaviors and recovery of EDA after behaviors was also documented.To demonstrate the range of behaviors among the students, behavior frequency each participant engaged in over the year-long period assessed is depicted in Initially, the EDA data were visually inspected by an experienced psychophysiology researcher (BF) for artifacts as the Q-sensors were placed either on the wrist or the ankle of the students. Any cases with significant artifacts in EDA during the times that were analyzed, as defined by a visual analysis of motion from accelerometer data in the x, y, and z directions at the same time as significant EDA artifacts were noted, or DC shift, indicating either loose or no contact between the skin and the Q-sensor , were exThe presence or absence of an anticipatory rise in EDA prior to a student engaging in problem behavior was analyzed. On average, across all episodes of problem behavior documented, across all students, the students displayed an anticipatory rise in EDA prior to engaging in problem behavior 60% of the time. However, individuals varied in the frequency with which an anticipatory rise in EDA was observed before the onset of the problem behavior see Table 2.On average, across all problem behaviors documented, the students’ EDA returned to median baseline values 45% of the time after engaging in problem behavior. Individuals also varied in the frequency with which EDA returned to median baseline levels after cessation of the problem behavior. Of note, the student who returned the most frequently to their median baseline EDA primarily engaged in out-of-seat behavior, while the student who returned the least amount of times to their median baseline EDA primarily displayed agitation see Table 2.Examples of the different types of EDA responses are illustrated in The findings from this exploratory study suggest that examining the relationship between EDA and problem behaviors is feasible in a naturalistic setting in a severely affected population with ASD. There was some loss of data due to artifact, which was expected due to the level of functioning of the students and the assessment of EDA prior to and during the engagement of problem behavior that involves motion, rather than in a well-controlled laboratory setting. However, given the exploratory nature of the study, the findings suggest that the collection of EDA in a population with severe ASD is possible, but investigators should be aware of a number of limitations that are likely to occur in this population.Variability was found in the incidence of changes in EDA prior to the occurrence of problem behavior, during the problem behavior, and after the occurrence of a problem behavior, targeting a unique set of severely affected individuals in a residential setting. The results indicate that 60% of the total episodes of problem behavior documented were associated with an anticipatory rise in EDA prior to engaging in problem behavior. This has important implications for efforts to utilize psychophysiological markers as a predictor of problem behaviors . This fiIn this sample, we also identified that over half of the students did not reliably return to their initial resting baseline EDA after engaging in problem behavior. This suggests that, in future work examining the relationship between EDA and behaviors, it will be critical to account for the potential confound of a lack of returning to baseline from previous behaviors for EDA, and which behavioral profiles are associated with lack of return to baseline. Additionally, this raises the possibility that interventions after the cessation of behavior might be beneficial in some individuals, targeting de-escalation.A number of limitations to the present study should be noted, as they affect the generalization of the results across a broad range of individuals with ASD. First, the students in this study ranged in age from 13 to 20 years, with an average age of 16, were all male and have severe ASD. As such, it is not clear how this generalizes to all individuals with ASD, and so future studies will need to examine data from a more diverse sample of individuals. Second, detailed data from only eight individuals were analyzed for this study, and so future research should aim to examine these results in a much larger group of individuals with ASD, which would also allow the examination of the impact of co-occurring conditions and medications on the EDA/problem behavior relationship. However, this remains of interest for the management of those with the most severe problem behaviors, who were studied herein, and the variability that will be important in future psychophysiological monitoring in this type of setting.Finally, when planning psychophysiological experiments in those with severe ASD, careful consideration should be given to the testing environment, the problem behaviors engaged in by the individual(s) to be studied, and the tolerance of biosensors on the individual. For instance, if data collection will be indoors and outdoors, EDA would not be an appropriate measure given that EDA readings can be influenced by changes in hydration status, relative humidity, or sweat, for example , 28, 29.The datasets generated for this study are available on request to the corresponding author.This study was carried out in accordance with the recommendations of the Institutional Review Board (IRB) at The Center for Discovery with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the IRB at The Center for Discovery. Data analyses were conducted at the University of Missouri under a reliance agreement between the University of Missouri Health Sciences Institutional Review Board and IRB at The Center for Discovery.BF conceptualized and designed the study, coordinated and supervised data management, analyzed the EDA data, drafted the initial manuscript, and reviewed and revised the manuscript. JL and TV collected and processed the initial data, and assisted with preparation of the manuscript. JC advised on the data handling and assisted with preparation of the manuscript. TH developed the program for data collection, supervised data collection at The Center for Discovery, and revised the manuscript. DB conceptualized the overall plan of the study with BF, supervised the research team and provided expertise and guidance regarding autism spectrum disorder and revised the manuscript. All authors approved of the final manuscript as submitted.This study was funded by the New York State Center of Excellence grant funds from the New York State Department of Health & Office for People with Developmental Disabilities (OPWDD), & private gifts provided to The Center for Discovery.DB is on the research advisory board for The Center for Discovery, where TH, JL, JC, and TV are employed. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.ASD, autism spectrum disorder; EDA, electrodermal activity; TCFD, The Center for Discovery; ASRS, Autism Spectrum Rating Scales; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders IV—Text Revision; IQ, intelligence quotient; ABAS, Adaptive Behavior Assessment System; VABS, Vineland Adaptive Behavior Scales; CTONI-2, Comprehensive Test of Nonverbal Intelligence—Second Edition; std. dev, standard deviation.


The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society’s journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions. Clinical tropical medicine research efforts have largely followed suit. A developing trend in clinical research is to look beyond the traditional referral centers and their patient populations, out into the communities and to integrate the “horizontal” influences of comorbidities, culture, health delivery systems, social determinants of health, and other contexts, rather than maintain an artificially narrow “vertical” focus on single pathophysiological entities. This new approach, using community involvement and practice-based research networks, has the potential to challenge assumptions and uncover new strategies for improving the health of the individual and the community.The American Journal of Tropical Medicine and Hygiene within the previous year. For the purposes of this award, clinical research was defined as the branch of health-care science that determines the safety and effectiveness of medications, devices, diagnostic products, and treatment regimens intended for human use.2 These may be used for prevention, diagnosis, treatment, or relieving symptoms of a disease. The scope also included studies of disease manifestation and progression, clinical epidemiological studies, and case reports of novel presentations or approaches to diagnosis or treatment. Review articles, meta-analyses, editorials, and treatment guidelines were excluded from consideration.In 2018, the American Committee on Clinical Tropical Medicine and Travelers’ Health (ACCTMTH), the American Society for Tropical Medicine and Hygiene’s clinical group, introduced an award to be given in recognition of the best clinical research article published in A selection committee of seven members was formed, composed of volunteers responding to the call for reviewers from members of ACCTMTH. All members of the committee were physicians, who have experience in both clinical care and research, as well as experiences working in global and/or low-resource settings. Each member reviewed, at minimum, a 3-month series of the journal to identify clinical research articles for consideration. A year’s worth of the journal, published between July 2017 and June 2018, was culled to 15 candidate articles in this first step .3 which were presented at the 2018 Annual Meeting.4At least two members of the selection committee reviewed each article identified, writing a summary and providing a score on a scale of 30. There were no a priori guidelines on how to score. Reviewers sought to identify those reports that demonstrated readability for a broad audience, and were both innovative and relevant with the potential to make a significant impact on health. The process resulted in three articles rising above the rest. These “finalists” were then ranked in order by each committee member, the synthesis of which resulted in selection of the article which would receive the honors,Plasmodium knowlesi; advances in the treatment of leishmaniasis; migration medicine; water, sanitation, and hygiene; disease elimination using mass drug treatment; One Health5 themes such as brucellosis; advances in xenodiagnoses; nosocomial spread of viral infections such as alpha virus in Asia causing severe fever and thrombocytopenia; and falsified medications. This represents a substantial increase in clinically applicable articles compared with a predominance of preclinical and basic science reports in the past.In addition to reports of clinical trials involving novel treatments or diagnostic technologies, the breadth of clinical studies now being published in the journal is impressive. This is reflected in articles that covered malaria treatment, its complications, and animal (now human) 3 This result—especially if replicated in similar settings—emphasizes the importance of conducting clinical and epidemiological research in the context of the primary care health system rather than only in larger centers, especially within narrow silos which can emerge from the way global health activities are funded by Western interests.Some interesting trends were noted in the articles that emerged through this process. One of the themes was the importance of doing clinical research outside of referral centers. A prime example of this was the finding that clinical characteristics of severe malaria presenting to rural, peripheral health centers were different from those previously observed in referral centers, and that there may be different methods that are optimal for the identification and management of severe malaria in these settings.6 The reality of application may differ from the ideals of implementation because of complex interactions of many factors in the patient, the health system, and the community. As part of their discussion, they observed, “A more comprehensive approach to case management is needed, rather than focusing on only a single diagnosis and treatment.”6 This points to patient-oriented outcomes, rather than mere surrogate markers, as the true indicators of success. Patient-oriented outcomes are difficult to affect and measure because of the many factors in play. Another group included patient-oriented outcomes in the study design but ultimately emphasized a surrogate outcome when no significant effect was seen in the former.7A related theme is the complexity which must be considered when implementing interventions. For example, one investigative team had a broad enough perspective to look beyond the narrow focus of the investigation protocol itself and identified unintended consequences of a well-conceived public health intervention.8 So, too, was the inclusion of the young.10 Whereas the findings may not have been surprising in terms of both efficacy and tolerability in children compared with young adults, toxicity in older patients with cutaneous leishmaniasis treated with systemic antimony drugs was increased to the point that it is not recommended.8 It was good to see actual data rather than leaving clinicians to extrapolate based on nonsimilar patient populations when making treatment decisions.Another theme was the importance of incorporation of both ends of the age spectrum. The inclusion of geriatric populations—a group that is often neglected but is increasing in size in tropical clinical research—was refreshing.9Finally, the importance of assessing cost-effectiveness and opportunity cost was apparent from the selected literature. Just because we can do something does not mean that we should—perhaps greater impact may be found elsewhere. One of the articles nicely described why diverting resources to extend the current 80% coverage of the intervention to 90% would not meaningfully decrease overall prevalence of the targeted disease. Instead, the resources could potentially make more significant health improvements if allocated to other areas.In selecting the “best clinical research article,” the committee was attempting to predict the future by identifying the work that will have the greatest effect on health in the tropics. The perspective reported here does not reflect a systematic review of the literature. It is the observation that those articles which most impressed the committee seemed to share these themes in common. The themes were not a priori selection criteria; they emerged from an ad hoc process affected by the shared biases of the selection committee. Ideally, these are biases which value recognition of a changing culture within clinical research, one that favors a more integrated and comprehensive approach to clinical tropical medicine research. We believe that the future will be shaped by well-designed studies that consider the entire community, including the complexity of interactions, the full span of its ages, and its priorities for health.


Background and Objectives: In pregnancies resulting from incest, the adolescent maintains close family and emotional relations with the aggressor, different from what occurs when pregnancy results from sexual violence by strangers. Evidence indicates that this type of relationship with the aggressor may interfere in the dynamics of such violence and the adolescent’s access to health services. Materials and Methods: The objective of this research was to describe and correlate aspects associated with pregnancy when resulting from rape of adolescents in situations of incest; rape when perpetrated by an unknown aggressor and an abortion as allowed by law was sought. Method: A cross-sectional, epidemiological study of adolescents treated at the Pérola Byington Hospital, São Paulo, Brazil, bringing an allegation of pregnancy, resulting from sexual violence and a request for abortion as allowed by law. A total of 311 adolescents, being 134 in the “pregnancy from incest group”, and 174 in the group “pregnancies resulting from rape by a stranger” were considered under the study variables; relationships were investigated using the chi-squared test and Poisson regression with robust variance. Results: The study included 137 cases (44.1%) of pregnancy resulting from incest, and 174 cases (55.9%) of pregnancy from rape by a stranger. In cases of incest, a declaration of religion (92.0%) was significantly more frequent, and the adolescents were approached in spaces considered safe or private (92.7%); the aggressor taking advantage of the adolescent’s legal condition of vulnerability as a function of age (83.3%). Cases of incest presented a lower median adolescent age and greater gestational development, with gestations being ≥ 13 weeks prevailing. Conclusion: Cases of pregnancy by incest presented indicators suggesting both proximity and relationship with the aggressor, and pregnancy at a very early age, which postponed the adolescent’s procurement of health service, and interfered negatively with abortion assistance as allowed by law. In the history of societies, incest has suffered conceptual variations in function of the historical moment, culture, social class, and religion. It expresses a particular form of power relationship .Psychological, social, and psychiatric theories, upon involving with incest as a concept have fostered amplifications concerning its consequences for evolutionary processes in families and societies . Incest Current understandings of incest must overcome the reductionism implicit in legal definitions; these often limit the phenomenon to biological or kinship degrees . To a ceSexual violence predominantly affects female adolescents, although results differ concerning consequences between genders . In caseAlthough sexual violence can affect women at any stage of life, cases of incest concentrate during childhood and adolescence. The consequences in this age group may be even more severe, since the violence affects these persons in transitional phases involving prominent psychosocial changes . Though Incestual relations can therefore interfere in the outcome of these pregnancies because of the aggressor’s role. According to Blake et al. , the delIn situations of incest, the close relationship with the aggressor may well be a factor that inhibits the communication of sexual violence to the police, particularly for the need to maintain the “family secret” and avoid the perpetrator accountability. In Brazil, such resistance can affect submission to a legal medical examination, since the procedure is required exclusively by the police and depends, therefore, on the police communication officer .There is also evidence that the victim/aggressor relationship can influence the mechanisms used to impose violence on such adolescent girls. While sexual crimes committed by strangers in circumstances of urban violence may be associated with an increased frequency of physical violence, adolescents in an incestual situation may be more prone to acts of coercion, threats, psychological abuse, fear, or even affected by respect for the privileged position of the aggressor within the family.There is little knowledge concerning the social-demographic characteristics of pregnant adolescents suffering incestuous sexual violence. Further, it is not sufficiently clear whether proximity to the aggressor interferes in legal abortion assistance when required by the victim. The objective of this research was to describe and correlate aspects associated with pregnancy when resulting from rape of adolescents in situations of incest, and rape when perpetrated by unknown aggressors, and a request for abortion as allowed by law was sought.A Cross-sectional epidemiological study was conducted using a database consisting patient information of those treated between July 1994 and December 2015 at Pérola Byington Hospital, Public Health Service of the State of São Paulo. This hospital, the legal reference hospital for situations of sexual violence and abortion, considers as adolescents, girls aged 12 through 17 years, as defined by the Child and Adolescent Bylaw .These two articles characterize situations of sexual violence that allow abortion in Brazil, as laid down in Penal Legislation Article 128. Article 213 defines as rape any non-consensual sexual act committed by the use of physical force or serious threat. Article 217-A, which deals with rape of vulnerable persons, covers sexual acts against persons under the age of 14 or against those of any age who cannot offer resistance or valid consent .For the study, the adolescents were allocated into two groups: (A) Adolescents with pregnancy resulting from incest, and (B) Adolescents with pregnancy resulting from sexual violence perpetrated by strangers. The incest concept adopted was the manifestation of sexual relationships between people who are members of the same family (except spouses), and the family condition was defined by consanguinity, affinity, and social function of kinship exerted by a person within the group .Thus, pregnancies resulting from incest were those in which the aggressor was the father, stepfather, brother, uncle, grandfather, cousin or brother. The study excluded cases of sexual violence perpetrated by known aggressors, which were not classifiable as incest.The data were extracted from a database organized in Microsoft Excel 2010 and transferred to Stata 11.1. The database was completed using a pre-coded supplementary sheet. Differing referees reviewed the consistency of the information included in each case. The data were examined; and discrepancies identified and corrected prior to the transfer to Stata 11.1.Incest was adopted as the dependent variable against cases involving an unknown aggressor. The study variables were analyzed according to these two categories. The socio-demographic characterization of adolescents was performed using the following variables: age group, ethnicity; religious belief, and form referral to the hospital.The characterization of the sexual crime was analyzed concerning intimidation, legal condition of vulnerability, event bulletin, forensic examination by an Institute of Forensic Medicine, and location where the adolescent was approached. The characteristics of the pregnancy and the outcome of the abortion request were evaluated according to gestational age; reasons given to not perform or not approve the abortion; and the method adopted for interrupting the pregnancy.For statistical analysis, frequencies and percentages were calculated to describe the adolescents’ profile and to estimate the prevalence of incest cases. The adolescents’ age and the gestational age were described using mean and median, respectively, according to data normality assessed by the Shapiro-Wilk test.Correlations between cases of incest and profile factors associating the adolescents and the environments where the rapes had occurred were investigated by prevalence ratio at 95% confidence intervals using the Chi-square test and Poisson regression with robust variance. Associations between the cases of incest for the adolescents’ age and gestational age were assessed (respectively) using the Student t test and the Mann-Whitney test, according to the normality of the observed data.The choice of specific tests was performed according to data normality and by comparison of interval estimates . In the The Research Ethics Committee of Juazeiro do Norte College, (protocol 1.287.857), approved the study. To ensure confidentiality, the study did not include registration of the adolescents’ identities. All adolescents received medical, social, and psychological advice, including guidance on legal and ethical issues relating to abortion and sexual violence. The Research Ethics Committee of Juazeiro do Norte College approved this study; however, the authors are not affiliated with this institution.The study included 311 adolescents with allegations of pregnancy resulting from sexual violence between the 1994 and 2015, being 137 cases (44.1%) of incest and 174 cases (55.9%) of sexual violence perpetrated by strangers. p < 0.001).Poisson regression  indicateRegarding gestation characteristics, gestational age presented a delay in search for care; the prevailing gestational age was above 23 weeks, which affected the variable of gestation non-approval because of advanced gestational age, making legal abortion impossible.The perspective of pregnancy outcomes due to incest allows association of several aspects. Variants such as religious belief, police participation, adolescent age, and gestational age when seeking care may contribute to clarify important characteristics of the event when comparing these variables with those of adolescents suffering from sexual violence by strangers. The results of this research point to consistent differences in these two groups, especially in gestational outcomes.The differences refer to the age range of seeking the healthcare service to perform an abortion; when it is impossible to perform it, since in Brazil the legislation limits abortion to 22 weeks. In relation to victims of an unknown aggressor, the more advanced gestational age occurs in incest victims.Another variable of great importance is the type of intimidation used against the groups. The characterization of rape of the vulnerable under Brazilian law is more prevalent in the incest victim group, pointing to the condition of lesser self-defense ability when the aggressor is a relative, since he enjoys the intimacy of relationship with the victim.This study began with the fundamental element of sexual violence, occurring in opposing contexts. At one extreme, incest is practiced within the family, where the aggressor takes advantage of trust and intimacy with the adolescent to initiate and maintain the sexual abuse. At the other extreme, the sexual violence practiced by a stranger, , configures as a violent crime common in large urban centers .In situations of alleged pregnancy resulting from violence, declaration for religion by the adolescent was highly frequent in both groups, although it was significantly higher in incest cases. However, a simple statement of religion or any religious practice, does not allow analyzing its influence as a factor relating to incest. However, the higher frequency of declaration of religion among the incest cases removes the popular belief that incestual sexual violence occurs more often in agnostic families. An American study conducted by Gervais 2014) lists incest as an immoral act, considered so, regardless of religious belief, including by those who reported being atheists [ lists inFor the criterion of ethnicity or skin color of the adolescent, there was no difference between the groups, not allowing analysis from an ethnic-racial viewpoint. This finding has important implications in a psychological context and for its more traditional authors, where the incest taboo is considered to be weaker among non-whites .Certain study variables indicated that the relationship between the aggressor and the adolescent produces clear effects on the total process of the pregnancy. The adolescents’ ages in incest pregnancies were on average, 1.2 years lower than those observed for those who suffered sexual violence perpetrated by strangers. In this case, the dynamics of incest must be considered, usually characterized by a recurrent sexual conduct often initiated during childhood .When including acts of vaginal penetration, incest exposes the adolescent repeatedly to the grievance of pregnancy, and may explain the higher precocity of pregnancies found in this study. In addition, the family, community, and public authorities often only perceive incest if a pregnancy occurs; the clinical condition cannot be hidden and reveals the family secret. In fact, there is evidence that the difficulty identifying and recognizing incestuous sexual abuse is directly proportional to the degree of kinship between the victim and the aggressor ,18.Authors, such as Zambon et al. , found tThe data found in this study corroborate the consensus that incest is predominantly intra-familiar, and the chronicity of these incestuous situations presents a clear relationship to the type of approximations that occur.Within the private space, the aggressor articulates the means necessary to secretly establish the sexual violence, and to protect himself from accountability .On the other hand, in sexual violence as imposed by strangers, the adolescent is generally approached during daily activities performed in public spaces. Zambon et al. (2012) showed that 72.6% of sexual abuse cases against children and adolescents occur in a domestic environment, being 80.1% by a known aggressor and 31.6% being incestuous .Intrafamily violence, or violence within the family, involves blood relatives who may (or may not) occupy the same residence; although the probability of occurrence of incest is greater among relatives living daily in the same household. Domestic violence, in turn, is not limited to the family and involves all the people who live in the same domestic space, bound or not by ties of kinship .To demystify certain ideas spread in a conservative society. Neither blood bonding nor sexual orientation dictates the occurrence or frequency of sexual abuse. Traditional culture in the education of children imposes and dictates warnings or carefulness concerning strangers. However, it is not common to warn children about protecting their bodies from their most intimate living partners, including parents or relatives.Pregnancy due to incest, by all of the factors listed, does not always decisively end the cycle of violence. Since it is a sort of taboo, it can remain a family secret; the difficulty of identifying the incest may be common to all concerned, even in situations that result in gestation.Incestuous sexual abuse is the more difficult complaint to be revealed and faced. When it occurs outside family relations, the complaint of sexual violence seems to be more frequent and the credibility of the victim’s narrative is greater. This does not occur when the abuser is kin. The family often makes an effort to maintain the alleged family harmony and normality, which would be threatened by the revelation . The domNevertheless, the grievance of pregnancy resulting from sexual violence seems to modify the secret scenario . In bothIn both groups, a high percentage of forensic examination completions by the Forensic Medicine Institute were observed. In Brazil and in many countries, this element brings evidence, and is part of the procedures considered necessary to bring accountability to the aggressor, and it suggests the perception by the victim and her family that sexual violence is a crime to be brought to justice, especially when it results in pregnancy, regardless of who is the aggressor.Although severely condemned in classic law texts, sexual crimes are considered as only weakly penalized by justice . In judiTaking advantage of the adolescent’s condition of vulnerability predominated in cases of incest. This reinforces the concept that there is a need within the family to grant invisibility to incest. To prevent identification of sexual violence and its consequent accountability, the abuser usually does not use physical violence, which significantly reduces the risk of producing physical evidence or victim resistance, a situation described by other authors . Even inHowever, in cases of pregnancy by incest, our finding of a higher prevalence of adolescent intimidation (yet due to their condition of vulnerability) diverged from other studies which point to both intimidation and psychological threats as the most frequent forms of coercion ,29. In aThe adolescent’s consent or agreement in these situations was reflective of the emotional and psychological vulnerability in those younger than 14 years of age. Authors, such as Cohen and Gobetti (1998), consider consent questionable even for adult women, because the performance of incestuous desires reflects a lack of mental structure. The aggressor however is incapable of inhibiting his desires for concretely living experiences that should be suppressed .The decision to abort an incestuous pregnancy is a complex issue for both the adolescent and her family; any decision remains subject to the strong influence of cultural, religious, and legal factors, which are widely different in each community or society. For example, Ramakuela et al. (2016) showed that in South Africa, incest was crucial to the decision to have an abortion among adolescents, since it is believed that keeping a pregnancy resulting from incest will curse the family and cause its rupture .According to the World Health Organization, abortion consists in expulsion or embryonic fetal extraction occurring before the 20–22th week of gestation, when the estimated fetal weight is less than 500 g ,32. In gThe gestational age at admission for health care was significantly higher (concentrating above 12 weeks) among adolescents bringing allegations of pregnancy resulting from incest. This finding has important implications regarding both the possibility and method of performing an abortion. In allegations of pregnancy by incest, the percentage of adolescents with gestational ages of greater than or equal to 23 weeks was significantly higher. This prevented approval for the abortion request.Approval of abortion was less frequent for adolescents having suffered sexual abuse from strangers. Pregnancy, as a result of a consensual relationship and sex with an intimate partner, whether antecedent or subsequent to the claimed sexual violence, was a verifiable condition; using incompatibilities between the date of sexual violence suffered reported, and (by obstetric ultrasonography), the estimated gestational age.Gestational age should be considered a relevant factor in legal abortion assistance, , since it occurs in a recognized period of intense physical and psychological changes, and increases the risk of negative consequences ,35. MoreThe results of this study reveal that during the 20 years of service provided by the Legal Abortion Referral Service, in the state of São Paulo, Brazil, an expressive number of alleged cases involving pregnancy by incest have been reported; this frequency has not been found in the literature in other regions of the country.Further, the general expansion of the concept of health as based on social-ecological modeling of the personal and environmental factors affecting access to health services has emphasized factors and determinants involved in the processes of health and disease, and further, require guarantees of such access for female adolescent victims of rape. Incest delays arrival at health service facilities, and seems to be an interference factor for lawfully permitted abortion assistance. Incest corroborates to reduce opportunities for female adolescents victimized by rape to obtain full healthcare assistance.This study is innovative for regarding the issue of pregnancy and its associated factors when resulting from incest. When considering the prevalence of such events and the extent of their consequences for the health of both families and society in general, this research underlines the need for further investigation by the scientific community.Cases of pregnancy by incest presented indications that both proximity to the aggressor, and type of relationship can result in pregnancies at a very early (adolescent) age. In the incest group, the study also evidenced delayed procurement of public assistance, whether for police authorities or health services. In some cases, this prevented legal abortion. In the group (victims of strangers), the demand for services commonly appears sooner.These findings interfere negatively in abortion assistance allowed by law, making it more frequent for incest adolescents to encounter, due to advanced gestational age, abortion as an unavailable option.