The Ebola epidemic in West Africa was stopped by an enormous concerted effort of local communities and national and international organizations. It is not clear, however, how much the public health response and behavioural changes in affected communities, respectively, contributed to ending the outbreak. Here, we analyse the epidemic in Lofa County, Liberia, lasting from March to November 2014, by reporting a comprehensive time line of events and estimating the time-varying transmission intensity using a mathematical model of Ebola transmission. Model fits to the epidemic show an alternation of peaks and troughs in transmission, consistent with highly heterogeneous spread. This is combined with an overall decline in the reproduction number of Ebola transmission from early August, coinciding with an expansion of the local Ebola treatment centre. We estimate that healthcare seeking approximately doubled over the course of the outbreak, and that isolation of those seeking healthcare reduced their reproduction number by 62%  59–66). Both expansion of bed availability and improved healthcare seeking contributed to ending the epidemic, highlighting the importance of community engagement alongside clinical intervention.This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’. By 30 MEbola spreads through contact with bodily fluids that continue to be infectious after death . This maThe exponential rise in case numbers in the summer of 2014 in Lofa County and elsewhere triggered a large-scale international response of humanitarian assistance to West Africa. In Lofa County, this led to a rapid expansion in ETC bed capacity, from 10 beds in June 2014 to about 100 by mid-August. Beyond its humanitarian contribution through the provision of appropriate care for a greater number of patients, providing a sufficient number of beds can contribute to curbing an epidemic by removing cases from the community and isolating them, thereby preventing further spread.As much of transmission of Ebola occurs in (not necessarily nuclear) families, communities and at funerals, behaviour change can have a great impact on the course of an outbreak. This makes it important to understand the cultural contexts and processes that can trigger such change as well as its impact on the transmission . ExperieMathematical modelling of EVD epidemics has previously provided insights into the different routes of Ebola transmission ,17 and tHere, we aim to characterize the epidemiological features of, and the public health response to, the EVD outbreak in Lofa County in 2014, and assess the role of the multiple components of intervention in the control of the outbreak. To tease out the impact of different clinical and community-based interventions, and to estimate the relative contribution of these to containing the epidemic in Lofa County, we fitted a mathematical model of Ebola virus transmission with a time-varying transmission rate to the series of ETC admissions. This allowed us to fully account for the progression of EVD in infected individuals and associated delays, and thus to pinpoint when declines or increases in transmission rates must have occurred to produce the observed time series of cases.2.(a)To record suspect cases of EVD and suspect community deaths, a case notification form was completed by the district health officer (DHO) or member of their staff. This identified: symptoms, date of onset of symptoms, prior exposure to a known case of EVD, attendance at a funeral or traditional healer, and family or community contacts to whom the individual may have transmitted the infection. Cases were considered suspect, probable or confirmed according to WHO and Liberian Ministry of Health and Social Welfare (MoH) case definitions . LaboratDuring the outbreak in Lofa County, a complete registry of deaths was not maintained and formal population-based surveys of knowledge, attitudes and behaviour relevant to EVD were not conducted. The chronology and nature of the interventions of various actors were derived from operational records, through participant observation and unstructured, qualitative interviews with key informants in participating organizations and the community. Media messages in the county were also informally monitored. Community-based interventions to control the EVD outbreak included: social mobilization to influence community knowledge, attitudes and behaviour; and outreach teams that assessed and transported suspect cases, provided safe burials and disinfected dwellings. The MoH, Médecins Sans Frontières (MSF) and UNICEF led the former activity, whereas the MoH and MSF provided the latter services. The number of individuals contacted per week by the MSF health promotion teams is presented as a measure of these community-based activities.(b)t, susceptibles (S) experience a (time-varying) force of infection λ(t). Upon infection, susceptibles move into the exposed (E) compartment, representing those infected but not yet infectious. After the incubation period, people in the exposed class move into one of two infectious (I) classes (with rate ρ), depending on whether they are healthcare seeking ospital, where these individuals may ultimately arrive) or not ommunity, where these individuals will remain). With time-varying probability ht, individuals leaving the E compartment enter the IH compartment where they remain in the community until they get admitted to the ETC , recover (RC) or die  and get a safe burial (BH). With (time-varying) probability (1 − ht), they enter the IC compartment where they remain until they recover (RC) or die  and get an unsafe burial . Individuals from the IH compartment who get admitted to the ETC are split into those (HD) who eventually die (DH) and get a safe burial, and those (HR) who recover (RH), with the relative probabilities of entering the HD or HR compartments given by the case fatality rate c. Hospital admissions (into the HR and HD compartments) occur with multiplicative gamma-distributed noise , a convenient choice for a rate that is subject to random variation [A stochastic compartmental model of Ebola virus transmission was constructed and parametrized using detailed information obtained from the line list of ETC admissions. The model extended the classic susceptible–exposed–infectious–recovered (SEIR) model as follows: at time ariation ,31. A scIH) and those that do not (IC), the ones that would seek healthcare (i.e. are in IH) but do not get to the ETC (because they die or recover before) are safely buried. The ones who would not seek healthcare (i.e. are in IC) are not safely buried and remain infectious (in DC) until they are buried (BC). While we did not have any data to inform this choice, the rationale is that these might be part of resistant communities who would not call for a safe burial. Note that, as healthcare seeking changes during the course of the outbreak, so does the proportion of dead that is safely buried.In the model, when infectious people are split into those that seek healthcare .R [fitdistrplus [IH), they would have an index for each of these transitions. The index with respect to any transition was maintained under other transitions such that, for example, people admitted to the ETC late in their infectious period would proceed to death quicker than those who were admitted early in the infectious period.Because a focus of this work was on timing, we used the patient data to parametrize the model with realistic transition time distributions. Transition times in standard compartmental models can be made to follow gamma distributions with integer shape parameters, that is Erlang distributions, by putting compartments in sequence . We fittR  package istrplus , and choWe assumed that the symptomatic period coincided with the infectious period, as suggested by a study of a previous Ebola outbreak where infection was found to have been transmitted by ill patients both in early and late stages of illness . We furtκt according to the observed mean , the time-varying community reproduction number  isAssuming that no transmission occurs in an ETC or during a safe burial, the force of infection at any time isAn exact calculation of this reproduction number calculated using a next-generation matrix  is givenThe ratio between the two reproduction numbers is approximatelyRH given in the electronic supplementary material.We calculated a range of values for this ratio using bootstrapped parameter values estimated from the line list of cases and using the exact formula for βt could then be used to track the behaviour of the transmission rate over time [The overall reproduction number at any time ise filter . The mode filter . The filver time ,41, and hearly, hlate, ε and τ).The initial conditions and the parameters of the time-varying rates were estimated during the fitting process: the number of infectious people in Lofa County on 26 May 2014 (one week before the beginning of the time series of ETC admissions), the mean and standard deviation of the transmission rate, and the four parameters governing the proportion of the population seeking healthcare ht fixed to its value in the first week.We adapted the model fitted to the ETC admissions data to explore counterfactual scenarios. To measure the impact of bed availability, we considered a model where limitations in capacity would prevent patients from getting admitted to the ETC. To do so, we modified our model to keep track of the number of people currently in the hospital. If this was at capacity, the infected individual would stay in the community and keep transmitting until there was space. After verifying that a model with estimated bed capacity as it was available during the outbreak  yielded the observed epidemic, we explored hypothetical scenarios where there would be either (i) no expansion of bed capacity  or (ii) no changes in healthcare-seeking behaviour, i.e. 3.Between 18 March and 9 November 2014, a total of 466 confirmed and probable cases of EVD were identified , of which 396 were ETC admissions (385 confirmed) and 70 community deaths (68 confirmed). The peak incidence of 67 reported new confirmed and probable cases of EVD occurred during the week of 18–24 August . This was followed by a steady decline to one confirmed case admitted to the ETC and no confirmed community death during the week of 20–26 October . The numMales (48%) and females (52%) were equally affected by the outbreak. Most (63%) of the cases were older adults , a third (33%) were young adults (15–39 years of age), whereas a minority were children . Overall, 310 (67%) of the admitted patients with confirmed or probable EVD died of the disease. Within Lofa County, the case fatality rate did not differ by district of residence, between men and women, nor did it change significantly over time. Of the confirmed and probable cases of EVD, 21 (5%) were healthcare workers, of whom 14 (67%) died, six recovered and one had an unknown outcome.The epidemic first affected the western districts of Foya, Kolahun and Vahun, and later the eastern districts of Voinjama, Zorzor and Salayea, Quardu Boundi . No caseThe delay between symptom onset and ETC admission increased from a median of 3 days in June (50% of cases being admitted within 2–4 days), to 5 in July (50% between 3 and 7 days), before dropping again to 3 in August (50% between 2 and 5 days), September (50% between 2 and 5 days) and October (50% between 2 and 4 days). Weekly changes in the delay to admission can be seen in Box 1.The early outbreak. The index case in Liberia, a 35 year old woman from Foya, had travelled to Guinea and became ill on 13 March. She was brought back to Foya, Liberia on 17 March by a 30 year old female relative and was admitted the following day to the Borma Hospital, Foya. She was confirmed EVD positive by testing at the Institut Pasteur Laboratory, Conakry, and died 20 March. Her female relative subsequently fell ill and was hospitalized at Foya Borma Hospital, but later fled to Monrovia continuing on to Firestone, Margibi County, Liberia where she died of confirmed EVD. Two male healthcare workers from the hospital, who had cared for the index case, aged 48 and 46, fell ill, were confirmed positive, and died on 31 March and 4 April, respectively. A 30 year old woman who had washed the clothes of the index case during her illness also fell ill, was confirmed positive and died on 1 April. Aside from this cluster, another case was confirmed in a 55 year old female from Foya who had returned from Guinea during the three weeks prior to the onset of her illness on 31 March 31. With the support of WHO, all deaths of confirmed cases received a safe burial. Following this cluster that occurred exclusively in Foya town, no further cases were confirmed in Lofa County until early June.The second wave of the epidemic began in Lofa County on 6 June when a case was confirmed in a 46 year old man from Foya district who had been partially trained as a nurse. In May, he had travelled to a nearby village in Sierra Leone where he had cared for his ill mother, administering two intravenous infusions and two injections of medication. His mother died later that month from confirmed EVD. After returning to Liberia, he developed symptoms on 2 June, and was admitted to the ETC, Foya, on 5 June. He was confirmed positive and subsequently discharged recovered.In the second and third weeks of June, a second large cluster of cases occurred in an extended family in Foya. The 65 year old matriarch of the family who lived with her husband in nearby Sierra Leone became ill on 20 May. She was taken to Foya by her family where she was admitted briefly to the Foya Borma Hospital with suspect EVD. As she was not improving, and before she could be confirmed as a case, she was taken to the family home in Foya where she began vomiting blood and died on 27 May. Her body was washed and dressed and transported in a rented minibus back to Sierra Leone where her burial took place. Subsequently, 16 people, including nine family members in Foya and seven individuals who attended the burial in Sierra Leone, died of confirmed EVD in both countries.Incident cases stabilized until mid-July, but thereafter there was a rapid and geographically widespread increase in reported number of admissions to the Foya ETC and community deaths owing to confirmed EVD.National and international response. The response to the EVD outbreak in Lofa County was led by the district and county-level MoH health team under the coordination of a National Ebola Task Force which was established on 30 March 2014 and comprised government agencies and international partners. On declaring the outbreak, the MoH recommended the avoidance of personal contact through handshakes, hugging and community gatherings and a halt to traditional burials, which typically involve family members washing the body and touching the corpse.In early April, the WHO conducted a needs assessment, the US Centers for Disease Control and Prevention supported the development of an epidemiological surveillance and contact tracing system and, from its existing operational base in Guéckédou, Guinea, Médecins Sans Frontières (MSF) provided technical advice and training in community health promotion, case management and the establishment of isolation facilities, but was not involved in the direct provision of services in Lofa County until August.By mid-July, WHO, MoH and MSF identified significant gaps in the response to the now-accelerating epidemic: low coverage of contact tracing, denial and resistance in communities, weak data management, inadequate infection prevention and control in health facilities, insufficient outreach capacity, insufficient safe burial capacity, and weak leadership and coordination at a national level . WHO proBy early August, however, it was apparent that the epidemic in Lofa County and elsewhere in Liberia was spreading out of control. The national government declared a 90 day state of emergency on 6 August, imposing a 21.00 curfew, closing markets, schools and other public institutions and restricting both public gatherings and the movement of people across international borders. A number of communities restricted the entry of individuals from elsewhere, especially those coming from other districts and neighbouring countries. On 7 August, WHO declared the EVD epidemic in West Africa a Public Health Emergency of International Concern, invoking the 2005 International Health Regulations  and estaClinical interventions. The first cases of EVD in Lofa County were identified and treated at Borma Hospital in Foya, an existing MoH facility. In response to the need for improved infection prevention and control, a 10 bed ETC was established on 20 April 2014 by the MoH with technical assistance from MSF, in an existing building located on the edge of the town of Foya that had formerly served as a refugee transit centre. Nursing, hygiene and administrative staff of the MoH were seconded to this unit with training provided by MSF. However, from the second week of April until the end of May, no further cases were identified in Lofa County. During this period, both the ETC and staff were on standby and community health promotion activities were minimal. Key informants indicate that most residents at the time doubted that Ebola was truly present in their communities.With the reappearance of EVD in June, a non-governmental humanitarian organization, supported by MSF, took over the management of the Foya ETC. However, rapidly increasing numbers of EVD cases in July led to overcrowding in this facility with up to 40 patients, and necessitated the construction of a new 100 bed ETC of wood and plastic sheeting adjacent to the original centre in early August. Patients were transferred into the new facility, built and managed thereafter by MSF, on 10 August. The new ETC was designed to emphasize transparency in its activities by allowing family and community members to see patients receiving care. Provisions were made to house out-of-town patients' families and to allow visits at a safe 2 m distance.Beginning in September, an MSF psycho-social team, comprising national and international mental health professionals, provided counselling and support for recovered ETC patients and their families both during their hospitalization and on their return to their home communities.By July, many health structures were closed or operating only intermittently owing to fear of disease transmission on the part of both patients and staff. However, beginning at the end of August, the MoH and several international partners provided training and equipment to strengthen infection control and triage practice in the existing healthcare structures, salary supplements to Liberian staff engaged in the Ebola response, and vehicles and fuel to the MoH health teams .Community-based interventions. A protocol to systematically investigate suspect cases of EVD in the community was established in early August, implemented first in the Foya and Voinjama districts, and later in the rest of the county. MSF and MoH set up Ebola telephone ‘hotlines’, enabling community members to alert the healthcare team to suspect cases and deaths. Calls were triaged, and an outreach team dispatched to investigate suspect cases or deaths. Transport of suspect cases, home decontamination and safe burial of corpses was performed according to established protocols [rotocols . The patrotocols ,49. FromContacts of suspect cases and deaths were registered by the DHO at the time of case notification. Contact tracing was conducted by community volunteers supervised by MoH staff for 21 days following their last suspected exposure, either in person or by mobile phone, according to WHO protocols . AccuratHealth promotion efforts by several non-governmental organizations began in March, but were of limited geographical reach and intensity owing to limitations in transportation and human resources. In the run-up to the county election in July, at least one candidate distributed distinctive hand washing buckets to a number of larger villages as a preventive measure. Yet, in July, an outreach team was forced to withdraw from one community when it met with community opposition and violence. With an increased availability of vehicles and personnel from MSF and other international partners after mid-August, health promotion activity intensified and extended to outlying communities. MSF anthropologists and health promoters together with Liberian staff knowledgeable about local customs and languages, met first with local village leaders and later with community members in public meetings. Priority was given to those communities in which cases had recently occurred. The teams explored the community's beliefs about EVD, EVD prevention, the treatment and services provided at the ETC, and sought to clarify any misconceptions. Whenever possible, teams were accompanied on their visits by patients from the community who had been discharged recovered from the ETC. Representatives of each community, including community leaders, received training in EVD and were invited to tour the ETC. After July, there were no further reports of Ebola response teams encountering community resistance or violence.Beginning in August, a range of communication strategies were used to promote the understanding of the real threat of Ebola, the early identification of symptoms, the prevention of spread of the disease, the use of the Ebola ‘hotline’ to refer suspect patients to the ETC, and the need for safe burial practices. Multiple, but not necessarily coordinated programmes, were launched by the national government, the United Nations Children's Emergency Fund (UNICEF), MSF and a number of media outlets. In September and October, radio and video clips using music, drama and personal testimonials in a range of local languages were made widely available. Local musicians appeared alongside MSF health promotion teams during community outreach. A number of MoH district health teams met with community leaders, youth groups, unions, marketing associations and community-based organizations to promote these messages.RC) was 4.5 .Our model reproduced the trend in hospital admissions between June and November . Becausef). The longest sustained period of transmission was in the five weeks between 30 June and 4 August, during which the reproduction number can be seen to steadily increase. The subsequent peaks in mid-August and early and late October are significantly smaller. After the first week of October, more than 78% of posterior samples of the reproduction number were below 1.The estimated community reproduction number (i.e. the average number of new cases caused by each case if there were no beds available to isolate them) shows a pattern of multiple sub-outbreaks followed by brief periods of no transmission, combined with an overall decline f. The lor = 0.38 , or by 66%. If individuals were assumed to be twice as infectious during the later stage of infection and burial, the effect was even stronger, with r = 0.33  or a 67% reduction of the reproduction number of those seeking healthcare .We estimated that healthcare-seeking behaviour increased during the course of the outbreak, from a median estimate of 36%  of the population seeking healthcare at the beginning of June to a median estimate of 87%  at the end of October. By comparing the late to early healthcare-seeking behaviour on a sample-by-sample basis, our median estimate suggests that individuals were 2.0  times as likely to seek healthcare late in the epidemic as early. With the parameters in our model, isolation in the ETC reduced the reproduction number of those that seek healthcare to a fraction Aggregated simulated trajectories of total incidence (in the community and the ETC) under the scenarios of (i) no bed expansion (and rejection of patients if no beds were available) and (ii) no change in healthcare-seeking behaviour from early in the outbreak are shown in 4.Lofa County was the first region in Liberia to experience the 2013–2015 EVD outbreak in West Africa, and it was struck severely. A rapid rise in cases over the summer of 2014 was followed by a fall in cases towards the end of August 2014, and control by the end of October. The behaviour of the epidemic in Lofa mirrors what has been observed across many regions of West Africa, and a better understanding of this behaviour can yield important lessons for investigating the epidemic elsewhere. Here, we analysed the impact of different clinical and community-based interventions that were put in place at different times, in an attempt to pinpoint what exactly turned the epidemic around.The main clinical intervention was the expansion of the ETC in Foya from a capacity of 10  to 100. We have estimated that the provision of isolation enabled through the expanded ETC reduced the reproduction number of those who entered the ETC by about two-thirds and thus made a strong contribution to the substantial decline in case numbers observed in the three weeks following the opening of the expanded ETC. Without the expansion, the outbreak would have continued to grow for weeks longer, and we estimated that hundreds of lives were potentially saved by this measure.The national government imposed a state of emergency in Liberia on 6 August. By closing markets, schools and restricting public gatherings and movement across international borders, this measure may have altered patterns of contact in communities and contributed to preventing geographical spread, but possibly not to a reduction in disease transmission, much of which occurs among family members . At the From the modelling analysis, it appeared that the expansion of the ETC capacity, occasional interruptions of transmission and improvements in healthcare-seeking behaviour all contributed to mitigating the epidemic and eventually stopping it. Two features stood out in the time-varying behaviour of the transmission rate: one is that the epidemic in Lofa appeared to have consisted of several subepidemics which intermittently stopped before starting again. This is consistent with geographically heterogeneous dynamics where outbreaks flare up and are subsequently controlled by a combination of local behavioural change and targeted intervention, but potentially trigger outbreaks elsewhere. The second feature is the overall decline in the reproduction number from August, leading to eventual extinction. This decline has been previously observed using a model of behavioural change that did not include the detailed information of the outbreak which we included here . It is iThe exact extent of healthcare-seeking behaviour was difficult to establish from fitting to hospital admission data alone, which did not contain any information on how many cases may still have been occurring in the community but went unreported. Still, our model suggests that it did appear to improve between the beginning and the end of the epidemic. Interestingly, much of the increase in healthcare-seeking behaviour appeared to happen before the start of health-promotion activities, indicating that attitudes may have changed substantially before the onset of these activities. In this context, it is important to bear in mind that the time course of healthcare-seeking behaviour was constrained by the particular structure of the model we chose. While the transmission rate was allowed to vary randomly and therefore increase and decrease at any point in time, we assumed that healthcare-seeking behaviour could only change in one direction over the course of the outbreak. If we had allowed similar flexibility in the way we modelled healthcare-seeking behaviour to the way we modelled the changes in the transmission rate, it might not have been possible to pinpoint these changes. The behaviour we found was consistent with observations that overall attitudes towards health institutions improved during the course of the epidemic. It helps explain the very sharp rise of cases admitted to the ETC in July (which was stronger than could be explained with a constant transmission rate), and it aligns with the fact that the outbreak was eventually ended relatively rapidly. Without further information on community behaviour, however, it remains difficult to establish these relationships with certainty.More generally, it would be desirable in the course of future outbreaks to implement concurrent community surveillance to directly monitor total deaths and their causes, and measure a limited number of key social variables. Assessing all-cause mortality within the community could provide an estimate of the number of suspect EVD cases in the community that did not present to the ETC for care or were not provided a safe community burial. This would allow ongoing measurement of healthcare- and safe-burial-seeking behaviour, including an estimate of the proportion of EVD in the community not being identified and properly managed. Similarly, if one had direct information on public attitudes , such information could assist in not only more accurately understanding and modelling the role of these factors in the evolution of the outbreak, but also in tailoring social mobilization efforts to increase their effectiveness in particular communities. While such studies are clearly secondary to immediate efforts to mitigate transmission and care for the sick, they could provide crucial information for evaluating and tailoring the ongoing outbreak response and planning for future such events.


Since 1965, the Korean physical therapist licensing examination has been conducted to foster professional physical therapists. As the responsibilities of a physical therapist include measuring and evaluating patients’ physical function and developing the competence to establish treatment plans and predict the outcomes thereof, the need for a new examination system to help develop these abilities has been pointed out. This idea led to the introduction of case-based items on the examination in 2014, and it is expected that case-based items will replace all 60 existing practice items [We conducted a survey of the programs of 14 universities and 19 colleges using a questionnaire to collect information about various characteristics of clinical practice from June to September 2016. Raw data were available from This research was authorized by the Institutional Review Board of Silla University (1041449-201708-HR-008).Representatives from 19 colleges and 14 universities answered and returned the questionnaires. The results of the survey are shown in A curriculum was designed that prescribed a period of 16 weeks of clinical practice, including 4 weeks of in-school training. Therefore, there were 640 hours of practice with 40 hours of practical training as suggested by the Korean Accreditation Board of Physical Therapy of the Korean Physical Therapy Association . The 5 mBased on the 2012 physical therapist job descriptions , an analSince 2014, the Korean physical therapist licensing examination has included 5 subjects covering 25 areas: basic physical therapy , diagnosis and evaluation in physical therapy , physical therapy interventions , medical law , and a practice examination  [Clinical practice is useful for students to improve their interpersonal relationship skills with the members of a hospital organization and to cultivate the ability to cope with various situations. The training also helps students establish a specific career plan after graduation and develop the skills required for treating patients. Moreover, it enhances student empowerment, which contributes to more effective decision-making skills and self-efficacy .In physical therapy education, clinical practice is an opportunity to apply theories learned in college in the clinical field and to learn how to apply specific skills. This is an important aspect of the curriculum, as it helps influence how the mindset of a professional physical therapist is established. It is critical for students to cultivate professional skills through clinical practice. Therefore, it is necessary to provide an environment with sufficient practical training to enhance practical skills and a professional mindset .Through clinical practice, which is a crucial process in physical therapy education, students experience learning in various physical therapy fields, practice the basic roles and skills of a physical therapist, and acquire the ability to cope with the changing needs of patients . In addiAccording to the study of Lee et al.  that anaAccording to the report of Kim and Lee , the higPractical programs presenting teaching methods  between clinical instructors and students have been described in several advanced countries belonging to the World Confederation for Physical Therapy, such as USA, New Zealand, and Australia . A standThis study identified the subjects most commonly taught in colleges as standard subjects .The learning objectives of the standard practice curriculum were selected according to the basic job functions of a physical therapist. These functions included disease evaluation and intervention and training, as outlined in the 2012 physical therapist job descriptions.The standard clinical practice curriculum was structured according to the subjective viewpoints of the researchers, based on preceding studies in the Republic of Korea and abroad and on a survey of domestic colleges. Therefore, these suggestions are limited to physical therapy education in the Republic of Korea.In conclusion, we suggest a standard clinical practice curriculum and learning objectives for physical therapy education in Korea, as presented in


In South Africa, gender inequality dominated by males and heterosexual HIV epidemic are associated with high HIV infection. Underlying epidemiological and social determinants driving HIV acquisition and transmission are critical to understand the extent and complexity of sexual networks as primary mechanisms through which HIV is likely to spread. The aim of the study is to provide an overview of empiric evidence that links the complex interaction of risk of HIV infection in men.We will conduct a systematic scoping review to identify, describe, and map literature on the dynamics of HIV infection in men, and we will determine the quality of the studies reporting on the dynamics of HIV infections in men. Primary research articles, published in peer-reviewed journals, review articles, and gray literature that address the research question, will be included. We will search PubMed, Web of Knowledge, Science Direct, EBSCOhost, Google Scholar, World Health Organization library, and UNAIDS database. Reference lists and existing networks such as government organizations and conferences will also be included to source relevant literature. Two independent reviewers will extract data in parallel from all relevant search engines, using specific inclusion and exclusion criteria. A thematic content analysis will be used to present the narrative account of the reviews, using NVivo version 10.We anticipate finding relevant literature on the dynamics of HIV transmission in South African men. Once summarized, data will be useful to guide future research.CRD42016039489PROSPERO The online version of this article (doi:10.1186/s13643-016-0398-y) contains supplementary material, which is available to authorized users. South Africa accounts for 18% of global HIV infections, with approximately 6.7 million people infected . With onFor decades, HIV surveillance and preventive intervention research has largely focused primarily on females –11. AlthDespite the high coverage of HIV counseling and testing (HCT) and antiretroviral therapy services in South Africa, a high number of people remain uninformed about their HIV status, majority being males, and do not perceive themselves as being susceptible to HIV infections and may therefore not take preventive measures to reduce HIV transmission and faster progression of acquiring infection to AIDS defining illness . PublishThe presented literature suggests the importance of understanding of HIV transmission dynamics in males and underscores the need for focused research to address this major gap in the knowledge of HIV epidemiology. The interactions of structural, behavioral, and biological risk factors of HIV acquisition and/or transmission are poorly understood and are a key to the design of HIV intervention programs. However, it is imperative that we understand the structural features of risks of HIV transmission in sexual networks as very little work has been done on characterizing these structures. Large complex studies are required to understand these risks, and as there exists no data for a clearer understanding on these complex interactions of risks. The purpose of the scoping review is to refine a future research agenda and provide directions to future research by establishing to what extent existing research has progressed towards understanding the dynamics of HIV in South Africa.To identify and describe the epidemiology of HIV in out of school menTo identify and describe HIV transmission dynamics in out of school menTo determine the nature and quality of studies reporting evidence on dynamics of HIV in menThe primary aim of the study is to map existing literature on the dynamics of HIV transmission in men in South Africa. In order for us to achieve the study aim, the following objectives are set:The current scoping review protocol has been prepared in consultation with the PRISMA-P statement  see Add. It has I.Identifying the research questionThe framework adopted for conducting the proposed review is by Arksey, H., and O’Malley, . BrieflyThe research question is: What is known from existing literature about the dynamics of HIV transmission in men in South Africa?What is the prevalence and incidence of HIV infection in out of school men of South Africa?Is there a relationship between the social networks and sexual networks for HIV-1 transmission in out of school men of South Africa?What interactions exist between biological, behavioral, and cultural factors in HIV-1 sexual networks?The research sub-questions are:II.Identifying relevant studiesThe study will use an amended PICOS  framework to determine the eligibility of the research question, as described in Additional file III.Study selectionPrimary research articles, published in peer-reviewed journals; review articles; and gray literature that address the research question, will be included in this study. All study designs will be included for review. Databases that will be used to source literature include; PubMed, Web of Knowledge, Science Direct, EBSCOhost, Google Scholar, World Health Organization library database, and UNAIDS database. We will also use reference lists and existing networks such as organizations and conferences to source relevant literature. The search terms will include “HIV infection in men and sex behaviors, or cultural factors, or social networks, or sexual networks, or phylogenetic or biological factors”. The language and year of publication will be restricted to English and between 2006–2016, respectively.One reviewer will conduct a comprehensive title screening by searching and uploading all literature search results on Endnote X7 software; all studies that do not address our research question will be excluded together with all duplicates. The final Endnote database will be shared for abstract screening; at this stage, we will use two independent reviewers to extract data in parallel, from all relevant search engines. The two reviewers will use the inclusion/exclusion criteria to identify relevant literature for inclusion and for further evaluation (s). Copies of full articles will be obtained and maintained.IV.Charting the dataInclusion/exclusion criteria, developed based on the research question will ensure correct identification and selection of relevant studies. To be included, studies must be focusing on HIV infection, transmission, or acquisition on heterosexual males. We will include both peer-reviewed publications and gray literature of all study designs with relevant interventions. We will exclude studies on HIV infections due to mother to child transmission of HIV and studies on high-risk men . The search strategies will be piloted to test the appropriateness of the selected databases and keywords in delivering relevant information/literature. The study selection procedure will be summarized using a PRISMA chart , study setting, and conclusions for the primary and the secondary outcomes of the interventions. An additional charting summary Additional file We will present a narrative account of findings from existing literature through thematic content analysis of the extracted literature, structured around the following interned outcomes: HIV transmission, HIV acquisition, and HIV infection. Results of the studies on HIV infection, acquisition, or transmission in heterosexual men outside South Africa vs South African men, on evidence of whether interaction of interventions leads to HIV infection (transmission or acquisition), will be coded by all authors independently.We use NVivo version 10 to present emerging themes according to the relevant interventions.CodingCategorize codes into major themesBuild theme-related themes (cut-and-paste technique)Display dataIdentify patterns in the data and identify sub-themesSummarizeThe below processes will be followed:Authors will interrogate the resulting themes and critically examine their relationship to the research question. Authors will also scrutinize the meanings of the findings as they relate to the overall aim of the study and address the implications for future research.Mixed methods tool will be used to assess the quality of evidence obtained from the search. The mixed method quality appraisal tool obtained from Mixed Methods Appraisal Tool (MMAT) Version 2011 [The current scoping review will provide evidence of the existence of complex interactions of risks undertaken by men, leading them to high risks to HIV acquisition and transmission and will provide evidence to refine future research agenda and provide directions to future research. While evidence suggest being a young male, having low level of education, unemployed, being Black African, and from a rural area predisposes males to high-risk behaviors for HIV transmission , 14, 16,With South Africa being predominated by unequal gender norms dominated by men, although importantly focusing on females, a holistic approach is needed to end the trajectory. It is imperative that we incorporate males in research to better understand the issues revolving around them and perhaps leading to their increased risk-taking behaviors. We anticipate finding relevant literature on the dynamics of HIV transmission in South African men. We will extend our review to include other countries to compare findings from other countries to those of South Africa. We will also include studies that focus on both males and females, but we will target results reporting on males. Because a huge amount of HIV research is produced globally each year, and we are interested on current and potentially relevant studies, we will limit our search to include the latest published studies from 2006–2016. It is essential to have a comprehensive and balanced account of previous work to provide a sound background of the research. It is because of this reason that the study will make use of a 10-year literature search. It will clearly define perspectives that have emerged and changed through the years as there has been extensive HIV research and interventions that have been conducted in the past 10 years. The purpose is to familiarize the reader with existing studies relevant to the gap in the knowledge, and a time shorter than the specified might not be sufficient to determine sustainable behavior in the targeted audience.The results will add an overview of documented evidence on complex interaction of risks in men and the dynamics of HIV transmission and will help identify requirement priorities for primary research in this area.


We present new mathematical and geological models to assist civil protection authorities in the mitigation of potential oil spill accidents in the Eastern Mediterranean Sea. Oil spill simulations for 19 existing offshore wells were carried out based on novel and high resolution bathymetric, meteorological, oceanographic, and geomorphological data. The simulations show a trend for east and northeast movement of oil spills into the Levantine Basin, affecting the coastal areas of Israel, Lebanon and Syria. Oil slicks will reach the coast in 1 to 20 days, driven by the action of the winds, currents and waves. By applying a qualitative analysis, seabed morphology is for the first time related to the direction of the oil slick expansion, as it is able to alter the movement of sea currents. Specifically, the direction of the major axis of the oil spills, in most of the cases examined, is oriented according to the prevailing azimuth of bathymetric features. This work suggests that oil spills in the Eastern Mediterranean Sea should be mitigated in the very few hours after their onset, and before wind and currents disperse them. We explain that protocols should be prioritized between neighboring countries to mitigate any oil spills. Marine pollution in the European Seas resulting from maritime traffic or offshore drilling is regulated by multiple institutions and conventionsWater circulation in the Eastern Mediterranean Sea has been shown to be complex and energetic with several alternating cyclonic and anticyclonic eddies, gyres and jets689910® and repositories in Greece and Cyprus. The latter data will allow to risk (or de-risk) parts of the coastline, and thus concentrate civil protection teams in areas where mitigation techniques are not only necessary, but urgent. A key driver for this work was the need to provide a benchmark methodology to assess oil spills in confined maritime basins, which record ever-greater ship traffic and industrial pressures in several parts of the world, including in the Eastern Mediterranean Sea where more than 73 oil spills have been recorded from 1977 to 2013 . Bathymetric, geomorphological, meteorological and oceanographic parameters were considered, in a first stage, as the main factors controlling the dispersion of oil slicks in the Eastern Mediterranean Sea512The methodology used in this work was developed under the umbrella of European Commission projects concerning oil spill response and predictions (S(p) = tan−1(|v(p)|), corresponds to the slope at point p of the topographic surface Z, whereas v(p) denotes the plane tangent vector defined as p) ∈ . In addition, A(p) ∈ . The above calculations have been undertaken using Matlab. The calculated slopes and aspects have been exported in.shp (shape) format in order to further been processed in ArcGIS 10.Step 1. Bathymetric features are known to be able to alter ocean circulation171822Step 2. Taking into account the results obtained in Step 1 see  we definStep 3. In this third step, we selected the maximum trajectory (maximum area covered) of the spills  and creaStep 4. Finally, we undertook a qualitative assessment of the relation between oil spill trajectories and seabed morphology see  and eval5The adopted methodology is summarized in o (NNW to N) (The results of previous studies171819A series of nineteen (19) oil spill scenarios shown in in-situ observations during the so far biggest oil pollution crisis in the Eastern Mediterranean, that of the Lebanese oil pollution of summer 2006Currents and eddies in the Eastern Mediterranean Sea are controlled by a strong thermohaline pattern, in contrast to Ekman currents in regions such as the North Atlantic and other open seas97In the Eastern Mediterranean, the nature of shoreline sediments is related to the shoreline morphology. The geomorphological mapping undertaken in this work reveals a straight coastline between the Al-Manzalah Lake (Egypt) and central Israel . A linea5The present work shows that the Eastern Mediterranean Sea presents high risk in terms of oil pollution, rendering the use of oil spill models crucial for the area. There are several reasons for the increased risk observed in the study area. First, the average age of vessels calling at Limassol, Alexandria, Valletta and Mersin is over 20 years compared to less than 14 years at the West Mediterranean ports of Algeciras, Augusta, Palma, Barcelona, Genoa, Fos and Gibraltar3 with plans to expand to host vessels up to 850,000 m3 in net volume; and b) the finding of the Zohr field in Egypt’s waters, adding to the already developing oil and gas production offshore Israel and the discovery of new hydrocarbon fields in Cypriot, Egyptian and Israel waters  serious marine accidents have been recorded  but moreOil spill contingency planning must start with the clear definition of assets and operations to be included within the planning scope31Tier 1 capabilities describe the operator’s locally held resources used to mitigate spills that are on or near an operator’s own facility. The resources also provide an initial response to spills that may potentially escalate beyond the scope of Tier 1 initial actions and capabilities.Tier 2 capabilities refer to additional, shared, national or regional resources necessary to supplement a Tier 1 response or support an escalating response. Tier 2 capability includes a wider selection of equipment and expertise suited to a range of strategic response options.Tier 3 capabilities are globally available resources that further supplement Tiers 1 and 2. They comprise the international resources necessary for spills that require a substantial external response due to incident scale, complexity and/or impact potential.After a range of oil spill planning scenarios are selected, consideration shifts to the development of appropriate response strategies, i.e., to available and viable response techniques that adequately mitigate the impact and consequences of each scenario. Planners should therefore consider how the response to a scenario might develop over time and how the strategy may need to adjust as the spill evolves. The strategy to be adopted should be focused on clear, attainable goals by first establishing a set of response objectives for the planning scenarios. Objectives are based on a number of inputs. However, those objectives that are largely common to all spill scenarios are to: (a) protect the health and safety of responders and the public; (b) control the source; (c) contain and recover spilled material; (d) maximize the protection of sensitive areas; and (e) minimize damage to environmental and socio-economic resources. Ηealth, safety and, in certain circumstances, security considerations are a significant part of a response and are always the top priority.Spill response equipment ;Logistical support service providers and equipment/supplies;Vessels of opportunity ;Local labour sources and volunteers; andSubject matter experts.The identification of sensitive resources and priority protection sites, as determined by the sensitivity mapping, provides the site-specific information to inform net environmental benefit analysis (NEBA) discussions and develop strategies that best meet the objectives of sensitive area protection and the minimization of damage. This signifies that scenarios that are more complex may require one or multiple strategies consisting of various combinations of techniques at different tier levels, possibly in different locations or for varying seasonality. For example, a scenario with the potential to occur both in winter and in summer when open water conditions exist will likely require multiple strategies, as the preferred mitigation techniques will change due to the seasonal conditions. A scenario with the potential for impact on offshore, near-shore and shoreline areas will require a strategy with a variety of techniques suitable for use in those unique environments. At present, the types of response resources that should be described include, but are not limited to:Once the most effective and feasible response techniques are identified for each scenario, a NEBA must be carried out to determine which of those technique(s) will have the greatest net environmental benefit. The NEBA process provides a means for selecting the best response actions that minimize potential impacts on people and the environment. It presents a useful framework to achieve science-based planning and stakeholder consensus prior to, and away from, the emotive atmosphere prevalent at the time of a spill. The NEBA uses the planning scenario information-including data on the environmental and socio-economic resources identified in the sensitivity mapping process-experience from previous spills, and scientific expertise to inform an assessment of the environmental and social impacts that could potentially result from the use of certain response techniques at specific locations. The NEBA process weighs the advantages and disadvantages, or trade-offs, of the available techniques so that an effective response may be formulated to achieve the maximum overall benefit for the environment. Finding consensus is an important part of the process; conflicts do occur, and an informed discussion should take account of the various stakeholder priorities and concerns that may be raised at each location.Natural recovery (i.e. no human intervention) is used as the benchmark against which to evaluate response actions. For example, if the use of intensive clean-up techniques on remote shorelines is not going to bring meaningful socio-economic benefits, or if it has the potential to exacerbate the ecological damage, its validity should be questioned. Such considerations should take account of the recreational, economic and wildlife uses of the shoreline, the safety of the public and responders, and the possibility of bulk oil remobilizing and spreading the contamination further afield.Through the use of NEBA, the relevant stakeholders in contingency planning should be able to understand the reasons why certain response options are included in the response strategy. If regulatory approval for a particular technique, such as dispersant application, is required, the NEBA discussion provides an opportunity for that technique to be evaluated and pre-approved for spill situations matching the planning scenarios. Should a spill occur, stakeholders only need to verify that the assumptions considered in the NEBA and the pre-approval are still applicable.Oil slick trajectories in the Eastern Mediterranean are related to the seabed morphology. This is because strong seabed irregularities, present in the study area, are able to alter the local hydrodynamic regime.Oil spill modelling suggests the most vulnerable areas to be the eastern part of the Levantine Basin, offshore Israel and Lebanon, the Cyprus shorelines and the Egyptian coastline.Shoreline susceptibility varies significantly depending on differences in its morphology, degree of exposure to wave action, on the existence of uplifted wave-cut platforms, coastal lagoons and pools and the presence of tourist and environmentally sensitive zones.A total of 19 oil spill simulations corresponding to 19 different locations, were combined with bathymetric, meteorological, oceanographic, and geomorphological data in this paper to conclude:This paper defends that key economic developments in the Eastern Mediterranean make oil spill models more crucial to spill monitoring and mitigation, and new legislative changes have recently made the interaction between Eastern Mediterranean countries more urgent than before. Recent hydrocarbon discoveries make the use of oil pollution dispersion models more than a necessity. Oil companies, licensed by the Republic of Cyprus to develop testing drills, are obliged to complete an Environmental Impact Study (EIA) according to national legislation. Oil spill dispersion models are part of this EIA. The EIAs are submitted to the Environmental Committee for approval before the execution of any testing drill. In addition, Israel has in October 2014 entered into the 2002 Emergency Protocol which accounts for prevention beyond the combating of oil pollution. Based on the results of this paper, we suggest the early deployment of coastal protection teams, following established protocols, in large oil spills accidents. Due to the significant environmental, social and economic impacts even a small oil spill can bring to the Eastern Mediterranean Sea, continuous improvement of the oil prevention and response capabilities is necessary. This can be achieved through investing in monitoring assets, technological innovation and forecasting models.How to cite this article: Alves, T. M. et al. Multidisciplinary oil spill modeling to protect coastal communities and the environment of the Eastern Mediterranean Sea. Sci. Rep. 6, 36882; doi: 10.1038/srep36882 (2016).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Staphylococcus aureus of clonal complex 398 (MRSA CC398) and enterococci were identified as relevant hazards. The release assessment showed that the probability of development of pleuromutilin resistance was high in MRSA CC398 (medium uncertainty) and low in enterococci (high uncertainty). A relatively small proportion of Danes has an occupational exposure to pigs, and foodborne transmission was only considered of relevance for enterococci, resulting in an altogether low exposure risk. The human consequences of infection with pleuromutilin-resistant MRSA CC398 or enterococci were assessed as low for the public in general but high for vulnerable groups such as hospitalized and immunocompromised persons. For MRSA CC398, the total risk was estimated as low (low uncertainty), among other due to the current guidelines on prevention of MRSA in place at Danish hospitals, which include screening of patients with daily contact to pigs on admittance. Moreover, MRSA CC398 has a medium human–human transmission potential. For enterococci, the total risk was estimated as low due to low prevalence of resistance, low probability of spread to humans, low virulence, but no screening of hospitalized patients, high ability of acquiring resistance genes, and a limited number of alternative antimicrobials (high uncertainty). This assessment reflects the current situation and should be repeated if pleuromutilin consumption increases substantially, resulting in increased prevalence of mobile, easily transmissible resistance mechanisms. Continuous monitoring of pleuromutilin resistance in selected human pathogens should therefore be considered. This also includes monitoring of linezolid resistance, since resistance mechanisms for pleuromutilins and oxazolidones are often coupled.Antibiotic consumption in pigs can be optimized by developing treatment guidelines, which encourage veterinarians to use effective drugs with low probability of developing resistance of importance for human health. In Denmark, treatment guidelines for use in swine production are currently under review at the Danish Veterinary and Food Administration. Use of pleuromutilins in swine has previously been associated with a very low risk for human health. However, recent international data and sporadic findings of novel resistance genes suggest a change of risk. Consequently, a reassessment was undertaken inspired by a risk assessment framework developed by the European Medicines Agency. Livestock-associated methicillin-resistant  In Denmark, all antimicrobials used for animals are prescribed by veterinary practitioners and sold through pharmacies or feed mills. Since year 2000, all antimicrobial prescription and sales records have been collated in a national database called VetStat. A prescription record includes information about type, concentration and amount of the antimicrobial used, animals treated, indication, age group, herd identification, name of prescriber, and livestock producer .www.danmap.org. The program is run by a One Health consortium of Statens Serum Institut, the National Veterinary Institute, and the National Food Institute.Since 1995, antimicrobial consumption and antimicrobial resistance in bacteria from animals, food, and humans have been monitored routinely as part of a coordinated national program: Danish Integrated Antimicrobial Resistance Monitoring and Research program (DANMAP) . The monThe continuous surveillance has increased awareness of the relationship between antimicrobial consumption in animals and development of resistance. Several initiatives exist to control and reduce the consumption in pigs. These include the Specific Pathogen Free (SPF) health scheme, banning of growth promoters, prohibition of prophylactic usage, and a control program called the “Yellow Card scheme,” introduced in 2010. This administrative system defines limits to antimicrobial consumption per age group within a swine herd per time period . These lIn addition, a working group consisting of stakeholder representatives and headed by the Danish Veterinary and Food Administration developed the first generation of antimicrobial treatment guidelines for pigs in 2006. The guidelines help the veterinarian in choosing the most appropriate drug for the respective infectious disease encountered. In the most recent version from 2010, the guidelines contain specific recommendations on the choice of drug as well as background information on the known percentage of resistance in the suspected causal pathogen, pharmacodynamics of the drug, and the probability of development of antimicrobial resistance transmissible to humans.The first Danish guidelines were developed without formal risk assessments, and this led to some controversy regarding the assessment of macrolides, resulting in a more thorough estimation of this risk . In the Currently, the guidelines are being revised. The part of the guidelines that cover the assessment on the risk to human health is built on a risk assessment framework inspired by a set of guidelines issued by the European Medicines Agency (EMA) in February 2015 . CurrentIn this article, the risk assessment for pleuromutilins will be presented. Pleuromutilins consist of a class of antimicrobials, of which tiamulin and valnemulin are of veterinary use exclusively and primarily used to treat diseases in swine. Pleuromutilins have so far been associated with a low probability of development of antimicrobial resistance of importance for human health, since no equivalent drug exists for human treatment and no important cross-resistances to other human antimicrobials have been described. In the 2010 version of the Danish treatment guidelines, tiamulin and valnemulin were therefore recommended for treatment of relevant infections in swine  of clonal complex 398, MRSA CC398] in swine treated with pleuromutilins indicated by international literature , low (2–10%), medium (11–30%), and high (>30%).The fourth step was the consequence assessment. The consequences of infection by resistant hazards caused by pleuromutilin consumption in pigs were assessed by two effects: (1) an increase in public health burden or (2) prolonged human illness and/or death. The public health burden was defined as a marked increase in the total number of carriers or infected people. This could pose a risk to society due to increased expenses related to the control of spread (screening and isolation procedures of patients), loss of work days, and an overall higher risk of severe illness due to increased exposure. Prolonged illness and/or death were measures for the severity of treatment failure in the individual patient due to resistance caused by pleuromutilin usage in pigs. Each consequence was assessed on a scale of very low, low, medium, or high based on the increase in cases caused by the resistance and the importance of the pleuromutilin and related antibiotics in treatment in Denmark.The risk estimate was a summary of the steps above, and it was based on a combination of the probability of the unwanted event and the associated consequences. If any of the probabilities related to release, exposure, or consequences were zero, there would be no risk.The level of uncertainty was described as high, medium, or low. Low uncertainty was used, where abundant data pointing in one direction were available, medium where only a limited amount of data were available, and high where no data were available, and expert opinion had to be used instead.A detailed description of what is included in the different elements is described by EMA , and a qThe EMA framework is very detailed and thereby contains many elements, reflecting its purpose as a tool of risk assessment in regard to application for marketing authorizations for new antimicrobial classes . PleuromLawsonia intracellularis), swine dysentery (due to Brachyspira hyodysenteriae), porcine colonic spirochetosis (due to Brachyspira pilosicoli), enzootic pneumonia (due to Mycoplasma hyopneumoniae), infections caused by Mycoplasma hyorhinis and M. hyosynoviae, and respiratory diseases caused by tiamulin-sensitive microorganisms  prescribed for Danish livestock are used in swine production, and the main area of use is group treatments, which is usually short term. In 2015, the annual consumption measured in active kilogram compound was 7,878 kg  . A cfr-like gene conferring phenotypic resistance with high MIC for especially clindamycin and linezolid was reported in different Bacillales and in a Danish strain of Clostridium difficile. It is yet to be established whether this has any clinical importance in humans in Denmark  . However Denmark . cfr genin China . No furtvga(C) genes have been found to contain the tetracycline-resistance gene tet(L), the kanamycin/neomycin-resistance gene aadD, and the trimethoprim-resistance gene dfrK (vga(E) genes were also found resistant to beta-lactams, tetracyclines, trimethoprim, macrolides, lincosamides, and spectinomycin and resistant to or with reduced susceptibility to quinupristin/dalfopristin .The ABC transporters induce cross-resistance between pleuromutilins, lincosamides, and streptogramin A and have the potential to cross-select for further antimicrobial classes , 31. Theene dfrK . Staphylopristin . The 275optrA genes have been reported in pork in other countries, but in Denmark, the optrA gene has to date only been reported in three enterococcal isolates from imported turkey, one isolate from Danish calf, and one human clinical Enterococcus faecalis isolate . A Swedish study testing clinical isolates of Brachyspira hyodysenteriae and B. pilosicoli showed slowly increasing resistances over a 20-year period (from 1990 till 2010) and declining resistances for the last 2–3 years of the study  or mobile—either carried by transposons or plasmids (staphylococci and enterococci). Anaerobe bacteria such as N = 70) and 68% of the finishing pig herds (N = 205) were found to be carriers  of swine origin showed that all of MRSA CC30 strains tested and 30% of the MRSA CC398 tested were resistant to tiamulin, while the MSSA strains of CC30 and CC398 showed 46 and 38% resistance, respectively. This indicates a high prevalence of phenotypic resistance, however, the resistance mechanisms were not identified . A small study on Danish mink farms showed resistance to tiamulin in 79.5% of the 39 MRSA CC398 isolates found. In Denmark, mink are fed with animal byproducts primarily consisting of slaughterhouse offal from pigs and poultry. The findings of MRSA CC398 in mink point toward transmission from pigs to mink through the feed .A study conducted at the Danish National Food Institute on MRSA and methicillin-sensitive entified . In the entified . Data frResistance to pleuromutilins or linezolid is not investigated as part of DANMAP . AccordiE. faecalis in pig cecal content at slaughter in 2015 was 24.7% .Enterococci are part of the normal intestinal microbiota of pigs and exist in abundance, thus it is expected that enterococci are also found on the living pig and are ubiquitous in the stable and surroundings. The prevalence of Resistance to pleuromutilin in enterococci has not been monitored in Denmark, and no international literature on the subject was found, so the release assessment is associated with large uncertainty.Enterococcus spp. in Denmark since 2002, involving annual susceptibility testing of isolates from Danish pigs at slaughter and Danish and imported pork. To date, no isolates have exhibited phenotypical resistance to linezolid. In 2015, 40 isolates of E. faecalis from pigs were tested, and all found sensitive to linezolid  and low for enterococci (high uncertainty).A limited amount of data was available as pleuromutilin resistance is not systematically monitored in Denmark. The screening of a national representative pool of MRSA CC398 for mobile-resistance genes reduces the uncertainty score around the MRSA CC398 estimate to medium, but the uncertainty around the enterococci remained high due to lack of data.The probability for cross-resistance to linezolid was considered to be medium for MRSA CC398 due to possible chromosomal point mutations (high uncertainty) and very low for enterococci (low uncertainty).In Denmark, pork is the most commonly consumed type of meat. The consumption of pork per capita is 56 kg per year, followed by beef (27 kg) and poultry (26 kg). In comparison, the average consumption of pork in EU-27 is 40 kg, followed by poultry (24 kg) and beef (15 kg) . Most poBetween 2009 and 2011, Danish Veterinary and Food Administration undertook a survey for presence of MRSA CC398 in fresh meat. The average prevalence was 4% in Danish and imported pork, 1–2% in Danish and imported beef, and 15% in the imported poultry meat. The samples were analyzed qualitatively (presence/nonpresence) . These fE. faecium was isolated from 6.2% and E. faecalis from 61.9% of 194 samples of Danish pork. Further studies on the prevalence of enterococci in food at point of consumption were on-going at the time of writing this article, but results were not yet available. The presence of enterococci in meat is considered to be independent of resistance genes and thus, humans are exposed to both resistant and sensitive enterococci through meat. Resistance to pleuromutilins is not monitored in enterococci in Denmark, but the prevalence of resistance to other antibiotics in enterococcal isolates in pork is substantially lower than in live animals . According to Table S. aureus CC398 and enterococci may spread by emission to the outside surroundings of positive swine farms. MRSA CC398 bacteria have been detected in the air and on the ground on the downwind side 150 and 300 m from positive barns, respectively. However, the probability of by-passers being contaminated with MRSA CC398 was assessed as low, while the probability of contamination through contact with soil or crops was assessed as low or unknown  or pleuromutilin-resistant enterococci through this route is assessed as low with low uncertainty. Other direct transmission routes are also considered to be low with medium uncertainty. For staphylococci, the probability of foodborne transmission is low (low uncertainty), whereas for enterococci, the importance of spreading through the foodborne route is unknown (high uncertainty).S. aureus and enterococci and to secure effective treatment options through the control of multidrug-resistant bacteria. Although the human pathogenicity of MRSA CC398 and resistant Enterococcus spp. is low, it is considered important to prevent the spread of these bacteria, especially to weakened and hospitalized patients. The costs associated with screening, isolation, and treatment of patients with clinical infections due to MRSA CC398 was estimated in Denmark in 2015. For patients admitted to intensive care, the expense was estimated to increase twofold due to extra precautions, prolonged hospital stay, and more complications, amounting to approximately €27,000 per patient . Thu. Thu2). tiamulin . HoweverEnterococcus faecalis is the frequent cause of urinary tract infections. These are usually mild but may be recurrent especially in the elderly and in patients with urinary catheters. In some of these patients, bacteremias and endocarditis develop. Resistance testing on enterococcal urinary strains does not include testing for linezolid, thus the burden due to consumption of pleuromutilins could not be estimated but it was judged to be negligible.Treatment failure was defined as prolonged human illness and/or death due to resistance to pleuromutilins.S. aureus in Denmark was estimated to be 36.7 cases per 100,000 inhabitants, corresponding to 1,973 bacteremia cases .E. faecalis was mainly associated with urinary tract infections as the primary cause of bacteremia, E. faecium was primarily associated with abdominal surgery. The 30-day mortality was high for patients with bacteremias—21.4% in patients with E. faecalis and 34.6% in patients with E. faecium.A Danish study published in 2013 estimated the disease burden due to severe enterococcal infections . The incN=1,715) isolated from November 1, 2015, to November 1, 2016, were tested for phenotypical resistance to linezolid. Of the 41 linezolid resistant strains, six were sent to the reference laboratory at Statens Serum Institut for whole-genome sequencing. In one linezolid-resistant E. faecalis, an optrA gene was found. This belonged to the sequence type (ST) 16, a ST that has previously been associated with pigs .Only a fraction of enterococcal isolates from blood cultures will usually be tested for sensitivity to linezolid. At Rigshospitalet , all clinical enterococcal strains . The strains were not examined for the presence of other transmissible genes but the resistance profiles of the tested strains suggested that none cfr-carrying strains were among them.None of the approximately 300 clinical VRE submitted to Statens Serum Institut for whole-genome sequencing carried the It is difficult to establish whether the high mortality of staphylococcal and enterococcal bacteremias would be influenced by an additional resistance to pleuromutilins or linezolid. For vulnerable groups—such as hospitalized and immunocompromised—the probability of negative consequences will be high, if the general resistance pressure increases. The risk for acquiring an infection with a multiresistant strain increases with increased length of stay and in patients who are admitted to intensive care or have undergone abdominal surgery. This often leads to long-lasting catheterization and the risk of colonization of indwelling catheters with multiresistant bacteria. These patients will often be treated with several antimicrobial courses, and this eventually causes a shift in the microbiological flora from more sensitive toward more resistant strains. Prolonged antibiotic treatment will also select for already resistant bacteria among the microbiome of the patient.E. faecalis or E. faecium, treatment failure mainly occurs in severely ill patients with bacteremia, significant comorbidities, and long hospitalization. For staphylococcal infections, treatment failure is mainly seen in complicated cases of bacteremia with no established primary focus for the infection or in bone infections, where the infecting strain might adjust to the human host and show slow or no response to the antimicrobial treatment.For patients suffering from infections with For these very vulnerable patient groups with multidrug resistant bacteria, linezolid and the anticipated new pleuromutilin for systemic treatment may constitute a relevant antimicrobial to consider. In addition, the consequences due to already existing pleuromutilin- or linezolid-resistant strains will be severe for the individual patient.Today, the prevalence of multidrug-resistant gram-positive human infections in Denmark in general is very low  and veryEnterococcus, it was assessed that there was a low probability of adverse consequences across the population (high uncertainty).Human carriage of MRSA CC398 and urinary tract infections with enterococcal strains are fairly common, whereas severe infections with MRSA CC398 happen only rarely and severe infections with enterococci are mainly associated with prolonged hospitalization. Pleuromutilin is not used for humans in Denmark, and linezolid is only used rarely, in specific hospital settings and in selected patient groups. However, linezolid is a last line drug reserved for the few infections, where other antimicrobials cannot be used. Therefore, the consequence assessment for MRSA CC398 was assessed as very low probability for the public in general, but high for vulnerable groups (low uncertainty), whereas for pleuromutilin resistant The current risk for human health-associated consumption of pleuromutilins in Danish swine was assessed as low under the current conditions. This is an increase compared to the previous assessment conducted in 2010, where a very low risk was found . A summaThe consumption of pleuromutilins in Denmark is low compared to other European countries  and has w) per 100 animals per day, for weaners to 21.8 ADDw per 100 animals per day, and for finishing pigs to 5.6 ADDw per 100 animals per day  and 0.95 for simple penicillin, sulfonamides, trimethoprim, and pleuromutilins  published a report on the disease burden due to resistant bacteria based on European surveillance data from 2007 . The repfections  could noStill, it must be assumed that the use of pleuromutilins will increase the release of MRSA CC398 and resistant enterococci from pigs to a certain degree, as will the consumption of other antimicrobials conferring coresistance to pleuromutilins.In Denmark, multiresistance in human pathogens is not endemic, and screening procedures and infection control measures at hospitals are very effective. This, combined with the fact that MRSA CC398 does not seem to have a high speed of transmission from pigs to humans or between humans, makes it plausible to estimate the risk of impact on human health to be altogether low. This also applies to multiresistant enterococci, where no significant transmission from pigs to humans yet has been described. However, a theoretical possibility of transmission of resistance genes does exist.The assessment was associated with some uncertainty due to lack of data and is very dependent on the current very low occurrence of mobile, genetic resistance mechanisms, low incidence of multidrug-resistant bacteria in the Danish population in general, and a very rare need for “last choice drugs” in severely ill patients. While the Danish surveillance system for many years has covered bacteria with known human pathogenicity, surveillance on other than known human pathogen bacteria such as commensals, and the occurring phenotypic resistance and resistance mechanisms in these is missing.The analysis showed that resistance transfer between species is complex and multifactorial. It is unlikely that all transmission pathways are known to us today. Sporadic findings are often reported, but lack of repeatability and data restricts the ability to assess how important such findings are and whether they pose a risk to public health. This also includes the lack of surveillance of resistance in anaerobe bacteria. The gram-positive anaerobe gut flora in pigs and humans might constitute a pool for resistance mechanisms, which constantly exchanges with other bacteria, including the ones that more frequently cause human disease.The increased use of whole-genome sequencing is likely to provide additional valuable knowledge on transfer and potential resistance risks, but the link to phenotypic and clinical resistance and, thus, importance for public health remain to be elucidated.Mathematical modeling is a valuable tool in simulating pathways and identifying ways of reducing resistance. However, the relationship between reducing consumption of antibiotics and reducing resistance is not necessarily linear and still needs to be established for modeling to have full value. This includes among others the fact that some resistance mechanisms are unlikely to reverse if they are associated with increased fitness for the bacteria , 69. FurWhen new relevant data become available indicating that there might be a change in resistance prevalence or consumption patterns, the present risk assessment should be repeated. This is especially important if the consumption of pleuromutilins increases substantially, and this leads to a higher prevalence of mobile, easily transferrable resistance mechanisms of importance to human health, or if linezolid and pleuromutilins becomes more important in human medicine.The risk related to antimicrobial resistance may be assessed in different ways. One simple way may be to use the WHO ranking of critically important antimicrobials, which in essence is based on the worldwide need for treatment in human medicine . The draWe were inspired by the EMA framework, which includes the risk pathway in details; from the use of pleuromutilin in pigs to the consequences in humans. Initially, we followed the EMA framework very stringent, in the exact order and in details for the many elements listed. This systematic approach was very effective to point out important gaps in the surveillance and knowledge of transmission routes and rates . HoweverIn addition, the EMA framework does not specify how the hazard identification should be undertaken and which criteria should be used to distinguish hazards from potential risks, for which a risk assessment is required. Should the selection, e.g., be based solely on resistance mechanisms where treatment failure is observed or is presence of resistance in bacteria from animals in itself a sufficient argument? Moreover, should the hazard identification be based on national or international findings? We decided to use international data for the hazard identification and national data for the release, exposure, and consequence assessment. We also decided to focus on the different ways in which resistance can be dispersed, and here the bacteria may be seen as a vehicle, not the hazard in itself. Moreover, we found that the EMA framework was most appropriate for resistance forms that are bound to specific bacteria with well-described transmission routes from animal to humans. In the case of transmission of mobile resistance genes, which may travel between different bacterial species at high speed, the EMA framework suffers from being insufficient, especially because the bacteria species is considered the hazard, not the drug use or the resistance genes.The effect on the environment was not assessed as this is outside the scope of the framework developed by EMA. In line, off-label use—including misuse—was not included in the analysis, but it is considered a very minor issue in Denmark. These shortcomings and limitations could be addressed in future research.As far as we are aware, this is the first public-accessible publication based on the framework developed by EMA for the assessment of the public health risk related to use of antimicrobials in livestock. The output is a risk assessment, which is one part of the risk analysis process. Other elements are risk management and risk communication. EMA states that this guidance aims to provide a systematic approach to the evaluation of the associated scientific data and to improve the transparency and consistency of the regulatory decision-making process—we agree that the guideline can be used for this purpose but that flexibility should be applied to ensure logic and easy communication to the relevant audience.Care should be taken to ensure a prudent use of antibiotics in livestock and only for treatment of disease, metaphylaxis, and planned eradication. Moreover, long-term treatments should be avoided. This will ensure that pleuromutilins will remain effective for the treatment of swine also in the future. In line, swine dysentery should be eradicated, because this will reduce the need for treatment .For most indications for which pleuromutilins are authorized, tetracyclines and macrolides can replace pleuromutilins, except for dysentery. But these antimicrobial classes are not perceived as having a lower risk for human health than pleuromutilins. Therefore, pleuromutilins were still recommended by the working group for sensible use in Danish swine for treatment of the relevant infection.The newest changes to the Yellow Card scheme are likely to lead to a slightly higher use of pleuromutilins but to a lower use of other antimicrobial classes that coselect for pleuromutilin resistance . It is dIn line with EMA, we recommend the establishment of routine monitoring of pleuromutilin resistance in relevant swine bacteria to develop an early warning system . PleuromStaphylococci spp.—including a genetic component to search for resistance genes—is recommended. At present, there is no systematic monitoring of Staphylococcus spp. or MRSA in pigs in Denmark. Enterococcus spp. are monitored as part of the program for monitoring of resistance to erythromycin, linezolid, and chloramphenicol—but this does not involve monitoring for resistance to pleuromutilins. The emergence of VRE in hospital settings is of special concern. A program for surveillance is being established in collaboration between clinical microbiological departments and the Danish health authorities. This surveillance program is expected to cover the emerging resistance for linezolid as well. In the existing collaboration between the veterinary authorities, DTU FOOD, and Statens Serum Institut, the establishment of a more thorough surveillance of resistance mechanisms is being discussed.As resistance in both human and swine pathogens seems to be emerging, there is a need for targeted surveillance of specific resistances. Focus on The current risk for human health associated with consumption of pleuromutilins in Danish swine was assessed as low under the current conditions. This is an increase compared to the previous assessment where a very low risk was found.Two hazards were identified: MRSA CC398 and enterococci. For MRSA CC398, the total risk was estimated as low (low uncertainty). For enterococci, the total risk was estimated as low (high uncertainty).The assessment should be repeated, if pleuromutilin consumption increases substantially, resulting in increased prevalence of mobile, easily transmissible resistance mechanisms, or if the need for linezolid as a last line human drug increases. Continuous monitoring of pleuromutilin resistance in selected human pathogens should therefore be considered.LA, MA, and US contributed to the design of the work, the risk assessment, and the drafting of the manuscript. JE-I contributed to the framework development and writing of the manuscript. JD contributed to the risk assessment.The authors JE-I and US certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors LA and JD are affiliated with an institution, which gives advices to Danish farmers and the agro-food-business. MA is affiliated with an organization, which gives advice to the veterinary pharmaceutical industry in Denmark.


The civil war in Syria is arguably the worst humanitarian catastrophe since the Second World War. According to recent sources, over 250,000 have been killed, the same number wounded or missing and over half of the country's population of 22 million having been displaced from their homes, with 3.8 million being made refugees.Aleppo, in the north of the country, has received far more than its fair share of mass destruction and has been the worst hit city in the civil war. It has seven remaining functioning hospitals, but supplies and medical care is dwindling. Several hospitals have been directly hit by bombing on more than one occasion and refugees head out of the city for medical treatment. One of the hospitals providing emergency care, including eye care, is Emil Hospital – located 70km from the centre of Aleppo. Emel Hospital provides most of the surgical services in the area, treating many severe injuries resulting from the violence. It is one of 42 similar field hospitals inside Syria, 65% of which have suffered attacks.The medical director of Emel Hospital is Ahmed Hassan Batal, a paediatric ophthalmologist from Saudi Arabia. Since the conflict began, he and his team of 10 doctors and 20 nurses have performed more than 9,000 complex surgical procedures on patients with horrific injuries caused by the violence. The medical facilities at Emel are barely adequate: much of the equipment is secondhand, having been donated from several sources, and there is a huge shortage of drugs and dressings.Thankfully, Emel Hospital has, at the time of writing, been spared the bombing that many other hospitals have endured. A neighbouring hospital, only one kilometer away, has been bombed twice. One can only imagine the anxieties of those working at Emel that it may suffer the same fate. However, Dr Batal describes the morale of the medical staff as remaining “very good”. He stresses the fact that staff members ignore the risks of working at the hospital for the benefit of all patients, whatever their beliefs and politics may be. Dr Batal himself has committed to working at the hospital until the conflict ends.Despite the daily challenges of working at Emel, Dr Batel has remained an active member of the Examinations Committee of the International Council of Ophthalmology (ICO) – an international organisation which represents and serves professional associations of ophthalmologists. In his role, Dr Batal reviews all ICO examination papers, sets appropriate questions, and ensures the validity, accuracy and standardisation of each examination paper. He has also agreed to pay the examination fees of all Syrian ophthalmologists wishing to take ICO examinations and has pledged to continue doing so until the conflict in Syria ends – thereby ensuring that Syrian ophthalmologists are not left behind in their professional development as a result of the conflict. As a result, 62 Syrian ophthalmologists have already sat the ICO examinations in Damascus and many more wish to take the examinations in 2017.I would like to thank Dr Batal on behalf of the ICO and the ICO Examinations Committee for his kindness and humanity. He is an example to us all.Simon Keightley FRCS FRCOphthDirector for ExaminationsInternational Council of Ophthalmologys.keightley@virgin.netEmel Hospital is in need of support. If you can help, please contact Simon Keightley via email: