Hydrographic surveys enable the acquisition and processing of bathymetric data, which after being plotted onto nautical charts, can help to ensure safety of navigation, monitor changes in the coastal zone, and assess hydro-engineering structure conditions. This study involves the measurement of waterbody depth, identification of the seabed shape and geomorphology, the coastline course, and the location of underwater obstacles. Hydroacoustic systems mounted on vessels are commonly used in bathymetric measurements. However, there is also an increasing use of Unmanned Aerial Vehicles (UAV) that can employ sensors such as LiDAR (Light Detection And Ranging) or cameras previously not applied in hydrography. Current systems based on photogrammetric and remote sensing methods enable the determination of shallow waterbody depth with no human intervention and, thus, significantly reduce the duration of measurements, especially when surveying large waterbodies. The aim of this publication is to present and compare methods for determining shallow waterbody depths based on an analysis of images taken by UAVs. The perspective demonstrates that photogrammetric techniques based on the SfM (Structure-from-Motion) and MVS (Multi-View Stereo) method allow high accuracies of depth measurements to be obtained. Errors due to the phenomenon of water-wave refraction remain the main limitation of these techniques. It was also proven that image processing based on the SfM-MVS method can be effectively combined with other measurement methods that enable the experimental determination of the parameters of signal propagation in water. The publication also points out that the Lyzenga, Satellite-Derived Bathymetry (SDB), and Stumpf methods allow satisfactory depth measurement results to be obtained. However, they require further testing, as do methods using the optical wave propagation properties. Bathymetric works that enable the measurement of shallow waterbody depths is necessary for acquiring geospatial information describing the marine environment. Information on a waterbody’s depth has a direct effect on navigational safety and efficiency, coastal zone management, the process of hydro-engineering structure designing and monitoring, and a range of other types of human activity at sea ,2.The most popular devices for waterbody depth measurement include Single Beam Echo Sounders (SBES) and MultiBeam EchoSounders (MBES). Even though SBES echo sounders continue to be the most commonly used bathymetric systems worldwide, it is the MBES echo sounders that, thanks to their large swath width, are able to ensure complete coverage of the seabed with depth data and enable the performance of such work in a relatively shorter period of time .However, over the last decade, the increasing impact of depth measurement methods providing alternatives to hydroacoustic methods has been observed. These methods include photogrammetric and remote sensing techniques that enable the acquisition of depth data to generate three-dimensional seabed models. Of all the measurement methods other than hydroacoustic, Airborne Laser Scanning (ALS)  deservesOther current alternative (and very quickly developing) methods for acquiring depth data include satellite bathymetry  and multAnother remote sensing technique that enables the performance of bathymetric measurements is the Airborne LiDAR Bathymetry (ALB), also referred to as the Airborne Laser Hydrography (ALH), which has been evolving rapidly in recent years . Its opeCurrently, the use of UAVs in hydrography has enabled the acquisition of high-resolution geospatial data and ensured considerable precision in determining their coordinates. The development of unmanned aerial vehicles is one of the challenges for the aviation industry, and they offer alternative measurement solutions, e.g., for terrain modelling, monitoring changes , and environmental protection . UAVs arThis study also presents the current methods for determining shallow waterbody depths based on an analysis of images taken by UAVs. The selection of the appropriate method is crucial, as it is planned to acquire accurate and reliable bathymetric data in the coastal zone. The accuracy of the determination of the waterbody coordinates must meet the requirements imposed for the order of hydrographic surveys according to the International Hydrographic Organization (IHO) standard S-44 . In viewSummarise the most promising methods for determining the waterbody depth. This literature review can provide a structured base of knowledge on the modern task of determining the waterbody depth based on images taken by an UAV. This study provides the reader with the basis for a detailed analysis of individually selected solutions;Analyse the literature, which enables the extraction of basic information from individual studies. The specification of waterbody descriptions, designed control points, as well as the hardware and software used may allow the selected method to be adjusted to the technical parameters of particular survey and research equipment. Moreover, the method for verifying the obtained measurement results in-situ;Compare and define the advantages and disadvantages of each particular method through an assessment of the results obtained by the method authors. With reference to the above, two points, differences and similarities were also defined. The values of individual errors were compared, thus enabling the selection of the most promising technique.The main aim of this publication is to compare modern methods for determining shallow waterbody depths. It will provide information useful for selection of appropriate method. It is achieved by:The remainder of this article is organised as follows: the “Materials and methods” section presents the concept of operation of five methods for determining waterbody depths, with their descriptions taking account of the data recording, location and mission preparation. The “Results” section summarises and comparatively analyses selected methods in terms of the obtained measurement results. The “Discussion and conclusions” section presents the formulated advantages and disadvantages of each of the analysed methods.Many of the methods described in this chapter are based on the Structure-from-Motion (SfM) technique. SfM  is a tecAn essential step when working with the SfM-MVS algorithms is the design and measurement of photopoints , which cThe use of the SfM-MVS technique to develop a DEM has been presented, e.g., in  for deveIn the following subsections, there are presented methods that use SfM data for shallow waterbody depth determination. Analyses dependent on the candidate frequency, radial wave number, equivalent depth and the wave angle. The analyses are based on a Fourier transformation. This stage involves such operations as the determination of optimum wave numbers and their directions, and the use of the Levenberg-Marquardt algorithm. Once this step is completed, a set of wave numbers and depths dependent on a particular frequency is obtained;The estimation of a single, best depth value, based on the dispersion relation. The previous step provided a set of wave numbers and depths, while this stage enables the determination of a single depth based on the set obtained. To this end, a Hanning filter is used;Estimation of the average running depth, aimed at obtaining a moving average value to eliminate problems related to the emergence of gaps in data, e.g., resulting from temporary loss of view during the course. At this stage, the value of a Kalman filter enhancement is calculated .A less popular, yet interesting, solution for determining depths is the use of the cBathy algorithm. The concept of the algorithm presented by  is basedA study by  describeBased on the cBathy algorithm, bathymetric measurements were conducted using the Unmanned Aerial System (UAS) on two waterbodies: the above-mentioned FRF in Duck, and on the Virginia Beach coastline (USA) . In the On the basis of the GNSS/Inertial Navigation System (INS), the GCP points were measured. The images were processed using the SfM-MVS technique in the Agisoft Photoscan software . In this way, a point cloud was obtained, which was later subjected to linear interpolation based on triangulation in the MATLAB software . Consequently, a DSM model was obtained. Moreover, an orthophotomap was generated in the MATLAB program. Prior to the application of the cBathy algorithm, the images were converted into grayscale. The image contrast was enhanced based on the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm, and the blank pixel values were replaced with time-averaged intensity values for particular pixels. The use of the cBathy algorithm parameters proposed in  enabled The photogrammetric measurement results obtained using the UAS system were compared with the results acquired from soundings conducted by a vessel equipped with an echo sounder and a Global Positioning System (GPS) Real Time Kinematic (RTK) receiver. The Root Mean Square Error (RMSE) range for depth measurements was 0.17–0.34 m. The greatest differences in the depth values could be observed near the pier and in close proximity to the coastline.The article  presenteFor testing purposes of the proposed method, recordings were made using an UAV in ocean waters located in Suruga Bay (Japan), at the mouth of the Oi River. For the video observation, a DJI Phantom 4 unmanned aerial vehicle  with a mounted camera with a resolution of 4K and a refresh rate of 29.97 Hz, whose horizontal angle was set diagonally to the coastline. As with each of the methods discussed, photopoints were designed and measured on land, and the image template fitting algorithm  enabled the detection of image coordinates in each video frame, which allowed orthogonal video images to be generated. The recording was also made using the hydroacoustic system that was applied to determine the depth Root Mean Square (RMS).The obtained depths were compared to the results obtained using the cBathy algorithm . Photogrammetric surveys were conducted using a Swinglet CAM UAV  with a Canon IXUS 220 HS camera  mounted on it. 2) was used to assess the fit of point clouds.As previously mentioned, the threat arising from the phenomenon of water-wave refraction can be eliminated, e.g., based on the SVR—a supervised algorithm used to predict discrete values. This regression model tries to minimise, in its computations, the error between the predicted value and the actual value . In the Based on the positive results of twelve out of thirteen different tests, it can be assumed that the results for the method using both the SfM-MVS and SVR techniques were shown to be very promising in terms of the depth measurement accuracies achieved. Moreover, this method is intended to be universal, i.e., independent of the UAV model and the equipment mounted on it. It was also proven that the training of a model from an area can provide results that are applicable on other, differing waterbodies. Moreover, several threats were defined, including the limitation of the method in areas where the seabed is characterised by the occurrence of dense sea grass or the lack of synchronicity between the point clouds obtained from the LiDAR and from the image. The authors of the method stress that work based on this model allows the accuracy requirements imposed on the IHO special order to be met .An interesting solution  for bathThe study was conducted in an area located on the Tyrrhenian Sea coast , along which an irregularly shaped coastline runs. In order to acquire measurement data, a HexaCopter UAV, equipped with a MAIA multi-spectral camera  comprising 8 multi-spectral sensors and a RGB sensor was used. The pre-processing of the image was performed using camera-dedicated MAIA software , which enables the correction of raw images and the generation of a multi-spectral image. Disturbances on the water surface due to sunny weather caused further disturbances that had to be reduced by using Hedley’s method, i.e., an upgraded technique for eliminating the “reflection” from remote sensing images, based on the use of near-infrared region . The samThe problem of image georeferencing due to the lack of possibility of using the SfM technique in the UDB method was solved by calculating planar deformation based on the knowledge of such parameters as location (based on GPS receiver indications), image size, course value and the angles recorded during flight. With reference to the SDB, an attempt was made to determine the waterbody depth using the Lyzenga  and StumThe authors believe that the technology using UAVs in bathymetric measurements may provide an alternative to research carried out by traditional methods using MBES and SBES echo sounders, yet only for waterbodies that do not require high accuracy. The results obtained by the novel UDB method were promising and reliable, as compared to the commonly known method based on satellite images. The depth values acquired using the Stumpf algorithm were similar to those calculated using the Lyzenga algorithm. It is worth mentioning that the Stumpf method is a simpler one, because it does not require as many regression methods, as is the case with the second algorithm.image adjustment;photopoint importing;camera position optimisation;point cloud construction;network construction;texture construction.Another method based on the SfM technique is the UAV-SfM method described by . The watRCE—DEM corrected elevation;E0—DEM elevation;WSE—water surface elevation.The elevation of the seabed model, taking into account the phenomenon of water-wave refraction, could be determined by applying the appropriate correction algorithm (1)ERC=EIt is stressed, however, that the algorithm can only be applied to a maximum depth of 0.7 m. It was also found that the greatest errors related to estimating elevation values were observed mainly near the shore or in areas with increased density of vegetation.i, ki), from which the water depth value (h) can be concluded while taking into account the dispersion relation, are obtained for each point. This method enables the estimation of waterbody bathymetry based on the propagation of electromagnetic waves that are recorded by a video monitoring system.The uBathy algorithm described in  refers tAs part of a study by , aimed aThe results of bathymetric measurements, obtained using the methods presented in f, i.e., the filtering characteristic times .For the cBathy, Depth Inversion, uBathy, and UDB algorithms, the depth RMSE values were provided and summarised in Based on Bathymetric measurements are often based on processing using the SfM, which is understandable in view of the advantage of this technique over traditional digital photogrammetric methods . ChapterThe unquestionable advantage of the SVR method is the opportunity to apply the model to waterbodies other than the areas on which the training was conducted. The solution is based on machine learning tools. The authors can demonstrate high compliance between the results obtained by this method with the results acquired using the LiDAR system. It should be mentioned, however, that these values were not compared to the depths obtained by traditional depth measurement methods applied in hydrography. Hence, the results obtained may not be fully reliable.The authors of the UAV-SfM method  used a nAs mentioned in Based on Depth RMSE values similar to those obtained by applying the uBathy algorithm were acquired for the Depth Inversion method. The results presented in  suggest Very satisfactory depth measurement results were obtained using the UDB method, in particular when applying the Lyzenga model. The algorithm, based on the commonly used SDB method, allows a measurement accuracy higher than that of satellite bathymetry to be obtained. The application of the UDB algorithm also enables high efficiency of bathymetric works. It should be noted, however, that bathymetric measurements are more accurate at shallower depths, and it is shallow waterbodies that are the focus of this publication. The authors believe that the technology using UAVs in bathymetric measurements may provide an alternative to research carried out by traditional methods using MBES and SBES echo sounders, yet only for waterbodies that do not require high accuracy. The results obtained by the novel UDB method were promising and reliable, as compared to the commonly known method based on satellite images. The depth values acquired using the Stumpf algorithm were similar to those calculated using the Lyzenga algorithm. It is worth mentioning that the Stumpf method is a simpler one, since it does not require as many regression methods, as is the case with the second algorithm. The tool for determining the shallow waterbody depth requires further testing, which is the main disadvantage of this method. Not all limitations have already been recognised, e.g., those related to image orthorectification.A common element of each method is the need to design and measure the GCP point network. This stage of work has a significant impact on the depth accuracy, considering that terrestrial control points should be located on the mainland and that their number must be proportionate to the tested surface size. Exceptions include waterbodies with high water quality. This is why the methods applied are geared towards bathymetric measurements carried out on shallow waterbodies. It should be noted that these methods are based on images taken by UAVs on individual waterbodies. On the basis of the performed analyses, it should be concluded that the most reliable method for determining the shallow waterbody depth is cBathy, as it is the only solution that is repeated in other studies (Depth Inversion and uBathy).


Background: This study assessed the hypothesis that violent behavior prior to admission prolongs psychiatric hospitalization and evaluated the likelihood of hospital discharge to a community care setting based on demographic and clinical factors, with an emphasis on violent behavior.Methods: We retrospectively selected 362 patients who were involuntarily admitted to a psychiatric hospital in Japan from December 1, 2015 to November 30, 2017, stayed longer than planned, and underwent review by a multidisciplinary team. We assessed (a) education and marital status and history of substance abuse, (b) the presence/absence and type of violent behavior that led to hospital admission, and (c) the discharge criteria. We divided the subjects into groups according to whether they had demonstrated violent behavior prior to admission and compared demographic and clinical variables between the groups using bivariate analysis. We also analyzed data using the Cox proportional hazard model, defining discharge to the community as the outcome. Age, sex, and variables that were significant at a level of P < 0.05 based on Cox univariate analysis were included in the multivariate models using the forced entry method.Results: The Violent group included 94 patients (26%). There were no significant between-group differences in age, sex, educational background, marital history, career history, or the history of substance abuse. However, hospitalization was significantly longer in the Non-violent group. The Cox proportional multivariate hazard ratios revealed that violent behavior prior to admission resulted in a higher probability of hospital discharge.Conclusion: Violent behavior prior to admission did not significantly contribute to prolonged hospitalization in patients who deviated from the treatment plan and had exceeded the planned hospitalization duration. Our findings recommend caution when using violence and impulsiveness observed during the acute stage to predict the difficulty of long-term treatment. Long-tePsychiatric hospital stays are more commonly prolonged in Japan than in other countries, and the environment of hospitalization wards and the community surrounding the psychiatric hospital is unique. There are approximately four times more beds  for psychiatric patients in Japan compared to the Organisation for Economic Co-operation and Development (OECD) average. These hospital beds continue to be used for the recuperation of chronic-stage patients , as well as the second and subsequent admission of patients who had been hospitalized multiple times during the period (eight patients). Thus, 362 patients were selected as subjects for our study. The study inclusion and exclusion processes are shown in We gathered data by retrospectively accessing electronic medical records. A structured data accessing, and coding protocol was used to ensure consistency in the order and method of data extraction. We employed each patient's summary at the time of discharge , and gathered demographic data, clinical data, data on the history of self-harm and other damaging behavior, and review by a multidisciplinary team.Discharge to community settings, such as home or other facilities, were defined as the outcome of this study. We excluded discharge due to transfer to other hospitals and death, because they could occur even under conditions where the adjustment of symptoms and the living environment had not been carried out sufficiently. Observations ended on January 14, 2020, and patients who stayed beyond this endpoint were categorized as censored subjects.We investigated the effect of variables that have been reported to be associated with hospitalization in previous studies. Demographic data included age, sex, educational background , lifetime marital history (presence/absence), and lifetime employment history  were collected.Clinical data included the length of hospital stay, discharge destination, primary psychiatric diagnosis according to Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems, the presence/absence of substance use disorder , intravenous sedation given/not given on admission, and implementation of electroconvulsive therapy (ECT) during hospitalization.We reviewed the entire disease history in the summary. The reason for admission was noted in the disease history. If there was violent behavior coded on the Modified Overt Aggression Scale, we judged that “Violent behavior that led to the current admission” is present. Next, we categorized these as verbal violence, violence toward property and objects, self-harm, and physical violence. It is important to note that this includes not only physical but also verbal violence, violence toward property, and self-harm.Data from the review by a multidisciplinary team were collected from the patients' electronic medical records. The review aimed to promote discharge by discussing the need for psychiatric hospitalization as well as measures and programs toward discharge and clarifying the planned period of hospital stay. Regarding the subjects' needs with respect to discharge, Tokyo Metropolitan Matsuzawa Hospital stipulates choosing multiple relevant items from the following: “Improvement of symptoms ,” “Insight of disease (patients' awareness of symptoms and treatment needs),” “Living skills ,” “Coping with symptoms (self-care ability to prevent relapse),” and “Preparation for living .” The presence or absence of each of these items was collected as a binary variable. “Willingness to be discharged after the assessment” was a free description of the subject's hopes and wishes to be discharged. The presence or absence of requests to be discharged was also collected as a binary variable.At the assessment, the multidisciplinary team reset the planned length of stay, but if the patient continued admission beyond that period, a review was held more than once during a single hospital stay. To prioritize early-stage assessments during hospitalization, we referred to the records of deliberations held for the first time.First, we divided the subjects into two groups according to whether violent behavior had or had not led to the current admission . We compared variables between groups using bivariate analysis. Chi-square tests were used to analyze between-group differences in sex, educational history, marital history, working history, substance abuse problems, intravenous sedation, ECT, and assessment of needs in prolonged-stay patients. Mann-Whitney U tests were used for between-group comparisons in age and length of stay.P < 0.001), even after a logarithmic transformation . All the explanation variables other than age were qualitative. We therefore established the occurrence of discharge to a community setting as the outcome, and used the Cox proportional hazard model to analyze the influence of multiple explanatory variables by taking the passage of time (length of stay) into consideration.Second, to investigate the influence of predictive factors for the length of hospitalization, we conducted survival analysis. The number of hospital days did not follow a normal distribution , and included them as independent variables, using the forced entry method.We performed Cox univariate analysis for each variable separately and investigated the relationships between the occurrence of discharge to the community and the latent predictive factors. Next, Cox multivariate analysis was used to assess the influence of independent variables on the discharge to community. We used age, sex, and variables that were significant at the We used the correlation matrix table for all the variables to confirm that there were no combinations of variables that showed high correlation coefficients (above 0.9) to assess multi-collinearity of the variables to be entered into the multivariate analysis. We also observed a log-log graph of qualitative variables that were finally entered into the model and confirmed that proportional hazard assumptions had been maintained. IBM SPSS Statistics for Mac, version 23.0  was employed for all statistical analyses. The level of significance was set as α = 0.05.This study was conducted in accordance with the recommendations of the Ethical Guidelines for Medical and Health Research Involving Human Subjects of the Japanese Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor, and Welfare. The need for informed consent was waived since this was a retrospective study. The research protocol was approved by the Tokyo Metropolitan Matsuzawa Hospital Ethics Committee  in accordance with the Declaration of Helsinki.During the observation period, 299 subjects were discharged to the community, while 43 subjects remained in the hospital to which they had been transferred. There were also some subjects who died or continued their stay at Matsuzawa Hospital without being discharged and were censored.The median length of stay in the Violent group was significantly shorter than the one observed in the Non-Violent group. The distribution of hospitalization days in the Violent and Non-violent groups was similar in the first quartile in both groups, but the median and third quartiles were larger in the Non-violent group. In other words, the distribution of hospitalization days in each group reflects a clear difference.The most frequent diagnoses were those of schizophrenia and schizotypal and delusional disorders, accounting for 74% of the cases. Diagnoses of diseases other than schizophrenia were relatively rare.There was no significant difference in occurrence between the two groups for subjects who received intravenous sedation on admission or ECT during hospitalization.In terms of a review by a multidisciplinary team, “preparation for living” was selected as the item which most needed this.The items assessed as being significantly more frequent in the Non-violent group were “Improvement of symptoms,” “Insight of the disease,” and “Living skills.” The “Willingness to be discharged after the assessment” was significantly more frequent in the Violent group.P < 0.01. Violent behavior that led to current admission was associated with a significantly higher likelihood of discharge. The variable “Needs for living skills” was close to reaching a significant association with a lower likelihood of discharge.In contrast to our hypothesis, in the subjects of our study, violent behavior prior to admission was associated with a significantly higher likelihood of discharge. In other words, it did not contribute significantly to prolonged hospitalization in patients who deviated from the treatment plan and had exceeded the planned hospitalization duration. The univariate analysis revealed that “Improvement of symptoms,” “Insight of the disease,” and “Living skills” were found to be significantly more frequent in the Non-violent group. The violent group more frequently expressed a wish to be discharged. The distribution of hospitalization days in the Violent and Non-violent groups was similar in the first quartile of both groups, but the distribution was larger in the median and third quartiles of the Non-violent group. The Cox proportional hazard model demonstrated an association between the violent behavior that led to the current admission and a significantly higher likelihood of discharge. The association between the “Needs for living skills” and the duration of hospital stay was close to reaching significance; other factors identified by previous studies  were not significantly associated with stay duration.Participants in the current study were long-stay patients who had exceeded the planned hospitalization duration. The length of stay in European and American countries is relatively short, and many previous studies that have investigated the association between violence and length of stay have mainly focused on acute care settings. Greenfield et al. observed a mean duration of 14.9 days in university-based, short-term inpatient psychiatric units . Di LoreThe results of the univariate analysis between the Violent and Non-Violent groups may partially explain the characteristics of patients who deviated from the treatment plan and had exceeded the planned hospitalization duration for whom hospital treatment had been initiated after incidents of violence; despite violent tendencies, these patients tend to have relatively mild symptoms, appropriate life skills, and may be able to show insight and express a wish to be discharged. They may be able to be discharged relatively early as long as their violent tendencies and impulsiveness improve during acute treatment. However, this result does not completely rule out the observer bias that that violence may result in lower estimates of needed support. This finding overlaps with those of Wolff et al., who noted that risks posed to other people tend to result in shorter hospitalization, and stabilization of acute crises during the first days of stay might prompt early discharge . Most prThe distribution of hospitalization days in the Violent/Non-violent groups indicate a clear difference. It may explain that the impact of other factors other than violence progressively exceed that of violence as the length of hospital stay increases. In a study that divided hospital stay into durations of less or more than 36 days, Di Lorenzo et al. hypothesized that aggressiveness itself could justify the difficulty in discharging patients, especially when it contributes to a vicious cycle of aggressive escalation . HoweverThe association between “Needs for living skills” and the length of hospital stay was close to reaching significance in the multivariate analysis. The factor of living skill may become more significant as the length of hospitalization increases. This finding is particularly important for promoting discharge support to community settings in Japan, where prolonged hospital stays beyond a few months are problematic. In our study, violent tendency was not associated with further prolonged length of stay. It may explain that the prolonged hospitalization in Japan does not necessarily imply intention to isolate the patients from a security point of view. The OECD reported that Japanese hospital beds contain many beds for long-term inpatients that are not classified as psychiatric wards in European and American countries ; our resThe factors identified by previous studies, such as age, sex, educational background, career history, marital history, and diagnosis, were not presently found to be significantly associated with stay duration. However, it is necessary to consider that our survey did not target patients for whom treatment had proceeded smoothly; we only targeted long-stay patients whose symptoms complicated the management of treatment, whose discharge dates were consequently adjusted, and were required to undergo review by a multidisciplinary team. The demographic profile of each patient's background information, such as age, sex, and diagnosis, may not associate with the length of hospital stays in a population longer than several months.The present study was subject to several limitations. First, although we have referred to the results of review by a multidisciplinary team by certified professionals, such as physicians, nurses, and social workers, we did not use a standardized assessment scale. This may have created an inter-reviewer bias. A standard assessment scale should therefore be used in future studies. For example, following previous studies, we would be able to use the Positive and Negative Syndrome Scale (PANSS) to assess symptoms, Social Behavior Scale (SBS) to assess social behavior, and Global Assessment of Functioning (GAF) for comprehensive assessment. Second, our survey was performed at a single institution. To verify whether our findings could be applied to other general clinical situations, a survey that expands the forum of research to other institutions is warranted. In addition, the length of hospitalization in Japan is much longer than that in European and American countries, and the legal system is also different. It should be noted that this is an exploratory study and may not be immediately generalizable to psychiatric wards in European and American countries. Third, this study did not target patients who had been discharged according to the initial plan, compromising the generalizability of our findings to participants who were discharged after a relatively short period. We may assess how each factor affects hospitalization in greater detail by expanding the range of selected subjects to patients who underwent treatment as planned and received no reviews by a multidisciplinary team and comparing those results to those presently reported. In addition, it may enable us to confirm in greater detail that the heterogeneous effects of violence vary with the length of hospital stay, as suggested in this study.Violent behavior prior to admission did not influence prolonged hospitalization among patients who deviated from the treatment plan and had exceeded the planned hospitalization duration. We recommend caution in using violence and impulsiveness observed during the acute stage to predict the difficulty of long-term treatment. The impact of factors such as living skills may become progressively greater than that of violence as the length of hospital stay increases. Further research that considers relatively patients of relatively shorter hospital stays may be needed to explore the heterogeneous effects of violence, as such effects may vary according to the length of patient's stay.The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.The studies involving human participants were reviewed and approved by The Tokyo Metropolitan Matsuzawa Hospital Ethics Committee . Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.HK designed the study, collected the data, undertook the statistical analysis, and interpreted the data. TO and NK designed the study and critically revised the first draft. HK wrote the first draft of the manuscript. All authors contributed to the article 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.


BJPsych International focuses on the Middle East, with papers on psychiatric care in conflict zones, the persistence of institutionalisation in Arab countries, service delivery in Iraq, improved media attitudes towards mental illness in Qatar and integration of mental health services into primary care in that country.This month's issue of  The authors discuss how the conventional definition of post-traumatic stress disorder may be an inappropriate descriptor of the associated emotional and behavioural challenges faced by their psychiatric infrastructures. Specific and valuable recommendations are made about how to achieve better outcomes for the mental health of a traumatised populace, in both the short and long term.Our theme this month concerns countries throughout the Arab world where there are major changes taking place in the recognition of mental disorders and delivery of services. As our authors Joseph El-Khoury, Andres Barkil-Oteo and Lynn Adam acknowledge, the Middle East has been an area of conflict for decades. Currently, 8 out of 20 Arab League of Nations states are involved in armed struggles.2 Whereas a revolution in community treatment took root in many Western societies 50 years ago, followed by the discontinuation of institutional care, she presents evidence (and an accompanying video) that psychiatric in-patient services are expanding – even in high-income Arab countries. Her discussion about why institutionalisation persists is controversial and provocative.In a related article, Joelle Abi-Rached considers a controversial topic, the continuing use of large-scale hospitals to contain the mentally ill in some countries of the region.3 Interestingly, an Iraqi Mental Health Act was passed in 2005, but its provisions are not widely implemented. Although there remain many challenges to delivering services to the mentally ill, enduring stigma being one of them, there is evidence that new models of primary care are being developed. Unfortunately, sectarianism and corruption persist, and prevailing attitudes toward girls and women constitute an additional impediment to progress.Then Aws Sadik gives us a valuable snapshot of Iraqi psychiatry as it is practised today, 17 years after a coalition of Western countries visited ‘shock and awe’ on the citizens of that country, destroying its infrastructure and destabilising the Middle East for decades to come.4 There are encouraging signs that stigmatising those with mental disorders is rare nowadays, and negative articles complain instead about the limitations of services to meet demand. The authors conclude that the media's portrayal of mental health in Qatar is more positive than in many other countries worldwide. Finally, Ovais Wadoo and colleagues discuss the history of mental health services in Qatar, which were established in 1971.5 A National Mental Health Strategy was published in 2014, following which there has been a trend to provide mental health services in collaboration with family physicians, emphasising the value of community-based specialist care. Qatar is leading the way with this enlightened vision. Mental healthcare is being integrated with the primary healthcare system and a training infrastructure to support it is being built too. The authors conclude that Qatar thus provides a model for other countries in the Arabian Gulf region to follow.We end this series of articles with good news about developments in Qatar, one of the wealthiest countries in the region. Khalid Elzamzamy and colleagues have reviewed the attitudes of the Qatar daily press to mental health issues, comparing their reporting with that on physical health.


This calls for the use of Integrated Approaches to Testing and Assessment (IATAs) for regulatory processes, which requires a comprehensive understanding of endocrine signalling mechanisms, but also an easy access to standardised methods. The relevance and reliability of new methods potentially suitable for regulatory application must be thoroughly assessed, and necessitates significant resource investment. The action of a new Public-private platform for the pre-validation of endocrine disruptors characterization methods, PEPPER, is described as well as its results.The current testing of substances regarding their potential endocrine disrupting properties is hampered by a lack of validated methods. Indeed only a few endocrine pathways can be investigated by these methods, leaving many unexplored, and some adverse effects cannot be detected due to the inappropriateness of the methods, such as long term effects due to early exposure, or metabolic disruption. Moreover, The European Commission is Revising Information Requirements for Regulatory Testing of Endocrine Disruptors (EDs).In September 2017 and April 2018, the Plant Protection Products and Biocide Products Regulations have respectively been amended to include scientific criteria for the determination of endocrine disrupting properties of chemicals ((EU) 2018/605 and (EU) 2017/2100).In December 2020, out of the 22 biocidal active substances discussed by the European Chemical Agency’s (ECHA) Endocrine Disruptor Expert Group, a conclusion could be reached for only 2 (considered endocrine disruptors), while for the remaining 20, more information was needed to conclude whether the criteria were met . RegardiIn October 2020, a first step was made by the Commission towards the revision of the information requirements for identification of endocrine disrupting substances, by amending the Biocidal Products Regulation (delegated Regulation 2021/525). The amendments take into account the “need to reduce testing on vertebrate animals and the need of a testing strategy and methods for the determination of endocrine disrupting properties of substances.” Moreover, testing for endocrine disrupting properties has become part of the “core data set” .Similar Activities are Ongoing Concerning Plant Protection Products and REACH Regulations.However, including the most recently adopted OECD Test Guidelines (TGs) or their updates in the standard information requirements will not suffice to facilitate the identification of all EDs. Indeed, the available TGs mainly focus on a few endocrine pathways  leaving many unexplored such as the retinoid or glucocorticoid pathways.Another aspect to take into account when considering the revision of the information requirements is the need of methods able to fulfil the three aspects of the criteria for the identification of EDs, as laid out in the Pesticides and Biocides Regulations, i.e., the demonstration of an endocrine mode of action, an adverse effect and the biological plausible link between both. In particular the need of methods facilitating the identification of modes of action calls for the development of targeted New Approach Methods not relying on animals.Many methods exist which are relevant to the identification of EDs. However very often their development was not intended for regulatory application.In the recent years, extensive effort has been dedicated to the identification of gaps in methods that can be readily integrated into a regulatory framework, leading to various publications  and are https://eurion-cluster.eu/] and intends to follow this line [European partnership for the assessment of risks from chemicals (PARC)].The first reason for this shortage of regulatory-relevant methods is a general lack of awareness of regulatory needs from the developers of methods, so that methods may not answer the “right question.” Recently, in order to reduce the gap between research and regulatory testing, the European Commission has issued research calls asking for methods to be developed for a regulatory application [e.g., European Cluster to Improve Identification of Endocrine Disruptors (EURION) Another reason is linked to the absence of documentation of the methods, pre-requisite to their transfer into a “naïve” lab and validation through a ring trial. This standardisation includes, e.g., the establishment of a Standard Operating Procedure clear enough to allow a new operator/lab to implement the method. It should describe precisely every step of the method and list technical requirements, as well as adequate acceptance criteria for the results obtained when running the method. “Historical data,” i.e., repetitions of testing of a substance using the same experimental conditions, need to be established by the developer. They will be the starting point of the demonstration of reproducibility of the method, and will facilitate the establishment of acceptance criteria for the results.https://ed-pepper.eu/en/) was recently (2020) created to work on this lack of standardisation. It aims to fill the gap between outputs of academic research and regulatory relevant methods, by organising pre-validations.The PEPPER platform  could be fully evaluated. Editors of scientific journals can require that, as supplemental materials, authors provide basic method information formatted as described in .In addition, methods are often referred to by different names under various circumstances, which is a significant challenge. It is suggested that methods names be harmonised, and perhaps even registered and deposited into a repository created by the community.In order to overcome the difficulties in finding test methods, a search has been conducted by PEPPER with a consortium made up of Altertox, Benaki Phytopathological Intitute, and the University of Paris. Artificial Intelligence-aided literature analysis was performed in order to identify methods with a potential to be used for regulatory purpose. Out of about 12,000 abstracts identified by the consortium, around 250 methods have been pre-selected .Interviews of researchers, regulatory agencies, industry representatives, both about their feelings on the needs, and the analysis of expressed needs by the regulatory authorities were conducted. A side outcome of these interviews was that a lot of unpublished methods are available in research labs, which could potentially be used to answer some regulatory-relevant questions.Once a list of methods of potential interest was established, a further analysis including practical considerations for a validation exercise  reduced the number of methods to about 75. Quantification of the readiness of the method to enter pre-validation, based on a “test readiness criteria” (TRC) approach  followedEventually, 17 methods were considered mature enough to be presented to a Relevance Committee composed of various stakeholders, such as national and international regulatory authorities, industry, NGOs, researchers, for selection. The methods were presented along with their computed TRC, their position within the OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupting Chemicals , their r• having a TRC of 75% of the maximum,• being on level 2 of the OECD Conceptual Framework,• addressing early/intermediate Key Events• addressing a knowledge gap on female reproduction/fertility via placental functionFor example, the first selected method , based oAnother selected method bears on the glucocorticoid receptor with a transactivation approach, focusing on a very early Key Event .The third ranked method, using zebrafish and looking at obesity through adipocyte size, has a 60% TRC, is on level 3 of the OECD Conceptual Framework, addresses plausibility and adverse effect .Once methods are chosen, field work starts with assessment of transferability, i.e., implementation of the method, following the SOP, in two or three naïve labs. This step usually leads to modifications of the SOP, e.g., to clarify some points, or make it applicable to different pieces of equipment. After successful implementation of the method, using a few test substances, the SOP is fixed and more substances are tested to further assess relevance and reliability of the method, as well as its applicability domain . The timEventually, the most tangible output will be the proposal of the methods to be included on the workplan of the OECD, to eventually be adopted as Test Guidelines. A less visible part is the dissemination of the knowledge of those methods in the European community, through participating laboratories, and scientists who help PEPPER in the validation.The need for more  methods in order to identify EDs is a position shared by many stakeholders, so is the recognition that (in most cases) the identification of an ED cannot rely on a single method, but requires results from several methods to be combined using a weight of evidence approach. Building an IATA can help this demonstration by providing a framework.PEPPER is addressing the issue from a specific point of view: it identifies methods that can fill the various testing gaps, it improves the description of methods  before their validation and it enhances their regulatory acceptance. The association funds and organizes the elements for validation.It has been demonstrated that it is uneasy to find methods in the literature and in databases, that are both mature enough to enter (pre)validation and fill recognised testing gaps in ED characterisation. Moreover, the scarcity of IATAs made it almost impossible to associate the methods to IATAs.It is not a common practice for method developers, nor in research calls, to suggest how a method could fit into a testing strategy or an IATA however it should be encouraged. Indeed, it would facilitate the regulatory uptake of the method. It seems nevertheless possible to enter a virtuous circle, with better practices in the description of methods in publications, and a greater use of databases on methods, together with an improved maintenance of the databases.


This study examines the connectedness between the US yield curve components , exchange rates, and the historical volatility of the exchange rates of the main safe-haven fiat currencies  and the leading cryptocurrency, the Bitcoin. Results of the static analysis show that the level and slope of the yield curve are net transmitters of shocks to both the exchange rate and its volatility. The exchange rate of the Euro and the volatility of the Euro and the Canadian dollar exchange rate are net transmitters of shocks. Meanwhile, the curvature of the yield curve and the Japanese Yen, Swiss Franc, and British Pound act mainly as net receivers. Our static connectedness analysis shows that Bitcoin is mainly independent of shocks from the yield curve’s level, slope, and curvature, and from any main currency investigated. These findings hint that Bitcoin might provide hedging benefits. However, similar to the static analysis, our dynamic analysis shows that during different periods and particularly in stressful times, Bitcoin is far from being isolated from other currencies or the yield curve components. The dynamic analysis allows us to observe Bitcoin’s connectedness in times of stress. Evidence supporting this contention is the substantially increased connectedness due to policy shocks, political uncertainty, and systemic crisis, implying no empirical support for Bitcoin’s safe-haven property during stress times. The increased connectedness in the dynamic analysis compared with the static approach implies that in normal times and especially in stressful times, Bitcoin has the property of a diversifier. The results may have important implications for investors and policymakers regarding their risk monitoring and their assets allocation and investment strategies. The outbreak of the COVID-19 pandemic in early 2020 reinvigorated the search for useful risk management, hedging strategies, and investors’ demand for safe-haven assets. Although traditionally major currencies have been regarded as safe-haven assets, several financial market downturns, such as the 2008 subprime crisis and the 2011 sovereign debt crisis, raised doubts about their diversification benefits in turbulent times. Demir et al.  identifi1The sovereign yield curve is one of the most recognized and familiar components of a centralized monetary system, which is also a major economic indicator, advocated by both academicians and practitioners. Previous studies , and the traditional safe-haven currencies are yet to be explored. Inspired by the growing stream of literature focused on the connectedness of various financial and economic variables, the current study analyzes the joint and pairwise connectedness of the yield curve components, Bitcoin, and five major safe-haven currencies . We explore their connectedness in a static framework and under different market conditions in a dynamic time-varying framework. The findings may enhance our understanding of the growing debate about the role of Bitcoin and major currencies in the context of portfolio management and the impact of yield curve movements in shaping their behavior. Given the growing interest in cryptocurrencies by investors, firms, and financial market participants globally, and their potential impact on market stability, we maintain that this is a timely investigation.To accomplish the aims of this study, we retrieve the daily historical data of the US terms structure yields, exchange rates, and historical volatility of the exchange rates for Bitcoin, Euro, JPY, CAD, CHF, and GBP. Our sample covers the period from May 11, 2010, to November 26, 2020, based on the availability of the matched data series. We estimate the US yield curve components using Diebold and Li’s  modificaOur study contributes to several evolving strands in the literature. First, we add to the studies dealing with the role of traditional safe-haven currencies in the framework of diversification and risk reduction under market stress .Our static analysis hints that Bitcoin exhibits a high level of independence to shocks from the yield curve components and from the main fiat currencies. These results imply that Bitcoin might offer hedging property. However, the dynamic analysis shows that Bitcoin is far from being isolated from other currencies or the yield curve components, even more so in stressful times. The results are consistent for both the exchange rates and the volatility of exchange rates. Notably, our time-varying analysis indicates that the connectedness increases due to policy shocks, such as the removal of the cap on the Swiss Franc against the Euro, the political uncertainty created by BREXIT, and the systemic crisis of COVID-19, suggesting that Bitcoin is far from being counted as a safe-haven asset. The results support previous studies that argued the limited risk reduction capability of Bitcoin and its failure to act as a safe-haven asset.These main findings may have implications for financial market participants and policymakers. Monitoring the connectedness across time may assist them with their hedging and risk management as part of their investment decisions, and improving their portfolio selections and asset allocation. Our findings underscore the importance of accounting for a dynamic methodology to comprehend the connectedness between Bitcoin, the main fiat currencies, and the yield curve components.The remainder of this paper is structured as follows. Section A growing stream of studies deals with the relationship between Bitcoin and conventional assets, which is part of the gradual integration of Bitcoin and cryptocurrencies into international financial markets.The second research stream that our paper extends is whether Bitcoin is integrated with or insulated from conventional assets. As we will discuss, the empirical evidence of Bitcoin being a safe haven is debatable. Therefore, our work adds a different perspective on testing Bitcoin’s risk reduction capabilities.Baur and Lucey  indicateUsing a multivariate stochastic volatility model and dynamic conditional correlation (DCC) approach, Kliber et al.  demonstrHowever, Smales  ruled ouRecent studies also exploit the COVID-19 crisis to explore the risk reduction properties of Bitcoin. Many studies, for example, Conlon and McGee , have exOur final contribution is the inclusion of the three components of the yield curve in our analysis. Doing so contributes to the growing field of studies dealing with the relationships among conventional currencies, Bitcoin, macroeconomic information, and monetary systems  and Bitcoin from Bloomberg. The exchange rates are not stationary, and therefore, we compute the first difference of levels for each currency. We confirm stationarity by employing the ADF tests. Lastly, we obtain the historical volatility of each fiat currency and Bitcoin from Bloomberg. Here again, the raw volatility series obtained from Bloomberg is non-stationary. Consequently, we take the first differences to ensure stationarity and confirm it with the ADF tests.Table Our empirical framework is composed of two methodological steps. In the first step, we use the dynamic modification of Diebold and Li  to NelsoSubsequently, we follow the methodology of Diebold and Yilmaz , 2014 foThe groundwork of the Nelson–Siegel model inspired Diebold and Li  to suggeMoreover, the transition equation isEstimating and examining the spillover and connectivity dynamics of variables in a certain system  may have different types of practices and approaches. We adopt the novel method of Diebold and Yilmaz , 2014 th6Diebold and Yilmaz , 2014 apkth order, N variable VAR:Following Diebold and Yilmaz , 2014, wEquation  describeH-step generalized variance decomposition matrix is given as DgH =  ej is a selection vector with jth element unity and zeros everywhere, and σjj is the jth diagonal element of Σ. Sums of forecast error variance contributions  are not necessarily unified, as shocks are not necessarily orthogonal in the GFEVD environment. Hence, we base our generalized connectedness indexes not on Dg, but rather on The traditional techniques like the Cholesky factorization for estimating orthogonal innovations are sensitive to variable ordering. Therefore, we follow the solution of Koop et al.  and PesaH-step-ahead variance decomposition component of variable i due to shocks in variable j. The connectedness table merely supplements i ≠ j. The off-diagonal entries of j to i is given as follows:To understand the connectedness and relationships between the variables of a certain system, Diebold and Yilmaz  construcNotably, the connectedness to and from may be asymmetric in the sense that i. In this case, the connectedness measure is computed as follows:Similarly, one can be interested in the total connectedness FROM all variables as a whole to variable j TO the system can be measured byAlternatively, the total connectedness of a single system variable i and the system as a whole is defined asIn this respect, the net total directional connectedness between a single system variable To have a general assessment of the degree of connectedness in the defined system, we use the summation of the values in the “FROM” column and “TO” row to measure the total connectedness:The total connectedness measure in the system is bounded in the interval of 0 and 1. The lower bound represents a variable system according to which no spillover risk exists, whereas the upper bound of 1 applies to the case of a full connectedness according to which all risks are generated by the system variable interactions.Following Zeng et al. , Diebold7We start our analysis by discussing the connectedness of the system that contains nine variables of interest ‒ the three components of the US yield curve, Bitcoin, and the five major safe-haven fiat currencies . We discuss the connectedness of the exchange rates and the yield curve components first, followed by the connectedness of the exchange rate volatility and the yield curve components.The results in Table Although the “TO” and “FROM” analyses highlight each variable’s contribution to the system, net transmitters and net receivers of spillovers must also be distinguished. This information is presented in the last row of Table Interestingly, all three components of the US yield curve or other currencies have negligible influence on Bitcoin. Most variations in the system are generated by the traditional currencies and yield curve components. Moreover, Bitcoin’s independence is evident in terms of Bitcoin contribution TO or FROM the system. Bitcoin contributes only 0.54% of the total variation TO the system and absorbs only 0.84% FROM the system. Consequently, the net spillover of Bitcoin is also negligible at ‒0.3%. Therefore, we might argue that Bitcoin exhibits risk diversification attributes and may hedge against changes in other safe-haven currencies or fluctuations in the yield curve. However, investors should keep in mind that these results also imply that, as a single asset class, Bitcoin is heavily exposed to its idiosyncratic shocks. For the other currencies, relatively larger spillover exists TO and FROM the yield curve components and within the currencies themselves.Next, we look at the pairwise spillover. To identify the net transmitters and net receivers of spillovers on a pairwise basis, we resort to network analysis, which enables us to easily analyze the pairwise connections of net transmitters and receivers of spillover. The left-hand panel of Fig. We extend our analysis and discuss the connectedness of the yield curve components and the volatility of the exchange rates of Bitcoin and the fiat currencies. We report these results in Table To analyze the pairwise connectedness of the volatility of the exchange rate series and the yield curve components, we look at the right-hand illustration in Fig. Our static analysis results accord with those of previous studies documenting the weak connectedness between Bitcoin and traditional assets , Bitcoin, and the components of the US yield curve . We use Diebold and Li’s  modificaWe contribute to the literature dealing with major currency interaction with both the yield curve and the dominant cryptocurrency, the Bitcoin. Given the growing popularity of Bitcoin among individuals, investors, and companies, we present an important attempt to track its potential bidirectional interplay with major currencies. In addition, we extend the examinations to include Bitcoin’s relationship with the yield curve components and reveal whether Bitcoin is connected or isolated from major currencies and conventional monetary assets.To determine whether Bitcoin has the property of a safe-haven asset, we took a step forward and employed a dynamic connectedness approach, which can distinguish its connectedness during various phases of the economic cycle covered in our sample period. Our dynamic analysis shows that its connectedness actually strengthens during crises and due to policy shocks. Moreover, we document an increase in connectedness due to the removal of the cap on the Swiss Franc against the Euro, the post-BREXIT political uncertainty, and the COVID-19 induced crisis. These findings from the dynamic analysis support previous studies and confirm that Bitcoin is far from being a safe-haven asset  can benefit from the results in this study to better understand the dynamics between the yield curve movements, safe-haven fiat currencies, and the Bitcoin. Consequently, it may help them improve their allocation and risk management decisions.Future works on the topic debated in this paper could be further extended in at least two interesting avenues. First, it would be valuable to explore the system connectedness with other leading cryptocurrencies apart from Bitcoin or extend the system explored to include precious metals from the commodity market. Second, it would be interesting to consider the varying effects of good and bad news on the connectedness of the system.


Genomics data are currently being produced at unprecedented rates, resulting in increased knowledge discovery and submission to public data repositories. Despite these advances, genomic information on African-ancestry populations remains significantly low compared with European- and Asian-ancestry populations. This information is typically segmented across several different biomedical data repositories, which often lack sufficient fine-grained structure and annotation to account for the diversity of African populations, leading to many challenges related to the retrieval, representation and findability of such information. To overcome these challenges, we developed the African Genomic Medicine Portal (AGMP), a database that contains metadata on genomic medicine studies conducted on African-ancestry populations. The metadata is curated from two public databases related to genomic medicine, PharmGKB and DisGeNET. The metadata retrieved from these source databases were limited to genomic variants that were associated with disease aetiology or treatment in the context of African-ancestry populations. Over 2000 variants relevant to populations of African ancestry were retrieved. Subsequently, domain experts curated and annotated additional information associated with the studies that reported the variants, including geographical origin, ethnolinguistic group, level of association significance and other relevant study information, such as study design and sample size, where available. The AGMP functions as a dedicated resource through which to access African-specific information on genomics as applied to health research, through querying variants, genes, diseases and drugs. The portal and its corresponding technical documentation, implementation code and content are publicly available. Modern biomedical research is strongly reliant on data repositories that are well-structured for the storage and retrieval of information. The number of biological and biomedical databases have increased over the last two decades, with resources for diverse organisms, molecules, interactions and pathways. The goal of research is often compounded by the complexity of these different sources and the amount of data that are being gathered from high-throughput technologies, which has also increased in the past two decades. However, low- and middle-income regions, such as Africa, are still not fully capable of tapping into genomic resources for biomedical application due to unmatched resources and needs. There is thus an urgent need to improve facilities, particularly for data generation, processing, storage and access, that will contribute to the implementation of genomic medicine in Africa. Recent initiatives have begun to enhance efforts to overcome the barriers for the use of genomics in Africa, including the Malaria Genomic Epidemiology Network  and the Human Heredity and Health in Africa (H3Africa) consortium .Current genomics and biomedical data and metadata in public databases are skewed toward populations of European ancestry. Many African populations remain underrepresented and the data that is available for Africa is not structured in a manner appropriate for the geographical, social and cultural diversity of the continent, with data generally being classified under Sub-Saharan Africa, with little reference to specific populations, or misclassified with other regional groups, as previously described ,3. RecenThe current underrepresentation of African data and metadata in public databases, as well as the implementation of insufficient classification methods of such data in these public databases, call for the inclusion of more diverse African samples in public genomic reference panels and databases, and highlights the need for a resource that can provide a more granular view of African and African-ancestry populations. This would illustrate the current status of research and implementation on the continent, as well as facilitate continuous progress of genomic medicine in Africa. An accurate representation of actionable genetic variants in Africa is required to facilitate genomic medicine research, including molecular markers that are relevant in the aetiology of diseases, variants that have been associated with specific clinically-supported drug therapies, and variants related to drug response. The ability to query and make use of the currently available data and metadata is critical. Unstructured and heterogeneous data hinders integration efforts and knowledge inference. Moreover, the scattering of data and metadata makes challenging the establishment of a clear genetic determinant map in Africa and affects our capacity to study its genetic diversity and the implication thereof in clinical studies for these population groups at a large scale.The existing challenges have prompted the development of a fit-for-purpose online database that contains relevant African-specific information related to genomic medicine extracted from public databases and further curated from the literature. This resource will be of interest to the African bioscience community, and genomic medicine stakeholders at large as it may facilitate the implementation of genomic medicine on African-ancestry populations worldwide. The need for an African-specific resource is justified by the extensive genetic diversity among populations across the continent, the data fragmentation across different existing resources, and the lack of appropriate annotation. The proposed resource, the African Genomic Medicine Portal (AGMP) provides curated information to guide the research and application of genomic medicine, pharmacogenomics, and clinical genetics within African-ancestry populations. The AGMP aims to provide a user-friendly resource specific to African research to support genomic medicine in Africa, a centralized root for African studies in genomic medicine available for public use and to supply the community with a well-curated and highly enriched content of genomic medicine that reflects the diversity of the genetic makeup in Africa.www.pharmgkb.org, accessed on the 25 July 2019) [www.disgenet.org, accessed on the 25 July 2019) [The development of AGMP v1.0 was initiated through a collaborative effort by H3ABioNet, the Pan-African H3Africa Bioinformatics Network members . Two prily 2019)  and DisGly 2019) . The piply 2019)  to allowhttp://eutils.ncbi.nlm.nih.gov/, accessed on the 10 January 2022) tool to retrieve the PubMed entries in XML format followed by a series of processes to tokenize and Lemmatise the text content. Finally, the list of biogeographical and ethnolinguistic terms was queried and the abstracts that matched at least one of the terms were retained for manual curation. The pipeline is implemented in the Nextflow workflow manager .To exclude non-African data from AGMP, a custom text-mining pipeline that identifies biomedical literature containing African-related biogeographical and ethnolinguistic terms from Medline abstracts was developed and applied to the retrieved datasets. These terms included a list of 104 biogeographical entities  and 146 African ethnolinguistic population labels. The pipeline used the “EDirect” , experimental analysis, cohort structure, and more . Drug identifiers from DRUGBANK were retrieved and added to the list of attributes.Drugs derived from the PharmGKB variants–phenotypes list have been annotated by identifying the commercial drug names, the FDA approval status, the indication information, and their conventional names from the International Union of Pure and Applied Chemistry (IUPAC) federation. This information was extracted manually from DRUGBANK   procedure to integrate data from different sources into a relational database. A series of interactive transformation codes were applied for this purpose. Manually curated data were examined for their consistency of using unique terminology in each column. All the data found to describe populations from Non-African ancestry were discarded from the source table. The quality assessment process consists of evaluating the fraction of missing data, the correctness of mapping to the target tables, harmonization of terminologies, harmonization of class labels and the presence of duplicates.https://agmp.h3abionet.org (accessed on the 10 January 2022). The search menus have been set up on the basis that most users would need minimum information i.e., the gene name, the variant ID, the disease name or the drug name to easily explore the content of the portal. The portal has been designed with a gene-centric focus which ensures that all the information related to genotype-phenotype data and the associated metadata are attributed to genes at the lowest level of granularity. For example, the user may have access to all the variants belonging to specific gene that include the star-allele types and the SNVs (single-nucleotide variants) related to drug-response or disease phenotype from a single web page on the portal attributed to that gene. With such an implementation, querying, navigating and extracting information from the portal would require only a few prior inputs from the user. Access to data in the portal is facilitated by a combination of an SQLite SQL data storage engine, a Python–Django web framework as an intermediate back-end and an interactive web technology front-end user interface. A Bootstrap framework along with open source JavaScript Libraries and custom CSS are used. The SQLite database consists of six tables linked together using the object relational model .The portal can be accessed on the link al model .The tablThe portal was developed to provide curated information on the genetic variations associated with disease aetiology and treatment in populations of African-ancestry as well as a broad overview of the disease-causing/-associated variants. We utilized PharmGKB and DisGeNET as data sources of the portal mainly for their high-quality content and for providing comprehensive and easy-to-access raw data. DisGeNET includes more than 357,000 variants related to 66,379 bibliography resources. PharmGKB includes 9151 variant-drug associations, including single nucleotides and star alleles described by 3007 papers. An exhaustive search for the African-related data content was difficult to achieve, therefore we opted to automate the identification of African-related biomedical literature to reduce the size of the bibliography resources to be curated. The text mining process allowed us to identify 846 and 164 relevant studies from DisGeNET and PharmGKB respectively. Furthermore, we identified 479 and 2584 variants that are linked to these biomedical literature entries described, respectively, by PhamrGKB and DisGeNET raw data content.In addition to studies on African populations identified from PharmGKB and DisGeNET, the content of AGMP included data collected from UniProt, DrugBank, Ensembl and PubMed, which was transformed into a relational database containing six tables, as shown on the entity–relationship diagram . The TabThe manual curation retained 815 studies, including 143 references from PharmGKB and 652 references from DisGeNET that are associated with populations of African ancestry. We identified a total of 556 genes, of which 461 and 95 are related to 552 diseases and 71 drugs, respectively. This represents only a fraction (5.5% and 2%) of the total genes annotated in PhamrGKB and DisGeNET. Many of these diseases are similar but were assigned to different Unified Medical Language System concept unique identifiers in DisGeNET. For instance, “Piebaldism” was described to be associated with SNP rs121913684. “Piebaldism With Sensorineural Deafness” was assigned to another identifier in DisGeNET and was associated with the same rs121913684. The total number of variants associated with the drug response phenotype is 286, of which, 234 correspond to SNVs and 52 are star allele variants.The frontend of the portal is divided into six main pages , displayed as a menu in the header. The search page has toggle switches that allow a combination of four fields  to be selected, along with the input field to provide search keywords . A complStudies about genetic markers from populations of African ancestry have been conducted by different research teams from around the world. The ‘country’ data of AGMP aims to assign the annotated variants in the database to a geographical entity. A geographical entity is an indicator of where the study participants were recruited, including names of the country and the region. The annotation is dependent on the level of detail provided by a study, usually in the publication. Many of these studies have used a mixed population either of total African individuals or combined with non-Africans. For example, Zimmerman et al.  studied AGMP includes data derived from 37 African countries, though we noticed a significant imbalance of identified variants number between the different regions of Africa A. With 6Variants identified in PharmGKB are associated with drug response phenotypes for 50 drugs approved for specific treatments . WarfariThe first version of the AGMP was implemented to provide high-quality and reliable information on genetic variants from African populations and populations of African ancestry for users with interests in genomic medicine. The primary sources of data were PharmGKB and DisGeNET supplemented with manual curation from the literature and links to other databases. These provide rich metadata for genetic variants in a standard format and use controlled vocabularies. The two databases are also recognized for the high quality of their content because of their rigorous processes of curation. For example, the PharmGKB curation panel of experts regularly verify the biomedical literature to integrate novel variants or update the information about the association with drug-response phenotypes , while DData profiling and curation for AGMP have highlighted some drawbacks in the current conception of DisGeNET and PharmGKB, as well as the practices of describing the experimental protocol and presenting data in genetic and genomic studies. DisGeNET was intended to give a broad overview of variant-phenotype associations. The data, however, are presented as a binary association without taking into consideration the ethnic composition of the original study participants, hence our need to use text analysis and manual curation to extract data and metadata. In contrast, PharmGKB has adopted specific guidelines to assign a biogeographical group to each association . AccordiThe under representation of some African regions in public databases has been extensively discussed in several papers ,3,27,28.The disproportionate skew in the geographical distribution of data may be due to numerous factors; one of the main factors being the data representation in PharmGKB and DisGeNET. Both resources contain more data from North Africa as a result of many mixed studies with southeastern European, Middle Eastern and Francophone countries. In addition, DisGeNET contains a large proportion of case studies from North Africa and has less representation of other regions of Africa. This skew does not exist in all other biomedical databases , and as more resources are incorporated into the Portal, the distribution should become more evenly spread. As such, the Portal will be continually updated and new data sources will be included in the future. One of the main aims of developing the Portal was to highlight such knowledge gaps and discrepancies within Africa so that we can better address these research questions in the future.We expect the AGMP to be a crucial source of information for the ongoing African research activities in pharmacogenetics and genomic medicine. As a product of H3ABioNet, a member of the H3Africa consortium, we have the opportunity to promote the AGMP among a large community of African genetics researchers, which will allow us to update, improve and diffuse its content. Besides its informative added value, throughout the processes of data profiling, curation and web application development, the project enabled H3ABioNet to develop a solid core of experts, including bioinformaticians, curators, computer scientists, clinical biologists and data scientists. The core group will have a critical role in ensuring the sustainability and update of the portal and to maintain its relevance to genomic medicine-related activities in Africa.The AGMP is a user-friendly resource that allows users to query curated African genomic variants linked to either clinical phenotypes or to drug response using gene, disease, variant and drug names. This portal should be of interest to the African scientific community, physicians and genomic medicine stakeholders worldwide, as it provides informative data for those working with individuals of African descent. In addition, our work emphasizes the importance of population sampling coupled to GIS data acquisition that can improve the granularity of the geographical location to better represent the genetic diversity in Africa. It would also help in linking non-genetic factor contributions to phenotype expression.Two strategies have been proposed to extend the capacity of AGMP and improve the content and features of the resource. In the first, a curation group is established to run updated versions of the data mining, cleaning and integration workflows with more robust methods. This includes the training of predictive models that could process, in high-throughput mode, Medline entries that are not necessarily described in DisGeNET or PharmGKB. This will also allow communicating information about variants that are specific to Africa or with higher prevalence in Africa. Additionally, the group will implement reliable methods to automate the processes of data extraction and curation by utilizing APIs and entity–relationship detection from the biomedical literature. The data curation team will also determine the feasibility-to-adopt in integrating new data sources to capture African data in the GWAS catalog and GWASdb. Second, we aim to increase engagement with the scientific community involved in genomic medicine research in Africa by promoting the portal to the wider community, establishing an extended network of experts and curators, and adapting the portal user interface to allow for direct submission of the data. Finally, in order to provide more detail related to the studies captured in the Portal, a notes section will be included in upcoming versions of the Portal, providing additional study information such as study type and sample size.The portal’s primary aim is to facilitate genomic medicine research by researchers and clinicians in Africa or those working on African-ancestry populations. Secondarily, the portal may also serve as a guide for healthcare workers for diagnosis and prognosis of diseases and adverse drug reactions within their patient populations in the future and improve their understanding of the genetic underpinnings of precision medicine in Africa. However, it should be noted that the portal is a research tool and should not be used for clinical decision-making; rather, it is intended to provide doctors with the developing knowledge of pharmacogenetics and precision medicine that may be relevant for their patient population.


Over the last few decades, changes in diagnostic and treatment paradigms have greatly advanced cancer care and improved outcomes . HoweverTo best illustrate this problem, immunotherapy, arguably the biggest advent in cancer pharmacological research within the past two decades, has been regularly pointed to as a possible cause for this sharp rise in cancer care costs . The tecWith more and more immunotherapeutic options available and with the average cost of these solutions being USD 145,000 per patient per year . In locaIn the field of surgery, technological advances have also sparked concerns. For instance, in specialties such as Urology, the use of robotic platforms to perform surgeries that could otherwise be carried out in an open/laparoscopic fashion represents a significant financial burden on final expenses ,11. The Given the conditions above, along with the fact that cancer is now the second leading cause of death in the US and most developed countries with an increasing number of cancer patients every day, addressing cancer care cost-effectiveness is of paramount importance from the perspective of all parties involved. ,16.A month of cancer treatment in the US can cost up to USD 60,000  . AverageTherefore, cost is a critical aspect to consider when delivering cancer care. Interestingly, while most cancer patients (52%) want to discuss costs with oncologists, only a minority (19%) will ultimately have such conversations ,22. IdenAs such, new models for the delivery of cancer care have been explored recently, stemming from the experience of managing other chronic disease patients. The National Committee for Quality Assurance has proposed a list of goals for patient-centered oncology care that aims to address the most common issues that lead to poor outcomes , includiA national survey conducted in the US in 2008 found that a vast majority of oncologists (84%) made their treatment recommendations based upon patients’ out-of-pocket spending. Strikingly, only a minority (43%) discussed costs with patients . Most prCancer patients often see multiple providers and frequently face a myriad of treatment options. Fragmentation of care is an unfortunate result of the current payment structure, which creates an environment that does not allow oncologists—who would otherwise naturally coordinate patient care—to bill for shared decisions, help patients navigate the system, or support them emotionally . These iAccording to the National Cancer Institute, the medical cost of cancer care in the US was USD 150.8 billion in 2018 and has been increasing substantially every year, even beyond previous predictions . This faSince the early 1990s, in order to offer more options to patients and clinicians in a timely manner, the US Food and Drug Administration (FDA) has been increasingly approving oncological drugs through accelerated programs . The ratWhen it comes to radiation therapy, the treatment cost is highly variable between countries, and within the same country at different hospitals ,35. PricIn the US, there is a critical need to control costs to ensure the sustainability of the healthcare system by reforming the payment structure on a national level. Controlling expenditure is a multifaceted challenge involving a wide range of factors. For example, healthcare spending has mostly increased due to higher drug costs, but there are several other contributing factors such as failure of screening programs, increased cancer prevalence, and increased staff costs, legal costs, and facility fees.The US healthcare system is currently being stretched thin by the increasing cancer incidence rates and the booming cost of medications and technologies. Moreover, the excessive utilization of inpatient and emergency services resulting from fragmented care delivery are all contributing to the overall financial burden of cancer care. New cancer therapies have taken center stage in the health policy debate of several high-income countries, not just in the US. The approaches chosen to make these agents available to patients vary greatly: what is easily approved with little questioning in one country may be rejected on the grounds of excessive cost in another, until a middle-ground settlement is reached between the authorities and pharmaceutical companies. A critical point to consider in this issue is that pharmaco-economic analyses have to be tailored to each country, factoring in its unique system and patient characteristics. Although this could be an obstacle to implementing global solutions, the principles applied in one country may be transferrable elsewhere.Across the European Union (EU) and the United Kingdom (UK), the cost of cancer therapy falls on third-party payers, usually either the government or sickness funds. The EU relies on the work of the European Medicines Agency (EMA) for the evaluation and supervision of drugs. Rather than replacing national drug authorities , the EMAA well-known example is the National Institute for Health and Care Excellence (NICE). This UK institution assesses new health technologies and the clinical effectiveness of different interventions. According to a study that compared the EMA’s decisions with those of a state member’s HTABs, overall agreement was found; still, the EMA did not carry out any pharmaco-economic assessments . HoweverInitiated by the European Society for Radiotherapy and Oncology (ESTRO) in 2011, the Health Economics in Radiation Oncology (HERO) project aimed to develop a comprehensive knowledge base and model for economic evaluations of radiation therapy treatments in Europe . The groAdditionally, given the recent political changes that caused the UK to leave the EU, it will be interesting to see how the UK will differ in its approach from the EMA. Moreover, with the rise of costly immunotherapies and the spiraling pressure their cost is applying on GDP allocations for health expenditures, more conversations will definitely need to take place around cost-effectiveness and the threat cancer care costs pose on European healthcare systems.In this Special Issue, we look for innovative comparative and cost-effectiveness analysis studies that can guide cancer management decisions and inform health policy. Several management strategies achieve similar performances in terms of disease control and survival for a wide range of indications, and the clinical decision is ultimately based upon the subjective criteria employed by the treating physician. Therefore, this topic aims to share new frameworks and concepts in order to determine the most cost-effective diagnostic and treatment strategies for maximizing the care of cancer patients and the utilization of resources.The rising costs in oncology have had different effects on the major stakeholders in the healthcare system. From a patient’s perspective, there is a critical need to find solutions that relieve the economic burden and financial toxicity of cancer care as it stands now. It is important to help alleviate the psychological impact of these problems in patients who are concurrently experiencing the anxiety of illness and death. For healthcare providers, there is a need to define cost-effectiveness tools and compare diagnostic and therapeutic strategies in order to improve patient-centered care. On a public health level, allocating resources appropriately and determining the effectiveness of different cancer care options are priorities for ensuring sustainable healthcare systems.Hence, for all the reasons listed above and many more, there is a critical need to implement cost-effectiveness analyses in order to better inform healthcare decisions in clinical practice. There is a sense of urgency to act sooner rather than later with sustainable solutions, or else we may soon face the crumbling of our healthcare systems.