Screencasting for Libraries, was released in 2012 [Screencasting, defined as creating a video recording with or without audio of real-time actions and/or content on a computer screen, has been of interest to libraries for some time now. An excellent early guide by tech guru Greg Notess, There are many options for screencasting tools, both free platforms offering basic features and paid platforms with greater complexity and sophistication. Of the latter, Camtasia (a product of TechSmith) and Captivate (a product of Adobe) are the best-known. As these platforms each require a fairly substantial financial investment and a steeper learning curve , many screencasters are turning to free tools, which are evolving to add features to their basic versions. Some tools have come and gone: Screenr and Screentoaster are no longer available, and the very popular program Jing, while still available, has been bought by TechSmith and is now called TechSmith Capture. CloudApp is a well-reviewed option that has entered the scene more recently, but Screencast-o-Matic remains an excellent and user-friendly option. This review will examine its features, advantages, and disadvantages.One of the most important features of Screencast-o-Matic is its ease of use, especially if you are familiar with the basics of programs such as YouTube and Zoom. Many users can create a usable video from scratch within half an hour of first using the tool. The audience for Screencast-o-Matic includes anyone with some familiarity with online tools who needs to create content such as brief tutorials of processes, demonstrations of software, visual cues to navigating websites, etc.However, taking a step back, no tool is completely ideal for every user. It is important to evaluate why users want to use the tool and what type of product they hope to create. The list of questions below was developed by science librarian Olivia Bautista Sparks to assist with selecting screencasting software, and it appears here with answers for Screencast-o-Matic . These qEitherDoes the software require installation or is it browser-based? YesDoes the software record audio during screen capture? MP4, AVI, FLV, GIFWhat types of files are created? No, unless you want to save videos to an accountDoes the software require a log in? Fifteen minutes (basic version)What is the maximum recording length? Can save files, can host videos on Screencast-o-Matic siteWhat are the options for video hosting? Can you save your files and host it on your own server? Are your hosted files in the public stream? It is easy to record; yes, you can pauseHow accessible is the recording menu? Are you able to pause your recording? Yes, yesAre you able to edit or annotate your recording? Are you able to upload your screencast to online video streaming sites ? Yes, using quick shareAre useable URLs provided? Yes, after uploading video to Screencast-o-MaticAre the embed codes provided or easily accessible? Screencast-o-Matic does what many other programs do, which is capture a series of actions and/or images on a screen. Most importantly, however, it enables the user to get up to speed easily and quickly with a minimum of technical expertise and without needing to sign up for an account or download anything. This is important for minimizing privacy concerns, or if a user does not have administrative rights to their own computer.Making a video recording on Screencast-o-Matic is pretty much a matter of stopping and starting the process with controls that appear very similar to those on YouTube and other sites. Users can choose various options before recording, one of which is whether to capture content from the screen, webcam, or both. Once the video has been recorded, the user can either save it onto their own device in MP4, AVI, FLV, and/or GIF formats (there are apps for iOS and Android users) or directly upload it for sharing and hosting to the Screencast-o-Matic site (account required), YouTube, or Google Drive. While it has been mentioned several times that Screencast-o-Matic does not have a steep learning curve, that does not mean that there is no curve at all. Like any tool, it takes some getting used to. In addition, a disadvantage for learners is that the tool's website does not have an obvious search function. While it has extensive lists of tutorials, blog posts, and support documents, finding specific information can be challenging (this reviewer has ended up using Google's site search function too often).On the other hand, there is abundant training and support available in general. The Blog, Tutorials, and Support pages each have articles and videos (of course!) to get users up to speed. Blog topics include “How Two Teachers Used Screencasts to Transform Education” and “7 Easy Editing Tricks for Social Media Videos.” Tutorial topics include a series of basic and advanced tutorials on editing, uploading, and other subjects, as well as technical topics such as using green screens. Support topics address IT questions for which users would request IT help, such as configuration, firewalls, and plan features. Screencast-o-Matic also offers a ticketing option—if you cannot solve your problem, you can submit a ticket to their support team.Screencast-o-Matic works with Windows, Mac, and Linux operating systems.screencast-o-matic.com/integrations) lists a wide range of more than thirty programs with which it can integrate. For some programs, like PowerPoint, the integration does not add much; the instructions say, basically, to “make a video recording of your presentation … and share it.” But for others, like Zoom, the integration creates something that is more than the sum of its parts. In this case (if you have a paid account), you can import Zoom meeting recordings into Screencast-o-Matic and then edit them [Screencast-o-Matic's “Integrations” page  adds the abilities to perform basic video editing, record audio from the computer, import narration and music, use scripted recordings, draw, zoom and create screenshots, create speech-to-text captions, use a green screen filter, and more. The Premier version  adds a custom video player and controls, a stock library, the option to share and collaborate with video hosting, a branded ad-free site, and 100 GB bandwidth, as well as other features. Team Plans follow these two bands of added features, starting at (for 10 computers) $9.50/month for the Deluxe and $17.50/month for the Premier.An important question is where Screencast-o-Matic sits (or wants to sit) on the continuum of screencasting tools. As a high-functioning platform at an unbeatable price, Screencast-o-Matic is a major player at the lower end of cost and sophistication, but as users want to dive deeper into the full range of options for creating more refined products, they may want to transition into tools like Camtasia or Captivate, even considering the functionality of the added features of the paid versions of Screencast-o-Matic.In the end, Screencast-o-Matic is an excellent tool for creating screencasts of solid quality, with its paid versions offering even more options for increasing the customization and sophistication of its products. It is easy to use and learn, has good documentation and support in its tutorials and blog posts, and offers flexibility for saving and sharing videos. This reviewer would strongly recommend it for creating high-quality screencasts with little fuss and learning curve and at no cost.


In 2019, the European Parliament and the Council adopted Directive 2019/790 on copyright and related rights in the Digital Single Marketin part responsible for delaying a number of events specifically surrounding the transposition process, with the result of stalling it. Such events inter alia include the release of the Commission’s guidance on the application of Art. 17, one of the most complex and discussed provisions in the DSM Directive.Two things are certain in all this. The first is that most EU Member States failed to meet the June deadline. The Netherlands was the first country to transpose the Directive in full.consideration in order to decide disputes submitted to them, because of the indirect effect that non-binding law has. In any event, in accordance with settled case law, the Commission’s Art. 17 guidance will not confer rights on individuals, which the latter may rely upon before such courts and authorities.Grimaldi (C-322/18) the CJEU “has consistently insisted that Article 267 TFEU confers on the Court jurisdiction to give a preliminary ruling on both the validity and the interpretation of all acts of the institutions of the Union ‘without exception’”.9Between 15 October 2019 and 10 February 2020, the Commission organised and held six stakeholder dialogue meetings to receive views regarding the application of Art. 17, in particular the cooperation referred to in paragraph 4 therein. Following these meetings, in summer 2020 the Commission launched a public consultation based on a document that, whilst building on the discussions held, also presented the initial views of the Commission itself.YouTube (C-682/18) and Cyando (C-683/18): albeit that these referrals were not, nor could have been, on the DSM Directive, the relationship between Art. 3 of the InfoSoc Directiveinter alia guaranteed by Art. 11 of the EU Charter of Fundamental Rights.Besides the delayed Art. 17 guidance, further events which are due to have an impact on the DSM Directive and its national (transpositions and) applications are also two forthcoming CJEU decisions. The first is the  ruling in joined cases In all this, also the discussion surrounding further proposed EU legislation will have, without doubt, an influence on the application of the DSM Directive, notably – once again – its Art. 17. In late 2020, the Commission unveiled its Proposal for a Digital Services Act (DSA).before its adoption is a complex one. Some of its provisions were the subject of heated debates, and their resulting wording owes to political and legal compromise. This, in turn, means that they are also complex provisions and that the story of the DSM Directive after its adoption will by no means be a straightforward one. The events described above are probably just a small glimpse into the future: litigation concerning the national provisions by which Member States have transposed or will transpose the DSM Directive is around the corner, and so are CJEU referrals from national courts. This is not a bad thing, nor is it something that casts shadows on the merits and quality of the EU copyright law-making process. Rather, it is testimony to the complexity of copyright, the variety of (contrasting) interests underlying policy- and law-making in this area, and the growing realisation that the incremental dialogue between legislature and courts – on both the EU and national level – is both unavoidable and welcome. So, no, things will not get any easier. Hopefully, however, they will become clearer ... in the end.In sum, and to conclude: the story of the DSM Directive


A man in his thirties was suspected of committing a sexual offense against a young girl. A video on his mobile telephone provided the only evidence. Photographs obtained from the video showed male genitalia in two views, with the penis in both views exhibiting unique pigmentation. We appraised this case with the cooperation of dermatologists, who diagnosed the pigmentation as male genital melanosis, a relatively rare disease, which matched that on the suspected perpetrator’s penis. Photographs obtained from the video were thus decisive evidence of sexual offense and identified the perpetrator. Establishing identity is a fundamental role of a forensic examination, with personal characteristics such as hair color, surgical scars, and tattoos serving as clues to the identification . In addiA man in his early thirties was suspected to have committed a sexual offense against a young girl, although he denied the accusation. The police found a video on his mobile phone in which the crime was recorded. Unfortunately, the video showed only the attacker’s genitals Fig. a. The suDuring the interrogation, we had obtained a screen capture of the video, and photographs were prepared of the pigmented penis. The dermatologists identified multiple sporadic macules with no scales, irregular borders, and varying shades of gray to black that were slightly dense at the tip of the glans penis. A gray-to-black single patch was also present in the distal portion of the prepuce Figs.  & 2. TheGenital melanosis in men is relatively rare, with an estimated incidence of 0.011% among dermatologic patients . BecauseThe decisive factor that made the suspect in this case admit guilt was not only the homology of penile pigmentation but also anxiety. In clinical practice, pigmented lesions of the genitalia always require exclusion of malignancy, represented by melanoma. Genital melanoma accounts for 8–10% of all genital malignancies and is the second most common genital cancer after squamous cell carcinoma , 6. AlthCharacteristic penile skin eruptions in the video image in this suspect allowed us to establish his identify and facilitate his confession. Previously, the distribution patterns of melanocytic nevi have been successfully applied to assess individuals via forensic image comparisons . Needles


To assess the sensitivity and specificity of common carotid ultrasound method for carotid near-occlusion diagnosis.Five hundred forty-eight patients examined with both ultrasound and CTA within 30 days of each other were analyzed. CTA graded by near-occlusion experts was used as reference standard. Low flow velocity, unusual findings, and commonly used flow velocity parameters were analyzed.n = 13, 13%), conventional ≥50% stenosis  and < 50% stenosis . No velocity parameter or combination of parameters could identify the 65 near-occlusions mistaken for conventional ≥50% stenoses with >75% sensitivity and specificity.One hundred three near-occlusions, 272 conventional ≥50% stenosis, 162 <50% stenosis, and 11 occlusions were included. Carotid ultrasound was 22%  sensitive and 99%  specific for near-occlusion diagnosis. Near-occlusions overlooked on ultrasound were found misdiagnosed as occlusions (Near-occlusion is difficult to diagnose with commonly used carotid ultrasound methods. Improved carotid ultrasound methods are needed if ultrasound is to retain its position as sole preoperative modality. Carotid near-occlusion is a variant of severe carotid stenosis where, in contrast to conventional ≥50% carotid stenosis, the stenosis causes the artery to reduce in size (“collapse”) distal to the stenosis –3. The csuspected near-occlusion) and was based on several databases [Despite a large number of studies of carotid stenosis, the approach to diagnose near-occlusion with ultrasound remains unclear –11. WorlThe purpose of this study was to assess if commonly used ultrasound findings can be used to diagnose carotid near-occlusion.We evaluated a dedicated retrospective near-occlusion research cohort from a single center including all cases that underwent CTA and ultrasound within 30 days of each other between January 2010 and December 2014. Cases underwent either ultrasound, CTA, or both based on clinical decisions, increasingly using both as routine. All ultrasound examinations were performed within the Department of Clinical Physiology at the University Hospital of Northern Sweden. Ultrasound exams of poor quality  were excluded. Cases with revascularization between exams were excluded. CTAs were performed at or sent to the Department of Radiology at the University Hospital of Northern Sweden. CTAs were performed as part of clinical routine using various machines and various protocols at the University Hospital of Northern Sweden and 11 referring hospitals.Near-occlusion was diagnosed when the distal extracranial ICA was reduced in size secondary to a proximal stenosis. Luminal reduction had to be visible as an extracranial ICA asymmetry . DiagnosThe 4403 CTA exams (4042 patients) performed during the study period were re-evaluated by one observer  . Twenty-likely near-occlusion . For flow velocity analyses, likely near-occlusions were arbitrarily assigned stenosis PSV 10 cm/s and EDV 3 cm/s as there was an assumed flow, not zero flow. Two observers (IBJ and LL) retrospectively extracted PSV and end-diastolic velocity (EDV) data from stored images between them (no double extraction) for velocity analyses. Reported diagnosis, including cases with low PSV, was diagnosed as near-occlusion or <50% stenosis, and any mention of unusual findings that might suggest near-occlusion despite high stenosis PSV  was noted by one observer (EJ). Suspected near-occlusion were cases where near-occlusion was at least suggested in the report despite high PSV, regardless of rationale. All ultrasound data extraction was blinded to CTA findings.Several experienced sonographers who were blinded to the CTA results performed the carotid ultrasound examinations as part of clinical routine. Specialists in clinical physiology  reviewed the images live and took additional images when needed. The same specialist signed the report. iU22 , LogiqE9 , and S2000 and Acuson Sequoia  systems were used. A standard protocol was used, including visualization of the common carotid artery (CCA), ICA, and ECA in transverse and sagittal section, with and without color doppler. Pulsed doppler velocity image was routinely gathered in mid CCA and at the point of maximum stenosis, but not distal to the stenosis. Stenosis velocity was the main feature used for stenosis grading, not diameter measurement of the stenosis. Cases with no measurable flow were categorized as occlusion. Cases without detectable flow through the stenosis but with flow signal detectable beyond the stenosis with an ICA flow profile were categorized as low PSV” is not well defined in the literature, we used both a Low PSV and intermediate PSV group in order to present as much data as possible. As low PSV should be specific for near-occlusion, to define it as lower than what constitutes a ≥50% stenosis is reasonable. To reproduce the methods of Khangure et al., “Low PSV” was defined as <125 cm/s, in turn based on that ≥125 cm/s is the threshold for ≥50% stenosis in two international consensus criteria [High PSV” was defined as ≥145 cm/s as this was the locally used threshold defined for ≥50% stenosis based on published criteria [Intermediate PSV.” The reported diagnosis was used to distinguish between <50% stenosis and near-occlusions among cases with low and intermediate PSV. To combine all approaches, “Any indication of near-occlusion” was defined as the combination of suspected near-occlusion, intermediate PSV, low PSV, and likely near-occlusion. Cases diagnosed as <50% stenosis in the ultrasound report was not considered to have any indication of near-occlusion.Since a threshold for “criteria , 15. “Hicriteria . The subPulsatility index (PI) was calculated as (PSV-EDV)/mean velocity, where mean velocity was calculated as EDV+(PSV-EDV)/3 . PSV andAny indication of near-occlusion on ultrasound was the main ultrasound outcome. Analyses of flow velocities were performed mainly to assess if flow velocity could be diagnostically useful among cases with high PSV without any indication of near-occlusion, but also to present flow velocities in all near-occlusions. Cases diagnosed as occlusion on ultrasound were excluded from flow velocity analyses.The side with the most relevant finding was analyzed. χ2-test, t-test, and ANOVA using REGW-Q post hoc test, as specified. Receiver operating characteristic was used, analyzing area under the curve (AUC); diagnostic thresholds were set for maximal Youden index (where sum of sensitivity and specificity is maximum) and for maximal Hirsch-index , calculating resulting sensitivity, specificity, and positive and negative predictive values. We assessed all 28 possible combinations of two velocity parameters: For each combination, we first assessed a scatterplot to determine the reasonable range of thresholds, if values above or below the thresholds should indicate near-occlusion, and if “and” or “and/or” type of combination should be used. Then, all possible combinations of thresholds within the reasonable ranges were assessed to determine which combination produced the highest Youden index and H-index. p < 0.05 was pre-specified as border for statistical significance. SPSS 24.0 and Microsoft Excel were used in the calculations.We used mean, standard deviation (SD), 95% confidence intervals (95%CI), 2-sided Five hundred forty-eight patients were included Fig. . Mean agany indication of near-occlusion, more often among those with full collapse  than those without full collapse   (Table intermediate PSV (but none with low PSV) and were mistaken for <50% stenosis in the ultrasound report. Near-occlusions with full collapse were more often mistaken for occlusion than near-occlusions without full collapse . There were 3 false positive near-occlusions on ultrasound, 1 erroneously suspected near-occlusion that was a 54% stenosis on CTA and 2 likely near-occlusion that were occlusions on CTA. No case with conventional stenosis and low or intermediate PSV was mistaken for near-occlusion. Thus, any indication of near-occlusion was >99% specific . When only cases with ≤7 days between ultrasound and CTA were considered, the sensitivity  and specificity  of ultrasound was similar to the outcome of the entire cohort.Twenty-two percent  of near-occlusions had On group level, near-occlusions had higher mean stenosis PSV, stenosis EDV, PSV ratio and EDV ratio, and lower CCA PSV and CCA EDV than conventional ≥50% stenosis Table . When onBlinded inter-rater reliability for near-occlusion diagnosis on CTA was good: kappa 0.80 (95%CI 0.75–0.84). Intra-rater reliability was kappa 0.75 (95%CI 0.60–0.90) and 0.88 (95%CI 0.76–0.99) for each reviewer.The main finding of this study was that most (63%) near-occlusions have high stenosis velocities without any clear difference from conventional stenosis in other commonly used parameters. Almost all commonly used velocity parameters were significantly higher or lower in this high-velocity near-occlusion compared with conventional ≥50% stenosis on group level. However, considerable overlap resulted in that no commonly used velocity parameters had >75% sensitivity and specificity, alone or in combination.Near-occlusion is an angiographic diagnosis defined by artery size reduction beyond a severe stenosis –3. Extenany indication of near-occlusion approach (22%) than Khangure et al. (15%) [low stenosis PSV (<125 cm/s) and was unclear about how likely near-occlusions were analyzed [suspected near-occlusion and intermediate PSV subset of any indication of near-occlusion. However, similar to Khangure et al., we found that no velocity parameter in the stenosis or CCA , alone or in combination, could differentiate between conventional ≥50% stenosis and the remaining near-occlusions with both sufficient sensitivity and specificity [With the expanded definition of near-occlusion, the sensitivity of commonly used ultrasound parameters for near-occlusion was low, but specificity was high, both in the current study and in Khangure et al., that also used this expanded definition . Similarl. (15%) . Khanguranalyzed ; the difcificity . As manysuspected near-occlusions were not pre-specified categories, hence not systematically used in our entire cohort, some with similar findings might have been missed. All these findings have been reported previously [It remains unclear how to best detect near-occlusion on carotid ultrasound, although it is certain that improvements are needed. First, it is unclear what the best threshold for a “low stenosis velocity” should be. A relevant factor is that cases below this velocity threshold will be diagnosed as either near-occlusions or <50% stenosis based on visual inspection of the stenosis severity. We found that three cases were misclassified on such visual inspection in routine practice, two near-occlusions as <50% stenosis and one 54% stenosis as near-occlusion, highlighting that this approach is not without problems. Similar misdiagnosis by interpreting near-occlusion with low flow findings as <50% stenosis has been reported . With theviously , 9, 18, eviously , 8. Howeeviously . Also, ueviously . Thus, wUltrasound as the sole preoperative modality is accepted or recommended in guidelines , 5, whicStrengths of the study are relatively large size, dedicated near-occlusion data collection, and use of same interpretation approach and image interpreter for the angiographic comparison as the pooled analysis of the NASCET and ECST trials . A limitNear-occlusion is difficult to diagnose with commonly used carotid ultrasound methods, foremost lacking in sensitivity. Improved carotid ultrasound methods are needed if ultrasound is to retain its position as sole preoperative modality.


The system was run for 2 years to study climate‐change effects on epiphytic bryophytes, but is also deemed suitable to study other understorey plants. Warm air and CO2 addition were applied in 1.6‐m‐tall, 1.2‐m‐diameter hexagonal open‐top chambers and the microclimate in the chambers compared to outside air. Warming was regulated with a feedback system while CO2 addition was fixed. The setup successfully heated the air by 2.8 K and increased CO2 by 250 ppm on average, with +3 K and +300 ppm as the targets. Variation was high, especially due to technical breakdowns, but not biased to times of the day or year. In the warming treatment, absolute humidity slightly increased but relative humidity dropped by between 6% and 15% (and the vapor pressure deficit increased) compared to ambient, depending on the level of warming achieved in each chamber. Compared to other heating systems, the chambers provide a realistic warming and CO2 treatment, but moistening the incoming air would be needed to avoid drying as a confounding factor. The method is preferable over infrared heating in the radiation‐poor forest understorey, particularly when combined with CO2 fertilization. It is suitable for plant‐level studies, but ecosystem‐level studies in forests may require chamber‐less approaches like infrared heating and free‐air CO2 enrichment. By presenting the advantages and limitations of our approach, we aim to facilitate further climate‐change experiments in tropical forests, which are urgently needed to understand the processes determining future element fluxes and biodiversity changes in these ecosystems.Future climate‐change effects on plant growth are most effectively studied using microclimate‐manipulation experiments, the design of which has seen much advance in recent years. For tropical forests, however, such experiments are particularly hard to install and have hence not been widely used. We present a system of active heating and CO 2 enrichment in situ in tropical rainforests using open‐top chambers and forced‐air warming. The system is suitable for treating shrubs, saplings, and epiphytes, while ecosystem‐level studies may need infrared heating and free‐air CO2 enrichment. Developing in situ experiments in rainforests is urgently needed to help understand the response of these ecosystems to global change.We introduce an effective experimental system for studying plant responses to warming and CO We asked how warming and increased atmospheric CO2 might interact to affect bryophyte carbon balances. In this shaded environment, it is not possible to achieve heating using passive OTCs. Therefore, the OTCs were actively heated, combined with a CO2 fertilization system in part of the chambers. This system, although here used for studying understorey epiphytes, also holds promise for the study of other co‐occurring plants like tree or liana seedlings and shrubs. The warming design is based on a system used by Cheesman and Winter  in the rainforest understorey of La Selva Biological Station, Costa Rica.To facilitate a wider application of climate‐change experiments in tropical rainforests, we here present the technical details, production guidelines, and effectiveness of a heating and COd Winter  for tree22.1The experiment was installed at the OTS  biological station La Selva, in northwest Costa Rica , with a typical tropical wet lowland forest climate. The annual mean temperature is 26.3°C and temperatures vary between ca. 20 and 30°C all year , which was set to the optimal pulse length and interval between pulses based on manual CO2 measurements before the start of the experiment  installed for 3–5 h  with no persons near, to avoid influencing the reading through breathing. CO2 was supplied from 50‐lb gas bottles (23 kg CO2 when full), with five bottles in use simultaneously for the 10 CO2‐enriched chambers. These bottles had to be exchanged approximately every 7–10 days, thus posing quite high operational costs. The walls of the chambers became covered in algae relatively fast and were cleaned every 6 months to reduce the difference in light conditions.All electronic regulators and controls were designed, built, and tested at the electronics workshop of the University of Oldenburg  and at paired outside reference points for the duration of the experiment  using standalone dataloggers with a resolution of 0.01 K and 0.01% RH and an accuracy of <0.05 K and 2% RH . The outside reference points started out with n = 10 but were reduced to 8 or 9 as loggers failed temporarily or permanently. When less than 10 loggers were measuring outside conditions, the chamber data were paired  with data from the nearest reference point. We also recorded temperature and RH in three controls and two CO2 chambers from February to August 2018, to control for chamber effects. As more loggers were thus needed in the chambers, outside reference points, which showed very similar temperature patterns among them, were then reduced to four, and further reduced to a minimum of two after more loggers broke down. Data from each chamber were now paired with data from the nearest of these few outside measurement points. Additionally, five chambers and five ambient plots without chambers were equipped with sensors for leaf wetness , wind , photosynthetically active radiation , global radiation , and rain , registering microclimate every 15 min by Hobo Micro Stations .We recorded air temperature and relative humidity (RH) in paired measurements inside the heated chambers  to avoid missing effects due to the low replication of sensors. We here report only the microclimatic effects of the setup, while the biological, bryophyte‐specific results will be reported elsewhere. We use °C for temperature and K for temperature differences. All plotting and analyses were done in R, version 4.02  using paired 33.1p < .05, Table The control chambers did not differ in mean temperature from the outside air, with, on average, 24.1°C (± 0.2°C between plots) outside and 24.2°C (± 0.4°C between chambers) inside Table . In the p < .05) in the chambers than outside in the late afternoon and early evening (4–9 p.m.), and also in the early morning (6–7 a.m.), by about 10%–15%  and leaf wetness were very similar between outside air and control chambers, with some differences only in the drier season Figure  and A8. % Figure . CompariWind speeds were always very low, mostly 0, both inside and outside of the chambers. Rain, or rather, throughfall amounts were spatially very variable with no reason to expect a bias related to the chambers. As the plastic foil used had a light transmission <100% and was covered to various degrees in algae through time, we expected a corresponding decrease in diffuse radiation. However, this difference was indistinguishable from the high background variability in light conditions in the forest understorey: PAR did not differ significantly between inside control chambers and outside overall Table , while f3.2t‐test, t = 10.2, df = 9, p < .001, Table Temperature increased significantly in all heated chambers, on average by 1.7 to 3.8 K, depending on the chamber  was most frequently higher by about 1.5 hPa (mostly between 0 and +2.5 hPa) in the heated chambers than outside Figures , A15. HoThe reduction in RH was most frequent either around 0 or above 4%, with a dip in between these values Figure . This ph3.42 fertilization, the mean CO2 level was considerably and significantly higher than that of the outside air, by between 131 and 402 ppm on average, depending on the chamber  = 5.51, p < .05). This can probably be explained by the accelerated air renewal in the heated chambers due to the warm air flowing out of the chamber faster than the air at ambient temperature. This effect could not be totally countered by the higher CO2 addition in the heated chambers. Variation between individual chambers could have been caused by differences in the output pressure of the CO2 pressure regulators or different resistances in the paths from the gas bottles to the chambers, and by the chambers trapping CO2 naturally produced by respiration processes.In the chambers subjected to CO42 concentrations on plants under field conditions in a tropical rainforest. The chambers themselves had a minimal effect on microclimatic conditions while the heating and CO2 treatments were very effective. The main undesired effect was a decrease in relative humidity associated with warming. This decrease is due to basic biophysical laws and cannot be avoided unless moisture is added artificially, which would greatly increase the complexity of the experimental setup. Whether the effects on the experimental outcomes are a problem needs to be evaluated for each research question individually. What is clear is that it does not fully reflect the effect of global warming on air humidity in the rainforest understorey. Even though the air over the continents might become drier under global warming  based on infrared heating  roof to effectively contain both the heat and CO2. Therefore, the choice of a warming and CO2 fertilization method depends not only on the processes studied but also strongly on the scale of interest. Our chambers are appropriate in small plots (up to a few m in diameter) and infrared heating with FACE in larger plots.An advantage of the infrared warming system used by Kimball et al.  is the a52‐fertilizing tropical understorey epiphytes or tree seedlings by leading warmed air and CO2 into open‐top chambers is a viable method to study climate‐change effects on plants in tropical rainforest understoreys. Control chambers had a minimal effect on microclimatic conditions, but with heating the relative humidity dropped. Since under natural climate warming understorey air humidity will probably remain high, we recommend adding a humidifier to the warmed air stream in future set ups to avoid changes in humidity as a confounding factor. For larger‐scales studies, which address ecosystem‐ rather than plant‐level processes, infrared heating combined with free‐air CO2 enrichment may provide a good alternative. However, in the rainforest understorey, which naturally has very low radiation levels, heated chambers offer clear advantages over infrared heating, providing a higher realism while hardly suffering from microclimatic chamber effects.Actively heating and CONone declared.Maaike Y. Bader: Conceptualization ; Formal analysis (supporting); Funding acquisition ; Methodology ; Project administration ; Supervision ; Visualization (supporting); Writing – original draft (lead); Writing – review & editing . Elodie Moureau: Data curation (lead); Formal analysis ; Investigation ; Project administration (supporting); Visualization ; Writing – original draft (supporting); Writing – review & editing (supporting). Nada Nikolić: Data curation (supporting); Formal analysis ; Investigation ; Validation (lead); Visualization (lead); Writing – review & editing (supporting). Thomas Madena: Methodology ; Validation (supporting); Writing – review & editing (supporting). Nils Koehn: Methodology . Gerhard Zotz: Conceptualization ; Funding acquisition ; Methodology ; Project administration ; Supervision ; Writing – review & editing .Appendix S1Click here for additional data file.


Electric Network Frequency (ENF) is embedded in multimedia recordings if the recordings are captured with a device connected to power mains or placed near the power mains. It is exploited as a tool for multimedia authentication. ENF fluctuates stochastically around its nominal frequency at  The vast amount of information contained in multimedia content, i.e., audio, image, and video recordings, has prompted perpetrators to commit forgery attacks distorting the digital content. Digital forensics advancements have experienced an exponential growth in the last decades, as digital manipulation methods are constantly evolving and affecting various aspects of social and economic life. To this end, emphasis has been put on advancing emerging technologies in the field of digital forensics, which can efficiently verify the authenticity of multimedia content and cope with multimedia forgeries. A comprehensive survey of image forensics techniques can be found in .In recent years, the Electric Network Frequency (ENF) has been employed as a tool in forensic applications. The ENF is a time-varying signal, which fluctuates around its nominal frequency, i.e., 50 Hz in Europe and 60 Hz in the United States. These fluctuations are due to the instantaneous load differences of the power network . They exhibit an identical trend within the same interconnected network. The ENF is a non-periodic signal, which can act as a fingerprint for digital forensics applications . It can To begin with, let us briefly survey ENF estimation in audio recordings, because the same ENF estimation methods are also applied to a one-dimensional (1D) time-series extracted from video recordings. A comprehensive study addressing the ENF detection problem was presented in , where mThe ENF can also be exploited to detect tampering in multimedia recordings. An edit detection approach taking advantage of the time-varying nature of ENF was proposed in . MultimeIn , it was Although significant attention has been paid to ENF estimation in audio recordings, it was found that the ENF can also be traced in video recordings. The ENF can be estimated in videos captured under the illumination of fluorescent bulbs in indoor environments . ENF varIn this paper, inspired by , an autoThe remainder of the paper is organized as follows. The ENF was initially introduced by C. Grigoras ,42 to atThe ENF is a non-periodic signal randomly fluctuating around the fundamental frequency.ENF fluctuations are identical within the same interconnected network.The ENF signal can also be found in higher harmonics .The most remarkable properties of the ENF signal are summarized as follows:Many approaches have been proposed to efficiently estimate ENF depending on the particularities of each recording.f is the fluctuating frequency representing the ENF component, A is the signal magnitude, and The ENF is embedded in the electric light signal. Assuming stationarity within short-time segments of the signal, the ENF is modeled asposed in .It has been shown recently that ENF traces can be embedded in video recordings due to light intensity variations. Such recordings are captured in the presence of fluorescent light or the light emitted by incandescent bulbs . The lig follows :(2)fE=|fV overlapping segments of L samples size. Each segment is shifted by S s from its immediate predecessor and is multiplied by an L-size rectangular window. Any temporal window can be employed in the pre-processing procedure. Afterward, the prevalent frequency of each segment is estimated by spectral estimation. Frequently, a quadratic interpolation is used to overcome the interference that hinders the entire procedure and results in more precise ENF estimation [The ENF estimation procedure in video recordings differs slightly from that employed in audio ones. The difference is in the pre-processing stage. Two cases are examined depending on whether the video recordings are static or non-static. Regarding static videos, the state-of-the-art  suggests97 Hz in . The bantimation . Subsequtimation ,9. Here,N regions with similar characteristics in the first frame of a video recording. Afterward, the mean intensity values Here, a video ENF estimation approach for static and non-static video recordings is proposed. It is based on the SLIC algorithm for image segmentation. The SLIC algorithm generates superpixels, which are regions of similar characteristics. The idea behind the proposed approach is that in regions having high luminance levels and not hindered by shadows or dark areas, light source variations can easily be detected, and thus, the ENF signal can be estimated more accurately. The first step of the proposed approach generates In the next step, the generated regions from the first frame are located in all d, as in . In thist, will be referred to as samples.A non-parametric, namely the STFT, and a parametric method, i.e., the Estimation by Rotational Invariant Techniques (ESPRIT), were employed for ENF estimation. Hereafter, the frames, indexed by L, lth segment, where The STFT is one of the most common methods in time-frequency analysis of signals. Assuming stationary within the short-time segments of the signal, the Discrete-Time Fourier transform is computed for each time segment :(4)Xl(ω)ESPRIT is also employed to estimate the ENF signal. Let W principal eigenvectors of Let atrix ϕ^ :(7)ϕ^=.The estimation of the ENF signal is significantly affected by the nature of video recordings. In static videos, ENF presence is not affected and, thus, estimation accuracy is much higher than that in non-static videos. There, continuous motion hinders ENF estimation accuracy. Many approaches aim at overcoming this difficulty. For this reason, the state-of-the-art approach for ENF estimation in video , which eSix different video recordings were recorded in Vigo, Spain, at a nominal ENF 50 Hz. Two different cameras were employed, namely, a GOPRO Hero 4 Black and an NK AC3061-4KN without an anti-flicker filter [Recording N average intensity values within the generated regions in each frame. All approaches were implemented in MATLAB 2016a. A 64-bit operating system with an Intel(R) Core(TM) iThe approach detailed in D, as depicted in The ESPRIT method was tested for ENF estimation in he MUSIC  where thhe MUSIC  was usedethod in . The comhe MUSIC  requiredThe static recording he MUSIC  resultedethod in  w.r.t. she MUSIC  one was The STFT method was employed for ENF estimation. The non-static video Video Similarly to video In order to assess whether the improvements in MCC of the proposed approach, employing SLIC and either STFT or ESPRIT against the MUSIC  is statiz transformation [For each video recording, the MCCs of the proposed approach and the MUSIC  undergo ormation :(10)z=0.K denotes the number of ENF samples. The test statistic K.The test statistic is given by:It is checked whether the test statistic he MUSIC  for eachIn all cases in he MUSIC .ENF estimation in static and non-static videos is a non-trivial task especially for complex environments comprising different objects, textures, and moving people. A novel automated approach has been proposed for ENF estimation in static and non-static videos recorded with CCD sensors. It is based on the SLIC algorithm for the generation of regions that share similar characteristics, especially luminance, where ENF variations can be precisely revealed. It has been demonstrated that the proposed approach, which applies either STFT or ESPRIT to a time-series created after SLIC, performs better than the MUSIC  in ENF eIn this work, we have explored multiple videos recorded by a fixed camera. A scenario with a moving camera would possibly raise additional difficulties in finding areas of similar characteristics, which are employed in the proposed approach. Consequently, difficulties in accurately estimating the ENF estimate would be anticipated. In addition, although the recordings were of escalating difficulty, there was no more than one person present in the scene. It is difficult to predict whether the proposed approach would perform equally well in an unconstrained environment with a moving camera and scenes with many moving persons.Future work will aim to extend this work by considering recordings that are captured by the rolling shutter mechanism of CMOS cameras. We are also interested in ENF estimation, when non-static cameras are employed. The latter scenario is very common in real-life applications due to the widespread use of mobile phones. Another challenging research direction is ENF estimation when multiple persons are recorded in the video.


Compendium of Materia Medica  comprise 80% of the composition of pig bile . An intea Medica . Recentla Medica  and alsoa Medica . Althougin vivo experiment was done using pigs. Three groups of pigs were fed GW4064, an FXR agonist that caused significant suppression of HCA species production, along with 30% increase in blood glucose levels and 69% decrease in blood glucagon-like peptide-1 (GLP-1) levels. When HCA species were administered, the blood glucose levels decreased and circulating GLP-1 increased, suggesting that glucose homeostasis and GLP-1 secretion were regulated by HCA species. Further in vivo testing was then done in two diabetic mouse models. HCA species administration to the mice caused the most significant lowering of blood glucose and the most improved glucose tolerance results compared to metformin at a dose 2-fold higher than HCA and to tauroursodeoxycholic acid (TUDCA). Circulating GLP-1 levels were also significantly increased in the HCA group.The first in vitro studies of the effects of HCA species were performed using the enteroendocrine L-cell lines, STC-1 and NCI-H716. Based on previous studies, which showed that BAs could induce GLP-1 release within 1–2 h  accumulation mediated by activation of TGR5 and also the effects of FXR agonists and HCA species (FXR antagonist) on the expression of the downstream FXR target, small heterodimer partner (SHP), and on GLP-1 secretion. These experiments are further discussed and diagrammatically illustrated in in vivo by comparing the effects of HCA species administrated to TGR5–/– and TGR5+/+ mice. Finally, a cohort of 55 participants comprised of 30 healthy, 18 pre-diabetic, and 17 newly diagnosed diabetic individuals were given an oral glucose tolerance test. Results revealed that GLP-1 secretion was much higher in the healthy group and that HCA species were inversely correlated with fasting and post-glucose load levels.The next set of Ruminococcus productis together with an unknown gram-positive rod called hyodeoxycholic acid-1 (HDCA-1) in the production of HCA species via bacterial biotransformation of β-muricholic acid (Although strong evidence was presented for the mechanism of action of HCA species in preventing or ameliorating diabetes, there are many unanswered questions that remain. The first fundamental question is how pigs developed the capability of producing HCA species in such large quantities. Previous studies have implicated gut microbiota such as lic acid . Other rlic acid  and convlic acid . Due to


Medical dispatchers have limited information to assess the appropriate emergency response when citizens call the emergency number. We explored whether live video from bystanders’ smartphones changed emergency response and was beneficial for the dispatcher and caller.From June 2019 to February 2020, all medical dispatchers could add live video to the emergency calls at Copenhagen Emergency Medical Services, Denmark. Live video was established with a text message link sent to the caller’s smartphone using GoodSAM®. To avoid delayed emergency response if the video transmission failed, the medical dispatcher had to determine the emergency response before adding live video to the call. We conducted a cohort study with a historical reference group. Emergency response and cause of the call were registered within the dispatch system. After each video, the dispatcher and caller were given a questionnaire about their experience.Adding live video succeeded in 838 emergencies (82.2% of attempted video transmissions) and follow-up was possible in 700 emergency calls. The dispatchers’ assessment of the patients’ condition changed in 51.1% of the calls , resulting in changed emergency response in 27.5% of the cases after receiving the video  compared to calls without video. Video was added more frequently in cases with sick children or unconscious patients compared with normal emergency calls. The dispatcher recognized other or different disease/trauma in 9.9% and found that patient care, such as the quality of cardiopulmonary resuscitation, obstructed airway or position of the patient, improved in 28.4% of the emergencies. Only 111 callers returned the questionnaire, 97.3% of whom felt that live video should be implemented.It is technically feasible to add live video to emergency calls. The medical dispatcher’s perception of the patient changed in about half of cases. The odds for changing emergency response were 58% higher when video was added to the call. However, use of live video is challenging with the existing dispatch protocols, and further implementation science is necessary.The online version contains supplementary material available at 10.1186/s12873-021-00493-5. When citizens experience a medical emergency and call for help, they contact an emergency medical dispatcher who can guide in first aid, including cardiopulmonary resuscitation , at the Our aim was to assess feasibility and dispatchers’ perceptions and response after adding live video from bystanders in emergency calls at Copenhagen Emergency Medical Services (EMS), Denmark. Our primary outcome was a change in the dispatchers’ emergency response after adding live video to the emergency call, and secondary outcomes included changed assessment of the patient by the dispatcher and whether live video was beneficial for the dispatcher and the caller.2. In case of an emergency, there is a single emergency phone number (112) to a call centre that identifies the need for police, fire or medical assistance. If the problem is medical, the caller is re-directed to the EMS, where medical dispatchers answer, process, and respond to the call by activating an EMS response and delivering medical advice [The study was conducted at Copenhagen EMS, which covers a population of approximately 1.84 million people and an area of 2559 kml advice . The medl advice , which il advice .From June 2019 until February 2020, all medical dispatchers at Copenhagen EMS could add live video to the emergency call , Unite Kingdom [The technical solution was provided by GoodSAM Instant-on-scene .All changes in emergency response including allocation of staff were included in the primary analysis. Secondly, the emergency response was divided into four main responses: Emergency response with lights and siren, emergency response without lights and siren, non-urgent ambulance, or medical advice or self-transportation. Non-urgent ambulance included all non-urgent transportation provided from EMS. The last category included medical advice, referral to a general practitioner, or referral the patient to the emergency department without transportation provided by EMS. After each attempt to add live video to the emergency call, the medical dispatcher filled out an electronic questionnaire about their experience , which is an open-source system developed by Vanderbilt University [After the live video had finished, the caller received a text message containing a questionnaire about their experience , the main criteria from Danish Index , and the patient’s gender. Results are reported with odds ratios (OR) and 95% confidence intervals (CI) and p-values where appropriate. If missing value for the confounding variable if was excluded from the analyse. Statistical significance was defined as p < 0.05. All analyses were performed using SAS Enterprise Guide version 7.1 statistical software.Data were analysed using descriptive statistics by means of frequencies (N) and percentages (%). Associations between categorical variables were analysed with Chi-Square test. Student’s p < 0.001). Patients were more often unconscious and experiencing seizures compared with other emergency calls without video, where chest pain, paralysis, and ‘unclear problem’ were more frequent. The duration of the calls with video was longer , and less frequent at night-time , compared with the reference group without video  of all emergency calls; it succeeded in 838 (82.2%) of these calls, and follow-up was possible in 700 calls (83.5%) , medium in 23.7% (n = 149/628), and poor in 6.7% (n = 42/628) according to the questionnaire. In three cases the audio connection with the caller ended after the live video transmission started.The medical dispatchers’ response rate for the questionnaire was 76.0% (637/838). The dispatchers found the video ‘extremely useful’ or ‘very useful’ in 88.6% of the emergencies and evaluated the quality of the video received as good in 69.6% of cases (n = 70/199). More breathing difficulties in 9.5% (n = 19/199) included obstructed airways in five cases. The dispatcher recognized other or different disease/trauma in 9.9% of the emergencies. Registered changes within the symptom-based categories in Dansk Index occurred in 14.8% of calls with video and 10.5% for the reference group without video. Dispatchers found that patient care, such as the position of the patient, quality of cardiopulmonary resuscitation or obstructed airway, improved in 28.4% (n = 165/580) of emergencies.The medical dispatchers stated that their assessment of the patient’s condition changed in 51.1% of the calls  after live video was available, according to questionnaire (Table p < 0.001)  for changing emergency response during the call if video was used. Odds for changing response was 58% higher when using live video when adjusted for age, criteria within Danish Index and gender, OR 1.58 (95% CI: 1.30–1.91) . The emergency response was upgraded in 9.9% (n = 63/632) of the emergency cases and downgraded in 19.9% (n = 126/632) according to the questionnaire.Change within the four main emergency response was 11.3% for emergencies with live video vs. 8. 0% for the reference group with no video (n = 539/604)). The reasons that dispatchers gave for challenging cooperation were: the caller was emotionally distressed , language barriers , the caller had difficulty following instructions , or the caller had barriers towards live video transmission . None of the other bystanders had barriers towards the video transmission.Dispatchers found the cooperation with caller unchallenging (89.3% (n = 7/108) were younger than 20 years and 6.5% (n = 7/108) were older than 60 years. Age was missing for three callers. The majority (97 3%) thought that the opportunity of video to EMS should be implemented, with only three saying they did not have an opinion. Ninety-nine % of callers were extremely satisfied or very satisfied with the help they received from 1 to 1-2.The dispatchers sent 513 electronic questionnaires , 111 of which were received back from the callers, giving a response rate for 22% for the bystanders. General experiences were positive towards live video transmission. Fig. . HoweverIt was feasible to add live video to the emergency call. The live video was evaluated as beneficial for the medical dispatcher, and their perceptions of the patient changed in 51.1% of the cases after receiving the video, resulting in changed emergency response in 27.5% of the emergency cases. The odds for changing emergency response were 58% higher when video was added to the call.Our results correspond to the small feasibility study, including 21 trauma cases from UK, that used the same technical solution as in our study. Video transmission was only started if the dispatch of the HEMS was under consideration and the criteria for dispatch of the HEMS had not already been met . In onlyOur study found relevant changes in health outcomes, both in relation to the patient and emergency response. Communication through a video link has been studied for hospital outpatients with chronic and stable conditions . PatientWe found that ‘giving eyes’ to the medical dispatcher could improve their situation awareness and thus the assistance they provide; this finding is supported by our previous study, which included closed-circuit television (CCTV) recordings of emergencies and interviews of the medical dispatchers involved. The study indicated that a medical dispatcher may not entirely understand the emergency setting from the verbal information given by caller . In our Only a small number of emergency calls had video added. Organizational studies have shown that introducing video consultations is a complex change that disrupts long-established processes and routines , 27. DurAlthough the solution seems simple, it is introduced to callers standing in the most stressful situation. Besides activating the link for video, they also must activate the loud-speaker function and accept transmission of video. In our study, 17.5% of emergency calls could not be established with a video, which is similar to that other studies have reported: 14.5% from Avest et al.  and 14.8A strength of this study was that we conducted a pilot project before implementing video and trained the dispatchers with simulation before adding video to the emergency call . All disFurther exploration is needed about how the dispatchers should approach emergency calls. Dispatchers are trained in traditional protocols based on verbal questions and answers. However, adding live video required a more comprehensive approach. More information is available, which also includes more non-relevant information increasing complexity for the decision-making process. Further exploration is also needed about cases in which video to EMS could be an advantage. Future studies could focus on potential critical patients that cannot communicate with the medical dispatcher, such as children, unconscious patients or maybe patients with languages barriers , which wIt was technically feasible to add live video to the emergency call. The medical dispatchers’ perception of the patient changed in 51.1% of the cases after receiving the video, resulting in changed emergency response in 27.5% % of the emergency cases. The odds for changing emergency response were 58% higher when video was added to the call. However, implementation and use of live video are challenging with the current standard dispatch protocols and further implementation science is necessary.Additional file 1. Questionnaire to the medical dispatcher after received live video from the bystander’s smartphone.Additional file 2. Questionnaire to caller after video transmission of video from their smartphone to the emergency medical dispatcher.


The accuracy of the video group for the chest compression region was high (p = 0.05). Participants’ experiences were divided into three categories: “unfamiliar but beneficial experience,” “met helper during a desperate and embarrassing situation,” and “diverse views on drone use.” Our results lay the groundwork for a development plan for providing emergency medical services using drones, as well as the preparation of guidelines for dispatchers on the provision of video instructions.This study compared first responders’ cardiopulmonary resuscitation (CPR) performance when a dispatcher provides audio instructions only and when both audio and video instructions are given. In the simulation, an automatic external defibrillator (AED) was delivered via drone in response to a cardiac arrest occurring outside a hospital setting. Participants’ qualitative experiences were also explored.An exploratory sequential mixed methods design was used. AEDs were delivered to college students via drone with one group receiving both audio and video instructions and the other receiving audio-only instruction, and differences in CPR performance and accuracy were compared. After completion, focus group interview data were collected and analyzed. Video-based instruction was found to be more effective in the number of chest compressions ( Despite advances in medical technology and improvements in economic standards, the prevalence of heart disease and resulting mortality rates are rapidly increasing in Korea due to the aging social structure and Westernized eating habits. Rapid and appropriate cardiopulmonary resuscitation (CPR) can improve spontaneous circulation recovery and survival in patients experiencing cardiac arrest . Brain dThe average arrival time of ambulances in Korea is 9 min . To imprA geographic information system model that can be used to deliver drones to patients experiencing cardiac arrest outside of a hospital setting was recently proposed . Such a It is not only important to provide medical services promptly in the event of cardiac arrest, but also to provide the services accurately. Accordingly, to increase the rate of CPR during cardiac arrest, it was performed based on the dispatcher’s instructions. In the event of an out-of-hospital cardiac arrest, dispatchers provide guidance to callers, helping them confirm cardiac arrest and initiate CPR until emergency rescuers arrive . CurrentThis study followed an exploratory sequential mixed method design. For the quantitative component, AEDs were delivered to college students by drones and CPR instructions were delivered by a dispatcher. A nonequivalent control group posttest only design was conducted between the group that received audio-only instructions and the group that received mixed video and audio instructions, to compare differences in CPR performance and accuracy. For qualitative research, after the participants’ experiments were completed, data were collected and analyzed through focus group interviews. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of the University of Semyung . Written informed consent has been obtained from all participants for their data to be used for scientific research.The drone used to transport the AED was equipped with a satellite positioning system (GPS) and high-definition camera  and a CPR quality assessment program connected to the manikin , as shown in The CPR performance evaluation was performed using Resusci Anne The focus group instrument consisted of three main types of questions. The first, introductory questions, explored basic personal information  training, or had actual CPR experience). Key questions asked about participants’ experiences of the drones and audio/video CPR instructions  Closing questions provided space for additional statements and thoughts related to the drones and performing CPR following the audio/video instructions.The experiment was conducted in a location with adequate lighting and where external noise was blocked. Consenting participants, who were eligible to participate in the study, were randomly allocated to either the group receiving audio-only instructions or the group receiving mixed video-audio instructions. Group randomization was based on a computer-generated sequence list. The randomized list was prepared by an independent research assistant who was not involved in recruiting participants and concealed in sequentially numbered, sealed, opaque envelopes. Participants acted alone as the first bystander and rescuer in a simulated situation where cardiac arrest was suspected. Participants were notified on the day of the experiment that an automatic defibrillator would be delivered using a drone. The participants performed CPR by calling the emergency medical system  at the simulation site and receiving instructions (audio/video) from the dispatcher, as shown in  Three CPR motion evaluators and one dispatcher were standardized through pre-evaluation and training, each with over 10 years’ experience as a first-class emergency medical technician or BLS-P-Instructor for the American Heart Association. The motion evaluators rated the performance of the control and experimental groups. The evaluators could not hear the dispatcher’s instructions, which allowed them to judge the CPR performances based on motions only.The guidance programed on the virtual 119 phone call explained the CPR algorithm (video/audio guidance) and informed the callers that ambulances and drones were being deployed. Based on a previous study , the simThe dispatcher conducted the training in an office isolated from the participants. The audio instruction (control) was performed flexibly so that it could be modified according to the participant’s understanding and performance using a basic mobile phone. The dispatcher wore a Bluetooth headset (SHM-612) capable of verbally transmitting and receiving CPR instructions. Video instructions  were performed using a video mobile phone. The phone had a 12-megapixel camera with a resolution of 2220 × 1080 capable of two-way video calls, and a Galaxy S8+, SM-G955U1 model with an HSDPA 150 Mbps (upload transmission rate). The dispatcher, while assessing the participant’s CPR performance through the audio and video, provided instructions, according to the American Heart Association guidelines, on things such as CPR sequence and posture correction.In To minimize the difference between the experiments in terms of collecting quantitative data, no advance education was provided to the participants. To minimize contamination and errors that could affect the results via the exchange of information about the experiment or acquisition of prior knowledge between participants, the control group (audio instruction CPR) and the experiment group (video instruction CPR) were assigned at unspecified times. Subsequently, the experiment was conducted individually.To collect qualitative data, focus group interviews were conducted with the 24 participants. Semi-structured interviews were conducted in groups of four to six participants, using open-ended questions. The participants agreed to participate in the recorded interviews, which were conducted in a quiet and comfortable seminar room.The data were analyzed using SPSS Windows 25.0. First, participants’ general characteristics were analyzed using real numbers and percentages, means, and standard deviations. Next, the Kolmogorov–Smirnov test was performed to verify the normality of the participant group, and then a non-normal distribution was verified using the Wilcoxon signed-rank test, a nonparametric statistical method.In the post-experiment interview, open questions were used; participants’ responses were recorded and transcribed verbatim. The analyzed results were made available to participants, so they could verify that their statements were transcribed without distortion. To secure transferability, focus group interviews were conducted in four groups, and data were collected up to the saturation state where no new content was yielded. Twelve participants received verbal CPR instructions, and 12 received CPR instructions over video. There was no significant difference in gender, age, height, and weight between the two groups, and thus, homogeneity was ensured .p < 0.01). The rate of chest compression was 47.08 ± 7.79% in the audio instruction CPR group, and 62.67 ± 12.75% in the video instruction group (p < 0.01). The hands-off time during chest compressions was 17.08 ± 2.71 s in the audio instruction CPR group, and 10.83 ± 2.92 s in the video instruction CPR group (p < 0.001). There were significant differences between the two groups in the number of chest compressions, rate of compressions, and stopping time.The number of chest compressions was 96.92 ± 12.33 in the audio instruction CPR group, and 121.42 ± 17.23 in the video instruction CPR group (p = 0.05). The total score for CPR performance was 19.25 ± 11.85 points for the audio instruction CPR group, and 63.17 ± 24.10 points for the video instruction CPR group, indicating that overall CPR performance was significantly higher in the audio instruction CPR group ; 119 reports and defibrillator requests were 0.92 ± 0.28 in the audio instruction CPR group and 1.42 ± 0.51% in the video instruction CPR group (p = 0.01). The evaluation score for the chest compressions, which measured the location of the chest compression, the shape of the performers’ hands, and their body posture, was 23.08 ± 1.38 in the audio instruction CPR group and 23.92 ± 0.29 in the video instruction CPR group (p = 0.05). The score for 1st cycle chest compression was 7.69 ± 0.45 in the audio instruction CPR group and 8.00 ± 0.00 in the video instruction CPR group, respectively (p = 0.01). The results showed that the accuracy of CPR, as gauged by the evaluators, was significantly higher in the video instruction CPR group in terms of consciousness check, 119 report and defibrillator request, and chest compressions compared to the audio instruction CPR group On the other hand, some students who had already completed BLS-P training were concerned that intervention would be delayed if they had to wait to be directed by paramedics in a real situation that required a rapid management process.“I thought that patients need to be treated quickly as in real life, but it was a pity and difficulty because I had to proceed with the paramedics.” (Participant 21)Some participants were also hindered by uncontrolled situational variables. For example, the defibrillator sounds made it difficult to hear the call.“It was a bit confusing because the defibrillator and the call sound overlapped.” (Participant 20)Furthermore, although the participants did not actually experience it, they were worried about what to do if the connection was lost during the call.“In the case of audio instruction, there is a risk that the mobile phone connection may not be successful, or the connection may be disconnected due to battery discharge.” (Participant 19).Most participants initially had doubts about the novel experimental method, but expressed their satisfaction, saying that they were immersed in the simulated situation as if they had actually experienced it, and that this experience would help a lot in actual practice in the future.“I think I had a good experience by performing the simulation well as in the real world. I think this simulation is a good idea.” (Participant 1)This category includes the subcategories of “comfort that you are not alone” and “compensation for insufficiencies.” Most participants relied on the dispatcher and the drone to compensate for their lack of knowledge and insufficient skills; thus, they resolved the situation.Most of the participants said they felt anxious, scared, and lonely, when faced with the burden of solving the situation on their own. The drones and dispatchers that appeared then gave them the comfort that they were not alone. Interestingly, even though the drone is a machine rather than a human, the participants expressed that they thought of the drone as an “assistant” or “I was not lonely because the drone came,” expressing that the drone provided them emotional comfort.“I was frustrated and embarrassed because I was going to do it alone in the situation where no one was there, but it was nice that the drone seemed to act as an assistant.” (Participant 22)In situations where the participants had to perform CPR on their own, not only those who did not complete BLS-P training but also those who completed it felt embarrassed. However, incomplete actions could be corrected through audio and video, so even participants who had not completed BLS-P training could follow it easily.“It was nice to see the treatment method through the video instruction, so I could correct the insufficient parts.” (Participant 9)This category includes the subcategories of “contradictory feelings about drone size” and “varying views on the accessibility of drones.” All participants commented on the innovation of drone use, but ultimately had different views on this aspect.Most participants thought the drone was too big, making it dangerous for both the patient and rescuer during takeoff and landing.“This is my first experience, but there seems to be a danger to both the requestor and the rescuer when the drone takes off and lands.” (Participant 7)However, one participant was satisfied with the large size of the drone, saying that it looked sturdy.“It was amazing and impressive that the drone looked so big and sturdy that it could deliver an AED through it.” (Participant 14)Most participants thought the method of receiving an AED via drone would be useful in environments where it is difficult to access defibrillators, such as in the mountains or in remote areas, and they expected that the quality of CPR would be improved compared to conventional single-person CPR.“I felt it was really practical. If I met a patient with cardiac arrest while hiking, I never thought of what a drone would bring in an environment without an AED.” (Participant 22)However, the participants highlighted some points for improvement. Some judged it not to be effective in this case because large drones could not access narrow places with lots of grass or leaves. In addition, many participants found that it was difficult to use the drone on uneven terrain because it is difficult for the drone to land on a slope. As the drone is so large, the AED landing location may be some distance away from the patient, considering the length of the wings.“When the AED arrived, it was so far away from the patient that it was unfortunate that there was a gap in the middle. I thought it would be better if the AED could come slightly closer to the patient.” (Participant 1)This study compared the difference in CPR performance and the accuracy of the first responder based on whether audio or video instructions were given by a dispatcher during a cardiac arrest outside a hospital setting. We also attempted to provide basic data that can be used to increase the effectiveness of out-of-hospital CPR by confirming the experience of audio and video CPR instruction and exploring how CPR performance is affected when a defibrillator is delivered using a drone.To increase the survival rate of patients with cardiac arrest, it is important for first responders to use high-quality CPR and rapid defibrillation. For high-quality CPR, chest compressions should be performed at a rate of 100 to 120 times/min, chest compressions at a depth of five cm or more, and the interruption time of chest compressions should be minimized (within 10 s) . First, In terms of CPR accuracy, judged by three evaluators, the chest compression score, which measured the location of the chest compression, the shape of the responder’s hands, and correct posture, was found to be more accurate in the video instruction group than in the audio instruction group. In-depth understanding of the experience of drone use, audio instruction CPR, and video- instruction was further analyzed, and the effect of experience on the CPR process was analyzed. When the drone delivered the automatic defibrillator, three categories of experience were derived: “an unfamiliar but beneficial experience,” “met helper during a desperate and embarrassing situation,” and “diverse views on drone use.” The category of “unfamiliar but beneficial experience” included the subcategories of “regret about poor performance” and vibrancy, as if experiencing a real situation.” The experience was unfamiliar because the provision of medical services via drone is not a common practice, and it was judged by the participants that the practical experience of providing the necessary defibrillation for cardiac arrest patients through drones had been provided. The participants received practical experience they would not otherwise have received, and that in itself made it a worthwhile experience for them. In addition, some of the study participants who had obtained the BLS-P qualification were concerned about the delay in intervention in coping with the CPR instructions as they were directed by the dispatcher. This result supports previous findings that it took more time to perform CPR correctly during a simulation and more stress occurred , than inThe category of “met helper during a desperate and embarrassing situation” included the subcategories of “comfort that you are not alone” and “compensation for insufficient areas.” In a study by The category of “diverse views on the use of drone” included the subcategories of “contradicting feelings about drone size” and “varying views on drone accessibility.” Most participants thought the drone was too big, making it dangerous during takeoff and landing. However, the results of a previous study found AED delivery by drones to be safe and not difficult . To reduThis study has several strengths. First, it demonstrated that delivering defibrillators using drones overcomes geographical and temporal limitations. Second, a mixed study, that analyzed the participants’ experience by interviewing them, was attempted. Third, it confirmed that video instructions can help ensure that CPR is provided accurately. Despite its strengths, this study also has some limitations. First, since CPR can be performed by anyone regardless of their age but this study’s participants were in their 20s, the generalizability the results is limited. Second, since there are the designated area for drones, their take-off and landing were limited in the study.This study provided evidence that there are differences. in performance, execution time, and accuracy of CPR performed by first responders, according to whether the dispatcher provides audio or video instructions, when an automatic defibrillator is delivered via drone during a cardiac arrest scenario outside a hospital. We also endeavored to gain an in-depth understanding of the experience of drone use and audio and video CPR instruction, and we sought to determine how the experience affected the CPR process. According to this study’s results, there were significant differences between the audio- and video-instruction groups, while performing CPR, in the number of chest compressions, rate of chest compressions, and hands-off time during chest compressions. In addition, regarding chest compressions, there were differences between the audio- and video-instruction groups in the location of the chest compressions, the shape of the hand, and the correct posture—which confirm the accuracy of the CPR. Three categories of experience were derived from the participants’ experiences: “unfamiliar but beneficial experience,” “met helper during a desperate and embarrassing situation,” and “diverse views on drone use,” and six sub-categories were extracted. These results are significant as they provide basic data that can be used in creating a development plan for emergency medical services using drones and preparing video-instruction guidelines for dispatchers.To activate medical services using drones, based on the current results, we propose a comparative study on the delivery of defibrillators using drones, and the transportation of defibrillators using ambulances after analyzing the routes appropriate for the region and terrain. Generalizability of the findings are severely limited because there is no system that uses AED-drones, currently. In addition, we propose that a follow-up study confirm the efficacy by developing a dispatcher guide that uses audio and video instructions. Additionally, further studies are required to confirm the effects of audio and video instructions on various age groups and in different areas and terrains where there are no restrictions on drones’ takeoff and landing.10.7717/peerj.11761/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.11761/supp-2Supplemental Information 2Click here for additional data file.10.7717/peerj.11761/supp-3Supplemental Information 3Sim Pad Skill ReporterClick here for additional data file.10.7717/peerj.11761/supp-4Supplemental Information 4Click here for additional data file.10.7717/peerj.11761/supp-5Supplemental Information 5Click here for additional data file.


Arteriovenous malformations (AVM) are defined as being quiescent vascular masses composed of mature vessels. However, recent studies reported areas of microvascular proliferation (MVP) in AVM, indicating a process of angiogenesis. As this finding questions the previous definition, the primary objective of this review was to evaluate whether angiogenesis occurs in vascular malformations of skin and soft tissue, and second, to identify potential factors involved in MVP.Due to the multifaceted nature of this subject, a hermeneutic methodology was used to select articles that were likely to provide a deeper understanding of MVP in vascular malformations. Through citation tracking and database searching in PubMed and Web of Science, relevant articles were identified. All study designs concerning occurrence of MVP in AVM of skin and soft tissue in all age groups were included in the study. The Newcastle-Ottawa scale was used for quality assessment.16 studies were included in this review which reported occurrence of MVP areas in between the otherwise mature vessels of vascular malformations. In these studies, angiogenesis was reported only in AVM-type of vascular malformations. Increased levels of pro-angiogenic factors were also reported and proliferation was found most prominently during adolescence. Finally, several types of hormone receptors also have been described in tissues of AVM.Overall, the reviewed data support occurrence of active angiogenesis, highlighted by the presence of MVP in the arteriovenous type of vascular malformations, and a possible concurrent lesion progression towards a higher Schobinger stage of clinical severity. The relative scarcity of data at present implies that further research is required to elucidate the nature of MVP in AVM, which could have implications for developing targeted pharmacotherapy.Active angiogenesis caused by MVP in AVM patients is known to be correlating to clinical symptoms and contributing to the progression of the disease, recurrence rate, and patient’s quality of life. Vascular anomalies are usually mass forming lesions of the vasculature that may affect capillaries, arteries, veins, and lymphatics, either single or in combinations. Despite being benign lesions in most of the cases, vascular anomalies can cause various serious complications depending on tissue type, location, and extent of the mass. Mulliken and Glowacki developed the first classification in 1982, and categorized vascular anomalies in vascular tumors and congenital vascular malformations, based on increased endothelial cells (EC) turnover in vascular tumors and a slowly progressive growth rate in the congenital malformations  thymidine incorporation in AVM. Quantitative measurement of [Methyl-3H] thymidine incorporation in cultured cells is widely used as an indicator of cell proliferation. There was no expression of adhesion molecules E-selectin/CD62 and VCAM-1/CD106 after IL-1β and TNF-α stimulation, whereas ICAM-1/CD51 was increased 6 to 15-fold compared to control [et al. on a patient with vascular proliferation in AVM reported increased serum levels of VEGF and matrix metalloproteinases (MMP)-9 (2-fold), Ang-2 (10-fold), Tie-2 (3-fold) compared to control sera (n=10), and decreased levels of platelet derived growth factor (PDGF), PDGF-AB, and PDGF-BB [In proliferation assays of cultured AVM EC interleukin-1β (IL-1β), tumor necrosis factor-alfa (TNF-α), interferon gamma (IFN-γ) and TGF-β, had no influence on [Methyl- control . The pre control . On the  PDGF-BB .p<0.0001). There was no expression in control tissue. Furthermore, GHR was highly increased in AVM tissue . When present, receptor density was similar between AVM and control. Patients with a clinical Schobinger Stage III AVM had increased GHR compared to Stage II lesions (p=0.05). Age, sex, and location had no effect on GHR expression (p=0.8). Expression of ER, AR, and PGR, which assumed to be responsible in AVM expansion, did not differ compared to control (p=0.2) [The presence of hormone receptors has also been reported in AVM. Expression of follicle-stimulating hormone (FSH), androgen (A), estrogen (E), progesterone (P), and growth hormone (GH) receptors was tested  -27. FSHR (p=0.2) .p<0.0001) [Interestingly, another study reported that 10 of the 12 (83%) AVM samples showed diffuse positive immunohistochemical staining for PGR compared to no expression in control tissue (<0.0001) . There wAlthough it is well known that AVM of skin and soft tissue gradually expand over time, the underlying mechanisms and pathological features are incompletely understood. The examined data in this review clearly suggest involvement of angiogenesis as can be understood from the histopathological identification of masses of proliferating microvessels in at least part of the reported lesions. In addition, the identification of multiple angiogenic factors in the sera or tissues of AVM patients could support this view. These findings could explain the episodes of abnormal sudden growth accompanied by discomfort up to serious complications in patients. This is further endorsed by the publications on patients with proliferative features in AVM who also showed a high Schobinger stage of clinical severity of the disease.Angiogenesis is regulated by the balance between pro- and anti-angiogenic factors. A certain disbalance could therefore drive vascular proliferation in AVM, potentially leading to lesion expansion . Growth The VEGF family of growth factors include the most important stimulators of EC migration and sprouting ,32. ThisLittle is known about the involvement of FGF in AVM expansion. They are nonetheless potent regulators of cell proliferation, differentiation, and function and could therefore be studied to identify their possible role in disturbed vessel growth present in AVM of skin and soft tissue . FGF wasin vivo, but promotes apoptosis in vitro [TNF-α is a cytokine also thought to be involved in angiogenesis. TNF-α is pro-angiogenic in vitro . In cultin vitro .Recently, a new angiogenic and anti-inflammatory agent, AGGF1, was reportedt o be highly expressed in activated EC and MC of AVM. The phophatidylinositol 3-kinase (PI3K) pathway is a regulator of cell growth and dysregulation of this pathway could support the proliferation of EC and disruption of vasculogenesis. Mutation of phosphatidylinositol 3-kinase subunits (PIK3CA), the gene encoding the subunit of PI3K, is associated with AGGF1 expression and will result in the dysregulation ,41,42. Ap<0.001). Also 18 pregnancies in 12 women were reported with untreated AVM stage I (n=11) and stage II (n=1), of which 44.4% led to progression of AVM to a higher Schobinger stage. However, there was no risk difference compared to non-pregnant women (p=0.20) [In a retrospective cohort study on natural progression and recurrence of extra cranial AVM, involving 272 individuals, 43.8% of the lesions progressed before adolescence, 82.6% before adulthood and 17.5% worsened at the age of adulthood. Diffuse AVM tended to progress more quickly, in both childhood and adolescence, compared to localized lesions ((p=0.20) .et al. found 50% of the proliferative foci to be multicentric and of which 38% appeared to have a solid growth patterns splitting up surrounding adipose and skeletal tissues. Patients in these series underwent surgical resection of lesion because of symptoms  [+CD133+ EPC were increased in stage III AVM (0.53%) compared to stage II (0.25%) (p=0.02). The expression of the vasculogenic factors stromal derived factor (SDF-1α) and hypoxia inducible factor (HIF-α) gene were determined by quantitative real-time reverse-transcriptase polymerase chain reaction. They were increased in Stage III (7.9-fold) compared to Stage II (3.3-fold) (p=0.02) and Stage III (7.6-fold) to Stage II (1.7-fold) (p=0.02), respectively. Expression of VEGF in Stage II and Stage III was similar (p=0.7). However, expression of VEGFR2, Neuropilin 1 and Neuropilin 2 was found to be increased in Stage II compared to Stage III (p=0.03). Taken together, these reported findings suggest that MVP, at least episodically, could lead to increase of the lesional mass of AVM.A study by Meijer-Jorna  growth) . It was  growth) . CD43+CDin vitro [Patients with AVM have the highest risk of progression to a higher Schobinger stage in adolescence suggesting that circulating hormones might contribute to AVM proliferation ,25. GH iin vitro ,46.Abnormal expression of GH was found in the endothelium and vascular SMC of AVM. GH could directly or indirectly, for example, through promotion of expression and activity of endothelial citric oxide synthase, be involved in AVM expansion ,45.FSH surges during adolescence and their receptor expression is reported to be elevated in AVM. Unlike GH, FSHR are not expressed on normal tissue ,47. FSH/et al., who found significantly higher proliferative (Ki-67) indexes of lesional EC and SMC in male patients than in female patients. The tissue extent of proliferation appeared also to be more prominent in males [None of the included studies found an association between sex, localization or age, and proliferation, with exception of Meijer-Jorna in males . Althougin males . Testostin males . Estrogein males . This doin males ,49.Progesterone is not involved in the onset of puberty or in the transition to adulthood, the timespan in which AVM tend to progress . The repet al. observed more extensive chronic inflammation in high-flow lesions than in low-flow lesions, although in this study no significant differences were observed between the high flow lesions with or without proliferating microvessels. The authors concluded that this might be due to the small sample sizes of at least part of the study materials [There is evidence that inflammation is a contributing factor in the pathology of cerebral AVM , and potaterials . Howeveraterials .MMPs regulate several functions related to inflammation, including activity and bioavailability of inflammatory cytokines and chemokines . MMP levHypoxia is a potent inducer of VEGF. The Hypoxia-Inducible Factor (HIF) pathway contributes to the regulation of both physiologic and pathologic vascular wall remodeling , and actSeveral suggestions have been made regarding the nature of neovascularization in AVM. Absence of a systemic angiogenic effect may indicate that the factors influencing proliferation are active locally. Cultured AVM cells showed a higher spontaneous proliferation rate compared to human umbilical vein, arterial, or microvascular EC. The proliferation rate of the AVM cells was not responding to inhibitory activity. These findings suggest that the high propensity to proliferate might be caused by an inherent defect . Embryonet al. identified a KRAS mutation in cerebral AVM lesions that coincided with dysregulation of the MAPK-extracellular-signal-regulated kinase (MAPK-ERK) pathway, which is also associated with the development of a number of types of cancer [Recently, several studies have unraveled a number of genetic mutations in AVM. Mutation of the mitogen-activated protein kinase 1 (MAP2K1) gene on EC was assumed to affect EC function and the initiation of pathological arteriovenous shunting through signaling activation of RAS/mitogen-activated protein kinase (RAS/MAPK). This aberration was also presumed to promote angiogenesis . Activatf cancer . The MAPf cancer ,64.HHT is a rare condition characterized by telangiectasia and congenital AF, and is caused by mutations in endoglin/CD105 and activin receptor-like kinase-1 (ALK1) ,66. Endop<0.05) compared to recurrent AVM 21.50±0.27 pg/mg and 545±243 pg/mg (p>0.05) [It is known that AVM can recur and expand following treatment. One study found levels of VEGF and VEGFR to be increased in recurrent AVM tissues when compared to primary AVM tissues. Average VEGF and VEGFR concentrations in primary AVM were 4.80±1.34 pg/mg protein and 61.80±20.85 pg/mg ((p>0.05) .p<0.001), whereas age, location, sex, and size of the lesion were not (p>0.05). Resection (with or without embolization) of the AVM had a lower re-expansion rate (81%) compared to treatment by embolization (98%). Embolization alone showed a higher risk of return 14.2 times (95% CI: 4.7-42.2) compared to resection (with or without embolization) (p<0.001). Lower staged AVM also had a lower recurrence rate (p<0.001). Resection (with or without embolization) also extended the period to clinically significant recurrence of the lesion; 57.3% re-expanded <1 year compared to 85.6% after embolization only (p<0.001). Multiple resections or embolization did not decrease the rate of recurrence (p=0.59) [In a retrospective cohort study, recurrence of AVM after intervention was 93%, during a follow-up of 8.9±5.2 years. The types of treatment, being embolization and resection (with or without embolization), were both independently prognostic for recurrence . This approach might be able to suppress the proliferation process and accelerate the process of decreasing microvessels density. In addition, several other anti-angiogenesis-based may be useful in the treatment of AVM. A currently common anti-angiogenic therapy in oncology is the application of bevacizumab, a monoclonal antibody that binds to VEGF-A . MutatioIn vitro and in vivo studies are necessary to further unravel which angiogenic mechanisms are involved and whether anti-angiogenic agents could have a significant role to inhibit vasoproliferation in AVM of skin and soft tissue. A large prospective cohort study is proposed to provide more insights in the relationship between vasoproliferation and clinical symptoms.This systematic review clearly supports the involvement of angiogenesis in the expansion of vascular malformations, and particularly in the subgroup of AVM. The studies confirmed that active angiogenesis is correlated with a higher Schobinger Stage in AVM progression. Expansion of AVM can have detrimental effects on both physical and mental wellbeing of patients, reducing the quality of life. Since there is no cure yet and recurrence rate after treatment is high for AVM, further research is therefore required to better understand the angiogenic microproliferative processes in AVM. This could serve to develop novel anti-angiogenic pharmacotherapy. Targeted pharmacotherapy directed to any of the pathways outlined in this review, may have therapeutic potential. This review is limited by the scarce amount of existing literature regarding angiogenesis in AVM of skin and soft tissue.