Low-cost video surveillance systems are attractive for Smart Home applications . Those systems use the flexibility of the Internet of Things to operate the video camera only when an intrusion is detected. We are the only ones that focus on the design of protocols based on intelligent agents to communicate the video of an intrusion in real time to the guards by wireless or mobile networks. The goal is to communicate, in real time, the video to the guards who can be moving towards the smart home. However, this communication suffers from sporadic disruptions that difficults the control and drastically reduces user satisfaction and operativity of the system. In a novel way, we have designed a generic software architecture based on design patterns that can be adapted to any hardware in a simple way. The implanted hardware is of very low economic cost; the software frameworks are free. In the experimental tests we have shown that it is possible to communicate to the moving guard, intrusion notifications (by e-mail and by instant messaging), and the first video frames in less than 20 s. In addition, we automatically recovered the frames of video lost in the disruptions in a transparent way to the user, we supported vertical handover processes and we could save energy of the smartphone's battery. However, the most important thing was that the high satisfaction of the people who have used the system. The Internet of Things (IoT)  has guidVideo surveillance over the Internet is a real-time service that applies to very varied environments  telecommunication operators proposing this service to their customers’ homes; (b) proliferation of low-cost video surveillance systems that any user can deploy; managing them through Web in a Smart Phone; (c) a mature industry appears producing technologies and proprietary equipment of very different type. Low-cost video surveillance systems  can be deployed using embedded computers like Raspberry Pi  and openCoverage deficiencies in LTE .Range coverage and radio channel interferences in WiFi , prolongBad planificafication of dense WiFi networks.Inefficient behavior of transport protocols of Internet in WiFi and LTE.Inefficient behavior of video servers .Inefficient behavior of video clients that cannot process the deadlines associated to the reception and visualization of video frames.Wireless Internet access suffers intermittent and sporadic service disruptions as is well known and we have shown it for LTE  and WiFiThe above adverse effects affect  the QualWe implemented our video surveillance system with open software platforms. Nevertheless, far from making a particularized implementation for our open hardware, we specified a software architecture based on software design patterns. Software design patterns are generic solutions for common design problems; they are reusable assets that help transfer knowledge from experts to newbies ,19 and tThe main original contribution of this paper is the novel design of a video surveillance system for Smart Home that mitigates the adverse effects of disruption of the real time video streaming service. This system includes an intelligent protocol among sensors, video server and the video client used by the moving guard. The novel specification based on software design patterns allows any researcher to implement it for any hardware architecture using their own software components. We implemented our system in a very low cost hadware architecture using cheap sensors and camera. We built a Smart Home model for measuring QoS and QoE parameters, battery’s energy comsumption for WiFi and LTE, and the arrival time of notification of intrusion detection to the guard wireless terminal. The experimental results showed the small time needed for the guard could come to the rescue while he can view video of the intruder’s actions. This is a novelty focusing in the surveillance system based on sensors, which have had a high interest of system testers (QoE).In Intelligent image processing. In ,21 videoSmart codification and compression of objects. The main idea is to reduce the needed communication bandwidth between server (that processes a high amount of videos) and client, sending only relevant information to the client (user) . Due to High number of video streams synchronization. Pereira et al.  proposedAndroid smart phone. The construction of an embedded system as a server and video processor is cheap because there are low economic cost freely distributed hardware and software to do it. However, in 31] is usFirstly, we review some works on video surveillance service to state the main idea and aspects related to our system. Secondly, we review works on mitigating the adverse effects of service disruptions and differences with our method and finally, we review methods for programming systems similar to ours. The current video surveillance systems are very sophisticated and propose a video treatment focused, among others, on:Current research in video surveillance systems does not focus on the communication of real time video to the guard’s wireless terminal (while he moves). This is due to the fact that usually, that video is received on a desktop computer  and the physical level of the communication network is mainly optical fiber-based. We focused into the exploration of the communication of the video using a wireless access network to Internet kernel. That is, both the video server and the guard’s wireless terminal connected to a wireless network (LTE or WiFi). The mobility of the guard is essential for early acting in the Smart Home just in case he is close to the Smart Home. If the guard could use a WiFi network , he would experiment video service disruptions. On the other hand, if the guard is not close to the Smart Home, and he wants to move rapidly to the Smart Home, while a colleague of him is visualizing the video, he would use LTE , to early visualize the movements of the thief. For both cases, the aim of our video surveillance system is to mitigate the adverse effects of real time video streaming service disruptions. In the same way, the smart phone of the guard must need to do vertical handover  between Based on the regulation of the transmission rate. They estimate the highest possible rate of video transmission .Based on adaptive video buffer. They seek the relationship between the occupation of the buffer and the selected video bit rate and the available bandwidth . LatencyBased on prediction of QoS parameters, which optimizes the allocation of resources and related variables in a control model such as the Markov Chains .To mitigate the adverse effects of video disruptions, there are several techniques, which we present next. We distinguish adaptive video streaming algorithms into three categories:Most of the above algorithms keep multiple copies of video content with different bit rates, which create a huge storage load on the video server. In addition, video transcoding is expensive and difficult to apply for real time video streaming. These are two important problems for our system of low economic cost and calculation power, so it was not possible to use them. However, the main problem we wanted to solve was the fact that the server closes the video session and the client must start again to download the video from the beginning. When this problem occurs, the previous techniques do not solve it.We next present other particular solutions.The authors of  proposedSeveral authors ,40,41 haWe have used the Proxy software pattern to mitigate disruptions applying that technique to different smart phones and operating systems ,43,44, sIn this paper we refine our previous unpublished studies in ,49 improNext, we review several similar works and analyze the contribution of the paper regarding the specification of the software architecture based on software design patterns.Sanchez et al.  presenteThe design of software based on software design patterns improves the quality of the artifacts produced and reduces the costs of software maintenance ,53. In aThe sensors are continuously sending sensed data (with a certain sampling period) to the alarm processor.The video camera starts operating once the Alarm processor fuses the sensor data and determines that an intrrusion has occurred. At that moment, the video will be stored in the video server memory (a file that works as a buffer) and simultaneously an instant message (Telegram application) and/or an e-mail are sent to the Client (guard). The file containing the recorded video can be used before the judge.Internet Protocol Address (@IP) of that server) in the instant message or in the e-mail text. If the Client receives the video while the server is producing it, the video will be delivered in real time. However, the Client could start an on demand video Streaming session whenever he wants, once the Video Server finished recording that video.The Client will receive a Telegram instant message and/or an e-mail. Whenever he wants, he can start a video streaming session on the Video Server, clicking a link . In that simple way, nested disruptions can be easily managed.Broadly speaking, the video surveillance system has the following main operations:An actor  is a person or other entity that interacts with the system been described. A use case (represented as an ellipse) describes the way an actor interacts with the system to reach its objective. In  we preseModel (Server): it is located in the Video Server . The Model consists in an Observer software pattern in charge to control de videos. An external Observer software design pattern abstracts the data model corresponding to the sensed data. That Observer is constantly testing the sensor data communicated to the Controller.View (Client or user): It consists of several views: the video display, the e-mail and Telegram messages interfaces and the links that allow starting the video streaming. Other simple view is the warning of disruptions.Controller: It is the most important software pattern. It is in charge to do all the control of video service disruptions, the control of the wireless channel to advertise possible disruptions and the cooperation with the sensor alarms. It consists in the cooperation among different standard software patterns that we present next. We distinguished internal software patterns to the Controller (inside the MVC) and other external software patterns to the Controller (outside the main MVC pattern). The appropriate selection of patterns must take into account the cases of use and quality requirements of the software, and the technology chosen . The sofThe internal software patterns are Proxy, Strategy and Adapter. The first implements the actions of our previous solutions (coordinate the Model and the different views). In addition, it is in charge to test the state of sensors, to fuse the sensed data and to determine if an intrusion has occurred . If a video service disruption occurs, it will invoke the Strategy, which will implement a particular algorithm for treating the disruption. This is very flexible design of software because the treatment of the disruption can be changed without changing the overall video surveillance system. The Adapter (ontologic software design pattern) receives data from the external Observer. That is, the sensed data are communicated to the Adapter which, can convert those data into the corresponding data service (we implement Web Services). The flexibility of this design decision allows the designer to change the communication of sensed data without change the overall video surveillance system. Ligth: Dimensions 65 × 11 × 13 mm, series Photoresistor-BH1750, measurements 1-65535 LX, sampling 2 s.Digital temperature (Ds28b20): Each device has a unique 64-bit serial code stored in its Read Only Memory (ROM), multipoint capability that simplifies the design of temperature detection applications, can be powered from the data line. The power supply range is 3.0 V to 5.5 V. Measures temperatures from −55 °C to +125 °C (−67 °F to +257 °F) ± 0.5 °C to the nearest −10 °C at +85 °C. The resolution of the thermometer is selectable by the user from 9 to 12 b and converts the temperature into 12 b codes in 750 ms (maximum).Infrared Barrier: 10.2 × 5.8 × 7 mm phototransistor, peak operating distance: 2.5 mm, operating range for collector current variation greater than 20%: 0.2 mm to 15 mm, typical output current under test: 1 mA, ambient light blocking filter, emitter wavelength: 950 nm.We built a physical model that emulates a typical Smart Home with several rooms, garage, stairs… . Within An Atmega 328 arduino microcontroller did the processing of the sensed data. We used a 20.7 Mpixels camera, LED flash, ½ 3 ′ ′ sensor, geotagging, and image stabilizer. To implement the videostreaming server and other storage control software, a RaspBerry Pi B+ was used with a 900 MHz quad-core ARM Cortex-A7 processor, 500 MB of RAM, 4 USB ports, 40 GPIO pins, interface of the camera (CSI), screen interface (DSI), Micro SD card slot and VideoCore IV 3D graphics core.We made use of Service Oriented Architecture (SOA) for implementing the software specified by software design patterns. Avila et al.  introducWith Raspduino, the Arduino sensor platform was interoperated with the RaspBerry Pi B+, enabling data to be collected: The sensor's identifier, the sensing measurement and a time stamp for that sensed value. These values are sent to a proxy capable of interacting with JADE agents. We defined the agents’ behavior which infere ab-normal situation (intrusion) based on the sensors’ values. Since JADE originally used its own ontology for the message passing, it was decided to make this communication interoperable through Web services. That is the reason why we installed WISG addon, which transforms those messages into Web services. With Web Services Description Language (WSDL) and Simple Object Access Protocol (SOAP), the data were passed to the Tomcat Web Application Server. Tomcat is necessary to support a Web browser compatible with the reception of video in Hiper Text Markup Language (HMTL) 5.If an alarm was generated, the PiCam would be triggered to record what happens in the Smart Home. That camera connected to the RaspBerry Pi B+ video streaming server called RPiCam, which did not record audio natively, but it recorded video in the Motion Joint Photographic Expert Group (MJPEG) version 4. It communicated video in H.264 format that can be received in HTML5 in the Web browser . We focus now in the video service disruption performance. We first model the occurrence of disruptions not mitigated. The second model corresponds with the mitigation of service disruptions with our technique. We compare the results of both models with the case in which no video service disruptions occur. The objective is to show informally the impact of our technique in QoS and QoE.C) will take sT time units (t.u.) to start the video streaming session and it will indicate the beginning of the reception of video packets ). After pt t.u., C will receive the first video package. From there, C will receive a new package after each id t.u. . Therefore, the optimal time (optT) that C takes to receive the whole video is the one shown in Equation (1): n is the total number of sent packets, sT is the initialization time of the session and pt is the arrival time of the first packet. Let us analyze the impact on QoS and QoE with a simple model abstracting details of the communication and observing only the amount of time and energy needed to send all the video. m video service disruptions  then the time (intT) it takes to receive the video will be considerably greater and is a function of the number of disruptions that occur and their duration (jTi), as indicated in Equation (2): iK are the numbers of packets received before the video service disruption i occurs and we assume that at least one is received before any video service disruption.In case there are An important adverse effect is the number of times a video packet is retransmitted. Equation (3) gives it: p units of energy consumption (u.e.), then the smart phone will be making an expense (extra inefficient battery consumption) indicated in Equation (4):In each of these retransmissions the packet is occupying the WiFi channel, preventing other packets from being communicated (thereby increasing the contention in the channel). In addition, if we assume that the smart phone has an expenditure of The most important adverse effect is the degradation of QoE . It is psT. In [sT and the retransmissions of packets. In addition, we automated the reconnection of the video streaming session to avoid the user having to do it manually. Thus, we reduced the adverse effect of video service disruption in the QoE. Our schemes can be adapted to build the solution presented in [This is not a particular problem of our system, but occurs in other scenarios. For example, in  authors Ts. In  a study Ts. In ,49 analyented in  taking i1I occurs, the packets are still stored until all the video packets are completed. To prevent the C from sending an order to stop the video streaming, we choose to store the video for a predetermined but configurable amount of time . At that time, the n packets of the video collected by the camera would be stored once the alarm server produces a new alarm.sT is one of the most important performance factors in video streaming. They compare the efficiency of RTSP and WebRTC for video streaming concluding that the second is more inneficient than the first. Thus we are in the correct line trying to avoid the C must restart the video session each time a video service disruption occurs.As verified experimentally by Santos et al.  Ts is onWith the new mitigation technique, the time to send the full video is given by Equation (5): With which, from Equations (1), (2) and (5), Equation (6) relates the different delivering times:Another important aspect is the battery energy consumption. With our mitigation mechanism, it is possible to minimize the extra energy consumption in retransmissions. Indirectly, this also improves the QoE because the user has more time to connect the video surveillance system. On the other hand, it is important to maximize the life of the battery to ensure greater tranquility of the user in such a way that it does not perceive it can disconnect from the system and not know what is happening in the Smart Home.To verify the operation of the video surveillance system, we implemented multiple tests. With those tests, we tried to observe the response times for the mitigation of disruptions of the real time video streaming service; the time of arrival to the client of the notifications via e-mail and Telegram; and the extra battery consumption due to real time video streaming service disruptions.It is widely known that the optimization of the measurement of the QoS parameters is not enough to ensure a general satisfaction of the user, because each person is different and has different expectations of quality. For this reason, the International Telecommunication Union (ITU) has published a new set of ITU-T recommendations focused on parametric QoE monitoring of video services ,73. We fAccording to  the sampQ1.How would you rate the design of the user interface of the application?Q2.How would you rate the usability of the application?Q3.How would you rate the interactivity of the application?Q4.Did you have problems accessing the application?Q5.Did the application have an execution error?Q6.Did the application reconnect the video without reloading the page?Q7.Did the application send e-mail and Telegram notification messages?We used the ITU P.800.1 for the opinion scale, and we asked the following questions (using a Google Forms form):The response classes for questions Q1, Q2 and Q3 were Excellent, Very good, Good, Improvable, Very improvable. The response classes for the remainder questions were Yes or No. Respondents answering yes to Q4 and Q5, were asked to identify the problem. We did that to have feedback and improve the application and on the other hand, to ensure that the responder answered conscientiously. Only two people contributed feedback.sT  and pt . We call user Waiting Time (uWT) the delay time in starting the video playback in the Client since he requested to open the video session (issue of a SETUP command in RTSP). That is, uWT is the time the Client  waits to receive and visualize the first set of video frames. Abstracting insignificant values of computation in the wireless terminal, we could consider: As mentioned in uWT < 10 s (according to [The rding to ) and becvpl) could explain part of the disruptions (Iz) and its duration, the jitter (id) and factor iK. We are not interested in verifying our high level abstraction model, but we consider very important to obtain the values for vpl in order to show if it will be less than 25% (vpl < 25), according to [The percentage of video packets loss (rding to .WpR and we considered that if it is greater than 3 (WpR > 3), then adverse effects will occur and the mitigation mechanism has not worked well. We obtained this limit from the experience with interviewees  in QoE measurements.The playback of video was embedded in a Web page (Web View). The Web page must be reloaded just in case the Video session must be restarted (long disruption or any other bad event occurred). We name this parameter bblk, b = 1..6) of five tests (tst) each. In each block, we considered different amount of disruptions. Specifically, we considered one disruption in 1blk and 4blk, two disruptions in 2blk and 5blk, and three disruptions in 3blk and 6blk. In this way, we wanted to do a full test of the mitigation of adverse effects of our video surveillance system. We used a 300 s video and intentionally provoked the disruptions moving along a full range and shadowed WiFi zones. We tested those parameters making a full campaign of experiments considering several disruption patterns. We did six blocks (iblk (i = 1..3).WTerm 1: Smart phone Celular Sony Xperia Z3 Compact; 127 × 64.9 × 8.6 mm; 1280 × 720 pixels (4.6′′); Android 5.0; processor of 4 cores (2.5 GHz), Graphic Processor Unit Adreno; Battery capacity 2.600 mAh; 2 GB RAM; LTE and WiFi (IEEE 802.11 g/n/ac). This terminal was used in the iblk (i = 4..6).WTerm 2: Laptop Mac Book Pro 15′′; 1920 × 1200 pixels (15.4′′); Mac OS High Sierra; 2.2 GHz quad-core Intel Core i7, Turbo Boost up to 3.4 GHz, with 6 MB shared L3 cache; 4 GB de SDRAM DDR3 (two moduls SO-DIMM de 2 GB) to 1.333 MHz; WiFi (IEEE 802.11 g/n/ac). This terminal was used in the We also considered different kinds of wireless terminals to observe the influence of video consumption and the wireless communications: < Back − Rpi Cam control allows the user to return to message notifications view.Google Chrome browser (version 54.0.2840.85 for WTerm 1 and version 54.0.2840.98 for WTerm 2), and tcpdump version 4.3.0, and Wireshark version 1.11.1 for capturing traffic in the video server.We used The place in which we did the test was the campus of the Escuela Politécnica del Ejercito (ESPE) in Sangolquí − Ecuador, closed to the installations of Computer Science Departament  in the uppest floor of the building. Several buildings and shadowed zones for WiFi and LTE surround the Department building. It is very appropriated to show the utility of our video surveillance system because a notification message can arrive to the Smart Phone of the guard that is in the campus and he will cross several WiFi shadowed zones before reaching the Smart Home model.uWT obtained for all blocks and tested in each block. We grouped the blocks attending to the number of disruptions. For nearly all experiments, the uWT for WTerm 2 was less than for the WTerm 1 (only the test number two was greater in WTerm 2 than in WTerm 1). This was due to the differences of bandwidth of WiFi and power processing of both terminals. uWT were that their maximum values were nearly less than 3 s (only in one case was greater but close to 3 s). This means that our mechanism is relatively fast and it will allow the guard to receive video and reconnect after a disruption quickly.The best news for vpl obtained for all blocks and tested in each block grouped by number of disruptions. There was nor correlation between the kinds of wireless terminals neither number of disruptions and vpl. This was because the loss of packets depends on the WiFi channel, not on the terminal. vpl were that their maximum values were nearly less than 3%. This means that our mitigation mechanism worked notably. This value of vpl could justify that in all cases we obtained WpR = 0. One important tip was that when disruptions last little time (less than 10 s), it was confortable to continue with video visualization. However, when the total visualization time reached 400 s (disruptions last more time) it was not confortable to continue visualizing the video.The best news for uWT, vpl and WpR are in consonance with the MOS.The above values of In uWT + 8 + G (s) the guard will receive the first images of the intrusion, where G is the time needed by the guard to discover the notification message and to click the link. We consider that in less than 20 s the guard could receive the intrusion images. That is, the guard will experiment a delay of 20 s about the movements of the intruder.Another source of delay in the reception of the first images of the instrusion and disruptions are the time needed to make the vertical handover between LTE and WiFi (or viceversa). We conducted other 24 tests to measure those delays with the Iphone Chronometer. It is very difficult to measure the influence of the redundant packets of video on the battery consumption. That is because the consumption of the battery does not follow a linear model, and not necessary all the redundant messages would consume the same amount of energy. We conducted several informal experiments in which annotated the amount of remaining hours of battery energy every 2 min for a video lasting 20 m. Then we introduce 3 disruptions and repeated the experiment. We found that in average the variation of the remaining amount of minutes was 2. That is, with the disruptions we lost 2 min of battery energy.In this paper, we have shown the performance of a technique to mitigate the real time video streaming service disruptions applied to a video surveillance system in a Smart Home model. We have proposed novel ideas and implementations of those ideas. The intelligent protocol communication among sensors, Alarm processor, video server and the client allow our system to mitigate disruptions. The novelty that represents to demonstrate that it is possible to deliver real time video of the intrusion to the moving guard is important. We have shown that our system is fast, it has very low cost and is programmed and implemented using a systematic hardware and software design (based on standard software design patterns) and implementation. The most important result is that the satisfaction of the interviewees was highly shown. Another important result is that informally we have shown that it is possible to save energy consumption in the Smart Phone.Future work includes more research in energy saving in the Smart Phone. We plan to design a formal model of energy saving for our system. We will consider battery drop models, formalization of energy wasted in sending a video packet and receiving it in the Smart Phone and the design and implementation of specific operation for an Observer and Strategy patterns that could monitorize the energy consumtion in the Smart Phone. We will consider professional people of videovigilance systems in order to better validate our system.


A lensmeter or lensometer is an instrument used to verify the prescription of eyeglasses or spectacles. Many lensmeters can also verify the power of contact lenses with the addition of a special lens support. The values obtained from a lensmeter are the values specified on the patient's eyeglass prescription: sphere, cylinder, axis, add, and in some cases, prism. It is commonly used prior to an eye examination to obtain the last prescription the patient was given, in order to expedite the examination.In one commonly used type of lensmeter the target seen through the eyepiece consists of a set of three wide lines with wide spacing between them and another set of three narrow lines with smaller spacing between them. These two sets of lines intersect at right angles. The closely spaced lines represent the sphere component of lens power and the thicker, widely spaced lines represent the cylinder power. In the case of a spherical lens, all of the lines of the target will focus at the same time, while in the case of a sphero-cylindrical lens, the lines will focus separately at different power drum readings (see illustration).In another type of lensmeter, a series of light dots forming a circle is used as a target instead of the two sets of parallel lines described earlier. If a spherical lens is measured, the circle remains a circle and the power drum is adjusted to obtain a sharp image of the dots. For sphero-cylindrical lenses the dots, when focused, will display a sharp ellipse. The major and minor axes of the ellipse can be read on the scale provided in the instrument.The target is imaged through a lens. The eyeglass lens under test is placed at the rear focal point of this lens. Light emerging from the spectacle lens enters the eyepiece which contains a reticle. The reticle is a permanently etched series of concentric rings used to measure and locate the prism base direction, and also contains orientation lines for each lens meridian and a protractor scale.For measuring the power of the lens, the power drum is turned until a clear and sharp image of the target is seen through the eyepiece. The power (in diopters) can be read on the scale on the wheel. For measuring the focal power of cylindrical and sphero-cylindrical lenses that have different powers in different meridians, the optics of the equipment can be rotated by turning the axis wheel. The angular position can be read on the circular scale of the axis wheel.The eyeglass lens to be tested should be placed on the lens stop so that the outside of the lens is facing the eyepiece and the side of the lens that sits closest to the user's eye is facing the instrument's light source.Before using the instrument, you should look through the eyepiece. The reticle should be in focus. If it is not, adjust the eyepiece until it is sharply focused.Periodically ensure that the power calibration of your lensmeter is accurate by following these steps:Turn on the lensmeter.Turn the eyepiece ring so that the reticule appears in focus.Turn the power wheel into the plus, then slowly decrease the power until the lensmeter target is sharply focused. Do not oscillate the wheel back and forth to find the best focus. The power wheel should read zero if the instrument is properly calibrated.If the power wheel does not read zero, re-focus the eyepiece and re-check the calibration. If the power wheel still does not read zero, the error must be compensated for in all future measurements made with the lensmeter, or the lensmeter needs maintenance. If dust falls onto the surface of the lenses of the lensmeter, blow it off with a clean bulb syringe, a dust brush or compressed air.Wipe the instrument's exterior with a soft cloth to prevent dust accumulation.Do not attempt to lubricate the instrument. If it feels tight, contact a qualified service technician.To prolong the life of the bulb, do not leave the instrument on all day.Cover the lensmeter when not in use to protect it from dust.


A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won’t significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated. With the rapid development of video game industry, video game plays an important part in our daily life. According to CNNIC (China Internet network information center), until June 2017, there are 751 million cyber citizens in China, one fifth of the world cyber citizens, and the amount of cyber citizens who play online video games is 421.64 million in China, and still keep increasing. It should be noted that most video games contain violent content . MoreoveMany behavioral researches have proved that long time exposure to violent video games is associated with aggression. Violent video games contains lots of shooting, stabbing, boxing and kicking actions to hurt other game characters to avoid being killed or to achieve the goal , which pNeuroimaging studies have deepened our understanding of violent video game effects. There are many task-functional magnetic resonance imaging (fMRI) researches about violent video games and aggression. According to In addition, quite a few fMRI researches about video games used to focus on the addiction aspect. Animal electrophysiological researches and human functional imaging researches have all proved that there existed a reward system, i.e., the dopamine neural circuit . Plenty In conclusion, abundant researches have showed that long time exposure to violent video games is highly associated with certain brain changes in many perspectives. Still, it should be noted that findings in behavioral researches can be confounded by subjects’ consciousness, task fMRI researches used to focus on one aspect of brain changes , and concerning addiction researches are still quite few . BesidesResting-state fMRI technique refines to measure the BOLD signal in the resting mood, the spontaneous brain activities without information import or export . The spontaneous fluctuations that occur during the resting state reveal the intrinsic functional architecture of the brain and are related to extrinsic behavior performance . What’s SD = 1.76, range: 17 ∼ 27 years) were recruited in this study, who played violent video games  more than 10 h a week in recent 3 months, while the non-violent video game group refers to participants who did not play violent video game at all. They were recruited through flyers posted across the campus of Southwest University, China. All of them had normal or corrected-to-normal vision and had no history of psychiatric or neurological disorders based on self-report. Before the experiments, all participants were informed of their right to privacy, and that they could quit the experiments anytime. After the experiments, each of them was paid $10 for their participation. Written informed consent was obtained from each participant, and this study was approved by the Administration Committee of Psychological Research at Southwest University. Three participants were removed from the sample due to excessive head motion during data preprocessing, and the remaining 49 participants were included in the formal data analysis.Fifty-two right-handed males . First, high-resolution T1-weighted structural images were acquired sagittally. The scanning parameters were as follows: 1900/2.52 ms (repetition time/echo time), 1 mm (thickness), 176 slices; 256 mm × 256 mm (field of view), 900 ms (inversion time), 9° (flip angle) and 1 mm × 1 mm × 1 mm (voxel size). Then, functional images were obtained using a T2-weighted gradient recalled echo planar imaging sequence with the following parameters: 25 axial slices; slice thickness = 5 mm; repetition time = 1500 ms; echo time = 29 ms; image matrix = 64 × 64; field of view = 192 mm × 192 mm; flip angle = 90°; voxel size = 3 mm × 3 mm × 3 mm; volumes = 200. During the resting state scanning, participants were instructed to stay awake with their eyes closed and not think about anything in particular.1) based on SPM82, which was run on the matlab R 2009a software3 (MathWorks Inc.). The preprocessing steps were as follows: (1) Images from the first 10 volumes at the beginning of the resting state scanning were discarded to eliminate magnetic saturation effects; (2) the remaining 190 images were corrected for slice timing and head motion correction to adjust the time series of the images . 27 violent video gamers and 22 non-violent video game participants were valid in the present study; (3) the structural images were coregistered to the mean functional image and were subsequently segmented as gray matter, white matter and cerebrospinal fluid employing the new segment method; (4) each functional image was normalized to the standard Montreal Neurological Institute (MNI) space with the application of DARTEL  (3 mm × 3 mm × 3 mm resampling); (5) after normalization, spatial smoothing was performed with an 8 mm full-width-half-maximum Gaussian kernel; (6) nuisance linear regression was performed with the white matter, cerebrospinal fluid and 6 rigid body head motion parameters; (7) the linear trends were removed, and finally, the images were temporally band-pass filtered (0.01–0.08 Hz) to reduce low-frequency drift and high-frequency noise  to that of the entire frequency range (0–0.25 Hz). Same as ALFF, the eviation .T-test.First of all, to see whether our grouping is correct or not, we examined difference of violent video game experience between violent video game experience group and the control group by performing an independent sample T-test between the BPAQ score of violent video game group and that of control group.To compare the results of spontaneous brain activity during resting-state fMRI and trait aggression measured by BPAQ and better understand our results, we also conducted the independent samples T-test on both ALFF and fALFF. AlphaSim correction was conducted for multiple comparison correction.To investigate the differences in spontaneous brain activation between groups, we performed two samples T-test based on violent video game experience showed that there were significant difference  between violent video game group (41.40 ± 20.85) and the control group (18.53 ± 18.66).Independent samples T-test based on BPAQ score showed that there were no significant difference  between violent video game group (68.89 ± 12.07) and the control group (66.42 ± 12.41), and there were no significant difference on physical aggression ; anger  and hostility . However, there were significant difference on verbal aggression  between violent video game group (14.36 ± 3.48) and the control group (12.21 ± 3.97).Independent samples T-test. The results showed that there was no significant difference between violent video gamers and their counterparts in ALFF, AlphaSim correction was performed with voxel size p < 0.001, and cluster size p < 0.05, voxel = 13, see Figure 1. There was no significant difference between violent video game group and the control group in fALFF, either.To examine the spontaneous brain activities between group of violent video games and group of non-violent video game, we performed two samples Resting-state fMRI were employed to investigate whether long time exposure to violent video games is related to abnormal spontaneous brain activities.T-test on violent video game experience showed that there were significant difference between violent video game group and the control group. The violent video game experience of former group is significantly higher than that of the control group, which proved that our grouping is correct and effective. This is the premise of further analysis.First, two samples T-test on BPAQ total score. The two group are not remarkably different on spontaneous activities or trait aggression. This is against our former hypothesis.For ALFF and fALFF, there were no significant difference between violent video game group and the control group, which is consistent with the result of two samples As mentioned in former fMRI researches , ACC, orIt should also be noted that ACC, OFC, and TPJ are the significant part in the DMN (the default mode network). DMN is distinctly important in emotion-processing, monitoring environment changes, self-introspection, maintaining self-awareness, and also extracting episodic memories . PreviouWhat’s more, our research findings is supported by increasing number of literatures claiming that the severe effect of violent video games is overstated ,b. FerguMeta-analyses investigating the potential correlates between violent video games and violent behaviors were positive but with small effect size ranging between 1 and 4%  and has One can speculate from the above findings that there is no causal link between violent video games and aggression. This is mainly because, firstly the cause of aggression cannot be simply illuminated. Many environmental factors, such as childhood trauma, family background, contribute to aggression, mutually. For instance, research conducted by In China, the risk factors are mainly biological causes like gene defect, IQ, and gender; family causes like family structure, parent–child relationship, parental supervision; social factors, especially the function of peer pressure and bullying. These factors will influence juvenile delinquency, more in a combined way than solely. Violent video games is not the primary cause of aggression. According to General Aggressive Model (GAM), after gameplay, the oppression, provocation and clues about aggression will affect individuals’ mental process, impelling the development of aggressive cognition, emotion and behavior. Moreover, repeated exposure to violent video games could reinforce this loop and the aggressive personality is developed. However, this theory doesn’t fully explained the relationship between violent video games and aggression, players are seen as passive, negative receiver to what are put on them. It failed to pay enough attention to the subjective initiative of players. Our research emphasis the necessity to develop more sophisticated model, as well as advanced methodologies, to better explain the possible factors and pathways will lead to aggression.There were also deficiencies in our study. First of all, our participants are all selected from college, whether our findings can apply to different groups remains uncertain. What’s more, given the fact that female violent video game players are quite few, our research target mainly focused on the males. The resting state brain activities in females and in male–female comparison worth further investigation. And further researches should also pay more attention to other potential aspects relating to aggression in more specific and sophisticated way.On the whole, our results suggested that there is no strong link between long time exposure to violent video games and spontaneous brain activity, didn’t show any neuropsychological evidence of aggression, enhanced our understanding to the relationship between long time exposure to violent video games and aggression.Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Written informed consent was obtained after detailed explanation of the study protocol, which was approved by the Ethics Committee of Southwest University. The Institutional Review Board at Southwest University (SWU) in Chongqing, China approved this consent procedure. Written informed consent was obtained from all participants. The Institutional Review Board at SWU approved all procedures.Informed consent: Informed consent was obtained from all individual participants included in the study.Conceived and designed the experiments: XG and WP. Performed the experiments: WP, XG, SS, FL, and CL. Analyzed the data: WP, SS, FL, and CL. Wrote the paper: WP and XG.The 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.


Cerebral arteriovenous malformations (AVMs) are abnormal tangling between brain arteries and veins causing an arteriovenous shunt called nidus with an intervening network of vessels from the region of formation and spans through the brain. AVM effect is debilitating to the affected individual due to associated persistent intracerebral hemorrhage, resulting in significant occurrences of seizures and neurological damage. Recent innovative treatments involve a combination of embolization (Embo) procedures followed by stereotactic radiosurgery (SRS), designed to optimize less-invasive practice for the obliteration of the AVMs. Three groups of investigators reported different outcomes based on obliteration rates and adverse events, making the effectiveness of options for therapy, controversial. We have taken the case-oriented-approach to highlight on varying outcomes from various studies and provide insights as to why findings from different operation settings could be so conflicting.We chose 18 articles for systematic analysis based on initial electronic database selection of 40 key papers already identified for inclusion, followed by independent blinding assessment by two co-authors. Our evaluation was based first on our specific inclusion criteria, examining method quality, obliteration rates, serious adverse events (SAEs) and mortality rates. Second, we made a comparison between SRS or embo alone treatments versus combined embo/SRS procedures, relative to AVM sizes, following Spetzler-Martin (SM) method. Third, we considered publications which had concrete statistics with well-defined P-values and clarified outcomes for accurate evaluation.We found that patients with small to medium-sized AVM were susceptible to either embo alone or SRS alone treatments, yielding obliteration rates from 71%-100%. Except for one report, giant sizes AVMs were not amenable to these single treatments, subjecting patients to embo/SRS procedures, which yielded mixed results: One group reported 52%-65% obliteration rates, compared to 23%-28% embo alone treatment. A second group contradicted this apparent beneficial outcome, obtaining obliteration rates of 53% with combined treatment compared to 71% with SRS alone, four-year postoperative. A third group reported there was no difference between single and combined treatments and obtained complete obliteration of 70%-82%, ranging from three-five-years postoperative follow-up. In all the cases analyzed, obliteration rates improved with time. SAEs, such as persistent hemorrhage and permanent neurologic deficits (P-NDs), as well as mortality, were minimal during intraoperative and postoperative follow-ups.The problem of conflicting outcomes in combined treatments of AVM by EMBO/SRS exists. Previous investigators, however, have overlooked to address this issue satisfactorily. Our analysis found that the reported inconsistencies in AVM treatment outcomes are attributable to key factors making therapy unpredictable, which includes: the size of the AVM, nidus localization and accessibility of either Embo or radiation dose applied, certain Embo materials lowering obliteration rates by masking radioactive effect on the nidus during SRS and follow-up timing for obtaining obliteration rates determine the extent of obliteration.We have indicated critical factors which require consideration when planning strategies for treatment of AVM patients and have made suggestions of how to overcome such hurdles.  Cerebral arteriovenous malformations (AVMs) are irregular connections of the brain capillary network -3. TypicThe etiology of AVM formation is not clear; nonetheless, it has been postulated that genetic factors involving gene alterations with subsequent overexpression or hyperactivity of blood flow hemodynamic regulatory elements, as well as, vascular endothelial growth factor (VEGF-A) signaling  might plAlthough AVM development can occur anywhere in the body, cerebral AVMs tend to be most debilitating, especially, if they reside in eloquent brain regions which are parts of the brain controlling speech, mobility and senses. AVMs in eloquent locations can rupture easily and cause intracranial hemorrhage, thus, presenting symptoms such as seizures, stroke, impaired speech, and vision, broadly classified as neurological deficits -9. OtherAVM is diagnosed by the use of computed tomography (CT) scan, magnetic resonance imaging (MRI) and cerebral angiography which involves X-radiation (x-ray) imaging, following contrast injection -11. BrieBetween December 2015-2016, we searched the medical literature analysis and retrieval system online (MEDLINE) database via PubMed, Excerpta Medica database (Embase) Database-Ovid, and Elton B. Stephens Co. (EBSCO’s) Medical Database for brain atrioventricular malformations and intracranial AVMs ranging from 1995 to 2016. We supplemented our searches with Google search engine on the same topic. The keywords used were as follows: brain AVMs, radiosurgical treatments, stereotactic radiosurgery (SRS), embolization (embo), combined embo/SRS, small AVMs, large AVMs, treatment outcomes.We obtained a total of 40 abstracts from the searches, out of which we chose 30 relevant full-text articles. Two reviewers who mutually agreed on inclusion/exclusion selection criteria screened the reports. Co-author one selected 20 articles (first set). Co-author two blinded to the first co-author, evaluated the 30 papers independently, screened and also selected 20 articles (second set). The two co-authors held a mutual consent meeting and selected 18 articles which appeared in both sets of selections to be included in the study and resolved any discrepancies to avoid observer bias in articles selection.Inclusion Criteria: Our inclusion criteria considered the following: 1) In-depth description of AVM surgery methodology. 2) Large patient population size . 3) Single SRS and combined embo/SRS treatments and outcomes. 3) AVM sizes and grouping by SM grading. 4) Serious adverse events (SAEs). 5) Obliteration rates. 6) Comparable statistical analysis. 7) How often the authors’ published in the field . 8) Case mortality. 9) Routine follow-up.Exclusion Criteria: Our study excluded the following criteria: 1) Non-brain AVM. 2) Conventional micro-neurosurgery. 3) Small patient population size. 4) Lack of in-depth description of methodologies. 5) Embo alone treatment/no SRS. 6) Invasive surgery or invasive neurosurgery. 7) No detailed statistical analysis . 8) Greater than 20% patient dropped out from follow-up.We assigned the following features in the articles and made comparisons in our assessment: 1) Treatment of large AVM sizes. 2) Obliteration rates (%). 3) Years of study conduction. 4) Patients with brain hemorrhage (%). 5) Permanent Neurologic deficits (P-ND) (%). 6) Mortality rates (%).We synthesized data from the articles, described the studies narratively and tabulated study characteristics. Presented in the textual format are results which are consistent with the data submitted. Thus, 18 AVM treatment full-length articles were selected, of which six contained single SRS or SRS, as well as, combined embo/SRS treatments, and 10 contained combined Embo/SRS alone treatments. We compared outcomes and pulled results which were similar and those that were contradictory or were not significantly different. Subsequently, a systematic review was carried out to assess methodological quality and outcomes.We excluded reports with small patient numbers in AVM combined embolization/SRS treatments to ensure confidence level (95%-99%) of a large number of patients were used to generate reliable outcome data. Since the issues, we were addressing were varied outcomes from different reports, it was critical to ensure that the outcome data we were comparing were generated with precision.Although we used obliteration rates, percent hemorrhage, and permanent neurological deficits (P-NDs) data from previous studies, all of the three authors examined the data from the articles and came to data agreement with reported numerical values via inter- and intra-observer angiography reviews. We subsequently confirmed obliteration rates, percent hemorrhage, and permanent neurological deficit (P-NDs) values reported in the articles. In an instant where there was a lack of quantitative obliteration rate, we averaged our estimation from the angiography and used the mean value. We found trends that might resolve issues of conflicting results, addressed later in this section.The AVM treatment techniques involve passing a tiny catheter into the cerebral vessels feeding it until it reaches the nidus . EmbolizStatistical methods typically used to quantitate outcomes are univariate  and multivariate Cox-regression or logistic analyses ,14,7, thAVMs sizes were determined using the Spetzler-Martin (SM) grading method  or by voBetramello, et al.  reported3 AVM size. He experienced an instant complete obliteration . Graph A, on the other hand, went through a second phase after the seventh year and the obliteration rate reached about 95% by 18 years. It seems from this analysis that the single SRS treatment has resulted in a better obliteration outcome than the combined treatment. The inference likely to be made from these two reports is that the SM sizes of the AVMs in both studies vary and so the comparison is being drawn between small sizes AVM in Figure  and larg3. These are obviously very complex and gigantic malformations. Thus the purpose for embolization with nBCA before SRS was to generate a combination of effects for an aggressive treatment which produced 63% obliteration rate by 10 years  and the initial mean volumes, which was 22 cmThis together with the reasonable adverse events (AE) reported, the outcomes they obtained are comparable to those reported by other investigators. Karlsson, et al. obtained similar results in 2007 ; they usIn the Pierot, et al. report of 2013 , they peBy the second year, about half of the nidus had obliterated Figure ; in the 3, with a median of 6.6 cm3 and median SM grade of III. Radioactive dosage median was 18 Gy. There was 19 years follow-up period (1987-2006). Percent obliteration was determined by MRI imaging or angiography images with subsequent data analysis. Hemorrhage, neurological deficits due to adverse radiation effects (ARE) and other parameters assessed. Summarized in Table In Kano, et al. 2012 paper , 120 AVMThe authors observed that patients with smaller AVM volumes had better success, as compared to those with large masses and that disappointingly, there was the overall reduction in the cumulative total obliteration rate with the combined treatment (53%) than single (71%). Similarly, several groups have shown a parallel trend of results -39. SiriThis finding provided awareness that successive SRS treatment of giant size AVMs is not an ideal strategy for treatment, in particular, if they localize in eloquent brain regions and accounts for the reason why the need of good embo materials is crucial for the reduction of large nidus sizes prior to SRS.Wang, et al. in 2014  used theThis review sought to use different case-oriented studies to show data from single as well as combined AVM treatment outcomes and how these results had been very diverse. A particular view of the literature has revealed several reasons why inconsistencies in outcomes reported by different groups should not be surprising. We determined significant bias introduction into the various studies from different clinical settings, which we have indicated below as crucial factors that require consideration when planning AVM surgery:1) AVM size and complexity determines the aggressiveness of treatment ,14,17. T2) AVM drainage into the deep venous system is a crucial determinant of neurological deficits; therefore, it is important to aim at preventing disruption of the AVM surroundings, as this can impair drainage and cause frequent hemorrhage ,16.3) The nature of adjuvant used in embolization is essential, as the liquid types, such as polyvinyl alcohol (PVA) and nBCA are leaky and can cause distal catheter gluing during surgery ,29. In f4) Staging the dosage of an embolization material per subgroup is an important determinant for an effective therapy and requires careful calculation. Under dosage will not work efficaciously and ultimately results in a reduction in obliteration rates; and over dosage can cause SAEs such as speech and vision impairment, partial paralysis, seizures and even increased mortality rates ,28.5) The depth and cerebral localization of the AVM is an important determinant of treatment strategy. If an AVM is in the non-eloquent region of the brain and not deeply embedded, the catheter can reach the nidus for both embolization and SRS procedures to a favorable treatment outcome. A giant AVM in the deep eloquent region, however, will either, a) presents itself as embolization and SRS resistant spot, or b) an attempt to treat it could result in a deleterious adverse event (AE) such as increased intracranial hemorrhage, loss of speech, vision, and stroke ,36. For 6) After performing embolization, recanalization of the nidus can occur in such a way that the blood vessel lumen of the occluded feeders to the nidus is restored spontaneously  and it c7) Liquid embolization materials such as nBCA and ethylene-vinyl alcohol copolymer (EVOH) can cause beam attenuation during GSK procedures such that the radiation dose (the number of kilovoltage radiation photons) reduces in an embolized nidus -47. Onyx8) Aneurysms are present in the arteries feeding the nidus and can rupture because of their delicate nature and cause bleeding in the AVM region . SRS pro9) Individuals diagnosed with AVM are at risk of suffering from intracranial hemorrhage, seizures, vascular diseases, neurological deficits, and stroke making it difficult for drastic surgery decisions for them. Therefore, pre-existence of any of these conditions prior to AVM diagnosis could result in higher risk of experiencing AVM progression into maturation -19, or iOur analysis set to determine reasons for inconsistencies in AVM combined embolization and SRS treatment outcomes. Certainly in a cohort study, if a subset of patients in a group encounters any of these nine setbacks mentioned above, it will influence a cumulative outcome. Our analysis clearly provides an awareness that the reported varying outcomes in the treatment of patients bearing giant size AVMs might be due to lack of blending all of these crucial factors when planning individuals’ customized treatments. Recent advances in endovascular techniques and discovery of better embolizing adjuvants should aid in minimizing these contradictory reports and bring about more reliable, efficient and safer operations.


Empower Stars! mobile video game grounded in behavioral and exercise theories with the purpose of coupling physical exercise with empowerment over disease in children with cancer.Medical advances continue to improve morbidity and mortality of serious pediatric diseases, including cancer, driving research addressing diminished physical and psychological quality of life in children with these chronic conditions. Empowerment enhances resilience and positively influences health, disease, and therapy understanding. We describe the development and usability assessment of a prototype Unity multiplatform technology provided animation and audiovisual features for immediate player feedback. Javascript, C#, Photoshop, Flash, and SketchUp were used for coding, creating graphical assets, Sprite sheets, and printing files, respectively. 3D-printed handles and case backing were used to adapt the iPad for physical exercise. Game usability, engagement, and enjoyment were assessed via a multilevel study of children undergoing cancer chemotherapy, their parents, and pediatric cancer health-care providers. Feedback crucial for ongoing game development was analyzed.Academic faculty, health-care providers, and community video game developers collaborated in this project. The iPadAir was selected as a delivery platform for its accelerometer and gyroscope features facilitating exercise design. Empower Stars! mobile video game was developed for children 7–14 years old with cancer. Active, sedentary, educational, and empowerment-centered elements intermix for 20 min of exercise within a 30 min “one-day treatment” gameplay session involving superheroes, space exploration, metaphorical cancer challenges, life restoration on a barren planet, and innumerable star rewards. No player “dies.” Usability assessment data analyses showed widespread enthusiasm for integrating exercise with empowerment over cancer and the game itself. Favorite elements included collecting star rewards and planet terraforming. Traveling in space and the Healthy Food Choice game were least liked. The need for improved gameplay instructions was expressed by all groups. The usability study provided essential feedback for converting the prototype into alpha version of Empower Stars!A prototype Adapting exercise empowerment-promoting video game technology to mobile platforms facilitates usability and widespread dissemination for children with cancer. We discuss broader therapeutic applicability in diverse chronic pediatric diseases, including obesity, asthma, cystic fibrosis, diabetes, and juvenile idiopathic arthritis. Recent advances in pediatric medicine have resulted in markedly improved patient survival, thus increasing prevalence of those living with diverse serious and previously often fatal pediatric chronic diseases, including cardiac, pulmonary, renal, autoimmune disorders, and cancer –5. Relatphysical QOL  and psychological QOL  dramatically affected during and after cancer treatment, have received comparatively limited attention  and mobile health ] are emerging as effective empowerment-promoting tools by improving one’s understanding of health, disease, and treatment options , 25–28. Empower Stars! (Empower Stars! video game and (2) the results of the multilevel usability assessment conducted to provide essential direction for creating the alpha version of Empower Stars!With these challenges and concepts in mind, we have been developing a video game technology that couples physical exercise with mental empowerment directed at simultaneous improvement of physical strength and endurance, and psychologic QOL of pediatric oncology patients , 36–40. r Stars!  The purpEmpower Stars! mobile video game, significant and essential groundwork had been laid in the process of creating an exercise–empowerment coupled video game using a PlayStation format  was created , 37, 40.Empower Stars! video game was designed and created. The driving hypothesis in the development of this video game was: the integration of physical exercise with empowerment-promoting strategies can be accomplished on a mobile platform to create a disease-specific video game therapy for children with cancer. The creation of this prototype video game also involved a lengthy, multidisciplinary process involving of youth video game developers at Spy Hop Youth Media, academic faculty, and a team of health-care providers who specialized in the care of children with cancer—nurses, child life specialists, psychologists, social workers, physical therapists, and pediatric oncology physicians. Grounded in exercise, behavioral health, and video game engagement theories  the video game would be engaging and usable and (B) important feedback collected in this usability assessment will provide positive and negative feedback critical in the creation of the alpha video game. Both qualitative and quantitative data were collected in this University of Utah Institution Review Board-approved study to obtain constructive feedback in the areas of usability, engagement, and enjoyment that were deemed critical for future game development and improvement  was used for statistical comparisons. GraphPad Prism  was used to generate the accompanying figures.The children’s assessment also contained two visual ranking scales for ranking of likability of (1) the eight main game environments and characters and (2) the five exercise mini-games and games. Mean scores were determined for each scale.Each study participant was also asked to complete a simple open-ended questionnaire entitled “The Three Things” to provide feedback regarding the three things they liked the best, the three things they liked the least, and the three things they would change about the video game. Answers that appeared at least two times were compiled and presented in a summary table.Empower Stars! video game was created for children ages 7–14 years with cancer undergoing chemotherapy. The initial focus was to create a proof-of-concept prototype to deliver a “one-day” intervention that consisted of 30 min of gameplay time which included 20 min of physical exercise using iPadAir and a specialized hardware case. Coupling physical exercise and mental empowerment as a video game intervention for children with cancer and other chronic diseases has been previously defined , a mobile platform promoting self-management in diabetes, the mobile medical app reSET™  for the treatment of substance use disorder, and the Jintronix Rehabilitation System® . Significant improvement in attention was seen in children with attention deficit hyperactivity disorder (ADHD), after 4 weeks of playing EVO , an iPad-based intervention designed for children with ADHD (It is encouraging that the U.S. Food and Drug Administration recently cleared digital therapeutic technologies, including BlueStarith ADHD . FinallyEmpower Stars! video game is to expand the current “one-day” prototype game version into the alpha version designed to deliver a multiday exercise–empowerment intervention for children with cancer. This would involve continued multidisciplinary collaboration among pediatric oncology care providers and video game developers to address the limitations of the current prototype. Results obtained from the 32 subject multilevel usability Empower Stars! assessment will be incorporated into the next version, with additional rounds of multilevel feedback obtained followed by a second multilevel re-assessment will be conducted to create the alpha version. Subsequent clinical testing of the alpha Empower Stars! would then allow identification of potential clinical benefits in children during and following chemotherapy, Incorporation of individualized goal setting, a powerful component of behavioral change, may also be feasible (Empower Stars! video game can lead toward adjunct digital therapeutic interventions in these and other pediatric chronic diseases. Development of video games as a digital therapeutic intervention is based on “software as medical device” pathway and is subject to regulatory compliance and pivotal clinical testing.One attractive development pathway for the prototype feasible , 129. OnEmpower Stars! video game defines the novel approach of directly coupling physical exercise with promoting personal empowerment over cancer using a mobile platform. Learning that children like and will play such a game, that parents endorse the incorporation of such a game into their child’s treatment program, and that there is strong approval by health-care providers together all support continued development of a disease-specific exercise–empowerment video game as adjuvant medical treatment. Continued multidisciplinary collaboration with incorporation of serial multilevel user feedback assessment is essential for the development of the alpha version of Empower Stars! video game that can then undergo efficacy evaluation in children with cancer. Once this has been accomplished, the stage is set for developing similar exercise–empowerment mobile video game interventions personalized for diverse pediatric chronic diseases. Coupling physical exercise with personal empowerment in a judiciously designed and disease-specific video game that is created on a mobile platform provides the opportunity for widespread, affordable application to children with cancer, and serves as a prototype for management of diverse chronic diseases across many ages.Creating hope, improving QOL, reducing stress, and increasing one’s sense of control over the seemingly uncontrollable are all important components of patient empowerment over disease. The prototype The Usability Assessment study was reviewed and approved by the University of Utah Institutional Review Board and classified as a Minimal Risk Study. Before study participation, signed assent forms from all participating subjects ages 7–14 years and signed parental permission forms from their respective parents, and signed consent forms were obtained for all adult study participants. There were no subject withdrawals.Empower Stars! video game content. SB, MB, RL, DL, ES, AS, and RS created and coded the story line, characters, exercise mini-game challenges, and music content of the prototype Empower Stars! video game, with ongoing consultation from GB and CB. CB and CM designed the Usability Assessment study and survey questionnaires, and GB consulted. CB was responsible for all Institutional Review Board-related documents and processes, wrote the initial manuscript draft, and conducted the Usability Assessment study, with assistance from AB and IP. CB and CM analyzed the usability assessment data. AB and IP contributed to pediatric chronic disease literature review, and all listed coauthors contributed to editing and gave final approval of the manuscript.CB and GB conceived of this project and defined the prototype CB and GB are co-inventors on two issued US patents 9,569,562 and 9,747,423 “Disease Therapy Game Technology.” These patents are related to the exercise–empowerment video game technology and are owned by the University of Utah. The remaining coauthors 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.


We introduce LEISR , a tool to infer relative evolutionary rates from protein and nucleotide data, implemented in HyPhy. LEISR is based on the popular Rate4Site  approach Evolutionary rate inference is a fundamental analysis in computational molecular evolution . A widelLikehood Estimation of Individual Site Rates). LEISR is available as part of a leading molecular evolution inference platform HyPhy starting with version ≥2.3.8.1Earlier versions of HyPhy  also contain the LEISR method, although those pre-release versions will have reduced functionality relative to the LEISR implemented in HyPhy version 2.3.8.LEISR can be used to infer relative evolutionary rates from either nucleotide or protein data, thereby providing a flexible and fast platform for rate inference that may complement codon-level rate inference.2We note that HyPhy contains several robust methods  under a user-specified substitution model , and infonly the relative site-wise rates to contain information about site-wise evolutionary rate heterogeneity. If branch length optimization considers rate variation, then this information will be “conflated” between these two parameters (branch lengths and site rates). In other words, one can view Rate4Site and LEISR as non-parametric rate estimation methods, whereas gamma and GDD are parametric estimation methods, and layering the two would be inefficient.Rate4Site offers two statistical frameworks for rate inference: maximum-likelihood (ML)  and empi.leisr.json. Site-wise rates are stored in the top-level JSON field mle, whose content field contains a row for each site’s inferred rates. Individual values in each row correspond to information given in the headers key. A general description of HyPhy output JSON contents is available from http://www.hyphy.org/ in the “Resources” tab.As LEISR inference proceeds, HyPhy will write markdown-formatted  status-iUsers are free to transform these rates in a manner that suits their given analyses. For example, Rate4Site computes a standard score for each site, and other applications have called for normalizing each rate by the mean (or median) gene-wide rate . This laWe confirmed that LEISR yields comparable inferences to Rate4Site using simulations. For each of three random phylogenies with 25, 50, and 100 taxa each, we simulated 10 replicate alignments, each with 100 sites, under the WAG model of protein evolution . Tree leWe then inferred relative evolutionary rates in LEISR in two modes: turning off rate heterogeneity during branch length optimization (“LEISR”), and specifying a four-category discrete gamma distribution during branch length optimization (“LEISR+G”). We again inferred rates in two modes in Rate4Site : without rate heterogeneity during branch length optimization (“R4S”) and with a four-category discrete gamma distribution (“R4S+G”). While the default number of rate categories for this step in Rate4Site is 16, but Rate4Site failed with errors for all 100-taxa simulations. We therefore used four rate categories, to both achieve a fair comparison with LEISR and to ensure that Rate4Site could complete inferences. For those runs which completed, we observed comparable run times between LEISR and Rate4Site. Finally, for each alignment inference, we normalized rate estimates by dividing all rates by the mean site rate estimate, as described earlier.R2 values for Pearson’s linear correlation between LEISR and Rate4Site inferences, computed across all simulations. The R2 values further increase as the number of taxa increases, although even with 25 taxa the agreement is remarkably high. This trend is expected because the precision of inference for individual site rates will increase for larger samples with more taxa In Finally, we examined whether the comparability in rate estimates from simulated data extends to empirical data. We inferred rates using both LEISR and Rate4Site on an established mammalian protein alignment of HRH1 receptor (histamine receptor type 1) genes consisting of 23 sequences and 507 sites, where the phylogeny had a total tree length of 3.30 and a mean branch length of 0.077 . We specR2 = 0.93. This strong of agreement with 23 sequences is consistent with the observed R2 values from the simulated datasets with 25 taxa (As shown in  25 taxa , in spit


Avian β-defensins (AvBD) possess broad-spectrum antimicrobial, LPS neutralizing and chemotactic properties. AvBD-12 is a chemoattractant for avian immune cells and mammalian dendritic cells (JAWSII) — a unique feature that is relevant to the applications of AvBDs as chemotherapeutic agents in mammalian hosts. To identify the structural components essential to various biological functions, we have designed and evaluated seven AvBD analogues.In the first group of analogues, the three conserved disulfide bridges were eliminated by replacing cysteines with alanine and serine residues, peptide hydrophobicity and charge were increased by changing negatively charged amino acid residues to hydrophobic (AvBD-12A1) or positively charged residues (AvBD-12A2 and AvBD-12A3). All three analogues in this group showed improved antimicrobial activity, though AvBD-12A3, with a net positive charge of +9, hydrophobicity of 40% and a predicted CCR2 binding domain, was the most potent antimicrobial peptide. AvBD-12A3 also retained more than 50% of wild type chemotactic activity. In the second group of analogues (AvBD-12A4 to AvBD-12A6), one to three disulfide bridges were removed via substitution of cysteines with isosteric amino acids. Their antimicrobial activity was compromised and chemotactic activity abolished. The third type of analogue was a hybrid that had the backbone of AvBD-12 and positively charged amino acid residues AvBD-6. The antimicrobial and chemotactic activities of the hybrid resembled that of AvBD-6 and AvBD-12, respectively.While the net positive charge and charge distribution have a dominating effect on the antimicrobial potency of AvBDs, the three conserved disulfide bridges are essential to the chemotactic property and the maximum antimicrobial activity. Analogue AvBD-12A3 with a high net positive charge, a moderate degree of hydrophobicity and a CCR2-binding domain can serve as a template for the design of novel antimicrobial peptides with chemotactic property and salt resistance.The online version of this article (doi:10.1186/s12866-017-0959-9) contains supplementary material, which is available to authorized users. Rapid emergence of antimicrobial resistance poses a major global threat to public health and the economy , 2. ExceBeta-defensins are small, cationic, antimicrobial peptides found in different living organisms –9. TheseMost defensin peptides characterized to date have a net positive charge, ranging from +2 to +9, and hydrophobicity of approximately 30-50% . It has http://zhanglab.ccmb.med.umich.edu/I-TASSER). The distribution of positively charged amino acids were evaluated using PyMOL (https://www.pymol.org/). Group 1 analogues, including AvBD-12A1, A2 and A3 were linear peptides, in which the six cysteines (C1C2C3C4C5C6 or C5C12C17C27C34C35) were replaced with structurally similar amino acid residues  as follows: AvBD-12A1: A5A12A17A27A34A35, AvBD-12A2: S5S12S17A27A34A35, and AvBD-12A3: A5A12A17S27S34S35. Additional modifications were introduced to these analogues to alter peptide hydrophobicity and charge. In AvBD-12A1, the four negatively charged amino acid residues (D3D8E21E29) were replaced with one polar and three hydrophobic amino acid residues (H3V8L21I29). In AvBD-12A2 and AvBD-12A3, D3D8E21E29 were substituted with positively charged residues R3K8K21R29. Group 2 analogues, including AvBD-12A4, AvBD-12A5 and AvBD-12A6 had reduced number of disulfide bridges without any additional modifications. To remove disulfide bridges, the cysteine residues (C1C2C3C4C5C6 or C5C12C17C27C34C35) of AvBD-12 were replaced with isosteric α-aminobutyric acids  to create AvBD-12A4 (U5C12C17C27U34C35), A5 (U5U12C17U27U34C35), and A6 (U5U12U17U27U34U35). Group 3 included a single hybrid peptide, namely AvBD-12/6. This analogue was designed using the backbone of AvBD-12, in which the negatively charged amino acid residues (D3D8E21E29) of AvBD-12 were replaced with amino acids (H3Q8Y21S29) of AvBD-6 at the corresponding positions. The hydrophobicity and charge of AvBD analogues at neutral pH were calculated using Peptide 2.0 (http://peptide2.com) and Peptide property calculator , respectively.The three dimensional structures of AvBDs were predicted by using the I-TASSER program  .All peptides were custom synthesized using the standard solid phase 9-fluorenylmethoxycarbonyl (Fmoc) method and purified by reverse phase high performance liquid chromatography (RP-HPLC) . The analogues AvBD-12A4, −A5, AvBD-12/6, AvBD-6 and AvBD-12 with varying numbers of cysteine residues were subjected to oxidative folding as described previously . ElectroEscherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Salmonella enteric serovar Typhimurium (ATCC 14028) and Staphylococcus aureus (ATCC 29213) were used to assess the antimicrobial activity of AvBD analogues. All bacterial strains were grown on Luria-Bertani (LB) agar plates or Trypticase Soy Agar with 5% Sheep Blood  plates at 37 °C. Antimicrobial activity was determined by a colony counting assay [× 105 CFU/ml. Twenty-five microliters of bacterial suspension and 25 μl of AvBD analogue solution were mixed in the wells of a 96-well polypropylene microtiter plate . The final peptide concentrations were 2, 4, 8, 16, 32, 64 and 128 μg/ml. The minimal growth medium without AvBD peptide was included as a negative control. The bacterial-peptide mixtures were incubated at 37 °C for 2 h, ten-fold serially diluted and plated on LB agar plates. The numbers of bacteria colonies were enumerated after 16 h of incubation at 37 °C. Antimicrobial activity was expressed as percent of killing using the following formula: (CFUcontrol - CFUtreated) / CFUcontrol × 100%. To assess the resistance of AvBD analogues to sodium chloride (NaCl), antimicrobial assays were carried out in the presence of 5 mM, 50 mM, 100 mM or 150 mM NaCl. All assays were performed in triplicate.s ATCC 293 were usng assay . In brie5 CFU/ml. The plate was incubated at 37 °C for 24 h and the lowest concentration that completely prevented visible bacteria growth was recorded. To complement MIC-ls assays, the minimum bactericidal concentrations (MBC) were evaluated by sub-culturing the contents of the first two clear wells obtained in the MIC-ls assay onto LB agar plates. All assays were conducted in triplicate. The lowest peptide concentration inhibiting more than 99% of bacterial growth was defined as MBC-ls. AvBD analogues were regarded as bactericidal if the MBC was no more than four times the MIC [The minimum inhibitory concentrations (MIC) of AvBDs were determined according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) , 28. The the MIC .2. CHO-K1 cells were cultured in the same media without 2% chicken serum. For CCR2-transfected CHO-K1 cells, the medium was supplemented with 500 μg/ml G418 was added (Sigma-Aldrich) [2. The cell cytotoxicity was determined using the MTT -2, 5-diphenyltetrazolium bromide metabolic activity assay according to the manufacturer’s instruction (Thermo Fisher Scientific). Briefly, cells (5 × 103 cells/well) were seeded in 96-well tissue culture plates, incubated overnight and treated with AvBDs at concentrations of 4, 16, 64 and 256 μg/ml for 4, 12, 24 and 48 h at 37 °C. After treatment, 20 μl of 12 mM MTT solution was added to each well. The plate was incubated for 4 h and read at 540 nm. Viability was expressed as percentage of viable cells relative to the untreated control. The experiments were performed in triplicate.Chicken macrophage cell lines MQ-NCSU and HD11 were maintained in RPMI-1640 media supplemented with 10% fetal bovine serum (FBS), 2% chicken serum, 100 U/ml penicillin and 100 μg/ml streptomycin (Sigma-Aldrich) at 37 °C in humidified air with 5% COAldrich) . Murine Migration of JAWSII and CCR2-CHO-K1 cells in response to AvBD-12 analogues was determined using a 48-well microchemotaxis chamber technique as previously described . Chemotaet al. [S. Typhimurium was cultured in Mueller-Hinton (MH) broth to mid-log phase and harvested by centrifugation at 5000 g for 10 min. Cell pellets were washed twice with 10 mM PBS and resuspended at a final number of 108 CFU. The cell suspension was incubated with 1 × MIC-ls of AvBD-12A3, AvBD-12/6, wild-type AvBD-6 and AvBD-12 at 37 °C for 30 min. Bacterial pellets were fixed in 500 ml of 2.5% (v/v) glutaraldehyde in 0.2 M cacodylate buffer at 4 °C overnight, washed twice with 0.2 M cacodylate buffer and dehydrated through ethanol gradient  for 15 min in each gradient. The samples were transferred into a mixture  of ethanol and tertiary butanol and then pure tertiary butanol for 20 min each. After gold coating, the specimens were observed using a scanning electron microscope .SEM was performed according to the procedure described by Cobo et al. . S. Typhp < 0.05 level were considered statistically significant, and at p < 0.01 level were considered extremely significant.Data were presented as the means ± standard deviation (SD). Differences between groups were analyzed using the one-way analysis of variance (ANOVA) followed by Duncan’s test for multiple comparisons using software SPSS version 19.0 . Differences at 1C2C3C4C5C6 (or C5C12C17C27C34C35) by A5A12A17A27A34A35 (AvBD-12A1) not only eliminated the three disulfide bridges, but also elevated the hydrophobicity from 33% (AvBD-12) to 47%. Additional H3V8L21I29 for D3D8E21E29 substitutions further increased the hydrophobicity to 53% and the net positive charge from +1 (AvBD-12) to +5 (AvBD-12A1). Changes from C1C2C3C4C5C6 to S5S12S17A27A34A35 (AvBD-12A2) or to A5A12A17S27S34S35 (AvBD-12A3) and changes from D3D8E21E29 to R3K8K21R29 (AvBD-12A2 and A3) eliminated all three disulfide bridges and increased the peptide hydrophobicity from 33% to 40% and the net positive charge from +1 to +9. AvBD-12A4, A5, and A6 respectively lost disulfide bridge(s) C1–5; C1–5 and C2–4; C1–5, C2–4, and C3–6. C to U changes did not affect the peptide hydrophobicity and charge. The hybrid AvBD-12/6 with the backbone of AvBD-12 and the positively charged amino acids (H3Q8Y21S29) of AvBD-6 retained parent peptides’ hydrophobicity (33%) and an intermediate charge (+5), compared to AvBD-6 (+7) and AvBD-12 (+1). The sequence, charge, hydrophobicity and number of disulfide bridges of analogues and wild-type AvBD-12 and AvBD-6 were listed in Table Substitutions of CSuperimposition of the predicted three dimensional structures of AvBD-12 and the structure of human β-defensin 6 (hBD6) revealed a similar N-terminal α-helix and an adjacent β2-β3 loop, in addition to the conserved internal β-sheet domains Fig. . The α-hE. coli, S. Typhimurium, P. aeruginosa, and S. aureus . AvBD-12A2 and AvBD-12A3 which had identical charge and hydrophobicity but altered locations of alanine/serine residues exhibited different killing activities against E. coli or P. aeruginosa  than the parent peptide AvBD-12 in killing eus Fig. . At 16 μ1-C5 or C5-C34) was shown to have weaker action than AvBD-12 against S. Typhimurium (p < 0.05). Group 3 or the hybrid analogue, AvBD-12/6 with the backbone of AvBD-12 and positively charged amino acid residues of AvBD-6 exhibited similar killing activities to that of AvBD-6  for Next, the MICs of AvBD-12A3, the most potent analogue, and the parent AvBD-6 and AvBD-12 were evaluated under conditions outlined in CLSI guidelines , 28. HigE. coli and P. aeruginosa, but only 30% to 60% of killing activity against S. Typhimurium and S. aureus  and hydrophobicity (40%) than AvBD-12 Fig. . AvBD-12eus Fig. . AvBD-12eus Fig. .Fig. 6EfCell cytotoxicity of most potent analogue AvBD-12A3 (+9) and the hybrid analogue AvBD-12/6 (+5) was determined. Exposure of chicken macrophage cell lines HD11 and MQ-NCSU, murine dendritic cell line JAWSII and CHO-K1 cells to AvBDs at concentrations of 4, 16, 64, 256 μg/ml for 4, 12, 24, and 48 h did not affect cell variability. Data on the highest peptide concentration (256 μg/ml) at various exposure times were presented in Additional file p < 0.01, Fig. Group 1 analogues AvBD-12A1, AvBD-12A2 and AvBS-12A3 showed minimal chemotactic activity for CCR2-CHO cells Fig. . HoweverS. Typhimurium bacteria treated with AvBD-12A3  showed significant difference in antimicrobial and chemotactic activities. Structural analysis of AvBD-12A3 revealed an outward protrusion of R29 side chain and parallel twist F28 aromatic ring. We hypothesize that the outward protrusion of a positively charged residue and an adjacent aromatic ring enhances the interaction between AvBD-12A3 and microbial surface components or CCR2, thereby facilitating antimicrobial and chemotactic functions.To further understand the structure-activity relationship, we designed and evaluated seven synthetic analogues of AvBD-12. In the first group of analogues, disulfide bridges were removed by replacing cysteines with structurally similar residues  whereas peptide hydrophobicity and charge were increased by substituting negatively charged residues with hydrophobic (AvBD-12A1) or positively charged residues (AvBD-12A2 and A3). All members of the first group demonstrated stronger antimicrobial activity than their parent peptide AvBD-12, indicating that cysteine-free (linear) AvBDs with a high net positive charge and moderate hydrophobicity can be potent antimicrobial agents. Such linear peptides can be synthesized without oxidative folding which simplifies the production process and reduces cost. In the present study, anti-/ml Fig. . Similar1 and C4 essential to the formation of first and second disulfide bridges are located at the CCR2 binding center [1-C5 bridge was nearly inactive against S. Typhimurium. These results collectively suggest that all three disulfide bridges are needed in the natural form of AvBDs to maintain tertiary structural features critical to interacting with microbial surface components and CCRs on immune cells.To assess the role of disulfide bridges independent of charge and hydrophobicity, we replaced cysteine residues with isosteric α-aminobutyric acids  to create group 2 analogues. Our data indicated that missing even one conserved disulfide bridge resulted in a significant reduction in AvBD’s chemotactic activity. Elimination of two or three disulfide bridges completely abolished the chemotactic activity for both avian CCR2-positive cells and murine immature dendritic cells. It has been shown that Cg center . Thus suS. Typhimurium with AvBD-12A3 and AvBD-12/6, and wild-type AvBD-6 and AvBD-12 caused similar ultrastructural changes, including cell deformation and membrane damage. Giant cells were only observed among treatment groups, indicating membrane permeabilization is an essential step in the killing of microbes by AvBDs.Besides antimicrobial assays, SEM was performed to illustrate the killing mechanisms of AvBD-12 analogues. Treatment of . Typhimurium was still severely inhibited by physiological concentration of NaCl (150 mM), suggesting that different mechanisms are involved in killing different bacterial species.Salt sensitivity is a major obstacle to the application of β-defensins as chemotherapeutic agents. Different strategies have been explored to increase the resistance of beta-defensins to salts, such as N-terminal deletion , combiniS. aureus protease or cleaved by metalloprotease, gelatinase or cysteine protease produced by other bacterial species [In the present study, we also determined the minimum inhibitory concentrations (MICs) of AvBDs. Using the standard Muller Hinton II broth, the MICs of the parent AvBDs and the most potent analogue AvBD-12A3 were much higher than the MIC values obtained under the low-salt and low-nutrient condition. We hypothesize that interference of initial peptide-bacteria interactions by cationic salts as well as enzymatic degradation or modification of AvBDs during bacterial growth in a nutrient rich Mueller-Hinton broth might have contributed to the decreased antimicrobial activity. It has been shown that human cathelicidin LL-37 could be hydrolyzed by  species . Proteol species –45. FurtThe three conserved disulfide bridges maintaining the tertiary structure of natural AvBDs are required not only for the chemotactic activity, but also for maximum antimicrobial activity. AvBD-12A3 with increased net positive charge and a CCR2-binding domains  demonstrated potent antimicrobial activity and retained partial chemotactic property. Analogue AvBD-12A3 may serve as a template for the design of novel antimicrobial peptides as therapeutic agents for both avian and mammalian hosts.


We report the first case of a young patient who presented with the features of Horner's syndrome following a spinal extradural hematoma resulting from a ruptured arterio-venous malformation (AVM). Since there were features of early compressive myelopathy as well, urgent magnetic resonance imaging (MRI) scan of the spine revealed features suggestive of an extradural hematoma in the cervico-thoracic junction. The patient underwent an emergent laminectomy with an evacuation of the hematoma. The histological features were consistent with that of an AVM. The initial presentation of a ruptured spinal extra-dural arterio-venous malformation (AVM) as Horner’s syndrome in a young male has not been reported in the literature to date. Extradural spinal hematoma accounts for only 5% of all reported spinal AVM cases at the initial presentation .Here, we report the case of an extra-dural spinal hematoma resulting from a ruptured AVM in a young male patient. He presented with the features of Horner’s syndrome along with the presence of sensory dysesthesia along the C7 and T1 dermatomal distribution on his left arm. He also had findings suggestive of an early compressive myelopathy. He underwent emergent laminectomy with an evacuation of the hematoma following which he had a good neurological recovery. The histopathological report confirmed the diagnosis of an AVM.A 16-year-old male from Terathum, Nepal presented to our out-patient clinic with a history of a sudden onset of drooping of his left eye lid followed by an abnormal sensation along the medial aspect of his left arm and forearm that developed over the previous three days. He had mild pain in the nape of his neck while he was removing mud with a shovel preceding these symptoms. He did not report any loss of consciousness, weakness of his arms or legs, or any bladder or bowel incontinence. He had no other significant past medical or surgical illnesses. There was no history suggestive of any bleeding disorders and the blood investigation did not reveal coagulopathy.On neurological examination, the patient was conscious and oriented to time, place, and person. There was a mild drooping of his left eyelid with the presence of miosis on his left pupil Figure .There was sensory dysesthesia along the C7, C8, and T1 dermatomal distribution on his left arm. The motor power in his upper and lower limbs was normal. There was however, evidence of early myelopathy with regards to the presence of hypertonia in the muscles and increased deep tendon reflexes. The clinical localization and diagnosis was probably due to an acute onset of extra-dural compressive pathology in the C7 –T1 region. Immediate magnetic resonance imaging (MRI) scan of the spine revealed findings suggestive of an acute extra-dural hematoma in the C7-T1 region with lesion being hyper-intense in the T1 and hypo-intense in the T2 weighted images (Figure The patient was immediately taken up for a laminectomy and evacuation of the hematoma. Intra-operatively, there was the presence of multiple tangles of small vessels incorporating within the hematoma and arising from the nerve roots at the dural sleeves.Post-operatively, the patient made a gradual recovery with the normalization of the deep tendon reflexes and improvement in the eye droop. The histology report was suggestive of an AVM Figure . The patient has been on regular follow up in our clinic and has not developed any new symptoms.The patient’s presentation as an extra-dural hematoma following rupture is an uncommon entity with a reported incidence of only 5 % among all spinal AVM's .In a recWe report the first case of an extradural spinal AVM in the cervico-thoracic junction presenting as Horner’s syndrome in a young male following its rupture.Spinal AVM’s have been classified into various categories as per the distribution pattern of its feeding arteries and the draining veins .The management of spinal vascular malformations depends on various factors such as their mode of presentation, the duration of clinical symptoms in patients, their radiological sub-types, and the availability of resources and skilled manpower .Spinal AVM’s should always be kept as a differential diagnosis of a spinal hematoma in any cases presenting with myelopathy following a trivial injury and without any prior history of bleeding disorders. Early diagnosis and its emergent evacuation is the cornerstone in the management for a good outcome. It is always advisable to send the hematoma for further histopathologic study so as to not miss such entities behind the bleed.Oldfield and Doppman had classified spinal vascular malformations into extradural, glomus, juvenile, and peri-medullary fistulas. Spetzler and colleagues also re-emphasized the fact to include the extra-dural variants into the classification of spinal vascular lesions as these lesions have the tendency to cause myelopathy owing to compression from venous channels, medullary venous congestion, vascular steal phenomenon, or from a resultant hemorrhage .In such cases of extra-dural AVM’s, only surgical interruption of the arterio-venous shunt near the dural sleeves of the nerve is required for a good surgical outcome . A ruptured extradural AVM in the cervico-thoracic region can present initially as Horner's syndrome. Therefore, it is prudent to have early appropriate radio-imaging examinations followed by an emergent evacuation of the hematoma for a better functional outcome. It is also advisable to conduct a biopsy for the histological confirmation of occasional hidden entities such as AVM.