Public health researchers are increasingly interested in assessing the impact of neighborhood environment on physical activities and chronic health issues among humans. Walkable streets and proximity to green space have long been believed to promote active lifestyles in cities, which contribute to positive health outcomes among residents. Traditionally, urban environmental metrics were calculated at the area level to describe the physical environment of neighborhoods. However, considering the fact that streets are the basic unit for human activities in cities, it is important to understand how the streetscape environment can influence human health conditions. In this study, we investigated the influence of street greenery and walkability on body mass index in Cleveland, Ohio, USA. Different from the area level and overhead view greenery metrics, we used the green view index calculated from the Google Street View to represent the amount of street greenery. The Walk Score was used to indicate the walkability of neighborhoods also at the street level. Statistical analysis results show that the Walk Score has a more significant association with decreased BMI for males than females and the street greenery has a more significant association with decreased BMI for females than males in Cleveland, Ohio. The results of this study would provide a reference for designing gender-specific healthy cities. Obesity rates have risen significantly in the last half-century in many countries . It was Physical inactivity is one of the major causes of obesity ,10,11. TThe built environment factors, such as higher housing density, existence of sidewalks, higher intersection density, easier access to transit, and greater land use mix, have been found to increase the walkability level and the frequencies and length of physical activities ,18,19. SBetter understanding of the association of obesity with urban environment would provide an important reference for urban planning to reduce obesity rates . StudiesIn this study, we investigated the association between BMI of residents and the neighborhood greenness in Cleveland, Ohio for different age–gender groups. Both the natural and the built environment features were considered in the analyses. The green view index (GVI), calculated based on the Google Street View images captured at different horizontal view angles, indicates the greenness of the neighborhood. Different from previous area level green metrics, the GVI quantitatively represents how much greenery a pedestrian can see from a ground level, which may have more direct connection with human behaviors ,23. The Cleveland is the second largest city in Ohio  and it hIn this study, we used a green view index (GVI) to measure the greenness of neighborhoods. The GVI quantifies the visibility of the street greenery based on the street-level images . To do tg_iArea is the number of green pixels in a static GSV image, and t_iArea is the number of total pixels in one GSV image. The GVI indicates the average percentage of greenery pixels in six GSV images at six different horizontal directions that cover the 360° views. Based on the image classification result, we further calculated the GVI using Formula (1),We used the Walk Score to represent the walkability in the study area ,25. WalkIn order to investigate the influence of street greenery (GVI) and walkability  on BMI, we conducted statistical regression models. Socioeconomic variables were included in the models as confounding factors. Based on previous studies ,14,26, wIn order to make the GVI, the Walk Score and the BMI data directly comparable to socioeconomic variables, we aggregated the site-level GVI map, Walk Score map and the BMI map to the census tract level by the mean value. To combine the effects of street greenery and walkability, an interaction term of GVI and Walk Score was also added in the statistical models. We first ran ordinary least-squares (OLS) regression models to analyze the associations between BMI and the independent variables  for different age–gender groups. Next, we checked for spatial autocorrelation of residuals in order to control the effect of the spatial autocorrelation, if any. Results show that there is no significant spatial autocorrelation in the residuals. Therefore, spatial regression model was not conducted. OLS regression model results show that the associations between the BMI and the independent variables vary among different age–gender groups. For the young females (18–29 years), the BMI has no significant association with both the Walk Score and the GVI . SimilarThe OLS regression analyses results for old-aged people (51–65 years) are presented in Increasing walkability along streets and neighborhoods helps to promote an active lifestyle, which has long been recognized as beneficial to human health ,20,25,29Parks and other forms of green space are among the key environmental supports for recreational physical activity . GuarantThere are limitations of this study that need to be discussed. Firstly, the current study was conducted at the census tract level in order to have more stable census data. However, using smaller geographical units would be better to reflect the connection between natural and built environments on individual BMI. This is because the physical environment would influence those people within walking distance, which means that finer geographic units or street-level analyses would better represent the interaction between human beings and the environment. However, getting reliable socioeconomic variables at the fine geographic level would be a challenge. The Walk Score could not fully represent the urban built environment and the walkability of neighborhoods. In future studies, more metrics describing the urban built environment should be considered for such analyses. This study found that associations between body mass index and Walk Score and Green View Index vary among different age–gender groups of people. The Walk Score has a more significant association with decreased BMI for males over females. The Green View Index has more significant association with decreased BMI for females than males, especially for middle-aged and retiree groups. The results point to an interesting conclusion that the existence of the urban greenery has a stronger correlation with BMI for females rather than males.


Solar energy generated by grid-connected photovoltaic (GCPV) systems is considered an important alternative electric energy source because of its clean energy production system, easy installation, and low operating and maintenance costs. This has led to it becoming more popular compared with other resources. However, finding optimal sites for the construction of solar farms is a complex task with many factors to be taken into account , which classic site selection models do not address efficiently. There are few studies on the criteria that should be used when identifying sites for solar energy installations . It is therefore essential to change the way site selection processes are approached and to seek new methodologies for location analysis. A geographic information system (GIS) is a tool which can provide an effective solution to this problem. Here, we combine legal, political, and environmental criteria, which include solar radiation intensity, local physical terrain, environment, and climate, as well as location criteria such as the distance from roads and the nearest power substations. Additionally, we use GIS data , land cover, and temperature) as further input parameters. Each individual site is assessed using a unique and cohesive approach to select the most appropriate locations for solar farm development in the Valencian Community, a Spanish region in the east of Spain. Sources of renewable energy (RE) have become a necessary alternative with which to face the growing and essential energy demand in the twenty-first century. Over the last decade, solar energy has emerged among the different types of REs  as one of the most promising RE sources to replace fossil fuels in meeting the world’s future energy needs  and other P such as voltage drops and network losses in the large-scale integration of PV power generation into electric distribution systems. Other studies explore the topologies used to interconnect PVPs with inverters (grid connectivity) and the technology developed for inverters in order to compare their efficiency, control, cost, and weight, and analyze future trends  and spatial analysis, which can provide considerable support to management and decision-making processes  from those aspects that simply limit or condition the activity . Secondly, technology criteria are not taken into account when in fact, depending on the type of technology chosen, solar farm activity may be limited to a greater or lesser degree in certain locations , land cover, and temperature) as further input parameters. Each individual site is assessed using a unique and cohesive approach to select the most appropriate locations for solar farm development in the Valencian Community, a Spanish region in the east of Spain. Our aim is to provide an innovative system for spatial planning problems by creating an argumentation map to analyze the different factors that determine the areas not excluded.The objective of this study is thus to provide a methodology with which to identify potential PV power generation sites in a specific area and thereby support the development of new PV power stations as well as strategic RE planning. Moreover, the results of our study can help find potential areas for solar farm development in any country.Further research might include other criteria like building costs and local demand which can also affect site selection. They could be applied in further steps to assess the candidate locations and select the suitable areas see Fig. , but theThis paper is divided into the following sections: after this introduction, information is provided on the area of study and the parameters used in the solar farm site analysis. Next, there is a description of the GIS tool used for data criteria management, as well as its integration for the area selection. This is followed by the results and discussion. The final section presents the conclusions together with some final comments.We apply the proposed GIS-based approach to select locations for the installation of solar power plants in the Valencian Community, a Spanish region in the east of Spain Fig. .Fig. 1St2)2, and located in what is known as the Mediterranean Corridor, a relevant economic area at the European level. Its current energy consumption stands at 23,000 GWh in 2018 and fossil fuels are the main source of energy (66%), with RE sources having barely been implemented. In fact, the Valencian Community is a region that consumes more energy than it produces, with a negative balance of approximately more than 2 GWh.In 2017, there were approximately 5 million inhabitants residing in this area, which represents 10.5% of the total population in Spain and occupies the second position in terms of population density  and Birdlife Special Protection Areas are also included.Regarding the Valencian Community, there are well-defined legal restrictions for soil use. The following laws related to preserving areas of ecological value have been approved:Landscape impactJob opportunitiesRural developmentAmong the social criteria that must be considered are those aspects that can influence the social value of PV power plants:Design: solar cells, type of PV panels, and grid connectivityInitial capital costDiscount ratesLifetime of the projectsThe electricity retail price which determines the profitability of solar farmsFinally, the technical and economic criteria are determined partly by the technological advancements and partly by the investment parameters for solar photovoltaic development. The technical and economic criteria are analyzed together since certain aspects determine others:All the above-described criteria are used throughout the four stages (levels) of the decision-making process see Fig. .Fig. 4MoThe first level of decision is determined by the political and legal conditions which establish whether a solar power plant can be installed or not. These conditions are set by the economic policies and environmental regulations made by the government of the region under study. In our paper, we consider those established by the Spanish government and the Valencian regional government, according to the division of competences set out in the Spanish Constitution. The reason for using legal exclusion criteria is that, for example, in the case of land classified as urban only houses or factories can be built there, while solar parks cannot be installed Law 10,. Other aOther environmental criteria which lead to exclusion are areas with risks involved, such as floods, landslides, and windy areas, or with geological characteristics that make the area unsuitable for installing PVPs.areas not excluded are identified, we step into the second decision level in which geographical location criteria are used. Solar radiation is the main and decisive factor (Gastli and Charabi 2 to max 219.7 W/m2).Once the In order to make the construction of the solar farm easier and taking into view possible repair and maintenance issues, those sites closer to roads are considered to be more suitable , so that the society or population affected can decide what the best locations are in order to protect high-value landscapes, generate job opportunities, and foster rural development. As can be seen in Fig. In future studies, economic criteria could be applied to these areas to identify the Bearing in mind the large number of parameters and the considerations regarding optimal and limit values, etc., the use of a GIS is essential for all the information to be integrated, organized, and processed, as well as for the territorial variables to be linked together with other variables. Consequently, all the data must be georeferenced.As mentioned above, the selection of high-potential locations for solar energy production requires the use of a GIS in its different stages. With the help of this tool, geographical data (criteria maps) can be transformed and combined to obtain adequate and useful information for decision making in the spatial arrangement and distribution of activities, identifying suitable locations for these activities, here in particular the installation of solar power plants , the National Geographic Institute (IGN), and the current Regional Department of Housing, Public Works and Territorial Planning, as well as a collection of thematic layers developed by the former Regional Department of Public Works, Urban Planning and Transportation. The solar radiation layer and the temperatures were obtained from the PVGIS website of the European Commission and from the Spanish Meteorological Service (AEMET), respectively.Figure green infrastructure and the risk cartography layers were overlaid and the protected and risk areas were eliminated from the total study area (1). The next stage was to intersect (3) the resulting layer from the previous operation (1) with the layer containing the urban planning information, where previously only those areas classified as common non-developable land (2) were selected. In this way, the areas were obtained which could not be excluded for environmental or legal reasons, i.e., the areas not excluded (4). Figure To be able to establish the not protected areas and those with no risks, the digital elevation model  enabled us to select the areas classified as having a land cover compatible with the installation of solar power plants (7). An analysis was carried out on land with soil classified as suitable for agricultural and livestock production, rice cultivation, growing citrus and other fruit trees, olive and other woody crops, arable farming, grassland, deciduous, coniferous and evergreen species, and electric power production, as well as scrubland, idle land, and bare soil land. Areas with a cover below 30% are selected Fig. .Another topographic restriction is altitude. Taking into account that the maximum altitude of the Valencian Community is slightly higher than 1800 m, most solar analysis studies on this region select land with gentle slopes and no altitude limit. However, as the whole study area meets the criterion of an average temperature between 10° and 20° C, the only climatic factor considered was altitude. Using a DEM, we obtained those areas that met the established conditions and converted the raster format into vector format (8).Next, we intersected (9) the layers containing the areas of influence of the electricity and road networks (5), the areas with suitable slope and orientation conditions (6), and land use/cover (7) and altitude information (8) thereby obtaining the most suitable sites for PV power plants.Finally, we intersected (11) the layer with the potential areas (10) with the layer containing the areas with no environmental or legal restrictions (4). The result was a total of 22 areas that met all the established conditions and criteria (12) Fig. .Fig. 8Hihigh potential areas for solar farm development is obtained. Figure The different areas are considered spatial objects, i.e., polygons in the vector model and grid cells in the raster model, and constitute location alternatives. In this final step, the layer which identifies the These potential locations should be assessed according to solar technology requirements so that economic criteria can also be considered. Their surface is between 10 and 50 ha and most of these areas are located in the province of Alicante.Assessing the different location alternatives in planning is a preliminary and decisive step when creating maps with suitable and economically viable locations for the usage of specific technologies.For the sustainable development of a region, it is extremely beneficial to identify areas of land for solar PV power development for the following reasons: (1) transmission planning is optimized; (2) master plans for solar energy production can be developed; (3) it provides timely access to the selected land; (4) environmentally sensitive lands can be identified; and (5) it provides certainty for the solar power market . Alternative locations identified by the screening must be assessed further which will lead to finding the most suitable site among all alternatives.geographically and economically suitable locations, which would be the third decision level. And finally, using these areas as an object of further analysis, a public participation process should be undertaken (fourth decision level), whereby the society or population of the area in question can decide what the best locations are in order to protect high-value landscapes, generate job opportunities, and foster rural development.In future studies, it would be advisable to use additional information and seek out expert opinions to create a ranking of suitable areas. It would also be interesting to incorporate the economic information of the selected areas to be able to identify the


To evaluate the opinion and perception of referring physicians regarding theradiology report, in order to develop tools that promote an improvement inits quality.We prepared a questionnaire containing ten multiple choice questions aboutthe radiology report, administering it to 70 physicians .Referring physicians  showed a preference forstructured reports, with a description explained in universal medicallanguage and a complete conclusion listing the diagnostic possibilities withthe degree of certainty. The examination technique should be described, andthe final report is best presented when it contains the final chart,together with images, as hard copies and in digital format. The respondentsalso reported having confidence in the opinion of the radiologist andexpressed the need for a direct channel of communication with the same.Referring physicians seek detailed reports (including a description of theexamination technique), preferably structured, with objective language andrelevant conclusions (the position of the radiologist on the case isimportant). It is necessary to discuss the differential diagnoses andprovide a form of contact between the parties. Although referring physiciansconsider the radiologist opinion relevant, they also want to analyze theimages on their own. The written radiology report is the most important and oftentimes only means ofcommunication between referring physicians and radiologists. It is included in themedical records of patients and plays a fundamental part in the way their clinicalcare is conducted. The report also incorporates the personal perceptions andabilities of the radiologist. As diagnostic methods become more complex, radiologyreports take on an even greater role.. Anotherstudy showed the preference of various imaging centers for reports to be structuredin ways that facilitate access to the information, invoicing, teaching, research,and other aspects. These andother characteristics form the basis of a radiology report and generate differencesof opinion regarding which is the best model to be adopted. However, the opinion ofthe referring physicians is also crucial to the process of improving radiologyreports, given that they will be the final recipients of the reports.There have been a series of studies evaluating the characteristics of and preferencesregarding radiology reports. One recent study demonstrated a certain preference ofradiologists for more detailed reports written in free text  andthat also include a description of the examination technique employed by theradiologist. The members of the group began their work by examining howradiologists approach the task of preparing their reports. They also attempted todetermine in what form the referring physicians preferred to receive those reports.They were then able to devise a series of recommended minimum requirements for thereports.The objective of this study was to evaluate what referring physicians expect from aradiology report and, upon careful evaluation of the results, propose practices thatmeet their expectations. We highlight the efforts made by The Brazilian College ofRadiology and Diagnostic Imaging in this regard, as clearly demonstrated by thecreation of a working group on radiology reportsThis was a prospective, cross-sectional, descriptive study, approved by the localresearch ethics committee. A questionnaire  composedThe questionnaire was structured in such a way that it could be easily read andcompleted in only a few minutes. Questions were mainly related to computedtomography and magnetic resonance imaging. Respondent anonymity was guaranteed, andit was therefore not possible to establish the individual characteristics of theparticipants. From among the completed questionnaires, we selected the first 35received from specialist physicians (over five years of experience) and an equalnumber received from resident physicians working in the corresponding specialties. Therefore, the final sample comprised 70questionnaires completed by physicians.The statistical analysis of the data collected involved descriptive analysis, throughthe calculation of absolute and relative frequencies. We also constructed barcharts.Among the respondents, clinicians were the most well represented, accounting for45.7%. On the basis of the responses, we found that 55.7% of the referringphysicians read radiology reports in full , 92.9% tRadiology reports are the principal means of communication between clinicians andradiologists. A referring physician oftentimes knows a radiologist only from thereports, and radiologists frequently do not know who is on the receiving end oftheir reports , how they are beingevaluated, or what is expected by the referring physicians. Although there have beenmany studies on radiology reports and their structure, few have researched whatreferring physicians in Brazil expect regarding such reports.A careful analysis of our results allows us to conclude that, despite the fact onlyapproximately half of the respondents reported reading radiology reports in full,most of the physicians who request radiology reports at our institution do trustthose reports, at least partially, as well as demonstrating a preference forstructured reports that describe the examination technique employed and containobjective conclusions. We also observed a clear preference for oral communicationbetween the radiologist and the referring physician., because there isevidence that a large number of physicians do not read the report in full and, insome cases, that will be the only section of the report that will be read. In ourstudy, most of the clinicians (55.7%) indicated that they read the report in full.Another significant proportion of the respondents (38.6%) stated that they read onlythe conclusion and skim over the report for additional information regarding thefindings. Another recent study showed that nearly half of clinicians (46%) read theconclusion and analyze the report further only if complementary information isneeded. The authorsfound that only 39% of the participants read the report in full. Another studyinvolving 200 physicians obtained similar results. The results of our study, like those of the twoabovementioned studies,6, show how important it is toconstruct an appropriate conclusion in a radiology report, given that a significantamount of physicians do not read the report in full.The European Society of Radiology recently published a reference handbook thathighlights the fundamental importance of the conclusion in a radiologyreport,6.The aim of the present study was to determine what level of trust referringphysicians had regarding radiology reports in a university environment. The vastmajority of the respondents (92.7%) indicated that they trust the reports onlypartially, stating that the reports were used to make secondary decisions, only 7.1%stating that they have complete confidence in the opinion of the radiologist. Noneof the respondents reported a lack of confidence in or disregard for the radiologistopinion. Our findings corroborate those of recent studies, one of which involved asample of nearly 4000 physicians, by demonstrating that 87% of referring physiciansrecognize the fundamental importance of radiology reports, in order to ensureexcellence in medical practice. Our studyinvestigated what is the best way in which to present the results of an examination,in the opinion of referring physicians. Most of the referring physicians surveyed(59.4%) stated a preference for the final report to be accompanied by printed photosand a CD with digital images. Another study also demonstrated that physiciansworking in university hospitals, a sample comparable to ours, prefer to receive thereport accompanied by a CD or DVD, whereas those working in public hospitals preferprinted photos. Making imagesavailable online is a new form of presentation that has also been gaining ground,because it reduces the costs of material and manpower, as well as making life easierfor the patient. However, thatform of presentation was not covered in our questionnaire, given that this optionfor sharing data is still not available at our facility.According to the American College of Radiology, radiology reports should containimages and multimediaidentified clarity as one of the facets referring physicians consider to be mostimportant in radiology reports. In another study, which included only X-ray reports, 39% of referringphysicians stated that the report was confusing and 51% stated that the initialreason for the examination to be requested was not covered at all. Clarity is ofessence in radiology reports, because it guarantees that the information beingtransmitted is precise and completely intelligible, thus directly benefitting thepatient. Therefore, we choose to evaluate the technical language used byradiologists. A considerable proportion (47.1%) of the referring physicians surveyedin the present study believe that although technical terminology can be used indescribing the findings, the report should include a conclusion from the radiologistexplaining the significance of those findings. However, approximately half of thestudied population reported having difficulty in understanding the language employedin radiology reports. Two studies, both conducted in 2011, presented divergingresults on the subject. In one of those studies, 77.5% of referring physiciansreported having no trouble understanding what the radiologist was attempting tocommunicate, whereas theresults of the other study suggest the need to create a universal medical languageto be used in radiological reporting. That divergence is reflected in our results, evidenced by theproximity of the proportions for two most common responses. Therefore, it is clearthat a significant proportion of referring physicians find it challenging tounderstand the technical terminology used by radiologists, which makes is necessaryto, at least in the conclusion, employ medical terminology that is a moreuniversally understood.A recently published study,4. In the presentstudy, we also evaluated the opinion of referring physicians regarding the way inwhich reports are structured and found that the vast majority of those physicians(67.1%) prefer structured reports to free-text reports, which were preferred by only17.1% of the respondents. Other studies have reported similar findings,7,11.The American College of Radiology and European Society of Radiology both recommendthat radiology reports be structured (divided into ordered sections) and employstandard terminology, in order to improve the way in which the results of aradiological procedure are communicated, as well as that the reports makeinformation easier to recover and reuse-14. The literaturealso demonstrates that, in comparison with free-text reports, structured reports canreduce accuracy and thoroughness. One recent study surveyed radiologists from differentcountries who had gathered for a European congress on radiology. Most of those radiologistsstated that the reports issued at the facilities where they work are alreadystructured to a certain extent, and that the adoption of fully structured reports isimpaired due to the complexity of the task of preparing such reports and the impactthat they would have on the productivity of the facility. That same group ofradiologists demonstrated a clear preference for what could be considered asemistructured report.Various studies have demonstrated that the format of the report has no significantimpact on reading time and comprehension.Describing the radiological technique used in an examination is considered afundamental element of the preparation of a high-quality report. The resultsobtained from our survey revealed that the vast majority (82.9%) of referringphysicians understand that it is important to describe the examination techniques in thereport. Our results are in line with those of other studies, which have also shownthat there is a preference for the technical aspects to be described in areport. Withinthat context, our study investigated whether referring physicians preferred a directconclusion leading to a single diagnosis or multiple plausible diagnoses for aspecific case. The majority (75.7%) preferred that a range of differential diagnosesbe described in the conclusion. Another group (17.1%) also considered the reportingof diverse diagnoses to be a positive thing, provided that the percentage certaintyfor each diagnostic possibility be displayed as well. That is still a rare practicein Brazil. Other studiescorroborate the participant preference for the inclusion of various differentialdiagnoses while also emphasizing the importance of clearly stating the degree ofcertainty for each hypothesis,17, a percentage being the best wayto express that,18. The suggested maximum number of diagnosticpossibilities to be included in a report is three; if there are more than three, theexamination should be repeated.Vague reports with ambiguous wording, in which the radiologist does not takeresponsibility for a diagnosis, are questioned by many referringphysicians,16.There are various situations in which it will be necessary for the radiologist andreferring physician to confer, such as when there is a relevant incidental finding.In our study, we attempted to determine what would be the best way to conduct thatconsultation. The majority (69.6%) of the referring physicians felt that theradiologist should converse with the referring physician directly, either in personor over the telephone. Other studies have also demonstrated that referringphysicians prefer to have a direct line of communication with the radiologist,stating that it is a top priorityOur study has certain limitations. The sample was relatively small, and all of theparticipants worked at the same health care facility in the same city. In addition,we did not perform an epidemiological analysis of the professionals who participated in the study. An analysis of those aspectscould reveal disparities between or among regions, professionals, (in terms of thelevel of experience), and genders.After analyzing the data collected in our study, we concluded that the referringphysician gives considerable weight to the opinion of the radiologist, underscoringthe importance of radiologists in ensuring excellence in medical practice. There isa preference for reports that are structured, are clear, and offer a simplifiedexplanation of the radiologist terminology, as well as containing a description ofthe examination technique employed. The conclusion of the report should receivespecial attention, being that it is oftentimes the first (if not the only) sectionto be read. Various diagnostic possibilities should be laid out by the radiologistand, when possible, should be accompanied by the corresponding degree of certainty.The report presented to the referring physician should contain the final report,together with printed and digital images. Finally, whenever it is necessary forradiologists and the referring physicians to communicate, there should be directcontact between the two.


Cell lines are in vitro model systems that are widely used in different fields of medical research, especially basic cancer research and drug discovery. Their usefulness is primarily linked to their ability to provide an indefinite source of biological material for experimental purposes. Under the right conditions and with appropriate controls, authenticated cancer cell lines retain most of the genetic properties of the cancer of origin. During the last few years, comparing genomic data of most cancer cell lines has corroborated this statement and those that were observed studying the tumoral tissue equivalents included in the The Cancer Genome Atlas (TCGA) database. We are at the disposal of comprehensive open access cell line datasets describing their molecular and cellular alterations at an unprecedented level of accuracy. This aspect, in association with the possibility of setting up accurate culture conditions that mimic the in vivo microenvironment  coculture), has strengthened the importance of cancer cell lines for continuing to sustain medical research fields. However, it is important to consider that the appropriate use of cell lines needs to follow established guidelines for guaranteed data reproducibility and quality, and to prevent the occurrence of detrimental events . Cancer cell lines are valuable in vitro model systems that are widely used in cancer research and drug discovery . Their uThe establishment of a new cell line is a very complex process that is still not well understood. The success rate for the establishment is low and unpredictable for any specimen of origin . This stRecent findings that were obtained by the characterization of hundreds of cell lines with omics technologies  reinforced the concept of cell line usefulness in medical research. Indeed, for the majority of the existing cancer cell lines, these data have been published and made available through online datasets, which made it possible to explore detailed molecular and cellular alterations, such as mutations , copy nuThe history of cancer research and the establishment of continuous cell lines are closely related . DiffereOverall, each new cell line has been necessary, over time, to understand step by step a new feature of cancer disease and to test the efficacy of anticancer drugs . The impHuman cancer cell lines continue to play a critical role in modern cancer research. Indeed, they are widely used as preclinical model systems for gaining mechanistic and therapeutic insight. Notably, with the advent of -omics technologies , recent http://www.broadinstitute.org/ccle. Following this comprehensive approach, an important preliminary result that was obtained by Barretina et al. revealed the possible association between Schlafen family member 11 (SLFN11) gene expression and sensitivity to topoisomerase inhibitors. In the paper by Garnett et al., by performing a similar integration between genomic and pharmacological data, it was possible to disclose the association between the EWS-FLI1 gene translocation, which is frequently found in Ewing’s sarcoma, and sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors, which are a class of drugs currently used in clinical trials for other cancer types. Both resources that were provided by Barretina et al. [http://www.cancerRxgene.org.In 2012 (and for the first time), two independent research groups that were led by Barretina et al.  and Garna et al.  and Garna et al.  are extra et al. . In the a et al. . The samDespite the enthusiasm generated by the aforementioned important works, it is important to consider that cell lines have important limitations, especially due to the differences in terms of gene expression, as compared to in vivo tumor tissues. Specifically, cell lines, when cultured in vitro, do not have interactions with other cell types; additionally, their growth is not under the influence of cytokines and other cell signaling molecules, and the native tissue architecture is lost. Moreover, the effects of in vivo drug distribution and metabolism are not easily matched in vitro . All of Klijn and colleagues  improvedhttps://tcpaportal.org/mclp/#/) for the research community to investigate tumor behaviors in a quantitative and efficient way and to compare the differences in protein expression across cancer cell lines and to in vivo tumor tissues.In parallel to advancements in the knowledge of genetics and transcriptomics of cancer cell lines, The Cancer Genome Atlas (TCGA) database  revealedhttps://depmap.org/portal/achilles/) to identify critical gene functions in 501 cancer cell lines. The authors identified genes whose expression is required for the proliferation or survival of subsets of these cell lines and developed an approach to identify the features that predict these gene dependencies. This cancer dependency map provides an innovative approach for defining and predicting genes that are essential for cell viability, which thereby facilitates the identification of cancer targets.The generation of these extensive datasets highlighted the need for functional assays to identify novel targetable genes. In this sense, it is important to consider the work by Tsherniak A et al.  that is https://portals.broadinstitute.org/ccle), where unbiased association analysis can be performed by linking the cancer metabolome to genetic alterations, epigenetic features, and gene dependencies [More recently, in 2019, data from two research papers added value to knowledge regarding the biology of the cancer cell lines that were included in the CCLE. The first study was published by Li et al. and focused on the metabolic diversity of 928 cancer cell lines derived from 20 cancer types . The autndencies . Overallndencies . Moreovehttps://cellmodelpassports.sanger.ac.uk/) interface developed at the Sanger Institute (UK)) due to the complexity of the newly derived datasets [Finally, wet laboratory researchers should have a friendly interface to explore the data on each cell line;  a list of 360 known cross-contaminated cell lines to address the important problem of cross-contamination. Most contaminants arise within the same species, with HeLa (as reported by Nelson-Rees approximately 40 years ago) still the most frequently encountered  among human cell lines, while interspecies contaminants account for a small, but substantial, minority of cases . In addition to the list of cross-contaminated cell lines, two important practical suggestions are provided: (i) Check the literature by searching the PubMed database while using the cell line name and “cross-contamination”; and (ii) Check the cultured cells; a cell line should be tested on arrival in a new laboratory, and all the cultures should be periodically tested while in use, before cryopreservation, and when thawed from liquid nitrogen [https://iclac.org/) created a website that is dedicated to the authentication of cell lines [https://iclac.org/databases/). The improper use of misidentified human cells can be avoided when carrying out research projects by performing regular checks on the cell lines used, given that these resources are now available to the scientific community.Cape-Davis et al. published  and madenitrogen . In thisnitrogen . An incrll lines . A list Mycoplasma contamination is the second critical issue to be discussed. This problem was first proposed in 1956, when it was discovered as a cell culture contaminant . MycoplaIn conclusion, the main reasons for both cross-contamination and mycoplasma infection are the same, namely, faulty cell culture techniques, inappropriate handling of cell lines, and a lack of knowledge and information regarding the consequences and effects of contaminants. Undoubtedly, according to current guidelines, it is good practice to obtain a cell line of interest from a qualified source, such as international cell line banks ,27,72. TAs discussed in the section dedicated to the history of cancer cell lines, over time, a number of different cell lines have been published in the scientific literature, especially in the 1970s, 1980s, and 1990s, with the aim of providing innovative in vitro model systems for experimental purposes. Recent findings highlight that the derived cell lines maintain most of the genetic alterations of the original in vivo tumor. Conversely, the transcriptomic and proteomic signatures of cell lines in most cases are completely different from their in vivo counterpart ,50. Subshttps://iclac.org/) that were taken to help the scientific community make false or misidentified cell lines more visible and to promote awareness and authentication testing as effective ways to combat the problem, authentication and mycoplasma infection testing are not universally practiced in preclinical research.In research laboratories worldwide, uncountable in vitro assays are performed daily while using cancer cell lines ,2,3,25. The importance of using authenticated and mycoplasma-free cell cultures is related to the fact that cancer cell lines, under the right conditions of use, still maintain most of the cellular and molecular alterations of the original cancer ,15,16,17Prospectively, we believe that cell lines will continue to support the scientific community by helping to obtain important results that can be translated from the laboratory bench to the patient bedside and by improving public health care. As discussed in this article, the growing use of massive sequencing technologies provides a wealth of information for each disease at an unprecedented level of accuracy . In this


Multiple technologies, procedures and programs call for fairly-based decisions for prioritization of healthcare interventions. There is a diversity of perspectives of what constitutes a legitimate decision, which depends on both the process and the reasoning applied. Current approaches focus on technical aspects while methods to support alignment of decisions with the compassionate impetus of healthcare systems is lacking.The framework was developed based on an analysis of the foundations of healthcare systems, the reasoning underlying decisions and fair processes. The concept of reflective multicriteria was created: it assumes that decisionmakers guided by a generic interpretative frame rooted in the compassionate impetus of healthcare systems, can sharpen their reasoning, raise awareness of their motivation and increase legitimacy of decisions. The initial framework was made available through a not for profit organization  to stimulate its development with thought leaders and stakeholders in an open source philosophy. Development was tailored to the real-life needs of decisionmakers and drew on several domains of knowledge including healthcare ethics, evidenced-based medicine, health economics, health technology assessment and multicriteria approaches.The 10th edition framework builds on four dimensions: (1) the universal impetus of healthcare systems, (2) reasoning, values and ethics, (3) evidence and knowledge on interventions, and (4) a transformative process. Mathematical aspects of the framework are designed to help clarify, express and share individual reasoning; this non-conventional use of numbers requires a cultural change and needs to be phased in slowly. The framework includes four tools for easy adaptation and operationalization: (a) concepts and operationalization, (b) adapt and pilot, (c) evidence matrix, (d) mathematical representation of reasoning. Application is useful throughout all types of healthcare interventions, for all levels of decision, and across the globe.By clarifying their reasoning while keeping decisionmakers aware of the impetus of healthcare systems, reflective multicriteria provides an effective approach to increase the legitimacy of decisions. Beyond a tool, reflective multicriteria pioneered by EVIDEM is geared to transform our vision of the value of healthcare interventions and how they might contribute to relevant, equitable and sustainable healthcare systems.The online version of this article (10.1186/s12962-018-0116-9) contains supplementary material, which is available to authorized users. Since the establishment of the first universal healthcare systems about 50 years ago, a number of domains of research and applications have emerged to operationalized the impetus which led to their creation. This compassionate impetus stemmed from providing care and alleviating suffering at the population level, thereby expanding the compassionate impetus which takes place at the individual level during a patient-healthcare practitioner encounter. Operationalization of such a noble cause meant providing the most relevant care at the individual and at the population level, and in a sustainable manner.The exponential increase of healthcare technologies, procedures and programs resulted in many benefits but the concomitant steep increase in costs have challenged the foundation of healthcare systems, calling for fairly-based decisions and prioritization of healthcare interventions. The WHO  recentlyBoth evidenced-based medicine, developed to ensure best choices at individual level, and health economics, developed to inform allocation of resources at the population level, and the associated cost-effectiveness paradigm, have contributed to the quest for legitimacy. Health technology assessment (HTA), developed to ensure best choices in a given society, was an important step in this quest , with a Healthcare ethics have built on theories established over the centuries to support legitimacy of decisions. Two decades ago, Daniels and Sabin  proposedMulticriteria decision analysis (MCDA) has emerged as a possible approach to further the quest for legitimacy in healthcare decisions , 10. MCDThe framework was developed based on an analysis of the foundation of healthcare systems, the reasoning underlying decisions and fair processes. It is assumed that legitimacy of decisions depends on consideration of such foundations, on a fairly-based reasoning , and on a fairly-based process .The foundation of healthcare systems is the compassionate impetus to achieve health for all. This can be expressed into three general ethical imperatives (normative aspects): (1) prevent/alleviate suffering in individual patients with relevant healthcare interventions, (2) prioritize those who are worst off while providing the greatest benefit for the greatest number, and (3) ensuring long term sustainability of healthcare systems; combined with the wisdom to make decisions adapted to the context (feasibility aspect). These aspects include elements of key ethical theories and positions such as deontology, distributive justice, utilitarianism and virtue ethics .At the individual level, the reasoning underlying a decision includes: (1) the general motivation of the individual, (2) the reflection on the criteria considered and the evidence  for each criteria for the intervention appraised, and (3) the conclusion of this reflection which represents the balancing act of one’s individual perspective and interpretation in regard of the healthcare system impetus. A fairly-based reasoning presupposes some alignment of the individual motivation with the compassionate impetus of healthcare systems.Institutional decisions require processes that support legitimacy. The A4R framework of Daniels and Sabin  proposesTo support legitimate decisions, the framework therefore needs to derive criteria from the impetus of healthcare systems, to structure the reasoning in all its aspects and requires a process derived from the principles of A4R. The concept of reflective multicriteria was created based on this analyses: it assumes that decisionmakers, when guided through a fair process by a generic interpretative frame rooted in the compassionate impetus of healthcare systems, can sharpen their reasoning, raise awareness of their motivation and increase legitimacy of decisions. An initial framework was thus designed as part of a research grant .The initial framework was then made available through a not for profit organization with free membership (the EVIDEM Collaboration) to stimulate its development for over 10 years (2006–2017). Development was tailored to the real-life needs of decisionmakers (bottom-up approach) and drew on several domains of knowledge including decision ethics, evidenced-based medicine, health economics, health technology assessment and multicriteria approaches. Below are examples of lines of reflection derived, through an open source philosophy, from academic and experiential knowledge of thought leaders and stakeholders for more than 40 countries who joined the membership.Reflection:If we attempt to derived criteria to operationalize this impetus using a single traditional ethical theory in healthcare , we will miss aspects of other traditional ethical theories , which are directly related to the compassionate impetus of healthcare systems and that are considered in real-life decisions to tackle ethical dilemmasApproach selected:Criteria are derived from the compassionate impetus of healthcare systems in a generic manner, and thereby incorporate aspects of major traditional ethical theories; each criteria is justified by at least one aspect of a traditional ethical theory. Ethical dilemmas are tackled by reminding decisionmakers of the ethical aspect underlying each criteria, and whether the intervention (or group of interventions) considered contributes to more relevance, more equity, more sustainability and is adapted to the context .The framework needs to be rooted in the compassionate impetus of healthcare systems so its basis is acceptable from a universal standpoint; resolution of ethical dilemmas that arise more and more often is then guided by the fulfillment of this impetus.Reflection:If we attempt to perform a value measurement based on all aspects except cost , it will not address the sustainability imperative. Similarly, the concept of cost-effectiveness considers cost as an element distinct of the value of an intervention.Approach selected:The value measurement integrate economic aspects ; if possible, cost effectiveness is omitted as a criteria as it is a composite measure combining data from several generic criteria ; this combination does not facilitate interpretation of concepts, and tends to create double counting and confused reasoning.For an application at the system level, the framework needs to prioritize (rank) interventions based on their fulfillment of the compassionate impetus of health care system , including financial sustainability; current approaches prescribe cost and effectiveness as opposed concepts rather than contributing both to the value of an intervention.Reflection:If, to assess the performance of interventions on each criteria, we use computed scoring scales as recommended in traditional MCDA , the framework will not address the fact that “interpretation of data that takes place during appraisals requires judgement” .Approach selected:Interpretative scoring scales were designed to capture the interpretation of numbers (rather than transforming numbers into other numbers); this is a non-conventional use of numbers since in this case numbers represent a judgment. Thus, if, for a given criteria, it can be agreed by users what constitutes low and high end of such a scale, then this criterion may be considered quantitatively; if not, quantitative scoring should not be performed, and solely qualitative considerations should be reported in the multicriteria grid.To facilitate sharing of reasoning among committee members and stakeholders, the framework needs to capture interpretation of evidence and associated inherent judgment that takes place on the spot in real-life deliberation.Reflection:If we attempt to have only a few criteria to keep the framework simple, it will not address the point that many criteria will anyway be considered during the deliberation leading to the decision. In addition, fulfilling the compassionate impetus of healthcare systems requires a comprehensive set of criteria encompassing the various aspects of legitimacy in a given context.Approach selected:The high level value system derived from the compassionate impetus can be structured into a set of generic criteria  to provide an overarching generic interpretative frame ; such generic frame can however be further specified with sub-criteria . The generic interpretive frame should not constrain reasoning but rather clarifies individual reasoning in the context of the compassionate impetus of healthcare systems. It needs to encompass a comprehensive set of criteria derived from this impetus. Difficulties in operationalization of a criteria  should not be a reason for not including it in a generic framework. Indeed, it is likely that it will be considered anyway during the deliberation and a comprehensive set of criteria is key in legitimate decisions. Finally, criteria need to be defined bearing in mind the multicriteria principles of non-redundancy, independence, operationalizability and completeness.The framework cannot be reductionist but it has to be pragmatic with regard to the number of criteria, and these criteria have to be legitimate in regards to the compassionate impetus of healthcare systems.Reflection:If we use traditional approaches focusing on preferences, we will not develop a reflection of what can be done collectively to develop interventions that are contributing to the compassionate impetus of healthcare systems.Approach selected:To raise awareness of the compassionate impetus of healthcare systems, the framework elicits, through direct weighting methods, the value system of an individual (or of a group) rather than preferences. The weights are thus independent of a given healthcare intervention. In this non-conventional approach, the trade-off between the criteria is the trade-off between the underlying ethical imperative of each criteria (e.g. equity). When aware of the ethical imperatives underlying each criteria, direct weighting techniques become values elicitation technique stimulating deeper reflection on individual value systems  Weighting therefore becomes a key element to the ‘reflective” approach, which only direct weighting methods can support (indirect weighting methods are not geared to stimulate reflection).Traditional weight elicitation techniques in MCDA are geared to elicit preferences of individuals, independently of the compassionate impetus of healthcare systems. Individuals making a decision with the compassionate impetus of healthcare systems in mind need to identify their individual value systems in this regard. This value system is therefore related to this impetus rather than to the specificities of the intervention assessed. Weighting should therefore be one independently of the interventions being assessed.Over the years, numerous lines of reflection have been made using this methodological frame of reflection, discussing with researchers and users in the organic manner that open source philosophy relies on.The framework is designed to support fair reasoning and deliberation to increase legitimacy of decisions. This is done by guiding decisionmakers through a fair process, using a generic interpretive frame rooted in the compassionate impetus of healthcare systems. Such frame, by providing a common road map is geared to facilitate communication across policy committee members, patients and physicians, and healthcare stakeholders at large.The framework builds on four dimensions described below: (i) Universal impetus of healthcare systems, (ii) Reasoning, values and ethics, (iii) Evidence and knowledge on interventions, and (iv) Transformative process over time. It includes four tools for easy adaptation and operationalization: (a) concepts and operationalization . However, to facilitate its understanding, its visual representation reflects the standard steps in MCDA   [(1) goaAlleviate/prevent suffering of patients .Prioritize those who are worst off while ensuring greatest good for greatest number .Ensure sustainability .Three ethical imperatives (normative aspects):Contextual imperatives (feasibility aspect), defined as the wisdom of making decisions informed by knowledge and adapted to context .To ensure that the universal compassionate impetus of healthcare systems  remains at the core of decisions, the framework includes generic criteria directly derived from this impetus. “Generic” is used in the sense of being applicable to all interventions, types of decision and region. Four universal aspects related to this impetus and 20 criteria, derived from informal and formal consultation and research , 16 are Concepts and definitions which provides a rationale on each aspect of the framework and a guidance for adaptation  combined with a narrative and face validity exercise to confirm that the weights reflect the value system of the individual  for each criterion for the intervention appraised? Evidence is made available for each criterion using instructions described in the Tool Evidence matrix, Additional file The individual reflection on:The conclusion of this individual reflection: the balancing act of these considerations is facilitated by the interpretive grid, which serves as a reminder us of the underlying ethical imperative associated with each criterion .Criteria are organized in an operationalizable framework, designed to structure and clarify individual reasoning in all its aspects:As illustrated in Fig. The way evidence and knowledge on interventions is conveyed to the decisionmaker has a critical impact on the decision. Therefore, detailed instructions based on good HTA practices  adapted The framework is designed to promote a fair process by stimulating reflection and deliberation, fostering transparency and clarity, ensure accountability and relevance of decisions while facilitating communication, participation and collaboration as well as appeal and revision. It is geared to generates a transformation of current processes into processes that are more aligned with the principles of the A4R.Individual reasoning made explicit through the interpretive grid of the framework becomes shareable into a group deliberation; each aspect of the grid is enriched by insights and reflection from other members of the group, transforming the individual perspective into a rich exchange though a deliberation leading to an equilibrium on which the group decision is based. Decisions made through such a process, with a constant reminder of the compassionate impetus, in a committee composed of members that represent the diverse perspective at stake, provides a good basis for legitimate decisions.The framework implementation is meant to be phased in carefully depending on the culture of the institution and the region in which it is to be established . Of note, although mathematical aspects of the framework are designed to help clarify, express and share individual reasoning, this non-conventional use of numbers requires a cultural change and needs to be phased in slowly.In a first step, the framework can be applied in a qualitative mode that uses the interpretive frame (multicriteria grid) to capture individual interpretations for each criterion in a narrative form  reflect its objective: support decision making, and the associated reasoning which requires consideration of evidence and values. The stylized V of the Logo Fig.  represenApplication is useful throughout all types of healthcare interventions, for all levels of decision, and across the globe. By design, the framework facilitates interpretations of any decision-making situation, both at the individual and a t the group level. This resulted in a variety of applications including coverage decisions , but also for benefit-risk evaluations, shared decision-making, clinical research question prioritization, design of clinical trials. Applications are ongoing in several countries, most of these are not public domain. A few applications of EVIDEM have been published , 20–27.For example, in Italy, the Lombardy Health Directorate developed a reflective multicriteria approach combined with the EUnetHTA core model to appraise health technologies; this has been in place to make coverage decisions since 2012 . The reaIn Colombia, the Ministry of Health and Social Protection, carried out a consultation to adapt EVIDEM criteria to the Colombian context, as part of its exploration of methodologies for coverage decisions. In this pilot, criteria weights were elicited through participation of more than 200 stakeholders including experts and citizens . A pilotRecently, the EVIDEM framework was adapted to build the list of priority devices for cancer care published in 2017 by the WHO. It was used as a mean to collect experiential knowledge from a diversity of experts around the world and to support the reflection leading to the inclusion/exclusion from the list of priority devices. The generic tools developed for this application were also designed to be directly usable, with some contextual adaptation, by members states to make fair decisions regarding medical devices .In 2017, to celebrate its 10 years of success and to facilitate its widespread use, the EVIDEM Collaboration resolved to make freely available the 10th edition of the EVIDEM Framework, with no legal binding. This represented the dissolution of the legal entity, the not-for-for profit EVIDEM Collaboration. This important step led to the transformation of the network of active members into an open international community who shares an interest in reflective multicriteria approaches.As mentioned by the Canadian Minister of Health Jane Philpott, Parliament Sept. 29, 2016, Canada and societies all over the world “need to find ways to put healthcare on the road to long-term sustainability”. EVIDEM is proposed as a common generic road map to collectively achieve health for all Fig. .Fig. 3A One can wonder what would happen if all levels of decisions were reminded to reflect on the compassionate impetus of healthcare systems and implement decision frameworks that remind them of it in their very design? If researchers and developers had in mind the constraints of HC systems to make their decision to develop? Regulators thinking not only of their remit but also encompassing the concept of sustainability that policymakers must consider? What would be our healthcare systems if all levels of decision had a clear idea of what patients need and how clinicians can best help them prevent and alleviate their suffering? Collectively, we can transform or establish more meaningful healthcare systems, with a vision that reflective multicriteria can help clarify in a diversity of contexts.A paradigm change is mandatory to adapt healthcare systems to the twenty first century. Reflective multicriteria rooted in the objectives of universal healthcare systems opens the door to a deeper reflection and proposes a fair process to increase legitimacy, accountability and reasonableness of decisions . ReasonaBy clarifying their reasoning while keeping decisionmakers aware of the compassionate impetus of healthcare systems, reflective multicriteria provides an effective approach to increase the legitimacy of decisions at all the levels. Beyond a tool, reflective multicriteria pioneered by EVIDEM is geared to transform our vision of the value of healthcare interventions and how they might contribute to relevant, equitable and sustainable healthcare systems. It is hoped that reflective multicriteria will continue contributing to the movement “en marche” which is transforming current approaches focused on technical aspects into holistic approaches rooted in the ethical frames underpinning social desirability . To paraAdditional file 1. Concepts and definitions with detailed rationale on each aspect of the framework and guidance for their adaptation and implementation.Additional file 2. Adapt and pilot. A step by step directly applicable manual to adapt and pilot the framework in context.Additional file 3. Evidence matrix, Detailed instructions based on HTA principles to research, synthesize and report evidence for each criterion; instruments to assess quality of evidence.Additional file 4. Data analysis and presentation; Excel calculator to facilitate compilation of data and narratives, perform calculation for quantitative approaches and combine them in visual representation to clarify reasoning.


Background: The maldistribution of licensed doctors is one of the major challenges faced by the Chinese health sector. However, this subject remains underexplored, as the underlying causes of licensed doctor distribution have not been fully mapped out. To fill the research void, this study theoretically modeled and empirically measured various determinants of licensed doctor distribution from both the supply and demand sides while taking the spillover effect between the adjacent geographical units into consideration. Methods: The theory of demand and supply is adopted to construct a research framework so as to explain the imbalance in the licensed doctor distribution. Both direct effects and spillover effects of the supply-side factors and demand-side factors are empirically measured with the spatial panel econometric models. Results: The health service demand was found, as expected, to be the major driving force of the licensed doctor distribution across the nation. That is, the increase in health services demands in a province could significantly help one unit attract licensed doctors from adjacent units. Unexpectedly but intriguingly, the medical education capacity showed a relatively limited effect on increasing the licensed doctor density in local units compared with its spillover effect on neighboring units. In addition, government and social health expenditures played different roles in the health labor market, the former being more effective in increasing the stock of clinicians and public health doctors, the latter doing better in attracting dentists and general practitioners. Conclusions: The results provide directions for Chinese policy makers to formulate more effective policies, including a series of measures to boost the licensed doctor stock in disadvantaged areas, such as the increase of government or social health expenditures, more quotas for medical universities, and the prevention of a brain drain of licensed doctors. Health manpower maldistribution has long been a major challenge faced by the health sectors around the globe, with most health workers concentrated in the developed areas ,2. This What factors may contribute to regional differences in the health manpower distribution? Many studies have tried to study health manpower maldistribution from an individual perspective . For exaAs an important part of the labor market, the distribution of health manpower is not only a function of health workers’ self-determination but also a “product” of macro-regional factors. At the macro-regional level, there is no widely used model for understanding the health manpower availability in a certain area. Scholz, Graf von der Schulenburg, and Greiner  found siIt is evident that why regional disparities exist in the distribution of health manpower is largely unanswered by existing studies. More studies are needed to explore the determinants of the health manpower distribution. To fill the research void, this study aims to model and measure the determinants of the licensed doctor distribution in China based on the theory of supply and demand. The research findings will serve as a basis for balancing the licensed doctor distribution in China. Licensed doctors are the most important component of health manpower in China due to their direct, significant role in healthcare delivery. In China, licensed doctors are referring to doctors with the certificate of (assistant) medical practitioner who are engaged in medical practice, exclusive of those in managerial positions . They caThis study represents one of the first attempts to interpret the licensed doctor distribution with supply and demand theory. The supply and demand theory has been widely employed to elucidate the dynamics of the labor market but has rarely been applied to the health field ,15. ThisThis study follows the strategy proposed by Zhu et al. to explore the determinants of the licensed doctor distribution based on the theory of supply and demand . The theOn the demand side, the population’s medical needs provide the fundamental impetus to hire licensed doctors. If there are no medical needs, licensed doctors would have no value . HoweverHypothesis 1.The health services demand in one provincial unit is related to the licensed doctor stock in the same provincial unit.In an ideal market, the licensed doctor stock is totally driven by the demand side, as there is no imbalance between supply and demand. In reality, the licensed doctor supply has normally failed to keep up with rising demand. Owing to the relatively undeveloped education system and growing medical needs, we reasonably believe that the licensed doctor availability in China is restricted, even to a large degree, by the supply side . The supAs the first stage, the education system serves as a pipeline from inexperienced students to skillful licensed doctors. Given that licensed doctors need to acquire professional job-related skills in order to provide quality services, medical education plays a crucial role in the supply of licensed doctors. More concretely, the education capacity determines the size of the pool of potential licensed doctors. Thus, this study hypothesizes that there is a positive relationship between the education capacity and licensed doctor stock as follows:Hypothesis 2.Education capacity in one provincial unit is related to the licensed doctor stock in the same unit.Next, following the graduation of medical students, the recruitment of licensed doctors relies on the attraction and retention of health facilities. In China, medical institutions are classified into two groups, public health institutions (not-for-profit) and private health institutions (for-profit). In public health institutions, the number of employees is mainly determined by the budget allocated, as a significant portion of government health expenditures are assigned to health workers . TherefoHypothesis 3.Government health investment in one provincial unit is related to the licensed doctor stock in the same unit.In private health institutions, licensed doctor enrollment is mainly determined by the investment of social capital. As far as province units are concerned, greater social health investment indicates an influx of more licensed doctors, as it brings more employment opportunities in private health facilities in its train. In addition, the competition of public and private hospitals tends to offer better working conditions, thus attracting more licensed doctors working in the area. Therefore, this study proposes the following hypothesis about the relationship between the social health investment and the licensed doctor stock:Hypothesis 4.Social health investment in one provincial unit is related to the licensed doctor stock in the same unit.In addition to the intra-regional factors, it is important to note that the spillover effects (the effects of within-province factors on adjacent provinces ) cannot Therefore, the licensed doctor stock in one provincial unit calls for explanation not only by the supply-side factors and demand-side factors in the local unit but also through its interactions with other provincial units. The stronger the supply-side and demand-side factors are in one area, the more likely licensed doctors in other areas are affected, and vice versa. For instance, if the government health investment in one unit is higher than in other units, licensed doctors from adjacent units are more likely to be attracted to it. Therefore, this study suggests the following hypothesis:Hypothesis 5.The health service demand, education capacity, government, and social health investment in one provincial unit are related to the licensed doctor stock in adjacent units.This study uses the licensed doctor density as the dependent variable. It is defined as the ratio of licensed doctor quantity to population size and conventionally calculated as the total licensed doctors per 1000 population (Formula (1)). It is widely used in the World Health Organization (WHO) reports, government statistical files, and academic research to evaluate the performance of a health system ,24,25,26Health services are defined as a certain quantity or a combination of different services, such as diagnosis, observation, treatment, and intervention services, that are delivered by health institutions . Health Medical schools serve health institutions by pipelining trained medical graduates into the health manpower pool. Even though the number of medical graduates does not fully represent the medical education capacity in one unit, it directly determines the number of potential health workers. The more students the medical education system trains, the larger the potential labor force for the health industry. To maintain consistency with the dependent variable, this study adopts the medical graduate density, i.e., the ratio of the number of medical graduates to the population size, to represent the education capacity in a unit.In the Chinese context, the health expenditure is divided into three parts: Government, social, and personal health expenditure. Government and social health expenditure correspond exactly to the government and social health investment. The government health expenditure represents the investment in the health care industry by all branches of governments, while the social health expenditure refers to the investment in the health care industry by all sectors of society other than the government . LikewisA summary of all the variables and their codes and descriptions is shown in This study uses the provincial level year-end data in China from the period 2012−2016. This study is based on the following model (Formula (2)) derived from the theoretical model in i represents 31 province units  and t denotes time t . The subscript As the spillover effects of within-province factors on other units should be considered, the traditional regression models fail to measure the spillover effects between adjacent geographical units. This study, therefore, adopts the spatial panel econometric models so as to produce a more accurate estimation of model coefficients and spillover effects . Spatialx in the geographical unit i on the health manpower density in the geographical unit i, averaged across all the geographical units. In comparison, the spillover effects (indirect effects) refer to the influence of a unit change in the independent variable x in all the geographical units excluding unit i on the health manpower density in the geographical unit i, averaged across all the geographical units. The total effects equal the sum of the average direct and average spillover effects and measure the impact of a unit change in the independent variable x in all the units on health manpower density in the geographical unit i, again averaged across all the geographical units [SLPM (Formula (A1) in al units .The procedures for the specification of spatial panel econometric models are shown in n does not equal T compared with the two-way fixed model. More specifically, a model with spatial fixed effects for short panels (n > T) and a model with time fixed effects for long panels (n < T). Furthermore, the choice between models with fixed and random effects should be made based on the Hausman test [In the first phase, the SDPM can be divided into a model with spatial-fixed effects , a model with time fixed effects , a model with spatial and time fixed effects (controlling the above two), and a random effects model based on different assumptions . Accordiman test .0: 0: θ = −θ = 0 and θ + β = 0 are both rejected, the most fit one would be SDPM [In the second phase, the Wald test  is employed to constitute the spatial weight matrix. The spatial panel econometric models are computed with the STATA 12.0  n > T). Therefore, the Hausman test was conducted to make a choice between the SDPM with fixed effects and the random effect model. After the Hausman test, the LR and Wald tests were conducted successively to determine whether the SDPM model could be simplified. After this step, the best model was obtained. The empirical results of the spatial panel econometric models for different subtypes of licensed doctors can be found in Following the procedures specified in the methodology section , this stThe best spatial panel econometric models for different subtypes of licensed doctors are listed in After all the best models were identified, the relationship between dependent variables and independent variables  were clear at a glance. However, the coefficients of variables in SDPM could not be explained directly as the effects of percentage variation in independent variables on dependent variables thanks to the unique characteristics of spatial panel econometric models, which have been mentioned in the methodology section. Thus, we decomposed the effects of the independent variables on the dependent variables into direct, spillover, and total effects based on the selected best models.Regarding the inpatient visits per capita, the estimated results showed a significant relationship between the inpatient visits per capita and the densities of clinicians, public health doctors and general practitioners, which were significant at the 0.01 significance level. A 1% increase in the inpatient visits per capita led to a 0.256% increase in the density of clinicians, 0.344% in public health doctor density and 0.703% in general practitioner density in the same unit.The government and social health expenditure per capita had both similarities and differences in driving the densities of subtypes of licensed doctors. They were both significantly related to the TCM doctor density and general practitioner density. A 1% increase in government health expenditure in the local unit could lead to a 0.139%  increase in the TCM doctor density in the same unit. In contrast, a 1% increase of government and social health expenditure per capita in the local unit could respectively result in a 0.302% and 0.425% increase in the general practitioner density in the same unit. The government health expenditure also affected the clinician density (a 1% increase in expenditure corresponds to a 0.085% increase in the clinician density) and public health doctor density . By comparison, a 1% increase in social expenditure per capita was also related to a 0.210% increase in the dentist density in one unit. As for the medical graduate density, only the density of clinicians was significantly correlated with the medical graduate density at the 0.1 significance level.As shown on the right side of This study considered the medical graduate density an important independent variable and then observed a significant relationship between it and the density of clinician density in the same unit. Intriguingly, the medical education capacity had relatively strong spillover effects on adjacent units compared to its direct effects. The results confirmed the positive and significant spillover effects of the medical education capacity on the densities of clinicians and dentists.In addition, the government and social health expenditure played different roles in the health labor market. As for the direct effects, different subtypes of licensed doctors showed different sensitivities to government and social health expenditure. First, government and social health expenditure per capita in one unit were both potent predictors of the density of the TCM doctor density, and GP density. These practitioners provide health services directly and thus by their nature are a major concern of the government and target of social health expenditure. Second, some subtypes of health technicians were sensitive to the investment of only one type of health expenditure. That is, the densities of clinicians, public health doctors were only sensitive to government health expenditure, while the densities of dentists were only significantly related to the social health expenditure per capita. Regarding the spillover effects, the social health expenditure in one unit exerted much more pronounced spillover effects on adjacent units than the government health expenditure. An increase of the government health expenditure per capita in one unit only served to increase the density of TCM doctors in the adjacent units, but the increase of the social health expenditure per capita in one unit was associated with increases in the densities of TCM doctors and dentists in the adjacent units. This indicates that the social health expenditure investment in one unit could also benefit its neighbors more through spillover effects.On the basis of a five-year (2012–2016) panel dataset, this study empirically measured the determinants of densities of different subtypes of licensed doctors in China. The supply-side factors, demand-side factors, and spillovers jointly drive how licensed doctors are distributed. In general, the direct and spillover effects of all the independent variables achieved statistical significance for at least one subtype of licensed doctor, which confirms the rationality and validity of the theoretical model, while the coefficients for the effects of the independent variables on the densities of different subtypes of licensed doctors varied greatly.On the demand side, the health service demand forcefully drove the licensed doctor density at the provincial level, while the outpatient and inpatient health service demand exerted relatively different influences, which also differed across subtypes of licensed doctors. Based on the empirical results of spatial panel econometric models, the densities of almost all the subtypes of licensed doctors were significantly related to the outpatient health service demand in the same units. It is not surprising that this study failed to find a significant relationship between inpatient health services per capita and the density of TCM doctors, which can be attributed to the relatively weak role of TCM doctors in inpatient services. That is, TCM doctors usually adopt non-surgical treatment methods, like herbal medicine, acupuncture, massage, and dietary therapy, for which patients do not need to stay in health institutions overnight. In addition, neither the outpatient nor inpatient health service demand is significantly correlated with the dentist density. This may result from the undifferentiated measurement of the health services demand. Due to data availability, this study only adopted total health service visits per capita rather than oral care service visits to predict the dentist density. However, dentists only provide a small proportion of health services and serve a smaller number of patients .With regard to spillover effects, the uneven health service demand indicated in the results is likely to induce a brain drain of licensed doctors by siphoning off the health talents of surrounding regions. However, only the density of clinicians was significantly related to the outpatient and inpatient health service demand in adjacent units. This may also be attributed to the direct role of clinicians in the outpatient and inpatient service delivery. What outpatient and inpatient services have in common is that they directly connect patients and licensed doctors. The more important a subtype of licensed doctors is in the health service delivery, the more likely this subtype of licensed doctors is to be attracted to a high-demand area. Accordingly, only the attraction and enrollment of clinicians can help meet the health service demands in local units more efficiently.These findings suggest that the government should take health service demand into the consideration of licensed doctor planning. At present, China only uses the licensed doctor density to determine manpower requirements and fails to consider the wide local variations in health service demand. More specifically, extreme health service demand differences could be observed at the provincial level . As validated by the results, the supply and demand theory works well in exploring the behaviors of licensed doctors at the macro level. Besides, the health service demand, medical education, and social health investment in one unit could significantly influence the licensed doctor stock in adjacent units. This study therefore provides a theoretical framework to understand the licensed doctor distribution, flow and brain drain between different regions in China and highlights an important research direction for further in-depth studies. The results provide evidence for Chinese policy makers to formulate more effective policies, including a series of measures for balancing the licensed doctor distribution in China: First, this study highlights that the health sector should proactively allocate licensed doctors through the health service demand. The low licensed doctor density in some units may result from the population’s inability to meet their medical needs. In those disadvantaged units, the government is supposed to take a stronger role to meet more of the population’s needs and strengthen the financial protection they have to avoid people falling into poverty because of illnesses. The more people’s needs are satisfied, the more power health institutions can obtain to attract and recruit licensed doctors. Second, due to the significant supporting role of medical education in neighboring regions, coordinated actions across borders are suggested for remote units to improve their medical education capacity together. The education sector is suggested to increase quotas for medical universities located in disadvantaged units. It is also the duty of the education sector to plan ahead to match medical student skills with the subtypes of licensed doctors in most need. Third, there is no doubt that the financial sector should keep prompting the influx of the government and private capital into the health labor market. The inflow of non-government capital to support proprietary hospitals also requires partnership between the public and private sectors. That is, the government can give social entrepreneurs tax exemptions or take other measures to encourage building proprietary hospitals while enlarging the recruitment pool of healthcare workers. More importantly, the different focuses of government and social capital make it possible to adjust the densities of certain subtypes of licensed doctors.