In low-resource settings, inpatient case fatality for severe acute malnutrition (SAM) remains high despite evidenced-based protocols and resources to treat SAM. Key reasons include a combination of insufficiently trained staff, poor teamwork and inadequate compliance to WHO treatment guidelines which are proven to reduce mortality. Checklists have been used in surgery and obstetrics to ameliorate similarly complicated yet repetitive work processes and may be a key strategy to improving inpatient SAM protocol adherence and reducing unnecessary death. Here, we share our experience developing and piloting an inpatient malnutrition checklist (MLNC) for children 6 to 59 months and associated scoring system to coordinate care delivery, improve team documentation, strengthen WHO malnutrition protocol adherence and facilitate quality improvement in a district hospital in rural Rwanda. MLNC was developed after careful review of the 2009 Rwandan National Nutrition Protocol and 2013 WHO malnutrition guidelines. Critical steps were harmonized, extracted and designed into an initial MLNC with input from pediatric ward nurses, doctors, a locally based pediatrician and a registered dietitian. A scoring system was developed to facilitate quality improvement. Using the standard Plan-Do-Study-Act cycle, MLNC was modified and progress assessed on a monthly to bimonthly basis. Significant modifications occurred in the first 6 months of piloting including incorporation of treatment reminders and formatting improvements, as well as initiation of the MLNC from the emergency department. The MLNC is the first checklist to be developed that unifies WHO 10 steps of treatment of inpatient SAM with local standards. Anecdotally, MLNC was observed to identify gaps in key malnutrition care, promote protocol adherence and facilitate quality improvement. Data gathering on the MLNC local facility impact is underway. Collaborative international efforts are needed to create an inpatient malnutrition checklist for wider use to improve quality and reduce unnecessary, facility-based child mortality. Globally, approximately 13 million children are diagnosed with severe acute malnutrition (SAM) annually, with 1–2 million preventable child deaths associated with SAM .10.1080/In low-resource settings, inpatient case fatality for inpatient malnutrition remains high despite availability of evidenced-based treatment protocols and resources ,5. Key rIn Rwanda, a national Performance-Based Financing (PBF) scheme was previously implemented to provide financial incentives to health providers for improvements in key national health priority output indicators related to maternal and child-care . One of We propose, that the development of a checklist to guide the inpatient management of malnutrition  in low-resource settings is a key strategy to adherence improvement to the inpatient WHO malnutrition protocol and reduction of unnecessary deaths from malnutrition at the facility level. The inpatient management of acute malnutrition is particularly amenable to a checklist format, given 10 clear steps outlined by WHO. Progression of treatment steps is largely the same from patient to patient with most deviations during acute stabilization. Similar to surgery, malnutrition requires effective communication, timely action and collaborative team effort to ensure high quality, efficient patient care and reduce deaths. A malnutrition checklist could improve communication, streamline documentation and improve delivery of evidence-based malnutrition care to patients from the time of admission through rehabilitation and discharge to improve adherence to WHO protocols and reduce mortality.Here, we describe development and pilot testing of an inpatient malnutrition checklist (MLNC) and scoring system for children 6–59 months. MLNC was developed to coordinate care delivery, team documentation, communication, improve inpatient WHO malnutrition protocol adherence and facilitate QI work on the wards of a district hospital in rural Rwanda. We hope that this shared experience and protocol to date can be used as a starting point for others to modify and utilize in their own settings. Additionally, we hope to raise awareness and call for an international collaborative to undertake the development of a global malnutrition checklist to be used as a resource in reducing child mortality.MLNC aimed to create a single, streamlined document that unified WHO and national Rwandan guidelines for inpatient malnutrition care that could be used by frontline healthcare workers as a guidance of critical steps in malnutrition management. MLNC was designed to coordinate an entire teams’ documentation of malnutrition care which can span weeks in duration. Thus, while initially filled out by a physician in the emergency department, the MLNC also includes documentation fields for nurses and/or nutritionists depending on workflow of the hospital. Lastly, a scoring system based on the MLNC was developed to enable hospitals to more easily implement quality improvement (QI) projects that identify and address gaps in key process indicators. In order to not disrupt regional requirements in medical record documentation, this checklist was implemented as additional rather than a replacement of routine documentation practices.A draft MLNC was developed in November 2015 after critical review of the Rwandan National Nutrition Protocol  and the Checklists were printed on colored paper to increase visibility in the patient chart and clean copies were kept in the emergency and pediatric departments. The emergency department doctor and nurse initiated the checklist, registered the child as having acute malnutrition, documented height and weight, and completed the initial medical management documentation. After transfer to the pediatric department, checklist documentation was reviewed and daily treatment iterated by the pediatric department staff . Generally, the nutritionist updated height, weight and calculated WHO z-scores; doctors prescribed feeding regimens and medications; and nurses documented care implementation and adverse reactions to feeding, such as vomiting. Pediatric team disagreements regarding care were addressed during ward rounds.Over the next 6 months, experience with MLNC was discussed during weekly QI pediatric team meetings and revisions made based on user feedback. Last, a simplified scoring system was developed to assess malnutrition protocol adherence based on MLNC documentation . The pediatric QI team at Rwinkwavu District Hospital in Rwinkwavu, Rwanda began its first QI project using the MLNC in September 2015 focusing initially on documentation adherence. The subsequent QI project narrowed its scope to address specific documentation gaps, such as identification of shock in the emergency department for children with a diagnosis of SAM. The Plan-Do-Study-Act (PSDA) cycle of QI was used to plan the QI project, establish baseline indicators, implement use of the checklist, and make modifications as time went on.MLNC was modified and progress of protocol adherence to the area of focus chosen assessed on a monthly to bimonthly basis. Run charts were displayed on the pediatric unit to track the progress of the QI project and to encourage staffModifications to MLNC during the first 6 months of use included clarifying criteria for advancing therapeutic milk feedings, prompts for medication provision on the appropriate day of treatment, medication dosage references, and guidance on discharge criteria and education. The nutritionist reported positive feedback related to the tool, particularly its ease in being able to monitor the daily progress of the patient, while the doctors felt that clearly outlining and prompting treatment for the 10 critical treatment steps was useful for proper treatment of malnutrition.Now that MLNC has been in use for over two years, efforts are underway to document the QI project outcomes and its effects on inpatient malnutrition treatment processes. The QI teams continue to meet regularly and have begun identifying more granular components of the MLNCs to focus on, such as hypoglycemia.Preliminary experience with a locally developed MLNC suggests it is helpful in simplifying the complex treatment of inpatient malnutrition. Anecdotally, the MLNC was successfully implemented to address gaps in key malnutrition care processes as well as facilitate QI which promoted coordinated delivery of inpatient malnutrition services with improved adherence to protocols.We experienced a number of challenges which will likely be common experiences to others using this tool or developing their own. First, the MLNC requires supportive implementation and leadership by respected mentors to facilitate the acceptance of the checklist and lead to improved team work. In our districts, we were fortunate that in addition to engaged hospital staff and regular support by a pediatrician and registered dietitian, hospitals are supported by routine QI mentorship through previously described MESH mentors –23 who pIn Rwanda, use of the MLNC has already expanded to a second District Hospital and we hope to share these experiences with other Rwandan facilities to improve the quality of care of inpatient acute malnutrition management regionally.More broadly, we hope that this work will be the first step in calling for a MLNC which has input from international stakeholders and might be used and adapted to local country settings to improve adherence to evidence based protocols for inpatient malnutrition treatment, ultimately resulting in decreased mortality related to malnutrition for children under five.


M = 13.08, SD = 1.91) attending an English school completed an online survey, which included a measure of moral development and questions regarding video game play. In contrast to previous research, male participants were found to have significantly (p = 0.02) higher moral reasoning scores than females. The results also suggested a transition in moral development, which takes place between the ages of 12–14. The results of moral development and video game played suggested both positive and negative relationships. Regression analysis suggested that there was a significant positive relationship between the more types of game genres played and higher moral scores. Although not significant, the results suggested a trend for the following variables; years playing video games, mature content, engagement, moral narrative, Grand Theft Auto, Call of Duty, and length of time playing video games which all had a negative relationship with moral scores. The implications of these results are discussed with regards to moral education and the variables involved in video game play, including the role of video game content.Due to the concerns over the effects of video game play, this study investigated adolescents’ moral development and their video game play. 166 adolescents aged 11–18 years ( Playing video games is a popular pastime, with 26% of under 18 year olds playing video games and the video games industry worth a total of $23.5 billion (statistics from the United States) . ResearcMoral B is described as more prescriptive and internal with an awareness of what ought to be . Moral BExamples of what could be considered amoral behavior can occur when playing video games such as Grand Theft Auto (GTA)  due to iDifferent measures have been used to define an individual’s video game habits and include experience and exposure to video games, this includes length of time playing video games . Many stMost research on the psychological effects of video games has investigated violent content therefore much of the research on morality has been limited to focusing on violent video games. Much of the literature has focused on violent content and in-game decisions; but it is important to consider other content in video games, such as mature content, to understand the potential relationship between morality and exposure to a variety of video game content. A recent model of media consumption and morality suggests that the long-term components of how media is received and appraised, relates to individuals’ selection of media, in this case their video game play , 2012. OM = 13.08, SD = 1.91). There were similar number of males and females , 36.1% of the sample entitled to free school1 meals. Free school meals (FSM) was taken as measure of Social Economical Status (SES). The majority of the sample had a White Scottish, Irish English or other background 94.0%. One local secondary school was used in the study which included a sixth form.Ethical approval was obtained from Bournemouth University, Science, Technology and Health Research Ethics Panel, and the study was carried out within accordance with the recommendations of Bournemouth University’s Research Ethics Code of Practice. All participants gave written informed consent in accordance with the Declaration of Helsinki, with written informed consent obtained from parents/guardians for all participants under the age of 16. A total of 166 participants took part in the study, consisting of secondary and sixth form students from United Kingdom school years 7 to 13  was used to create an online survey for administration to participants. The survey was piloted to three secondary school pupils before the main administration. The survey took around 40 min to complete and was administered during lessons. The researcher delivered a 10 min presentation to brief students about the research and how to take part in the survey, followed by general information about how students should complete the survey individually. The instructions for the SRM were read aloud with a fictional example used to aid understanding. Finally the first question of the SRM was read aloud for the participants to think about to illustrate that this is the part that required decision making. If the participants were happy they wrote their full name at the start of the survey to consent. The researcher walked around the classroom while the students completed the survey to make sure students taking part could access the link and to offer help where needed. r = 0.69 and test retest reliability r = 0.88 . This is less time consuming compared to other similar measures of morality that require moral decisions and evaluation to be made, such as the Moral Judgment interview, which can take over an hour . It alsor = 0.88 .Video game play was developed and adapted from previous research, into a questionnaire to include a greater range of response options for game play, than has been used in previous research including number of favorite games . QuestioThis measure consisted of 19 questions regarding how the participant usually feels when playing a video game and a score is given to represent the level of engagement (Yes = 2 Maybe = 1 and No = 0). The maximum score on the measure is 38 α = 0.85 .2.Participants’ responses for each question were categorized into a stage of development and moral type, A or B. The eleven questions are split by themes: questions 1 to 4 Contract and Truth; questions 5 and 6 Affiliation (related to helping family and friends); questions, 7 and 8 Life questions, 9 and 10 Property and Law and finally question 11, Legal Justice. There are four stages of development (1–4) with three transitional stages in between each stage. A response is scored by matching the response to the appropriate Criterion Justification (CJ). The CJ are responses grouped by moral concepts, such as; empathic role taking, intrapersonal approval and prosocial intentions and include sample responses listed below to assist matching; for example “you may become friends” , p. 71. This study aims to examine the relationships between moral development, video game play and moral scores (SRM) .Table 3 supported this F = 7.06, p < 0.001, and ω2 = 0.16, small effect. Gabriels4post hoc tests in particular show a change between 12 and 14 years (p = 0.002).Figure t-tests showed a significant sex difference for years playing, number of genres played, Content Rating and Length of time (p < 0.01) with medium to large effect sizes but not significant for engagement (p > 0.05). Table p > 0.001), and gaming status (p > 0.01). Males were between 7 to 16 times more likely to have to these variables in their game play.Table t(131) = 2.34, p = 0.02, r = 0.2. The findings for gaming status suggested that participants who played games were a Global stage higher than those who do not play video games. However, the non-gaming group (n = 9) was small in comparison to the gaming group (n = 124).Table Table This study examined moral development (SRM scores) and video game play. A significant change in moral development was evident in the sample between the ages of 12 and 14. Additionally, it was found that secondary and sixth form students’ moral development is immature and still developing. Interestingly males were found to have higher moral scores than females, in contrast to much previous research which has found that females within this age group have higher levels of moral reasoning . Males wn = 9), showing that a high majority of the sample were playing video games, further demonstrating the importance of gathering these data. Conversely, the engagement variable was not significantly different for males and females; this could suggest that the sex difference in video game play could be closing as both were similarly engaged with the game played. Additionally, it could suggest this experience does not differ between the sexes.As expected moral type was shown to predict moral scores; moral B predicted higher moral scores. The sex difference in video game play that was found could be connected to the sex difference in morality or alternatively other factors could be of influence. The sex differences were similar to those found by The number of genres of video games played was shown to be a significant predictor of higher SRM moral scores. This suggests that certain aspects of game play could have a positive relationship with moral development such as playing a variety of genres of video games. Furthermore, some gaming variables had negative relationships but none were significant predictors of lower moral scores, including; years playing video games, mature content, engagement, moral narrative, GTA, COD, and length of time playing video games. These non-significant variables could suggest that video game play and content may not have a direct relationship with morality. Nevertheless the finding that males had higher video game play consumption and displayed higher moral scores, suggests that video game play could potentially be supporting of moral development, Another explanation is that that those with higher moral scores, more mature moral reasoning may also be more proficient at morally disengaging through justification, e.g., it is just a game. This is supported by previous research that found that moral disengagement took place in video game to avoid conflicts with enjoyment of the game and with in-game decision making . Further5 of the sample listing at least one violent game among their favorites. Further research also is needed to examine the trend of violence having a positive relationship with SRM scores and mature content having a negative relationship with SRM scores. This could suggest different types of content have different influences, and perhaps mature content could be of more concern to moral development than violent content. This is interesting as normally games with mature content also contain violent content. Furthermore, violent content was encountered frequently in this study with 68.9%The SRM measure has a sub heading of reasoning that includes “prosocial intentions,” research into violent video games and the relationship with prosocial behavior is of current debate . Thus itWhile a cross-sectional design allowed for the data to be collected within the time frame, the limitations are that participants are compared to each other, rather than their own development. Therefore, cause and effect cannot be determined, but used to identify trends for future research. Also only one school was used for data collection; For moral development, future research could examine finding that of females in secondary and sixth form displayed lower moral scores. In addition, an exploration of whether a change occurs in moral development between the age of 12 and 14 (years 7 and 9) is needed. The results in general suggest, in support of previous studies, that the relationship between morality and video games is a complex one. Further research in this area is needed to gather in-depth gaming information from participants and to investigate variables such as years playing. In addition, the group of adolescents playing video games for an excessive length of time needs further investigation; to examine the role of high game play on development and whether this can become a pathological level of use. These results have broader implications for video game rating systems, moral development and education but also specific implications for parents and the adolescents’ video game play. In sum the results suggested a mixed relationship between video game play and moral development. With further longitudinal research the relationship between moral development and video game play could be discerned.The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.SH contributed to the conception, design, data collection, and analysis. All authors contributed to the manuscript revision, read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We present Direct Assessment, a method for manually assessing the quality of automatically-generated captions for video. Evaluating the accuracy of video captions is particularly difficult because for any given video clip there is no definitive ground truth or correct answer against which to measure. Metrics for comparing automatic video captions against a manual caption such as BLEU and METEOR, drawn from techniques used in evaluating machine translation, were used in the TRECVid video captioning task in 2016 but these are shown to have weaknesses. The work presented here brings human assessment into the evaluation by crowd sourcing how well a caption describes a video. We automatically degrade the quality of some sample captions which are assessed manually and from this we are able to rate the quality of the human assessors, a factor we take into account in the evaluation. Using data from the TRECVid video-to-text task in 2016, we show how our direct assessment method is replicable and robust and scales to where there are many caption-generation techniques to be evaluated including the TRECVid video-to-text task in 2017. Describing image content precisely, either still images or video, is difficult because images are visually rich and because their content can be interpreted in so many ways. Recent years have seen huge growth in the ways in which we can access images and video online. Services like Netflix and Amazon Prime now bring moving images into our homes and onto our devices and social media services like Facebook and Twitter have created new ways in which we find this content.tagging, which involves identifying a set of objects or activities present in an image or video. Tagging is not an exhaustive process in that it does not provide complete description of content. While images and videos can be tagged manually, as a result of developments in machine learning and in particular deep learning, we can now do this automatically with good accuracy, with a wide spread of objects and activities, and with reasonable computational overhead [Current approaches to describing images and video on the internet is by overhead .There is a large volume of scientific activity in the multimedia community to evaluate the effectiveness of automatically generated image and video descriptions with a variety of benchmarking activities and data challenges. These include the semantic indexing task for video in TRECVid , 3, the activities that happen in a video, the actions and movements of objects, where simple tags are not rich or powerful enough to capture those activities or the movements. For example, temporal relationships can occur like somebody did something and then something else happened, or spatial relationships can be important like somebody did something while behind them something else happened. Such relationships are just not suited to being described by simple tags.When it comes to describing video content, tagging becomes less attractive for video than it is for images. This is because objects in a video can appear and disappear or be occluded during the playback of a video. Thus tagging, if it was to be used, would need to be temporal and perhaps localised within video frames to show the objects that are being tagged. Tracking of tagged objects throughout a video shot might then be done based on bags of tags, one bag for each frame or object appearance. More problematic is detecting and then describing the The alternative representation for videos is captions, descriptive narrative text which explains or describes what is happening in a video. The problem with using captions is that by its nature, videos can be so rich in terms of their content and there can be so much happening in a short video clip, that unlike image tagging where there can be a ground truth against which to measure, there is no single correct caption for a video.In this paper we present a way to evaluate the accuracy and effectiveness of automatically-generated captions for short video clips. Our approach uses human assessments as part of the evaluation process and our work was carried out in the context of the 2016 and 2017 TRECVid Video-To-Text (VTT) pilot and full tracks respectively. The paper is organised as follows. In the next section we motivate the work by showing the need for having a human-in-the-loop for evaluations where there is no gold standard or ground truth against which to measure automatically. We then describe how in previous work we have involved human assessment in evaluations of the accuracy of machine translation. Following that, we give an overview of the TRECVid VTT task, the data used, runs submitted by participants in 2016 and metrics used while after that we describe our contribution, a method to incorporate human assessments into video captioning. Finally, in the last section we describe how we have used this human-in-the-loop for a subsequent evaluation.We know it is difficult to evaluate generating video captions, either manually or automatically generated, because there is no absolutely correct answer, and thus nothing to measure new systems against. This creates challenges in terms of scientific validation and replication. Scientific research demands evaluations which are reliable and reproducible and thus independently verifiable and we want to achieve this with automatic captioning so we can see which techniques and approaches work best. While this may appear to be an intractable situation, there are other areas of research where even without ground truth, evaluations can be carried out. One of those is in social media research where there is a huge surge of interest because of the importance of social media in our lives and because social media data is now easily available.Research into social media can often have the aim of identifying some forms of behavioral patterns, such as sentiment towards issues or products, or the distribution of demographics interested in some topic, or tracking the spread, or the truthfulness, associated with news. Validating such patterns can involve tracking individual users and surveying or interacting with them. Yet social media users are scattered and generally unavailable for one-on-one interaction or for providing feedback to researchers to validate the patterns they are trying to identify or to prove.This evaluation dilemma—how to prove research findings in a credible and reproducible way when there is no ground truth—is addressed in  which deIn the case of work reported in this paper there is not a single ground truth caption for a video but instead there are many ground truths as a single video clip can have very many truthful descriptions of the video content depending on perspective, recent history, domain familiarity, even emotional state. In such an environment, asking a user to caption a video, even asking several users to caption the same video, and then measuring automatically-generated captions against these, is not robust or reliable science. What we are trying to do here is to measure the accuracy of automatically-generated video captions, some of which may be fully accurate and correct while some others will be inaccurate because the caption generation techniques are not perfect. So instead of measuring the generated captions against some pre-defined ground truth, we bring human assessment into the process and we build on parallels with human evaluations in machine translation, which we describe in the next section.Evaluation in many areas of natural language processing (NLP) takes inspiration from Machine Translation evaluation, including the tasks of automatic summarization  and gramTo this end, the main benchmark in MT is the Workshop on Statistical Machine Translation (WMT), which has recently changed status to a conference but retains the original acronym. At this workshop, upwards of 150 world-leading MT systems annually participate in an evaluation campaign, and where the official results comprise human evaluation of systems . In WMT,Recent developments in MT have seen the development of new human assessment methodologies, one of which has been adopted as the official method of evaluation at WMT, called Direct Assessment (DA) . DA invoIn the case of MT, since genuinely bilingual human assessors are difficult and expensive to source, evaluation using DA is structured as a monolingual task, where the human evaluator is required to compare the meaning of the MT output with a human-produced reference translation, working within the same language. Assessment scores are collected on a 0–100 rating scale, which facilitates comparison of system performances based on human assessment score distributions. In addition this also allows high-quality crowd-sourcing via quality control mechanisms based on significance testing of the score distributions provided by workers. The latter is highly important for carrying out assessment via the crowd, as due to the anonymous nature of crowd-sourcing services, interference from workers attempting to game the system and to maximize their profits is unfortunately unavoidable. Even when actively rejecting assessment tasks submitted by dubious crowd-sourced workers, low quality task submission rates have been reported to be as high as between 38% and 57% .The advantages of DA over previous methods of human evaluation are:Accurate quality control of crowd-sourcing ;Absolute assessment of system performances which allows measurement of longitudinal improvements in system performance ;Results for both individual translations and for systems have been shown to be almost perfectly repeatable in self-replication experiments , 14, 17;DA has been shown to be up to 10 times more effective at finding significant differences between competing systems compared to previous methodologies ;DA has been shown to be efficient and cost effective for tuning automatic evaluation metrics .In this paper we follow the Direct Assessment methodology used in evaluation of MT, and apply it to the monolingual task of comparing the quality of automatically generated video captions. In the next section we describe the video-to-text track in TRECVid, the data collection we used, the videos and the sets of descriptive captions generated for each, as well as the various evaluation metrics used in TRECVid.The TREC Video Evaluation (TRECVid) benchmark has been active since 2003 in evaluating the effectiveness of content-based video retrieval systems working on problems including, but not limited to, semantic indexing, video summarization, video copy detection, multimedia event detection, and ad-hoc video search. TRECVid is organised and run each year by the National Institute of Standards and Technology (NIST) in the US. In 2016 a new showcase/pilot “Video to Text Description” (VTT) task . In the For TRECVid VTT in 2016 a dataset of more than 30 000 Twitter Vine videos had been collected automatically. Each video has a total duration of about 6s. A subset of 2 000 of these videos was randomly selected and annotated manually, twice, by two different annotators. In total, 4 non-overlapping sets of 500 videos were given to 8 annotators to generate a total of 4 000 text descriptions. Those 4 000 text descriptions were split into 2 sets corresponding to the original 2 000 videos. Annotators were asked to include and combine into 1 sentence, if appropriate and available, four facets of the video they are describing:Who is the video describing ;What are the objects and beings doing? ;Where is the video taken When is the video taken After annotations were completed, an automatic filtering was applied to remove very short generic descriptions which resulted in only 1 915 videos as the testing dataset.https://www-nlpir.nist.gov/projects/tv2016/pastdata/video.to.text/.The VTT task for participating groups was as follows: given a set of 1 915 URLs of Vine videos and two sets (A and B) of text descriptions (each composed of 1 915 descriptor sentences), participants were asked to develop systems and submit results for automatically generating for each video URL, a 1-sentence text description independently and without taking into consideration the existence of sets A and B. For distributing the video data we used the Twitter public streaming API to collect the URLs of the vine videos and we distributed the URLs. Each team downloaded their own copies of the videos and this complies with the terms and conditions for use of vine videos. The data used in the experiments in this paper is available without restriction, including a readme file to explain data format, at In total, 16 individual complete “runs” were submitted to the description generation subtask. Evaluation of these was done automatically using standard metrics from machine translation (MT) including METEOR*  and BLEUSystems taking part in the VTT task were encouraged to take into consideration and to use the four facets that annotators used as a guideline to generate their automated descriptions.In addition to using standard MT metrics, an experimental semantic similarity metric (STS)  was alsoFigs The BLEU* results in In order to give the reader some insight into the descriptive captions actually generated, in one of our evaluation videos a young girl on a floor, indoors, plays with a dog. For illustrative purposes we have created a video re-enactment and in Below are the submitted captions for this video from across the groups (we have eliminated duplicate captions from among the 16 submissions).a girl is playing with a babya little girl is playing with a doga man is playing with a woman in a rooma woman is playing with a babya man is playing a video game and singinga man is talking to a cara toddler and a dogWhat this shows is that there are good systems that do well in assigning captions, and others that do not do well in terms of the captions that they generate. Similarly there are videos which are easier to caption than others, and each approach does well on some videos and badly on others, but not consistently so. For detailed information about the approaches and results, the reader should see the various group workshop reports from the participating groups and these are MediaMill from the University of Amsterdam , the InfIn addition to the BLEU* and METEOR* metrics, a semantics-based metric was also used in the VTT evaluation. This was the UMBC EBIQUITY-CORE metric  developeInstead, as http://swoogle.umbc.edu/SimService/, to calculate semantic similarities among submitted captions. For the best-performing submitted run from each of the 5 groups (according to the other measures), for each video plus one of the sets of human annotations, we calculated the 6 × 6 STS similarities allowing us to see how semantically “close” or how “far” each of the submitted runs and the human annotation is to the others. Averaged over the 1 915 videos, this is shown in We used an API to the UMBC STS semantic similarity score available at What we observe from this analysis is that the INF group from Carnegie Mellon generates captions which are closer to the captions generated by the others including the humans than do the groups from NII, MediaMill, DCU, Sheffield, or even the human annotation, in that order. This is visible from the graph in wisdom of the crowds type of evaluation, where the “best” performing system was the one that was close to all the others, and had fewest outliers, then the INF submission would be best. However this is evaluating caption performance from within the set of submitted runs rather than externalising the evaluation process, and this says nothing about absolute, only comparative performance.What this analysis means that if there was a The first observation to make about the VTT task is that there was good participation from among TRECVid groups and that there are submitted captions with impressive results. Not all generated captions are correct or impressive, but there are enough good ones to be encouraged, meaning that proper evaluation for this is really now needed.comparative performance across participating groups but such analysis does not offer any possibility for longitudinally tracking any progress over multiple iterations of the VTT task.In terms of metrics used, METEOR* scores are higher than BLEU*, and in retrospect the CIDEr metric   should aOne aspect that became apparent as we looked at the approaches taken by different participants  is that Inspired by the many advantages of Direct Assessment for evaluation of MT systems outlined earlier, we investigate the possibility of adapting DA human assessment to evaluation of video captioning. In DA, the standard set-up for MT is to present human assessors with a human-produced reference translation and an MT output in the same language and ask them to rate how well the latter expresses the meaning of the former. In DA for MT, it is necessary to create a human-produced high quality reference translation as a target of gold standard instead of the original source language input, to avoid requiring bilingual human assessors. In the case of video captioning, substitution of the video with a human-produced caption would be risky, due to the ambiguity involved in a human coming up with a caption for a video, as there are many correct but distinct captions for a single video, the meaning of which may not directly correspond to one another, unlike reference translations in MT. This risk is clearly illustrated in Fortunately, however, substitution of the video with a human-produced caption is not only risky, it is also unnecessary, as the video can itself be included in the evaluation and viewed by the human assessors before they rate an automatically generated caption. Subsequently, we ask human assessors to firstly watch the video before reading the caption, and then assess how adequately the caption  describes what took place in the video. Assessors are asked to rate the caption quality on a scale of 0 to 100.As in DA for MT, we devise a mechanism for distinguishing genuine and diligent human assessors of video captions from those attempting to game the service or those who are simply not applying sufficient human intelligence to the task, by establishing the consistency of individual workers at scoring high and low quality captions for videos in the test set.We therefore include in the evaluation of systems, an additional system comprising a set of human annotations for the video captioning test set, (A), that will act as a set of captions for which we expect to receive high scores from workers. We then create a corresponding set of low quality captions for those videos by automatically degrading each the human caption in (A). Captions are automatically degraded by randomly selecting a non-initial/non-final sequence of words within the original human caption and replacing it with a sequence of words randomly selected from the human caption of a different video. In this way, the sequence of words being substituted is a fluent sequence of words, making it difficult to spot without reading the entire caption, to help avoid further gaming approaches. The length of the phrase to be replaced is determined by the number of words in the caption to be degraded, as shown in To illustrate these substitutions, As in MT evaluation using DA, Human Intelligence Tasks (HITs) are structured as 100-captions per HIT (or 100-translation HITs for MT) as this allows a sufficient number of pairs of high quality and low quality captions to be hidden within HITs and collected from each worker who participates. A minimum of 10 such pairs of high and low quality captions are collected from each worker and a paired significance test is then applied to the score distributions of high and low quality captions for each individual worker. The p-value produced in the test is employed as an estimate of worker reliability to score low quality captions lower than the corresponding high quality captions, with a lower p-value indicating a more consistent human assessor.In order to investigate the viability of our new video captioning human evaluation methodology, we carried out an evaluation of systems participating in TRECVid in 2016, described earlier in this paper. We include in the evaluation a single submission for each team that participated in the competition, nominated by the team from the runs they originally submitted.All data was collected anonymously, and the study conformed to the guidelines and principles of the Declaration of Helsinki. The protocol was approved by the Dublin City University School of Computing Research Ethics Committee as it falls under the University’s category of “notification only” and was given a waiver of the requirement for signed consent because it is an anonymous online survey.Crowd-sourced workers were paid at the same rate as in our MT experiments, at 0.99 USD per 100-caption HIT, and including the 20% Mechanical Turk fee this resulted in a total cost of 110 USD for the evaluation of five systems, or 22 USD on average per system. The cost when adding additional systems increases at a linear rate. A total of 90 workers completed at least a single 100-video caption HIT on Mechanical Turk with a relatively high proportion of those, 72 (80%), meeting our quality control requirement of a p-value less than 0.05 for significance of differences in scores they assigned to high quality and low quality captions. In addition to including high and low quality captions within HITs, we also include exact repeats of the same video and caption sampled across all systems included in the evaluation, in order to check that workers who can distinguish between the quality of high and low quality captions, also consistently score repeats of the same captions. 100% of workers who passed quality control also showed no significant difference in score distributions for repeat assessment of the same caption.z scores which are the number of standard deviations from the mean a data point is according to that individual’s mean and standard deviation score overall. This allows any possible bias introduced by, for example, an overly harsh worker evaluating a higher number of captions from any system. Scores provided are then averaged for each caption in the test set, as some captions will have been assessed once and others multiple times, and this avoids final scores inadvertently being weighted by the number of times a given caption was assessed. The final score for a given system is then simply the average of the scores attributed to its captions.Final scores for systems are computed by firstly standardizing the raw scores provided by each worker to z score distributions for systems according to Wilcoxon rank-sum test. As expected, the human captions, Human-b, achieve the highest score overall, at 88.2%, and including such a human system allows an estimation of the score that could be expected from a system that has effectively solved the video captioning problem. Scores for the automatic systems range from 37.7% to 66.2%, showing the best automatic system to be still some distance from human annotation quality. In terms of statistical significance, we see an almost absolute ranking of systems, with only a single pair of systems (INF & DCU) tied with no significant difference in their scores.z scores for systems, the official method of system ranking we recommend. The very high correlation between scores for systems confirms that the method of evaluation is reliable, producing system rankings that are almost perfectly reproducible for evaluation of video captioning.In order to investigate the reliability of the results produced by the new DA video captioning evaluation, we re-ran the evaluation in an entirely separate and repeated data collection/assessment on Mechanical Turk and compared results. As mentioned previously, in MT the use of automatic metrics is validated by how well a given metric correlates with human assessment. Since we now have human assessment of captions for systems participating in TRECVid 2016 VTT, we can therefore examine how well metric scores used to produce the official results in that year’s benchmark correlate with human assessment. As can be seen in negative correlation of METEOR* scores with human assessment of −0.602 for video captioning, as shown in Finally, STS scores also show low agreement with human assessment, as the scatter plot in p < 0.01) and STS (at p < 0.05).It should be noted, however, that the correlations we report here may not provide an entirely reliable evaluation of metrics for VTT. Both the human and metric-based evaluations reported are only based on a small sample of five VTT systems, and therefore correlation point estimates are not highly reliable. Significance tests, recommended for evaluation of MT metrics and also suitable for VTT metric evaluation, such as Williams test , 32, do In this paper we have introduced direct assessment, a method for incorporating human judgments into an evaluation of automatic video captioning. Using data from the 2016 VTT track in TRECVid we have shown how this method is robust. Even though direct assessment requires human judgments and ratings of how well a caption describes a video, this can be outsourced to a service like Mechanical Turk meaning it can be carried out in a relatively cost-effective manner.One of the known problems with crowdsourced judgments as we use in direct assessment, is achieving consistency and quality across human judges. We address this by automatically modifying candidate captions and degrading their quality and examining how the degraded captions are rated by the human judges. This allows us to apply quality control to the assessors meaning that direct assessment can be replicated consistently, something we demonstrated in the paper.As part of the evaluation of performance in the VTT track in TRECVid 2017, we used the DA method in addition to BLEU, METEOR and the other standard metrics with an increased number of groups participating as described in . We used


The Grog Survey App is a visual and interactive tablet computer-based survey application. It has been shown to be an accurate and acceptable tool to help Indigenous Australians describe what they drink.The Grog Survey App was used to enquire into patterns of drinking in a stratified sample of Indigenous Australians in urban and remote/regional sites during testing of the App. The App asked about the last four drinking occasions in the past 12 months, including preferred alcohol types and containers; and symptoms of alcohol dependence, based on ICD-11 descriptions. Drinking patterns are presented here using medians and interquartile ranges, and the thresholds set out by the Australian National and Health and Medical Research Council guidelines. Patterns of consumption are compared by gender and remoteness, using Wilcoxon rank-sum test to compare medians. Logistic regressions tested whether alcohol types and drinking containers varied by remoteness.r = 0.34–0.38).In this stratified sample most people either consumed nothing (21.7%), or consumed quantities which placed them at short- (95.6%) or long-term risk (47.8%) of harms. Drinkers in remote areas were more likely to drink beer, but less likely to drink pre-mixed spirits. ‘Stubbies’ and other beer glasses were popular in urban areas, compared with ‘slabs’ (cases of beer) in remote/regional areas. The use of improvised containers (i.e. empty juice bottles) did not vary by remoteness. Nearly one in six (15%) current drinkers reported experiencing at least two symptoms of alcohol dependence at least monthly. Average drinks per day was the consumption measure most highly correlated with each dependence symptom (The App was able to capture a wide range of preferred alcohol types and containers, and demonstrate a diversity in how alcohol is consumed. This detail was captured in a relative brief survey delivered using an interactive and appealing tablet computer-based application. Alcohol is consistently reported as a key concern for Aboriginal and Torres Strait Islander (Indigenous) peoples and communities of Australia , 2. As wHousehold surveys help inform communities and policy-makers about a range of health risk behaviours. However, there is a lack of reliable data on alcohol use in Indigenous Australians –14 whereSeveral studies, ranging from single communities to national household surveys, have reported on patterns of drinking in Indigenous Australians. Many of these were conducted two to three decades ago –19. MostSeveral authors have commented on the difficulty of obtaining accurate self-report data on alcohol use from Indigenous Australians due to factors such as episodic drinking and sharing of drinks  that areTo address these difficulties in collecting self-report alcohol use data , we developed the Grog Survey Application  , the peak body for Aboriginal community controlled health services in South Australia; and the Aboriginal Drug and Alcohol Network, representing Aboriginal alcohol and other drug workers in New South Wales. Ethical approval was obtained from AHCSA (#04–15-621) and from Metro South Health Human Research Ethics Committee in Queensland (#HREC/16/QPAH/293).As recruitment was designed to test the validity of the App with a range of drinkers, and for both genders, stratified convenience sampling was used. Recruitment has been described elsewhere . We aimeIn urban Queensland (Qld), recruitment was based in an Indigenous primary health care service and surrounding community (August to November 2016). In South Australia (SA), recruitment centred on a regional ACCHS and a remote Aboriginal community controlled drug and alcohol ‘day centre’ . Individuals were eligible for inclusion if they self-identified as being Aboriginal and/or Torres Strait Islander and were 16 years or older. Exclusion criteria included obvious intoxication. Participants were reimbursed for their time with a store voucher.Development of the App and the composition of its survey items have been described elsewhere . BroadlyThe App includes: culturally appropriate questioning style and gender-specific voice and images; ‘translation’ to colloquial English and (for audio) to the local Indigenous language (Pitjantjatjara); interactive visual approaches to estimate quantity of drinking; images of specific brands of alcohol, rather than abstract description of alcohol types (e.g. ‘spirits’); images of commercial and make-shift drinking containers (e.g. empty soft drink bottles); an option to estimate consumption based on the individual’s share of what the group drank; key time points to explain time references for communities that do not routinely use calendars  method  to assess = .81, n = 181, all participants; rs = .81, n = 147, drinkers only). In this testing in regional/remote South Australia and urban Queensland, the App was also found to be highly acceptable [The App has been found to be as good or better at identifying risky drinking compared with a clinical interview by an Aboriginal health professional . Averageceptable .Some people’s hands shake when they stop drinking or before their first drink of the day. How often does this happen to you?”; 2) Loss of control – “Some people feel like grog is the boss of them. How often do you feel grog makes all the decisions ?”; and 3) Prioritising alcohol over other things – “Some people spend more time drinking grog than doing other things they need to do, like looking after family, culture or work. How often does this happen with you?”. Responses for each item were indicated on a five point Likert scale ranging from ‘never’ to ‘most days or every day’. Participants were considered to be dependent if they experienced two or more symptoms at least once per month.Participants were asked about: 1) Alcohol withdrawal tremors – “We expected that drinking patterns, and container usage would vary by remoteness. Specifically, we anticipated that individuals in remote communities would be more likely to use non-standard drinking containers.All analyses were performed in R . MediansSD = 13.9) years. Just under half of participants had completed high school beyond Year 10 . The majority of participants were unemployed . Employment did not significantly vary by remoteness . However, more males (42.9%) were employed, than females .Participants were 263 Indigenous Australians  from four communities . Participants had a mean age of 38.7  said that they drank alcohol in the previous 12 months . However, despite stratification for gender, men were more likely to be classified as drinkers than women .In keeping with the stratified recruitment, nearly eight in ten participants . Among drinking participants, drinking occasions were relatively infrequent, with a median of 3.5 drinking occasions per month (IQR = 4.7). However, the median number of standard drinks per occasion was high, at 17.3 (IQR = 19.5). When drinking is averaged over the month, participants consumed a median of 1.6 (IQR = 4.2) standard drinks per day. The median drinking group size was four drinkers (IQR = 4.0). Most drinkers (79.6%) reported having had a ‘dry patch’ (i.e. an extended period of time where they did not drink in the past 12 months). Median dry patch duration was 60 days (IQR = 128.5).The majority of drinkers in this stratified sample consumed at levels which placed them at short- (95.6%) or long-term risk (47.8%) of harms from drinking. Only a small number of drinkers reported drinking below the recommended national guidelines .In this sample, drinking patterns did not vary by remoteness. Wilcoxon rank sums tests showed that the number of drinking occasions per month, average standard drinks per day, standard drinks consumed per drinking occasion, and group drinking size were similar for participants in urban and in remote/regional settings  current drinkers. A series of logistic regressions were conducted to better describe whether remote/regional drinkers were more or less likely to report certain types of alcohol and drinking containers. While remote drinkers were more likely to drink beer, they were less likely to drink pre-mixed spirits  were used more in remote/regional areas. The use of improvised containers (i.e. an empty juice or soft drink bottles) did not vary by remoteness Table .Table 4r = 0.34–0.38), however, other drinking indicators (drinking frequency and drinks per occasion) also each correlated significantly with each symptom of dependence. There was a strong correlation between each of the three dependence symptoms (r = 0.57–0.61).Nearly one in six 15%) of current drinkers reported experiencing at least two symptoms of alcohol dependence at least monthly. Table % of currThis study is unique in that it presents detailed examples of alcohol use behaviours in Indigenous Australians from two states, and from both urban and regional/remote settings, using a newly designed, tablet computer-based survey tool. Unlike national household surveys , 7, thisThis sample was stratified as it was part of a study designed to test the App’s performance across a range of drinkers. The results on drinking patterns are valuable as an illustration of the range of drinking patterns, and the ability of this survey tool to capture them. However, they should not be mistaken for prevalence data.Relative to national averages, this sample’s participants tended to be older, and it included more males, and more unemployed individuals. By contrast, in the 2016 Australian census, 50.4% of Indigenous people are female, the median age is 23 and 18.2% are unemployed . More thWe set out to recruit different types of drinkers but were unable to recruit many drinkers who consumed within recommended national guidelines . This could be because lighter drinkers were not known by Aboriginal field research assistants to be drinkers, and so were less likely to be recruited with this convenience stratified sampling. It also could have occurred if low risk drinking was relatively uncommon in the relatively low socio-economic regions where recruitment took place. By comparison, just over one in eight (13%) urban Indigenous Australians in a national urban household survey were low-risk drinkers in a 1994 survey, which is reportedly one of the most accurate available , 12. ThaEpisodic drinking was common in this sample, with relatively low frequency of consumption . However, when people did drink, they reported a high median number of standard drinks per occasion . These figures are plausible, as a similar heavy episodic pattern of drinking was seen in the 1994 national survey of urban Indigenous Australians (aged 14+), in which the commonest category of consumption was 13+ standard drinks per occasion  , 29. InsPattern of drinking to intoxication is also seen in the developing world, where drinkers tend to be polarised into non-drinkers and risky drinkers, with few low-risk drinkers . StudiesDrinkers in this sample sometimes had protracted dry periods between drinking days (median of 30 days for men and 90 days for women). We expected that drinkers from remote communities would have longer dry periods than urban drinkers, particularly as some remote participants came from regions where access to alcohol is restricted. However no difference was found in dry period length based on remoteness . This finding is consistent with studies , 32 thatDry periods, such as those reported in this study, would be difficult to capture in commonly used survey and screening tools. For example the screening tool AUDIT-C (Alcohol Use Disorders Identification Test-Consumption), which is recommended for use in Aboriginal community controlled health services in Australia, would not capture this information as it assumes regular patterns of drinking. For example, AUDIT-C question 1 asks: “How often do you have a drink containing alcohol?” .The Australian Bureau of Statistics’ National Health Survey uses a seven day diary method . Our datAs our sample was stratified by drinking levels it is not suprising that we did not find differences in quantity consumed between urban and regional/remote sites. National surveys of Indigenous Australians report that individuals from non-remote areas (55%) are significantly more likely to consume alcohol at levels which place them at short-term risk of harms from drinking than those in remote areas (48%) . This maAmong urban and remote drinkers, beer (60.7%), premix (46.6%) and spirits (19.9%) were consumed by most drinkers. While urban drinkers were twice as likely to report having consumed premixes, remote/regional drinkers were 2.6 times likely to report beer. These findings reinforce the challenge of supply control measures that target only one alcohol type (e.g spirits or cask wine). Some studies suggest that Indigenous Australians who drink (as with other drinkers) may switch their preferred beverage type to access the cheapest alcohol , 37. ThiThis is the first study to report on preferred drinking containers, including non-standard containers such as empty soft drink or juice bottles or a metal mug (pannikin) that alcohol is poured into. The interactive tablet computer interface allowed collection of such detail. Data from this sample suggests a diversity in container preference between the urban and remote/regional sites. We had expected remote drinkers, who are often drinking in bush or parkland, to be more likely to use improvised containers. However, improvised containers were used just as commonly in urban settings. This may reflect both the culture of sharing, and relative socioeconomic disadvantage of the recruitment sites.A broad pattern emerged where remote/regional drinkers were more likely to consume from containers in which alcohol is typically sold in bulk (i.e. cans of beer sold in a case) and less likely to drink from single containers commonly available from licensed venues . This may be due to travel by remote drinkers to access alcohol if they live in a community with alcohol restrictions. If so, they may purchase alcohol in bulk . Also, iThe App survey included a screen for dependence based on an operationalisation of the three key features of alcohol dependence (ICD-11) . Depender = 0.61), or prioritising alcohol over other things (r = 0.57). Similarly, as expected, the average number of drinks per day was also modestly correlated with symptoms of dependence (r = 0.34–0.38). Further validation study, and data on the prevalence of dependence would be valuable to assist with service planning, particularly given the reports of shortage of detoxification and residential rehabilitation beds for Indigenous communities [Concerns have been expressed about the ability of researchers or clinicians to measure dependence across cultures, including how readily certain concepts such as salience or loss of control translate across cultures . Howevermunities .As this study used stratified sampling, these results do not provide estimates of prevalence but rather examples of a range of drinking patterns. The higher unemployment rate found in this sample may have been associated with higher alcohol consumption figures consumption . There wA stop-start pattern of drinking with heavy per occasion consumption was common in this stratified sample of urban, regional and remote Indigenous drinkers. The wide range of preferred alcohol types and containers suggests a diversity in how alcohol is consumed, including differences by remoteness. These survey results demonstrate the depth of detail that can be collected using a visual, interactive and appealing tablet computer-based format. This tablet computer-based App was able to reach a population otherwise difficult to observe by conventional research strategies. Such technology offers new potential to understand drinking patterns in populations that can be hard to reach by pen-and-paper or face-to-face surveys.


Mycobacterium marinum is an opportunistic pathogen inducing infection in fresh and marine water fish. This pathogen causes necrotizing granuloma like tuberculosis, morbidity and mortality in fish. The cell wall-associated lipid phthiocerol dimycocerosates, phenolic glycolipids and ESAT-6 secretion system 1 (ESX-1) are the conserved virulence determinant of the organism. Human infections with Mycobacterium marinum hypothetically are classified into four clinical categories (type I–type IV) and have been associated with the exposure of damaged skin to polluted water from fish pools or contacting objects contaminated with infected fish. Fish mycobacteriosis is clinically manifested and characterized in man by purple painless nodules, liable to develop into superficial crusting ulceration with scar formation. Early laboratory diagnosis of M. marinum including histopathology, culture and PCR is essential and critical as the clinical response to antibiotics requires months to be attained. The pathogenicity and virulence determinants of M. marinum need to be thoroughly and comprehensively investigated and understood. In spite of accumulating information on this pathogen, the different relevant data should be compared, connected and globally compiled. This article is reviewing the epidemiology, virulence factors, diagnosis and disease management in fish while casting light on the potential associated public health hazards. Mycobacterium marinum, M. fortuitum and M. chelonae are among the most identified NTM mycobacterial species associated with fish mycobacteriosis  , lipoarabinomannan (LAM), phthiocerol dimycocerosates (PDIMs), phenolic glycolipids (PGLs)  (Gangadharam and Jenkins ) Draper . These g Brennan .M. marinum is an ubiquitous waterborne bacterium with an optimal growth temperature around 30 °C, which causes the infection of bats, fish, mice and amphibians after its inoculation  have been recorded to induce pathogenicity in fish  causing sturgeon mycobacteriosis as evidenced by PCR-denaturing gradient gel electrophoresis and library sequencing of rpoB gene  examined spleen samples from striped bass Morone saxatilis  and the frequent transfer of fish between the aquaria  were associated with acute and sub-acute infections  which if interrupted, attenuation of M. marinum in mammalian, fish, and protozoan cells will occur, referring to their significance for the pathogen in different hosts  can play an important role as a virulence effecter. Partial regaining of secA2 virulence following the overexpression of PknG confirms the role played by this protein in controlling the mycobacterial virulence and restoring blockage of phagosomal maturation  isolated from different sources  was first explained in 1997  and then a secondary amplification using FRET in real-time PCR.Direct sequencing from fish tissues can be a useful option when the culture of Mycobacteria fails , but still only certain strains of M. marinum have zoonotic potential  to help guide therapeutic options  lesions marked by superficial cutaneous infection, appearing in forms of crusted or ulcerated nodules or verrucous plaques. These single lesions develop within weeks or months of contact with infected fish  lesions with inflammatory nodules or in a sporotrichoid spreading pattern or with abscesses and granulomas in an immune-suppressed patient. This ‘sporotrichoid’ infection starts with distal inoculation and can progress to nodular lymphangitis (Bartralot et al. M. marinum appears as deep infections associated with or without skin infection signs including arthritis, tenosynovitis, osteomyelitis and/or bursitis. Type IV M. marinum is disseminated infection with lung disease and other systemic manifestations. Bacteraemia is very rare but may occur in severely immuonocompromised patients (Bhatty et al. M. marinum infection were also reported. Severe intranasal lesions resulted also from M. marinum infection (Asakura et al. Type II 12.M. marinum infection is practically required for rapid recovery in man, avoiding progress to deeper tissues. Insufficient data about efficacy of many treatment regimens (Gluckman M. marinum is a naturally multi-drug resistant organism, and the treatment is primarily dependent on the investigators and their personal experiences (Edelstein The proper treatment of Gluckman  render tM. marinum is more resistant. Treatment of infected deeper structure takes longer periods and the acquired resistance has not been recorded in M. marinum while clinical awareness is very important to initiate the diagnosis and the treatment (Aubry et al. M. ulcerans in the murine footpad model (Trigo et al. M. marinum infections.In case of a sporotrichoid distribution pattern, a combination of two drugs, namely ethambutol and rifampicin is recommended. Streptomycin, isoniazid and pyrazinamide should be excluded from treatment regimens because M. marinum infection can have adverse effects on the fish of fresh water, marine and brackish water, constituting zoonotic implications. The data on the pathogenesis and virulence factors of M. marinum are still scarce and questionable. Further studies are required to trace the immune defense responses against M. marinum infection in fish. Prophylaxis and vaccine development are extremely important to protect different aquaria from M. marinum infection. The advent of molecular diagnostic tools and advanced epidemiological studies on fish mycobacteriosis can enhance our understanding of the strategic plans designed for controlling such disease. Due to its communicable public health hazard, the disease should be cautiously avoided by voiding swimming in fish pools and wearing gloves during handling and processing of fish. Future studies should also evaluate the application of phage therapy in the fish aquarium to prevent and control M. marinum infection.Piscine mycobacteriosis arising from


Biomolecular recognition using a multivalent strategy has been successfully applied, this last decade on several biological targets, especially carbohydrate-processing enzymes, proteases, and phosphorylases. This strategy is based on the fact that multivalent interactions of several inhibitory binding units grafted on a presentation platform may enhance the binding affinity and selectivity. The zinc metalloenzymes carbonic anhydrases  are considered as drug targets for several pathologies, and different inhibitors found clinical applications as diuretics, antiglaucoma agents, anticonvulsants, and anticancer agents/diagnostic tools. Their main drawback is related to the lack of isoform selectivity leading to serious side effects for all pathologies in which they are employed. Thus, the multivalent approach may open new opportunities in the drug design of innovative isoform-selective carbonic anhydrase inhibitors with biomedical applications. The bicarbonate is then displaced by a water molecule and released into the solution leading to the catalytically inactive acid form of the enzyme. The regeneration of the basic form is carried out by a proton transfer reaction from the active site to the environment with the assistance of histidine residues. There are 15 known isoforms in humans, and 12 of them are enzymatically active, and thus considered targets of carbonic anhydrase inhibitors (CAIs). By taking advantage of 40 years of research and with the help of structural studies, different drug design campaigns inspired new ideas and contributed significantly to the discovery of effective inhibitors with diuretics, antiglaucoma, anticancer, or antiobesity properties, or for the management of a variety of neurological disorders, including epilepsy and altitude disease . NF. NF11, o2 hydration assay method against cytosolic isoforms hCA I, hCA II as well as the two tumor-associated isoforms hCA IX and hCA XII showed a low nanomolar activity of NHFS 14 with inhibitory activity ranging from 0.67 to 6.2 nM against all tested isozymes. Comparison of the inhibitory activity of the multivalent NHFS 14 vs. the monovalent inhibitor, revealed an increased inhibitory potency for the multivalent system respectively of 32 times for hCA I, 72 times for hCA II, 14 times for hCA IX and 5 times for hCA XII. Multivalent effects were detected only with hCA I and hCA II with a relative potency normalized to the sulfonamide units (rp/n) being equal respectively to 2.7 and 6. No multivalent effect was observed for hCA IX and hCA XII. The difference of the effect was hypothesized to come from steric hindrance effects as hCA I and II are monomeric and hCA IX and XII dimeric enzymes. This may also suggest that multivalent binding occurs through enzyme clustering. [Inhibition study realized with a stopped-flow COCurrently, other silica nanoobjects are investigated as potential multivalent systems with potential applications in the field of carbonic anhydrase inhibition. Nanorods did become particularly attractive within the nanomaterial-based compounds for biomedical applications, as they possess specific optical and thermal features that make them proper innovative tools. Nanorods are perfectly suited for Near-InfraRed light (NIR) absorption and conversion of its energy into thermal radiation with the generation of very minimal structural defects to the material after its exposure to multiple cycles ,17,18. S15 was achieved by means of autocatalytic reduction of chloroauric acid with ascorbic acid in the presence of cetrimonium bromide, silver nitrate, and ultra-small gold nanospheres according to the procedure described in the literature [N-hydroxysuccinimide/1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (NHS/EDCI) catalyzed amidation protocols to afford the CAI ethylaminobenzenesulfonamide coated nanorods 16 and the 2-methoxyethylamine derivative nanorods 17 as a negative control. The obtained gold shells 15, as well as the coated nanorod batches 16 and 17, were properly characterized for their physical and optical properties by mean of Transmission Electron Micrograph (TEM) and optical extinction spectra  and human mammary adenocarcinoma MDA-MB-231 (MDR) cells after exposure to 24 h. Both HCT and MDR cell lines under normoxic and hypoxic conditions were incubated with CAI- and 2-methoxyethylamine capped nanorods orods 16 . Such re2 . This study was the first to report and successfully proof the biomedical application of CAI coated nanorods as potential tools for the treatment of hypoxic tumors and therefore expressing the hypoxia-induced hCA IX isoform. Further studies using the in vivo model of the disease will be necessary in order to give full credit to the research outcomes.As reported in Vibrio cholerae, Trypanosoma cruzi, Leishmania donovani chagasi, Porphyromonas gingivalis, Cryptococcus neoformans, Candida glabrata, and Plasmodium falciparum) which was detected only for some of them [n”, allow a precise number of functional groups to be incorporated in the macromolecule by means of standard protocols.Dendrimers are defined as repetitively branched molecules that assume spherical and symmetrical morphology. Dendrimeric scaffolds have been found useful for various applications such as the biomedical ones, which are pertinent for the purposes of this review . Some of of them . The cho of them ; (ii) thN-hydroxysuccinimide (NHS)-activated carboxylic ester of the phenyl sulfanilamide 18.The synthetic chemistry approach applied is depicted in 18, the sulfonamide functionalized dendrimers 19–22 and the reference CAI dorzolamide (DRZ) were assayed in vitro for their inhibition properties against the physiologically relevant hCA isoforms  and the data are reported in The activated ester 19–22 possess inhibition potencies towards the hCAs tested, which progressively increase with the generations (1 (KIs) from G0 to G3 registered potency improvements (rp) of 9142 for hCA II and of 6333 for hCA XII respectively. The rp normalized data onto the sulfonamide units (n) inserted in each dendrimer (rp/n) were of 285.7 for hCA II and of 197.9 for hCA XII, respectively, thus indicating significant multivalency effects.Overall, the obtained kinetic data showed the dendrimeric derivatives erations . Such a erations . As repotions . In particular, the CAI derivatized G1–G3 generations showed a remarkable ability to maintain constantly reduced IOP values over the experiment time course of 120 h. Although additional studies were not conducted, it is reasonable to speculate that such performances were obtained by means of various effects collectively taking place, which among others, include the release of the CAI units by hydrolytic processed [The same study reported the successful application of such compounds for the management of ocular hypertension in an animal model of glaucoma. Quite interestingly, all G0–G3 CAI coated dendrimers showed intraocular pressure (IOP) lowering effects far more superior and time lasting when compared to the standard CAI rocessed  and tran23 and polyol-scaffolds 24–26 . To prepare the cyclic peptide, cyclization under high-dilution conditions was followed by oxidative cleavage of serine side-chains in order to unmask the glyoxylic aldehyde groups. The synthesis of the linear peptide was realized via acetylation of the N-terminal position, followed by cleavage and deprotection, and finally, oxidative cleavage of serine side-chains. Hydrazone and oxime ligation were performed respectively with the corresponding monovalent hydrazide or oxyamine sulfonamide inhibitors. [Both peptide scaffolds ibitors. 27 and 28 were less potent than the monovalent system against the membrane-bound isoforms hCA IX and hCA XII. The only improvement of potency was observed against hCA II with a relative potency (rp) increased by 13- and 5-fold, respectively.The inhibitory activity showed that multivalent oxime conjugates 29 and 30 showed an improved potency against hCA II, hCA IV, and hCA XII compared to the monovalent inhibitors. Moderate multivalent effects against isoforms II, IV, and XII with rp/n > 1 were characterized. In each case, the pre-organized multivalent conjugates made of the cyclic scaffold, 27 and 29, were more potent than the conjugate made of the linear scaffold. The results obtained in this study suggest that the multivalent effects act through an increase in the local concentration of CA inhibitors against the enzymes. [Multivalent hydrazide conjugates The multivalency approach was successfully applied to the design of CA inhibitors belonging to a variety of classes  ,31,32 an


Kidney transplantation is the most efficient method of renal replacement therapy. When this method is performed, native urinary bladder is the preferred urinary reservoir. However, in some patients with an anatomically and functionally abnormal lower urinary tract, the urinary bladder cannot be used for transplantation. In these patients, urinary diversion should be performed before kidney transplantation. We present a case of a 32-year-old male patient with orthotopic kidney transplantation performed using a colon pouch (Mainz-pouch III). He was born with severe anomalies including sacral agenesis, anorectal atresia, and hypospadias, which were corrected during childhood. Neurogenic bladder with severe vesicoureteral reflux led to end-stage renal disease. This dysfunctional bladder was unsuitable for kidney transplantation, and a staged approach for future transplantation was chosen. The first step was the creation of urinary diversion. Due to a short appendix, we created a continent, colon pouch (Mainz pouch III). Two years later, orthotopic kidney transplantation was performed using a right cadaveric kidney. The renal vessels were anastomosed to the aorta and inferior vena cava and the pyelon to the native ureter. Four years after transplantation, the patient has stable renal function without any complications. This is the first documented case of using Mainz-pouch III as a reliable option for kidney transplantation in selected patients. At the beginning of the era of kidney transplantation (KT), a normal urinary bladder was considered an indispensable condition. Over time, the patients with dysfunctional urinary bladders became candidates for transplantation. The first KT using an ileal conduit in a patient with a severely damaged urinary bladder was done in 1966  have abnormalities of the lower urinary system, which can lead to kidney deterioration . In the Urinary diversion is defined as the redirection of urine flow from its physiological route as a consequence of a diseased or defective ureter, bladder, or urethra. In most cases, this diversion creates a route that leads to the skin (urostomy), but it could also lead to other systems . Some of them have a continent mechanism (Mainz pouch I), and others do not . Definitive urinary diversion includes ureterosigmoidostomy (Mainz pouch II), incontinent cutaneous urinary diversion , and continent cutaneous urinary diversion .We present a patient from our transplant center in whom orthotopic kidney transplantation was performed using a colon pouch (Mainz-pouch III). This is the first described case of such transplantation in the literature.The patient was born with significant congenital abnormalities  . ImmediaThe first operation was performed in November 2012 using a midline laparotomy approach. Because of recurrent left sided pyelonephritis, we removed the left kidney along with the ureter and removed urostomy. The right kidney and right ureter were preserved. Another part of this operation was the creation of urinary diversion for future transplantation. The small and large bowel were mobilized carefully. Preoperatively, we planned to create an ileocolonic reservoir (Mainz pouch I); however the appendix, which serves as the connection between the skin and the pouch, was too short. Therefore, we decided to perform another type of urinary diversion, Mainz pouch III. Mainz pouch III is a colonic, continent reservoir. We isolated a part of the ascending and transverse colon (approximately 35 cm) for the creation of a reservoir with adequate capacity. The operation was performed as initially described by Leissner et al . The rigEscherichia coli and Proteus mirabilis, more than 100 000/mL, both sensitive to ampicillin, piperacillin + tazobactam, cefuroxime, and gentamicin. A combination of piperacillin and tazobactam was administered (2 × 4.5 g intravenously) for 14 days, followed by cotrimoxazole prophylaxis (450 mg once daily) for six months. From the time of operation to the present, immunosuppressive protocol consisted of corticosteroids, mycophenolate mofetil, and tacrolimus. Twenty days after the operation, the patient was discharged from the hospital with excellent kidney function: serum urea 6.3 mmol/L and serum creatinine 103 μmol/L.In November 2014, through the Eurotransplant allocation system we received an offer for a left cadaveric kidney. The donor was a 45-year-old male with brain death resulting from a traumatic bilateral subdural hematoma. The HLA matching was as follows: HLA-A (1 match), HLA-B (0), HLA-Cw . UrinaryIn January 2015 (two months after the operation), the patient was admitted to the hospital for the removal of the JJ endoprothesis. During general anesthesia, we entered the pouch through the urostomy site in the umbilicus using a semirigid ureteroscope. Some mucus was found in the pouch and was removed. The protected anastomosis between the ureter and the pouch was visualized, and the endoprothesis was grasped and removed . One weeCurrently the most common type of urinary diversion in the kidney transplant population is the ileal conduit (or Bricker operation). The use of a colon conduit was first described by Tunner et al in 1971 . Over tiThe study with the largest number of transplanted patients with urinary diversion included 54 patients with 59 renal transplants . All patThe experience of using the large bowel for urinary diversion in KT is very limited. In Mainz pouch III as a continent, colonic pouch was first introduced in 2000 . An expeIn our center, we also started to use Mainz pouch III for urinary diversion in patients with gynecological tumors and after pelvic irradiation. This valuable experience allowed us to use this procedure as pretransplant preparation for our kidney transplant recipients. We want to point out that such operations should be performed in centers with adequate experience, especially in cases when, instead of one demanding operation, an intraoperative finding necessitates the use of a different, even more demanding, operation.The patients who undergo this type of urinary diversion must be informed about the risks of the procedure, including the risks associated with self-catheterization, and should be assessed for compliance. Self-catheterization is mandatory in continent cutaneous diversion, and most authors agree that, although potentially complicated by chronic bacteriuria, it is safe for immunosuppressed transplant patients ,13. The This technique has some advantages compared with ileal or ileocolonic urinary diversion: preservation of the ileocecal valve (without negative influence on stool frequency and enterohepatic circulation), normal intake of vitamin B12, and normal bile acids absorption . AnotherThe population of KT patients with urinary diversion is small, and their outcomes are difficult to compare due to different types of operations. The 5-year graft survival is up to 78% and 15-year graft survival is up to 69% .The use of bowel segments in urinary diversion in KT patients is associated with an increased incidence of urinary infections, metabolic changes, and possible tumor development. A few studies reported that chronic bacteriuria or urinary tract infections (UTIs) did not lead to graft loss, but the incidence of UTIs was high ,17,18. IDifferent studies show different prevalence of metabolic changes – from no changes to 85% ,22. The The development of neoplasms, mainly due to chronic immunosuppression, is a well-known possible long-term complication of organ transplantation. Primary neoplasms can be found in urinary diversion in nontransplanted patients . There iIn conclusion, the native bladder is the most efficient reservoir used for KT. Patients with severe anatomical or functional abnormalities of the lower urinary tract require urinary diversion before transplantation. Mainz-pouch III, as a colon continent pouch, can be used as a reliable type of urinary diversion in selected transplant patients.