Substantial progress has been achieved in the last two decades with the implementation of measles control strategies in the African Region. Elimination of measles is defined as the absence of endemic transmission in a defined geographical region or country for at least 12 months, as documented by a well-performing surveillance system. The framework for documenting elimination outlines five lines of evidence that should be utilized in documenting and assessing progress towards measles elimination. In March 2017, the WHO regional office for Africa developed and disseminated regional guidelines for the verification of measles elimination. As of May 2019, fourteen countries in the African Region have established national verification committees and 8 of these have begun to document progress toward measles elimination. Inadequate awareness, concerns about multiple technical committees for immunization work, inadequate funding and human resources, as well as gaps in data quality and in the implementation of measles elimination strategies have been challenges that hindered the establishment and documentation of progress by national verification committees. We recommend continuous capacity building and advocacy, technical assistance and networking to improve the work around the documentation of country progress towards measles elimination in the African Region. The WHO global vaccine action plan 2011-2020 outlines a goal for the elimination of measles and rubella in at least 5 WHO regions by 2020 . As of AElimination of measles is defined as the absence of endemic transmission in a defined geographical region or country for at least 12 months, as documented by a well-performing surveillance system. The 3 criteria for verifying measles and rubella elimination include: i) the documentation of the interruption of endemic measles and rubella virus transmission for a period of at least 36 months from the last known endemic case; ii) the presence of a high-quality surveillance system; iii) measles virus genotyping information that supports interruption of endemic transmission , 8. The The framework for documenting elimination outlines five lines of evidence that should be utilized in documenting and assessing progress towards measles elimination: 1) a detailed description of the epidemiology of measles and rubella since the introduction of measles and rubella vaccine in the national immunization program; 2) population immunity, presented as a birth cohort analysis with the addition of evidence related to any marginalized and migrant groups; 3) quality of epidemiological and laboratory surveillance systems for measles and rubella; 4) sustainability of the national immunization program, including resources for interventions to sustain elimination; 5) genotyping evidence that measles and rubella virus transmission has been interrupted , 8.When evaluating the lines of evidence, NVCs and RVCs are expected to review all the available data at both national and subnational levels that can be assessed to determine whether elimination has been achieved. The five lines of evidence facilitate a comprehensive evidence-based assessment of population immunity at all levels, immunization program performance and the capacity to sustain elimination.The WHO African regional standards for case-based measles surveillance have been in place since 2004, with an update in 2015 to include an optional elimination-standard surveillance which is recommended for countries with confirmed measles incidence approaching or less than 1 per million population. Elimination standard surveillance is expected to improve the sensitivity of measles surveillance by employing a broader suspect case definition requiring detailed active investigation of all suspected cases. As countries approach the elimination threshold, it will be critical to investigate each confirmed case of measles to determine sources of infection and reasons for lack of immunity. It will also be crucial to collect throat swab samples for viral genotyping, in addition to the serum specimens collected for serological confirmation. Elimination standard surveillance requires robust surveillance and laboratory capacity, as well timely and intensive investigation of sporadic as well as outbreak cases and is expected to be more costly to implement .The sensitivity of measles surveillance and the quality of data generated is critically important in the verification process. Without adequate surveillance sensitivity consistently attaining the performance indicators including characterization of circulating viral genotypes, it is difficult to generate evidence required to verify elimination. For example, NVCs in some countries in the WHO European region have been unable to determine whether disease transmission remained endemic or was interrupted. Reasons included inadequate surveillance systems with low sensitivity producing incomplete surveillance data that could not be clearly interpreted to demonstrate evidence in support of elimination; as well as inadequate or incomplete evidence of population immunity . In ordeThe measles verification framework shares similarities with the polio-free certification process. For a region to be certified polio free, the Regional Polio Certification Commission (RCC) will consider the following: i) the absence of wild poliovirus for at least 3 consecutive years from any source, in the presence of high quality, certification-standard AFP surveillance; ii) high routine immunization coverage with the third dose of oral polio vaccine (OPV3); iii) the completion of phase 1 poliovirus containment activities; iv) country readiness to respond to any poliovirus importation; v) the presence of a functional National Certification Committee to critically review, endorse and submit complete documentation to the RCC –14.In March 2017, the WHO Regional office for Africa developed and disseminated regional guidelines for the verification of measles elimination. Official communication was sent from the WHO regional office to 32 of the 47 countries in the region between May 2017 and February 2019, requesting them to establish an NVC and to commence the work of documenting progress towards elimination according to the regional guidelines and documentation template. WHO offered technical and financial assistance to establish NVCs. Not all countries were invited to establish NVC at the same time for several reasons. First, there is a limited number of technical staff from the WHO regional and sub-regional offices available to conduct briefings of the newly established NVCs. Second, countries were selected based on their relative progress towards the measles elimination targets in those countries nearing the elimination targets, and the potential advocacy value of NVCs to advance the implementation of elimination strategies in countries requiring significant improvement in their national immunization performance to advance towards measles elimination. A staged implementation of NVCs also allowed lessons to be learned from the initial country experiences.The global framework and guidelines outline the process and requirements for the documentation of measles and rubella/CRS elimination. At present, in the absence of a formal regional goal of rubella/CRS elimination the African regional guidelines are limited to the verification of measles elimination. The regional verification framework, the process and the role of the verification structures was presented and discussed in various annual meetings of national immunization program managers’ in 2018 and 2019. Additionally, an initial workshop was conducted in March 2018 to orient the members of the RVC. The first five countries to submit documentation of progress to the RVC were reviewed in May 2019. The status of establishment and functionality of NVCs as of April 2019 is summarized in Despite the creation of NVCs and the organization of briefings for the NVC members, as of May 2019, only 8 countries in the region have begun to document progress toward elimination. A summary of the most common impediments in establishing NVCs and documenting country progress is detailed below.Inadequate awareness: national immunization program managers do not fully understand the purpose and function of NVCs. The justification and terms of reference for NVCs as well as the process of documentation of progress were presented in annual program meetings. However, misconceptions persist including the opinion that countries need to establish NVCs only when they get closer to claiming measles elimination status. Actually, the process of documenting progress with NVC oversight is expected to help weak performing countries to critically review their data, improve program performance and benefit from the advocacy of the NVC with national authorities and partners.Multiplicity of committees: discussions with various national immunization program managers have revealed concern about the existing multiplicity of national committees and advisory groups to support immunization. There is a limited pool of dedicated and available scientists and experts to engage in such voluntary work, especially in the smaller countries. WHO AFRO has indicated that countries may opt to utilize the expertise in the current national polio certification committees for the purpose of measles verification if practical. However, it is necessary to amend the terms of reference and nomenclature of the committee and conduct a technical briefing of the committee members.Availability of technical experts: WHO recommends that the membership of NVCs include specialists from various fields  who will participate in the committee on a voluntary basis. However, in smaller countries, the available pool of high-level expertise from academic, research and clinical settings is often limited. In addition, available experts often have multiple professional responsibilities and engagements, and often are already engaged as members of NITAG, National Polio expert committee, national polio certification committee, or national polio containment taskforces.Prioritization of verification work: national immunization program staff handle numerous programmatic priorities and are fully engaged in a multitude of activities, including the development of annual and multiannual plans, development of GAVI application documentations, new vaccine introductions, SIAs, program assessments and appraisals, outbreak response activities and responding to the effects of civil conflict and natural emergencies. The NVCs require the attention, time and dedicated support of the national immunization program team, and the WHO country office immunization team to be fully functional.Inadequate human resources at regional level: there is a limitation of program staff in the WHO regional and sub-regional offices responsible for the overall coordination of measles and rubella elimination work. For this reason, it was not possible to quickly scale up and establish NVCs in multiple countries, conduct initial briefings and provide continuous to support the work of the NVC including associated work with data management and regular follow-up of the verification documentation at country level.Inadequate funding to support country level NVC activities: WHO provides catalytic funding for the establishment and functioning of the NVCs at country level. These funds cover costs related to the organization of technical meetings, joint working sessions to analyze data and prepare the country progress reports, supply stationery material and cover costs related to in-country travel when necessary. Currently, the WHO Regional office has limited committed funding to support NVC activities, requiring prioritization in the support to countries to establish NVCs.Data quality: in many countries in the African region, vaccination administrative data overestimates the levels of population immunity as compared to survey and WHO UNICEF estimates of coverage. This discrepancy also exists in data at the subnational level. As a result, unless there are recent coverage surveys done to estimate subnational levels of coverage, it is often difficult to assemble accurate information regarding population immunity levels [y levels , 16. They levels .Incomplete implementation of measles elimination strategies: as of April 2019, only 27 of the 47 countries in the region have introduced MCV2 in their routine immunization schedule. For countries having MCV2 for more than 3-5 years, the drop-out rate between MCV1 and MCV2 is more than 10% in 17 out of the 26 countries for 2017. This is a major programmatic weakness having a bearing on the documentation of one of the lines of evidence [evidence . In the Surveillance funding gaps: forty four out of 47 countries in WHO African region have been implementing measles case based surveillance since at least 2006, with the support of a network of national and regional referral measles serological laboratories. However, over the past five years, the quality of case-based surveillance has not been improving across the region despite the fact that countries are approaching the 2020 target date for elimination [mination . This isStock out of lab test kits: the regional serological measles laboratory network consists of 49 national and subnational laboratories in 44 countries across the region. The network is supported by WHO to implement standardized testing methods, utilizes similar test kits and is supported with periodic external quality assurance and accreditation exercises. In the period from 2015 to 2017, nearly all the laboratories in the regional measles laboratory network experienced prolonged periods of stock-out of laboratory test kits as a result of delays in resupplying attributed to inadequate funding. This has seriously limited the surveillance system’s sensitivity and its ability to generate high quality information for the purpose of verification [Lack of genotypic data: despite the availability of services in the regional reference laboratories to perform molecular characterization of measles and rubella viruses, many countries have not yet made full use of this opportunity and therefore lack the baseline data required to assess endemic transmission patterns and distinguish them from importations that is important for the verification of elimination [mination .Inadequate data on CRS occurrence: CRS sentinel surveillance is established in only 9 countries across the region. However, several countries have some documentation from retrospective case reviews. CRS is often not recognized commonly as a clinical condition, and requires more specialized clinical skills and diagnostic equipment for initial case detection, there is lack of adequate documentation at country level [ry level .Previous experience with polio certification: countries across the region already have extensive experience with the process of preparing polio eradication progress reports and national certification documentation. The lessons from African regional certification of polio eradication are being utilized to ensure that the NVCs and the RVC establish robust processes from the outset [e outset , 14.Functional regional commission: the regional director of the WHO African regional office has officially nominated the members of the Regional Verification Commission. The commission received its introductory briefing in March 2018. The second RVC meeting in May 2019 was used to review the progress reports from 5 countries. The RVC review of country documentation has helped to identify the strengths and weaknesses in country programs with regards to documenting the lines of evidence. The lessons from this exercise will be used to assist other countries, to use the opportunity to critically review their program data and the implementation of measles elimination strategies.Advocacy value of verification committees: while the main objective of the NVCs and the RVC is to support countries to develop high quality documentation of progress towards elimination along the five lines of evidence, the terms of reference of the NVCs were designed to include advocacy as one of the key functions in their respective countries and at regional level for the RVC. The members of the committees are prominent clinicians, academicians and researchers whose professional reputations can garner support, visibility and influence policy makers in favor of measles elimination.External technical assistance: to advance the work of verification of measles elimination, the WHO regional office received support from the US Centers for Disease Control (CDC) to complete a detailed analysis of programmatic data in Seychelles and Rwanda to compile their initial documentation submitted to the RVC. This work has helped to critically examine data quality and availability issues, as well as to refine the documentation template.Country by country verification: the verification of measles elimination is assessed country-by-country, unlike the polio eradication program, where certification is done only on a regional basis. Such a country-focused approach gives high performing countries the opportunity to get official recognition for their progress and motivates others to strive to attain the elimination targets. In addition, when countries are presenting their progress report to the Regional Verification Commission, other NVCs and national immunization program managers are invited to participate and learn from the other country experiences.In order to address these challenges and strengthen the ability of NVCs to document progress towards measles elimination, the following priority actions will need to be taken at regional and country levels.Raise awareness: utilizing all opportunities to communicate to the national authorities and immunization program managers regarding the value NVCs can provide to assist countries with documenting progress towards measles elimination and advocating for better government ownership and partner support.Document and disseminate progress: scaling-up the documentation of progress towards measles elimination among the high performing countries to help them verify elimination as early as possible and to document the advocacy work of NVCs.Technical assistance: develop a regional pool of consultants that can assist countries in preparing the initial documentation of progress for review by NVCs.Capacity building: WHO will continue to build the technical capacity and broader programmatic understanding of NVC members by engaging them as participants in immunization program technical meetings.Networking: create opportunities and platforms for better networking and experience sharing among NVCs.Funding: WHO and partners to allocate predictable funding to support the work of NVCs.Sub-national documentation: in large countries, explore the possibility of NVCs monitoring and documenting progress toward measles elimination sub-nationally by province/State/Region level with their own documentation exercise. This will be a resource intensive exercise to be done in one or two countries, making sure not to burden national programs and in such a way as to carefully document lessons.The authors declare no competing interests.


When patient-reported measures are translated and cross-culturally adapted into any language, the process should conclude with cognitive interviewing during pretesting. This article reports on translation and cross-cultural adaptation of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire into Afrikaans (for the Western Cape). This qualitative component of a clinical measurement, longitudinal study was aimed at the pretesting and cognitive interviewing of the prefinal Afrikaans (for the Western Cape) DASH questionnaire highlighting the iterative nature thereof. Twenty-two females and eight males with upper limb conditions were recruited to participate at public health care facilities in the Western Cape of South Africa. Cognitive interviews were conducted as a reparative approach with an iterative process through retrospective verbal probing during a debriefing session with 30 participants once they answered all 30 items of the translated DASH questionnaire. The sample included Afrikaans-speaking persons from low socioeconomic backgrounds, with low levels of education and employment (24 of 30 were unemployed). Pragmatic factors and measurement issues were addressed during the interviews. This study provides confirmation that both pragmatic factors and measurement issues need consideration in an iterative process as part of a reparative methodology towards improving patient-reported measures and ensuring strong content validity. The DASH, developed in 1996 by the Institute of Work and Health (IWH) in the context of Canada, has been translated into many languages from around the world with 12 language versions for developing countries , p, pbest eThe iterative nature of the process is considered a strength. A limitation of this study is that the PI had no prior experience with CIs.This study highlights the process of CI employed in the pretesting and cognitive interviewing of the prefinal version of the Afrikaans for the Western Cape DASH-PAV. It is recommended that pragmatic factors experienced during CIs be addressed with adaptations such as the availability of reading glasses or through experience with the target population and/or similarities between the interviewer and the target population. In addition, measurement issues have to be addressed and evaluated in subsequent interviews. A further recommendation is to consider stopping CIs once it is evident that pragmatic and measurement issues were addressed as part of a reparative methodology with an iterative approach following translation and cross-cultural adaptation of the DASH. This study also provides evidence for content validity of the newly translated and cross-culturally adapted Afrikaans for the Western Cape DASH questionnaire.


The early delivery of effective analgesia is considered to be an important component of pre-hospital trauma care; however, the provision of analgesia by pre-hospital clinicians is often inadequate. While a number of studies have explored the underpinning attitudes and barriers to the paramedic administration of analgesia in various patient groups, specific barriers which prevent the paramedic administration of pre-hospital analgesia to adult trauma patients in the UK are poorly defined. The aim of this small study was to identify and define potential barriers to analgesia administration in this specific population. In doing so, this study will increase awareness and will form an important basis for future work aimed at improving the delivery of pre-hospital analgesia to adult trauma patients in the UK.Twenty paramedics employed in an urban ambulance service in the UK volunteered to participate and were recruited into this study. Semi-structured interviews were conducted with participants during 2018 in order to explore the potential barriers to analgesia administration. An inductive thematic analysis was undertaken on interview transcripts and potential barriers were defined from the themes identified, by reviewing the coded data within each theme.All of the participants completed the study which identified 12 potential barriers to the paramedic administration of pre-hospital analgesia to adult trauma patients. These barriers were diverse in nature and related to factors including the patient presentation, paramedics’ perceptions of pain, the cautious use of analgesics, paramedics’ scope of practice, organisational procedures and clinical guidelines, as well as factors relevant specifically to the pre-hospital environment. Some of these barriers may be modifiable through improved paramedic education and training or by widening of the paramedic scope of practice, whereas others may not be modifiable.There were a number of limitations to this study including the use of volunteer self-selection which may present a source of self-selection bias, the recruitment of paramedics from a single system which reduces the generalisability of the results and the absence of a second researcher.The identification of these potential barriers should form a basis for future work aimed at improving the paramedic delivery of pre-hospital analgesia to adult trauma patients. While many of the barriers identified may be present across pre-hospital care systems, some may be specific to the system in which this study was undertaken, to other urban systems or to paramedic practice in the UK.


Plant sexual systems play an important role in the evolution of angiosperm diversity. However, large-scale patterns in the frequencies of sexual systems  and their drivers for species with different growth forms remain poorly known. Here, using a newly compiled database on the sexual systems and distributions of 19780 angiosperm species in China, we map the large-scale geographical patterns in frequencies of the sexual systems of woody and herbaceous species separately. We use these data to test the following two hypotheses: (1) the prevalence of sexual systems differs between woody and herbaceous assemblies because woody plants have taller canopies and are found in warm and humid climates; (2) the relative contributions of different drivers  to these patterns differ between woody and herbaceous species. We show that geographical patterns in proportions of different sexual systems  differ between woody and herbaceous species. Geographical variations in sexual systems of woody species were influenced by climate, evolutionary age and plant height. In contrast, these have only weakly significant effects on the patterns of sexual systems of herbaceous species. We suggest that differences between species with woody and herbaceous growth forms in terms of biogeographic patterns of sexual systems, and their drivers, may reflect their differences in physiological and ecological adaptions, as well as the coevolution of sexual system with vegetative traits in response to environmental changes. The sexual systems of plant species play a significant role in the evolution of angiosperm diversity , variatiThe evolution of plant sexual systems has been widely hypothesized to be closely linked to the evolution of plant growth forms  the geographical patterns in sexual system composition differ between woody and herbaceous species; (2) the relative contributions of different drivers  to these patterns differ between woody and herbaceous species. Dioecious species are more common in humid areas and in floras with older and more woody species, whereas hermaphroditic species are more common in temperate arid areas of northwestern China and in floras with younger and more herbaceous species.Flora of China (Flora Republicae Popularis Sinicae (126 issues of 80 volumes), Seeds of Woody Plants in China (http://efloras.org/). The Tree of Sex  and journal publications , Higher Plants of China, The Atlas of Woody Plants in China (http://www.nsii.org.cn/), and screened. NSII included over fifteen million specimen records that are published recently. In total, our dataset consists the distributions of 19,780 Chinese plant species with data for sexual systems.Data on the distributions of plant species were compiled from all national, provincial and local floras, including Species distributions were rasterized to a grid with a spatial resolution of 100 × 100 km to eliminate the potential bias of area on subsequent analyses. We removed the grid cells with less than 50% of their area along the country borders and coastal areas. In all, 949 grid cells were included in the analyses reported below.Flora of China  during the flowering period , and henTo evaluate the effect of evolutionary time  on biogeographical patterns in sexual system compositions, we used the average genus age derived from three phylogenies including Flora of China . As lower and upper limits of mature height are normally reported for most species in floras, we used the average of lower and upper limits to represent the mature height of species. Species without erect stems  were excluded from our analyses following Plant mature height and longevity of plant species are expected to be positively associated . Here weFirst, based on the data of sexual systems, growth forms, and distributions of all species, we calculated the proportions of species with different sexual systems within each grid cell for all species together and for each growth form separately. We used Pearson correlation coefficients to evaluate the similarity between the geographical patterns in the proportions of different sexual systems of woody and herbaceous species  and used Dutilleul’s t test to evaluate the significance of these correlations due the influences of spatial autocorrelation on significance tests  of the GLM model. Modified t tests were used to correct for the effect of spatial autocorrelation on p values  with quasi-Poisson residuals to evaluate the explanatory power of each predictor on the proportions of sexual systems per grid cell and this was conducted separately for each of the three species groups . The climate variable , genus age, and plant height were used as predictors and the proportions of each sexual systems per grid cell were used as response variables. The explanatory power of each variable was estimated as the adjusted Rp values .To evaluate the influences of growth forms on the relationships between the proportion of sexual systems and different predictors, we first built spatial linear models (SLM) for the combined dataset of sexual system for both growth forms together using spatial simultaneous autoregressive error (SAR) models. SLMs could account for the effects of residual spatial autocorrelation on the significance tests of regression slopes . The cliAll analyses were performed in R 3.4.3 .P > 0.05; The spatial patterns in the proportions of hermaphroditic and monoecious species per grid cell were consistent between woody and herbaceous growth forms  by improving the efficiency in pollen and seed dispersal, which further promote the maintenance and continuation of species populations  tend to exhibit short life-cycles, fast rates of population but limited resource accumulation  was higher in southern China than in other regions. This finding supports the hypothesis that dioecy is more common in tropical and subtropical floras where climate is warm and humid (Rhamnus and Acer) is higher in Northeast China with relatively higher AET and MPWQ compared to other regions in China. These results reveal that the differences in requirements for hydrothermal conditions between woody and herbaceous growth forms may influence their geographical patterns in proportions of sexual systems, consistent with our hypothesis. Generally, woody species often have deep roots, and herbaceous species have relatively shallow roots. Therefore, herbaceous species have lower efficiencies in soil water usage and are more sensitive to reduced water supply compared with woody species , which might be due to the higher population turnover rate and faster adaptation to climate of herbaceous species than those of woody species , the Strategic Priority Research Program of Chinese Academy of Sciences (#XDB31000000), and National Natural Science Foundation of China .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.


Helicobacter pylori in the etiology of gastric cancer has been elucidated , based on changes to the fecal microbiota in hepatocellular carcinoma patients. This dysbiosis index may have the potential to diagnose those with the disease and may in the future determine prognosis at different stages of hepatocellular carcinoma .One area where microbiome profiling could potentially improve patient outcomes is as a diagnostic tool to identify those at high risk of malignant transformation or to identify the stage of cancer development. The diagnostic potential of the gut microbiome is highlighted by Fusobacterium spp. in the development of OSCC . The influence of the oral microbiome may also extend beyond the oral cavity, as shown by Chen X-H. et al., who demonstrate that gastric cancers exhibit increased abundance of taxa normally associated with the oral microbiome. The presence of H. pylori in these gastric samples also impacts upon the composition of these communities, suggesting that H. pylori may have a central role in the development of dysbiosis. The involvement of H. pylori the development of gastric biofilms is further explored by Rizatto et al., who discuss the potential role and mechanisms of biofilm formation in the gastric mucosa and identify future directions for this research area.The collection continues with several studies of the oral microbiome. The oral cavity is one of the most diverse areas of the human GIT and an increasing number of studies are demonstrating the increased abundance of F. nucleatum and Streptococcus gallolyticus subsp. Gallolyticus. Ma et al. present a timely and comprehensive review of the impact of the gut microbiome on cancer chemotherapy. Continuing this topic, Cong, Zhu, Zhang et al. present novel data showing the impact of chemotherapy on microbial networks in the intestinal microbiota, opening up the possibility to explore how these changes impact upon chemotherapeutic outcomes. The same authors also investigate the effect of surgical interventions on the gut microbiome of patients with CRC . These data show that surgical interventions have a strong impact on the microbiome resulting in increased levels of Klebsiella spp., which was significantly linked with lymphatic invasion.The intestinal microbiota is under intense investigation for its roles in regulating metabolism, immunity, and the interaction with cancer cells. In addition, specific pathogens have been implicated in carcinogenesis including Wu et al. present exciting data showing that chitooligosaccharides protect mice from colorectal carcinomas by reducing the levels of Escherichia-Shigella, Enterococcus, and Turicibacter and by promoting the growth of butyrate producing bacteria.Targeted interventions to restore healthy or beneficial microbiomes are still in their infancy. Here, In summary, this collection offers an insight into the developing area of microbiome research in oncology, and highlights the growing potential of these scientific tools for improving diagnosis and treatment of these devastating diseases.The manuscript was written and prepared by GM and NA-H. 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.


Food Safety Commission of Japan (FSCJ) was requested by the Ministry of Health, Labour and Welfare (MHLW) to conduct a risk assessment of cattle meat and offal imported from the United States of America (U.S.A.), Canada and Ireland. FSCJ assessed potential influences on bovine spongiform encephalopathy (BSE) risks to human health in cases of the alteration of cattle age to be allowed to import of cattle meat and offal from the three countries, from the current under 30 months of age to no age limitation, in line with the international standards for mitigating BSE risks. FSCJ judges that the control measures regarding “risks related to slaughtering and meat processing” are appropriately implemented in the three countries. FSCJ concludes that potential variations of BSE risks to human health by removing the age limit on cattle meat and offal excluding specified risk material (SRMs) imported from the three countries in line with the international standards is negligible. Using reference materials and documents submitted by the MHLW regarding the bovine spongiform encephalopathy (BSE) situations in the three countries, FSCJ assessed the risk of BSE agent in cattle meat and offal in relation to border measures such as slaughter age limitFSCJ assessed potential influences on BSE risks to human health in cases of the alteration of cattle age to be allowed to import of cattle meat and offal from the three countries, from the current under 30 months of age to no age limitation, in line with the international standards for mitigating BSE risks.The cases of classical BSE continue to decrease and are scarcely reported in recent years worldwide.Due to the decreased numbers of cattle exposed to BSE prion, the historical and existing risk factors are expectedly reduced to large extents in the three countries currently evaluated.Therefore, even in countries where typical BSE has occurred in cattle born within the last 11 years, the risk of developing typical BSE is estimated to be extremely low as long as the control measures related to the historical and existing risk factors of BSE in live cattle are properly implemented. In addition, assuming the control measures are maintained at the same level as the current level, the frequency of occurrence is estimated to remain below the current level.Terrestrial Animal Health Code  ] does not set a an age limit for trade in beef, FSCJ decided to evaluate whether or not the risk of variant Creutzfeldt-Jacob disease (vCJD) associated with intake of the BSE prion has reached to an extremely low level.Under these situations, FSCJ decided to assess the risk of meat and offal through the verification of control measures such as specified risk material (SRMs) removal and ante-mortem inspection in cattle at the slaughter house of these countries. While an international standard [The OIE The results of the risk assessment are summarized below.Terrestrial Code)2) are recognized to be effective toward preventing the incidence of classical BSE in these countries. Therefore, FSCJ judges the incidence of classical BSE continually to be quite unlikely and/or to remain below the current level.In the three countries, indigenous classical BSE cases have not been confirmed in the U.S.A., and few cases of indigenous classical BSE are confirmed in Canada and Ireland at present. Thus, the control measures against historical and existing risk factors (the Sc) in the classical BSE-infected cattle, the amount distributed in the tissues other than SRMs is extremely low. Epidemiological information on vCJD cases supported this observation. Therefore, it is assumed that the removal of SRMs ensures, if any, the negligible intakes of PrPSc through meat and offal. Moreover, the ante-mortem inspections remove the cattle manifesting the clinical signs.According to the data on the body distribution of abnormal prion protein  imported from the three countries after the age limit is removed. Assuming that current risk control measures are continuously implemented as mentioned above. For the atypical BSE, the previous assessment on “BSE counter measures applied to domestic cattle” has concluded that vCJD is highly unlikely to develop in association with consumption of classical BSE prions through cattle meat and offal (excluding SRMs) under the continuous implementation of current control measures against BSE, and new findings affecting this conclusion are not available.Considering thoroughly available evidence, FSCJ reached the following conclusion on the risk of BSE agent in cattle meat and offal imported from the U.S.A., Canada and Ireland by increasing the age limit from the current 30 months of age in line with the international standards. FSCJ concludes that potential variations of BSE risks to human health by removing the age limit on cattle meat and offal (excluding SRMs) imported from the three countries in line with the international standards is negligible.FSCJ drew this conclusion of the assessment assuming that current risk control measures are continuously implemented. Therefore, risk management organizations should continuously collect related information, particularly regarding feed regulation, surveillance, ante-mortem inspection of slaughter and control on SRM removal.


The upper cervical region is a complex anatomical structure. Myodural bridges between posterior suboccipital muscles and the dura might be important explaining conditions associated with the upper cervical spine dysfunction such as cervicogenic headache. This cadaver study explored the upper cervical spine and evaluated the myodural bridges along with position of spinal cord in response to passive motion of upper cervical spine.A total of seven adult cadavers were used in this exploratory study. The suboccipital muscles and nuchal ligament were exposed. Connections between the Rectus Capitis Posterior major/minor and the Obliquus Capitis minor, the nuchal ligament, posterior aspect of the cervical spine, flavum ligament and the dura were explored and confirmed with histology. The position of the spinal cord was evaluated with passive motions of the upper cervical spine.In all cadavers connective tissues attaching the Rectus Capitis Posterior Major to the posterior atlanto-occipital membrane were identified. In the sagittal dissection we observed connection between the nuchal ligament and the dura. Histology revealed that the connection is collagenous in nature. The spinal cord moves within the spinal canal during passive movement.The presence of tissue connections between ligament, bone and muscles in the suboccipital region was confirmed. The nuchal ligament was continuous with the menigiovertebral ligament and the dura. Passive upper cervical motion results in spinal cord motion within the canal and possible tensioning of nerve and ligamentous connections. The relationship between the upper cervical spine and headaches has been established . MusculoAny structure in the upper cervical spine such as the intervertebral disc, spinal ligaments, muscles, articulation, dura, and nerve roots could be a generating pain source and causing musculoskeletal dysfunction leading to cervicogenic headaches . MovemenIn order to prevent compression of the dura mater during motion of the spinal column, the dura is anchored in the vertebral canal by multiple fibrous connections . These mPosterior to the spinal column is the nuchal ligament, the cephalic extension of the supraspinous ligament. It extends from the C7 spinous process and attaches to the cervical spinous processes and midsagittally along the occipital bone, terminating at the external occipital protuberance . The majIn the upper cervical region the presence of fascial connections between the Rectus Capitis Posterior Major, Rectus Capitis Posterior Minor, and the Obliquus Capitis Inferior and the dura have been demonstrated . These cA total of seven adult cadavers , all over the age of 50 were used in this exploratory study. All cadavers were acquired from the Anatomical Board of the State of Florida, following standard protocols according to Anatomical Board regulations and Florida State Law; all of them had been embalmed with a formalin-based solution. No medical history was known about any of the cadavers. Students of the Doctor of Physical Therapy program at Florida Gulf Coast University had previously performed dissections of the cadavers, though leaving the suboccipital region intact. The skin and superficial fascia over the posterior neck region was removed. Following this the trapezius and the splenius capitis were detached from the occiput, as was the semispinalis capitis. Following this the suboccipital muscles and the nuchal ligament were exposed . The conAfter posterior exploration was completed, three specimens underwent a transverse cut between the occipital condyles and atlas, with an anterior reflection of the skull and pharynx, allowing for a direct transverse view of the spinal canal, dura and meningovertebral connections . These tTo determine what type of fibrous tissue connects the nuchal ligament to the dura we decided to further analyze this connection. In order to provide histological information, we cut the C1 and C2 segments, including all soft tissues, of one of these three specimens and decalcified it in an aqueous solution of sodium citrate and formic acid, until test samples of this solution added to an ammonium oxalate solution did not form any precipitate (the sample was checked weekly). Once decalcified, the specimen was embedded in a paraffin matrix and thin sectioned with a microtome to a thickness of five μm. Sections were mounted to glass slides and stained using Masson’s Trichrome staining protocol to identify collagen fibers in the final sections. Finally, specimens were imaged using transmitted light with a Zeiss Axioskop II microscope and Lumenera Infinity digital camera.Our tissue samples as demonstrated in The dissection of our specimens confirmed this that there is a deep fascial connection between the Rectus Capitis Major, Minor, and the Obliquus Capitis Inferior, and this appears to be blending with the dura in the spinal canal. The myodural bridge in our samples appeared fairly wide and covered a large portion of the posterior arch of atlas on each side . In all In the sagittal dissection we observed that the nuchal ligament was continuous with the dura between the occipital bone and atlas and the atlas and axis  and 7. AThe dural sac and spinal cord moved within the spinal canal as a result of motion of the upper cervical spine. Flexion and extension resulted in forward and backward movement of the spinal cord respectively. Rotation resulted in homolateral movement and concurrent tensioning of the contralateral spinal nerve  and 9.The aim of this cadaver study was to explore the upper cervical region for soft tissue connections between the suboccipital musculature and ligaments and the dura mater. The superior cervical vertebral column is a very complex anatomical region. There appears to be a clear anatomical relationship between muscular, ligamentous, soft tissues and the dura mater in the high cervical region. Dissection both in the sagittal and the transverse plane demonstrates clearly that the epidural space of the upper cervical spine contains many connective tissues and fascia layers that merge and blend together regardless of their origination  and 2. OIt was observed that the nuchal ligament has a direct connection with the dura and blends with the meningovertebral ligament to blend with the dural sac. This observation concurs with previous reports about the nuchal ligament dural connection . HistoloThe secondary aim of this study was to identify how the position of the spinal cord within the vertebral foramen of C1 changed during passively induced motion of upper cervical spine. When the cervical spine was extended in our cadavers it was observed that the spinal cord appeared to move forward within the spinal canal . It can When C1 was rotated on C2 in our specimens we observed that there was an ipsilateral movement of the spinal cord within the spinal canal . As seenThis cadaver study cannot be used to determine the clinical consequences of the collagenous connections between the nuchal ligament and the dural sac and the myodural bridges (with and without movement). However, these connections might be able to help explain cervical-cephalic pain and conditions such as cervicogenic and tension type headaches. Cervical pain patients can present with a variety of musculoskeletal myofascial syndromes in the upper quadrant and reduced active and passive movements . The preA possible drawback of this study was the use of formalin-embalmed specimens were used. It is well-known that the fixation and desiccation effects of formalin solution can cause tissue dehydration and shrinkage and might have affected the presentation and density of the tissues we observed . This miOur cadaver study confirmed the presence of a large network of tissue connections between ligament, bone and muscles in the suboccipital region. There was a fairly wide myodural bridge between the Rectus Capitis Major, Minor and the Obliquus Capitis Inferior and dura sac in the spinal canal. We observed that the nuchal ligament was continuous with the meningovertebral ligament between C2 and the dural sac. Histology revealed this connection was high in collagenous tissue similar to that of the nuchal ligament and the dura. Additionally, a clear connective tissue strand with the same tissue formation was identified between the posterior arch of C1 and the dura. It was demonstrated that passive motion of the upper cervical spine and C1 results in a change of position of the spinal cord within the spinal canal and resulting in tightening of the myodural, meningovertebral ligaments, and spinal nerves. Future studies should further evaluate this relationship and determine the clinical significance.10.7717/peerj.9716/supp-1Supplemental Information 1Click here for additional data file.


Surgery is an important part of the management of patients diagnosed with DFO. It consists in some selected patients, to remove all or part of the infected bone(s) or even to amputate all or part of the foot. Despite the use of sophisticated imaging techniques, it is however difficult to remove all the infected tissue while respecting the principles of an economical surgery. Bone biopsy performed at the margins of the resection permits to identify residual osteomyelitis and to adjust the post-surgical antibiotic treatment. Some recent studies have reported the way to perform bone margin biopsies and have assessed the impact of the bone results on the patient's outcome. However, the real impact of a residual osteomyelitis on the risk of recurrent DFO is still debated and questions regarding the interpretation of the results remain to be solved. Similarly, the consequences in terms of choice and duration of the antimicrobial treatment to use in case of positive bone margin are not clearly established. Osteoarticular infections occur in 20 to 60% of diabetic foot infections and profoundly worsen the outcome of the patients The main limitation of the surgical part of the treatment of DFO is the uncertainty about the persistence of residual osteomyelitis following bone resection. Indeed, if all the infected bone tissues have been removed, the infection is no longer an osteomyelitis (or an osteitis) and can therefore be treated as a soft tissue infection (except periarticular structures such as tendons and ligaments). This is of importance since the prognosis of non-bone infections is better and the antibiotic therapy is easier regarding the choice of the antibiotic regimens and their duration than that of DFO The aim of the present narrative literature review is to provide readers with up-to-date knowledge on the different surgical approaches for DFO and the consequences of bone examination results  in terms of antibiotic treatment. The summary of the recommendations/current state of knowledge regarding surgical bone biopsy in patients treated for DFO is presented in Table Surgical removal of the entire infected bone has been considered in the past and even recently as the standard treatment Surgery is the unique means to drastically reduce the amounts of bacteria present in bones and sometimes in contiguous tissues . Surgery consists in these settings in draining pus and removing economically all necrotic tissues et al. showed that limited resection  of the infected phalanx or metatarsal bone under the wound, together with removal of the ulcer site, was effective to obtain complete wound healing et al. reported a consecutive series of 185 diabetic patients with osteomyelitis of the foot and histopathological confirmation of bone involvement, all treated surgically, including 91 conservative surgical procedures The IWGDF guidance on diabetic foot infection proposes to favour a surgical approach of DFO in case of systemic signs of infection, substantial cortical destruction, osteolysis, macroscopic bone fragmentation (sequestration), an exposed bone within a forefoot ulcer, open or infected joint space and when the patient has prosthetic heart valves Conservative surgery does not entirely the risk of transfer syndrome as shown by Aragon-Sanchez et al. who reported new episodes of osteomyelitis in 16.9% of the patients Relapsing osteomyelitis episodes observed in patients operated for a DFO are not univocal. The new osteomyelitis may be in relation with a new episode of infection of the initial foot ulcer or at the adjacent rays in relation with the transfer syndrome. Another cause may be the absence of sterilization of the initial infected site although remission of DFO can be obtained despite the complete excision of the infected bone. The rate of remission may however be lower when there is a residual bone infection In a series of 66 cases of amputations defined as surgical removal of bone for DFO, 39 (59%) had remission at 12-month follow-up The dorsal and plantar approaches to metatarsal head resections in patients with DFO have been compared regarding the recovery time and the development of complications Two different types of bone resection should be considered, one is the amputation of a ray that can be at a metatarsal or phalangeal level creating one bone stump and the other is a resection of a joint  in which there are two bone stumps. During the amputation, a bone margin biopsy is recommended while it is less clear that a biopsy should be done at each bone stump in case of conservative surgery. A bone biopsy performed at each stump appears to be ideal as there is no apparent reason which supports that the infection would only spread to proximal or distal direction. On the other hand, a bone biopsy at both stumps is likely to complicate the intervention. In case of a trans-articular amputation, it seems more appropriate to remove the cartilage which is avascular and therefore less able to defend itself against the pathogens. Whatever the type of surgery, it is important to take a bone sample with proper precautions to avoid the contamination of the samples i.e., by changing gloves, using sterile surgical instruments and a no-touch technique during the biopsy. External needle biopsy does not seem adequate since the level of amputation is not known with precision before the intervention and is not suitable for obtaining a bone margin biopsy.While it is recommended to use both histology and culture to affirm the diagnosis of osteomyelitis We are unaware of any studies that assessed the concordance of pathogens between the amputated bone and the residual stump microbiology. Another point in the daily practice is the difficulty to interpret the culture results especially when bacteria from the skin flora have been identified which may indicate a possible contamination of the bone samples. This issue has been addressed in a recent paper from Mijuskovic et al. who reported a series of 51 consecutive patients operated for toe or forefoot amputation White et al. prospectively studied a series of 25 patients with a suspicion of DFO who had combined histologic and microbiologic evaluation of percutaneous bone biopsies In their recent study, Schmidt et al. sent the bone margin specimens to two board-certified pathologists with expertise in bone pathology who both used a strict classification of histopathology definitions for the diagnosis of osteomyelitis Data on the optimal antibiotic therapy to administer after bone resection of foot amputation in these patients are lacking. Current guidelines recommend treating with antibiotics for up to 6 weeks if the culture demonstrates pathogen(s) or if the histology demonstrates osteomyelitis The optimal duration of DFO is a difficult subject as only one randomized controlled study has addressed this question In the study from Johnson et al. the mean ± SD antibiotic duration was 37.6 days ± 24.1 versus 17.7 days ± 29.6 (p=0.001) in patients with positive and negative bone margins, respectively The presence of bacterial biofilms may be of importance regarding the choice of the antimicrobial treatment given the differences in efficacy of antibiotics against planktonic and slow-growth bacteria (e.g. rifampicin versus beta-lactams which only work against multiplying bacteria) As many of the bone biopsies contain bacteria embedded into a biofilm, this may explain why rifampicin and fluoroquinolone combination regimens  are likely to be associated with a better outcome of the patients Bone resection and minor even major amputations are unlikely to remove all the bacteria involved and it seems therefore important to obtain data on the persistence of infected tissues including bone. Most but not all the studies have reported a negative effect of residual osteomyelitis on the outcome of patients operated for DFO. A lot of questions about the examination of the bone specimens  have not yet been solved. Some studies have pointed out the discrepancies between culture and histology of bone margin biopsies. These studies suggest that some of the positive cultures of bone margin biopsies are in fact in relation with contaminated specimens. Histology may help interpret the results of bone margin biopsies but the delay for obtaining the results in the daily practice appears to be a serious limitation in its routine implementation. In addition, the reliability of histology in these settings is an issue as suggested in some studies. The type and duration of the antibiotic treatment to consider in patients with a persistent osteomyelitis on the bone margins are currently unknown.In conservative surgery, bone specimens should probably be taken at both proximal and distal margins which, however, complicates the procedure, especially if both histology and culture are performed systematically. The role of molecular genetic techniques in the detection of bacteria in bone margin biopsies is not clearly established. These techniques do not provide information on the antimicrobial susceptibility profile of the bacterial strains identified. In the absence of indication regarding the pathogenic role of the organisms identified by these techniques, no recommendations have been made so far on their use in these settings. Data on the choice and duration of the antibiotic treatment to prescribe following bone margin biopsy are lacking. The first question is about the use of empirical post-biopsy antibiotic therapy while waiting for the results. Given that a bone and joint resection or even an amputation of all or part of the foot has just been performed in a context of a possible infection, it seems logical to consider an empirical antibiotic therapy started intraoperatively after the tissue samples have been taken and continued until the results of culture are available. As some of these patients are operated while receiving antibiotics a negative result should be interpreted with caution. If a bacterial documentation has been obtained prior to the surgery and histology is positive antibiotics should probably be administered and should be stopped if histology is negative. This raises the potential interest of histology examination in these settings. In the cases of negative culture and positive histology without previous documentation, antibiotics should be chosen taking account of the antibiotics which led to a negative culture. The duration is another difficult as the optimal duration of antibiotic treatment for DFO is not known. The last edition of the IWGDF recommends consider treating DFO with antibiotic therapy for no longer than 1-2 weeks if all infected bone has been surgically removed Additional clinical studies are necessary to answer some unsolved questions about surgical bone biopsy in the setting of DFO. Some standards for further clinical studies should be reported such as the description and gradation of soft tissue infection, the morphology and location of the tissue defect, details on concomitant peripheral artery disease, on severity of diabetic neuropathy, on surgical technique of amputation and wound closure, and on pre- and postoperative antibiotic treatment. These studies should address (i) which clinical intraoperative findings warrant the retrieval of a bone biopsy, (ii) how should a bone biopsy be retrieved , (iii) which histology criteria for the presence of acute or chronic osteomyelitis should be used and (iv) how should the biopsy be handled for microbiology assessment.


We report the case of a patient who presented for back pain with paresthesia, and the CT showed vertebral lysis of aneurysmal origin. The aneurysm of the thoracic aorta compresses the anterior surface of the dorsal vertebrae and by mechanical effect is responsible for the destruction of the opposite bone. The knowledge of this cause is very important considering the frequency of other tumoral and infectious causes of this affection. In the majority of cases, pseudotumoral vertebral lysis is a radiological sign leading to a tumor origin  or infectious origin (tuberculosis). The aneurysmal origin is a cause that is potentially rarely described in the literature, chest CT angiography plays a key role in diagnosis, and the diagnostic range must include this etiology to prevent serious complications.We report a case of a 50-year-old patient with no medical or surgical history who has progressive worsening dorsalgia, with recent paresthesia of limbs and chest pain.The clinical examination objectified back pain in the first dorsal vertebra with paresthesia of the limbs. The biological examination was normal. A radiograph of the dorsal and lumbar spine showed lysis of the vertebral bodies of D2, D3, D4, and D5. CT confirmed the lysis of the vertebral bodies of D2, D3, D4, and D5 , but it An aneurysm is a permanent and localized dilatation of an artery of more than 50% compared to the normal diameter, with a loss of parallelism of the edges . AccordiVertebral erosion secondary to an aortic aneurysm is most often located in the anterior region of the vertebral body; the suggested physiopathological mechanism is a repetitive mechanical pressure causing relative bone ischemia, leading to lysis and bone destruction ; the assThe main signs that reveal the diagnosis are spinal pain and neurological deficits (paraparesis or paraplegia); however, infection and inflammation are not uncommon , 5.The pseudotumoral aspect of bone erosion can orientate as in our case towards a tumoral  or infectious (tuberculosis) origin .The thoracoabdominal CT angiography is the reference examination, and it allows studying the whole thoracoabdominal aorta and its branches and assessing the relationship with the different adjacent structures ; it also makes it possible to objectify the signs of aneurysmal rupture  or predictive signs of rupture, such as rupture of the continuity of parietal calcifications and the sign of the crescent or the sign of the draped aorta 6]; the latter is of great diagnostic value, and it is considered positive when the posterior wall of an aortic aneurysm is draped or molded on the anterior surface of the vertebra, with loss of the fat planes located between the aneurysm and the vertebra. Its presence indicates a weakening of the aortic wall and an imminent risk of rupture , 6.; the latMagnetic resonance imaging may be indicated in stable patients for comparative monitoring of lesions , but CT Spinal pain associated with vertebral osteolysis is most often directed towards tumor or infectious etiologies. The aneurysm of the aorta is a rare etiology but must be mentioned in order to avoid the evolution of serious complications.


Following publication of the original article , it was Journal of Reproductive and Developmental Medicine published out of the Red Hospital of Fudan University.Dr. Finnell formerly held a leadership position with the now dissolved TeratOmic Consulting LLC. He also receives travel funds to attend editorial board meetings of the


Primary and secondary lung cancers are the most common clinical conditions that thoracic surgeons have to deal with: primary lung cancer, in fact, is one of the most frequently diagnosed cancers and is the leading cause of cancer-related death worldwide . On the Pulmonary metastasectomy has gradually become a frequently performed procedure among thoracic surgeons, particularly after the publication of the encouraging results of the International Registry of Lung Metastases and several other retrospective studies concerning pulmonary metastasectomies . More re


Human interventions on coastal areas are always causing environmental impact; however, most of the times inventories of those interventions are possibly not well structured, and surely without a specific standard. The raw data presented shows an exhaustive and systematic revision of satellite images on 1700 km of the Caribbean coast of Colombia, where 2743 human interventions were identified. These interventions are classified in 38 categories in order to assess their environmental impact at a regional scale. The filtered data shows the environmental impact obtained for each category and the values allotted to each of the four parameters used for this evaluation. Moreover, the data is filtered for each of the five environmental coastal units in which the Caribbean coast of Colombia is divided by national regulations. Finally, the filtered and processed data shows the analysis done to obtain the graphical results of a previously paper (An evaluation of human interventions in the anthropogenically disturbed Caribbean Coast of Colombia  Specifications table•This dataset of human interventions allows to do several extra and derived analysis of the environmental impact caused on Colombian coastal zones, with emphases on the 1700 km on the continental Caribbean seafront.•The calculation to obtain the simplified environmental impact assessment is of great interest to researchers and technicians looking for examples of quick and reliable EIA examples.•This dataset shows step by step how to identify and register human interventions in coastal areas using an open source tool such as Google Earth. It also shows how to process, calculate and graphically represent the environmental impact in a simple way, which could be very useful for professors in environmental and marine sciences.•The dataset is formed by three spreadsheets, which allow future researchers and practitioners to repeat the same process in three levels of complexity: raw data for inventory of human interventions, filter and process data for calculations of environmental impact and analysed data for statistical and graphical representations.•The dataset can be used as a baseline for long-term monitoring of the human interventions on the Caribbean coast of Colombia and their environmental impact on coastal and marine ecosystems.1DiB_Intervencoast_tables_Raw) includes the raw data of all 2743 human interventions found on the Caribbean coast of Colombia, and is used to register an inventory of 1700 km of coastline. This raw data file has 40 datasheets in which the first shows the seven categories and 38 types of human interventions used, with their codes, descriptions and quantity of data (The dataset contains five files: three spreadsheets in MS Excel format (xlsx) and two geographical files in Google Earth format (kmz), which are presented as supplementary material. The first spreadsheet ( of data . The sec of data . The difIntervencoast_tables_filtered.xlsx) has five datasheets with consolidated, filtered and processed data. The first datasheet includes the frequency of 38 human interventions in each typology per each ECU (The second spreadsheet (each ECU . The roweach ECU . This seIntervencoast_tables_filtered.xlsx has the filtered data used to graph the main frequency patterns of human interventions on the Caribbean coast of Colombia. The second datasheet of Intervencoast_tables_filtered.xlsx shows the same data of the first one but filtered to the 29 typologies found in the study area. These filtered data were those used by the article The third datasheet of Intervencoast_tables_boxplot.xlsx) includes the data filtered and organised to obtain the graphs 4, 5A and 5B of the article The third spreadsheet (The two Google Earth files (kmz) that complement the dataset show the geographical location of each position mark describing the human interventions in the study area, which comprise the complete inventory. Those two files have the same information, but organised in a different manner, in order to make easy their consultation and manipulation. One of the kmz files groups the 3957 position marks for the 38 typologies of human interventions. Meanwhile, another file groups the position marks within the five ECU. These two files are of the utmost importance for any researcher or practitioner interested to see some specific human intervention or geographical sector, because the software of Google Earth allows to navigate virtually on the study area .Fig. 4Ex22.1Colombia has officially three coastal zones, according to Decree 1120 of 2013: Continental Caribbean Coast, Insular Caribbean Coast and Pacific Coast. The dataset shown in this article covers the first of them. In the same Decree, five Environmental Coastal Units (ECU) are defined for the study area: La Guajira peninsula (GUAJIRA); the northern slope of the Sierra Nevada of Santa Marta (VNSMR); Magdalena Delta and Canal del Dique (MAGDIQUE); Sinu Delta (SINU); and Darien Gulf (DARIEN). Their boundaries are shown in Sierra Nevada de Santa Marta massif and the southernmost end (Panama border) correspond to more resistant igneous and metamorphic rocks The approximately 1700 km shoreline of the study area alternates between deltaic plains and low coasts with high coasts of mountainous segments According to National Statistics Institute 2.2The inventory of human intervention in the study area was compiled using the structure of coastal uses and activities proposed by Botero The instrumentation for data collection relied on the software Google Earth because it provides easy access to numerous satellite images of the study area with adequate horizontal and vertical resolution to observe the earth relief and identify geomorphological units, both natural and anthropogenic ,12. The 2.3The environmental impact assessment was calculated from a simplified version of the Conesa The authors declare that they have no known competing financial interests or personal relationships that might have appeared to influence the work reported in this paper.


Foods journal has been published.The Mediterranean diet is now well known worldwide and recognized as a nutrition reference model by the World Health Organization. Virgin olive oil, prepared from healthy and intact fruits of the olive tree only by mechanical means, is a basic ingredient, a real pillar of this diet. Its positive role in health has now been a topic of universal concern. The virtues of natural olive oil, and especially of extra virgin olive oil, are related to the quality of the fruits, the employment of advanced technologies, and the availability of sophisticated analytical techniques that are used to control the origin of the fruits and guarantee the grade of the final product. With the aim of enriching the recent multidisciplinary scientific information that orbits around this healthy lipid source, a new special issue of  This Special Issue collected specific articles from different areas of research. To produce a high-quality oil it is necessary to start from the right selection of cultivars in the olive production region. Therefore, the Special Issue dedicates an article to the varietal authentication of extra virgin olive oils . The proVirgin olive oil is a phytocomplex, a product containing hundreds of non-glyceridic substances that are responsible for the coloring of the product or contribute to the hedonistic value. They may also have antioxidant or other properties beneficial to health. An important class of such compounds is the pigments. The methods for determining them were the subject of a specific article that describes how to quantify the total amount of carotenoids and chlorophyll derivatives .The wide range of molecules present in olives and virgin olive oil also includes polar lipids such as glycerophospholipids and glycolipids. A specific article describes findings on the identification and characterization of such polar lipids, their potentiality as markers of the identity and traceability of olive oil, and their potential impact on nutrition and health .The best oils of all time are the oils produced in the last 20 years thanks to the improvement of hygiene standards and the development of technological innovations. The application of ultrasound to olive paste is among the most relevant innovations. It started from research laboratories and reached the market. The strength of this innovative process lies in the change of traditional milling. The device that combines ultrasound with heat exchange significantly increases the quantity of oil produced and the level of biologically important phenols .Studies of the favorable effects of olive oil bioactive ingredients are continuously opening new paths for medical and pharmaceutical research. A special chapter of this Issue discusses pharma-nutritional evidence that indicates how EVOO bio-phenols might exert important physiological actions that bring about cardioprotection, chemoprevention, and a lower incidence of neurodegeneration. The study focuses on recent findings that elucidate their molecular mechanisms of action .n = 1128) and the MEDiterranean Islands Study (MEDIS) (n = 2221 adults from various Greek islands) studies. The use of olive oil in food preparation and the bio-clinical characteristics of the Greek participants were investigated in relation to successful aging. It is suggested that primary public health prevention strategies to promote healthy aging and longevity should encourage the enhanced adoption of practices based on the exclusive use of olive oil for culinary purposes [The consumption of dietary fats, which occur naturally in various foods, poses an important impact on health. The last contributions reports the results of the adults from Athens metropolitan area (ATTICA) (purposes .


The WISDOM Personalized Breast Cancer Screening Trial: Simulation Study to Assess Potential Bias and Analytical Approaches by Martin Eklund et al., the authors describe a simulation based on the Women Informed to Screen Depending on Measures of Risk (WISDOM) (In the article (WISDOM) , 2. The (WISDOM) . This evA primary study objective of WISDOM is to test whether personalized screening is safe, as measured by the noninferiority in the proportion of stage IIB or higher cancers found in the personalized and annual screening arms . While tThe purpose of screening is to detect early, asymptomatic disease that is potentially curable . ClinicaTo properly evaluate screening strategies for breast cancer, a natural history model of this disease should consider growth and development from a size below the detectability threshold of the technologies under investigation. This allows for the incremental benefits of earlier detection with more screening to become apparent. The omission of early-stage disease in this model’s design is fundamentally limiting and masks differences in disease stage between personalized and annual screening strategies.The authors have no conflicts of interest to disclose.


Indian communities have the ancient cultural practice of gentle oil massage for infants which has been shown to play a beneficial role in neuro-motor development. The concept of incorporating nanosized liposomes of micronutrients  in the body oil leverages this practice for transdermal supplementation of essential micro-nutrients. This paper describes the experience of developing an intervention in the form of body oil containing nanosized liposomes of iron and micro-nutrients built on the social context of infant oil massage using a theory of change approach. The process of development of the intervention has been covered into stages such as design, decide and implement. The design phase describes how the idea of nanosized liposomal encapsulated micronutrient fortified (LMF) body oil was conceptualized and how its feasibility was assessed through initial formative work in the community. The decide phase describes steps involved while scaling up technology from laboratory to community level. The implementation phase describes processes while implementing the intervention of LMF oil in a community-based randomized controlled study. Overall, the theory of change approach helps to outline the various intermediate steps and challenges while translating novel technologies for transdermal nutrient fortification to community level. In our experience, adaptation in the technology for large scale up, formative work and pilot testing of innovation at community level were important processes that helped in shaping the innovation. Meticulous mapping of these processes and experiences can be a useful guide for translating similar innovations. Globally, almost 50% of under-five children suffer from hidden hunger due to deficiencies in essential nutrients, with majority of these children being from developing countries . In IndiThis paper describes the journey of developing an innovative intervention for prevention of micronutrient deficiencies in children. The intervention involved use of a nanotechnology platform in the form of nanosized liposomes for fortification of body oil which is traditionally used for body massage in Indian infants. The intervention of nanosized liposomal encapsulated micronutrient fortified body oil (LMF body oil) was developed as part of a proof of concept randomized controlled study conducted among rural Indian infants to evaluate the effects of such an intervention on micronutrient deficiencies and neurodevelopmental outcomes.In order to develop a complex intervention for healthcare delivery, it is important to understand the social context, acceptability and final sustainability which may have a significant effect on the outcomes , 8. DeveUsing the ToC approach, we describe various steps in the process of development and implementation of the intervention: (i) design (the construction of an intervention); (ii) decide (the decision making processes while developing the intervention); (iii) implement and monitor .The intervention of LMF body oil was developed and implemented for a proof of concept community-based clinical study in rural Indian children. This was double-blind placebo controlled randomized study in 444 infants to evaluate whether use of this intervention during 1st year of life can improve nutritional anemia and neuromotor development. The intervention of LMF oil was developed by researchers at Indian Institute of Technology Bombay (IITB), Mumbai, India and the study was implemented at in population of 22 villages of Vadu health and demographic surveillance (Vadu HDSS)  by reseaThe causal pathway for ToC was developed through discussion with stakeholders involved in the development and implementation of the intervention. The initial pathway was presented in a workshop on “Effective Delivery of Integrated Interventions in Early Childhood” organized by Saving Brains Learning Platform, amongst other peer groups of various projects and was modified through feedback from peers and reviewers. The final pathway was developed after iterative inputs from the key stakeholders involved in the study i.e., investigators from partner institutes and implementers of the intervention. As this was a proof of concept project, the pathway focusses on the design, decide and implementation part of the process and does not largely cover monitoring and evaluation part of the ToC cycle. The pathway was developed through backward mapping of the activities that led to certain evidence-based decisions and changes in the work plan.Newborn oil massage is an ancient cultural practice in South Asian countries with some reported health benefits , 11. Thein vitro and in vivo animal models for transdermal delivery of nutrients at supplemental doses  that can penetrate through the intact skin while massaging with the fortified body oil. This concept of LMF body oil emerged through initial meetings amongst scientists from KEMHRC and IITB. It was perceived that as the concept was based on the traditional practice of infant oil massage, it was likely to receive greater compliance and acceptability in the Indian community and can potentially overcome barriers associated with non-compliance to oral micronutrient supplementation  for proof of concept evaluation of LMF body oil in a community-based project for improvement in neurodevelopment, prevention of iron deficiency anemia and vitamin D deficiency in rural Indian children. This was an interdisciplinary collaboration between technology scientists and medical as well as public health scientists. The proposal received funding from Saving Brains Platform of Grand Challenges Canada .Before implementation of the study, a formative study was conducted in the study area for the community-based clinical trial . This waThe caregivers in the household were asked by field research assistants about whether they practiced oil massage for their infants, age of onset for oil massage, till what age was the massage practiced, frequency of massage, choice of oil and perceived benefits of oil massage. The survey results supported the available evidence on oil massage as more than 90% of the caregivers practiced oil massage for their infants, believed that it was useful and also showed willingness to switch to a new oil formulation if that contained micronutrients. Majority of the households (about 65%) used marketed oils for massage. In all the households, infants were massaged in the morning before bathing. In 85% households, massage was initiated within the first 2 weeks after birth and in 94% households the massage was continued up to at least 9 months of age. This information demonstrated feasibility for implementation of study oil massage throughout the 1st year of life, especially in the second half of infancy when the prevalence of nutritional deficiencies rises.The composition of LMF body oil was finalized through review of literature and discussion with subject experts. The composition was devised taking into consideration the physiological requirements of the micronutrients with reference to the available national nutritional guidelines such that doses of none of the nutrients exceed 100% dietary requirement for the given age .The physiological requirements of iron extensively rise after initial 6 months of life, whereas the iron requirements are minimal in the first 6 months due to redistribution of iron from fetal hemoglobin and supply of highly bioavailable iron through breastmilk . PhysiolResults from the formative study indicated that the local community was not in practice of using any particular natural oil, as majority of households used some form of marketed body oil. Based on review of literature regarding the choice of oil for infant massage, it was decided to use sunflower seed oil as this is a rich source of essential fatty acids and has demonstrated benefits in reducing morbidity and mortality in preterm newborns .The regular practice of oil massage in the local community involved massaging infants in the morning, although some households practiced massaging at bedtime as well. The formative study demonstrated that the infants were bathed soon after this massage. It was felt that this practice may not provide adequate time for absorption of the liposomes due to wash off during bathing. Hence, we planned to implement the LMF body oil massage intervention at night before bedtime .The LMF body oil was planned to be used throughout 1st year of life, during which the baby grows in size and body surface area changes which can lead to change in the volume of oil used for body massage. Also, there may be variability in the volume of oil used by each caregiver for a given size of a baby. It was important to finalize and fix the unit volume of oil to be used daily which would deliver the required dose of nutrients. A pilot study was carried out in 10 infants of various ages which demonstrated that sunflower seed oil in the volume of 2.5 mL was adequate to massage torso and extremities in first 6 months and was just adequate to massage extremities in the 6–12 month old babies . Hence, The patented nanotechnology for preparation of micronutrient nanoparticles was available at laboratory scale and used organic solvents (methanol) for preparation of the liposomes. Additionally, the technique used (thin film hydration) was difficult to scale up for large scale manufacturing , 29. We The storage stability of the LMF body oil was also evaluated. Suitable packaging was used for providing monthly supply of LMF with instructions for storage away from light and heat. Calibrated cups were provided for measurement of accurate volumes of LMF. As the oil was to be used for a double blind randomized controlled study, test and placebo oils as well as low and high strengths of the oil were color-coded without disclosing the composition.We decided to evaluate the tolerability of LMF body oil in healthy adults and subsequently in healthy children before proceeding with the randomized controlled study in infants to rule out any irritation potential of the LMF body oils. The need for conducting these studies was perceived after discussion with subject experts as there is some earlier evidence on role of iron in oxidative stress in skin tissue  and furtThe first study was conducted in 26 healthy adult volunteers using single application of closed patch test (containing the product) under occlusion for 24 h. Subsequently, tolerability studies were conducted in 15 healthy adults and 15 healthy children aged 8–24 months where predefined quantity of highest strength of the LMF body oil was applied locally on the extremities for 15 days. In all the above studies, skin erythema and dryness were measured before and after the study using Draize score . The higBefore proceeding for the use of randomized controlled study, acceptability of using LMF body oil was assessed amongst the participants of the two tolerability studies. Acceptability of the oil was assessed for its appearance, texture, fragrance, ease of use and overall evaluation using visual analog scale of 0 to 5 where 0 indicates poor acceptability and 5 indicates best acceptability (The community-based study consisted of administration of LMF body oil and a placebo oil to 222 infants respectively starting from age of 4–7 weeks till completion of 12 months. The implementation at the manufacturer level involved manufacturing of about 500 liters of oil including both test and placebo oil following the good manufacturing practices. At field level, a team of field research assistants, clinical coordinators, laboratory coordinator and project manager were hired and trained for the study protocol. Study documents including case record forms, participant information sheet, informed consent forms, logs for study activities and compliance cards were developed by the implementation team. The study team was trained for completing all the study activities as per the decided timeline.During implementation of the project, the caregivers were trained about massage with LMF body oil at baseline visit in the study clinic. The field research assistants were trained to supply oil bottles on a monthly basis and monitor the intervention through fortnightly visits as well as through use of compliance cards. Additionally, during implementation, we found that checking the quantity of unused oil was a good measure of compliance. For non-compliant households, despite regular follow up by field research assistants, additional visits and counseling by a senior project staff were required and was found to facilitate compliance in majority of the households.There were certain challenges encountered during the various phases of work. The laboratory technique available for preparation of nano-encapsulated liposomal micronutrients needed to be changed and a green technique needed to be developed and optimized for further scale up. Identification of the service provider for scaling up an innovative technology was a challenging task. Transdermal supplementation of nutrients is an innovative mode of delivery. Although technology has been tested in preclinical and clinical studies for efficacy and tolerability, exact proportion of absorption of encapsulated nutrients through pediatric skin is not known. Lastly, there were various challenges during implementation which have been depicted in in vivo animal models of anemia has been reported in the literature (The intervention of a body oil that contains nanosized liposomes of micronutrients is a completely innovative intervention that was developed from laboratory-based technology to a proof-of-concept community level project. Transdermal iron replenishment using biophysical techniques such as microneedle patches and iontophoresis in terature –35. Howeterature . There iterature . Thus, tDuring development and implementation of LMF body oil, various aspects of the intervention needed to be addressed. These included feasibility of scaling up the intervention and implementing it, assessing acceptability by the local population and overall safety of the innovative intervention as well as developing measures to improve compliance to the intervention. This being a complex health intervention, lack of effect can be due to failure of implementation rather than genuine ineffectiveness . Hence, Our experience of using a causal pathway for ToC for development and implementation of LMF oil has several learnings . The cauWhile developing the innovation through the collaboration of scientists from technology and public health domains, the causal pathway helped to map steps where collaborative inputs from all stakeholders were useful in scaling up and evaluation . This alOne of the limitations while developing this causal pathway was that it was developed retrospectively. Secondly, although the initial design and decide phase of the work was not dependent upon the external funding, it was carried out only after funding for the proof of concept study was available, thus leaving less time to carry out certain study related activities. Despite the limitations, the ToC approach for this project describes how a technology innovation can be based on a traditional practice and can be translated into a viable public health intervention.ex vivo studies and studies in human volunteers and also evaluate the efficacy of LMF oil in anemic children. We plan to scale up the manufacturing of LMF oil for larger public health use through transition to scale programs which will include monitoring and evaluation part of ToC cycle.In future, we plan to mechanistically evaluate the transdermal penetration of each ingredient of the oil through Use of the causal pathway helped to clearly understand the intermediate steps taken and barriers faced during development of an innovation for transdermal delivery of nutrients, leveraging a traditional practice and its pilot implementation at community level. In our experience, adaptation in the technology for large scale up, formative work and pilot testing of innovation at community level were important processes that helped in shaping the innovation. Meticulous mapping of these processes and experiences can be a useful guide for translating similar innovations.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Ethics Committee, KEM Hospital Research Centre, Pune. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.AA, AB, SJ, and RB were involved in conceptualization of the research idea and writing of proposal. AA, AB, and RB were involved in designing of innovation. AA, MK, and RB were involved in technology scale up of the innovation. AA, HL, AB, and SJ were involved in implementation of the innovation at community level. AA attended the ToC workshop organized by Saving Brains Learning Platform and wrote the first draft of the manuscript. All authors reviewed and provided inputs on the causal pathway developed and read and agreed with the manuscript and conclusions.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.