The design of green infrastructure in urban renewal sites is complex, requiring engagement with existing communities and future sustainable development goals, consideration of existing and future urban forms, changing climatic conditions, and the sites often being in low-lying and flood-prone areas. Traditional street tree decision-making approaches are inadequate for addressing the scale, environmental complexity, and mutability of decisions involved in urban renewal projects—new tree selection approaches that consider complex competing criteria for tree selections addressing stormwater management systems, visual assessment and solar amenity are needed. This paper describes a new method of multi-criteria street design decision modelling that combines outputs from hydrology modelling, digital procedural tree modelling and urban form analysis, with animation and gaming technologies. We evaluate our approach through application to the design of a large-scale, urban renewal project underway in Melbourne, Australia. The results of the study demonstrate the functionality of our model, which allowed the simultaneous output of streetscape visualisation, with tree selection responding to integrated stormwater management infrastructure and flooding, along with the likely overshadowing conditions of urban renewal built-form. Our multi-criteria approach makes a significant contribution to the tools available to urban designers, planners and landscape architects in their pursuit of smarter streetscape design decisions that respond to complex spatial, cultural and climatic urban challenges. Urban form, commonly referred to as urban morphology, or the urban ensemble, is a result of interactions between past planning decisions, building, infrastructure, road networks, and existing conditions ,2,3,4, rThese contemporary concerns and goals are diverse, and complex, ranging from reduction of urban heat, reduction of stormwater flooding, reduction of arable land development and reduction of car dependence. Often, to meet these goals, urban renewal projects, which repurpose or ‘renew’ ex-industrial greyfield sites close to central business districts for high-density housing, are proposed. To successfully meet these goals, urban renewal projects require substantial departures from traditional, past urban norms ,14,15,16The design and planning of sustainable urban renewal is challenging . InteracStrategic selection, placement and spacing of street trees can support urban climatic performance in aspects such as heat moderation and storm water control, and support sustainable development goals by increasing the thermal comfort and visual attractiveness of streets for active transport ,28,29. UTo address this challenge, we developed a visual-functional street tree-decision support approach and evaluated it through application to an urban renewal proposal test case in Melbourne, Australia. The approach builds on a previous tree decision-support model by the authors that integrates tree visual and shade performance. This enhanced model adds two new environmental performance criteria, a protection from winter over-shadowing component and a stormwater control measures component.In this paper, we provide a brief background and limitations of current tree decisions and modelling methods for Storm Water Control Measures (SCM) , seasonaUrban renewal projects are often located on flood-prone land close to waterways at the base of hydrological catchments, as proximity to water was a critical consideration for their past, often industrial, land use. The existing drainage infrastructure is often inadequate for servicing higher residential densities and the greater intensity rainfall events associated with climate change ,38,39. GModelling and mapping can be used to visualise the likely extent of flood events in existing urban form for LSIO overlays. While modelling of the extent of stormwater flooding for existing conditions is complex as both the overland flow and the underground pit and pipe system must be considered, modelling the impact of SCM design options considering future urban form proposals is exponentially more so ,45,46,47Recently, the outputs of SCM design models have been coupled with models for quantifying the impact of different tree type seasonal variation (evergreen or deciduous) and percentages of canopy cover, the most notable of these being the Urban Multiscale Environment Predictor (UMEP)  and the Though SCM-focused street tree-decision modelling may strongly suggest elimination of deciduous trees in favour of evergreen trees, this choice would exacerbate temperate climate, higher density urban development problems of deep winter overshadowing  and woulDepending on urban canyon geometry (street width to building height ratio) and street orientation, higher density developments in temperate climates can have hot, solar-exposed streets in summer when sun angles are high, and gloomy overshadowed solar-deprived streets in winter when sun angles are low see , making One of the most substantial barriers to understanding the future light conditions of urban renewal projects is that size and height regulations for buildings are often specified in a written  planning guideline format. These regulations are also often driven by considerations such as historic norms, market forces, street activation requirements and density targets rather than environmental performance .These written regulations are difficult to include in models run for other purposes such as ecosystem service calculation, and thus most environmental modelling methods, developed to quantify the interactions between sunlight, urban tree canopies and built form , focus oRecent attempts to couple tree impact calculation with proposed urban form scenarios, including the thermal comfort mapping approach by Coccolo et al. , the iTrWhile there are emerging modelling approaches capable of improving environmentally responsive tree decision-making, there are still problems with their adoption and implementation . Each mofirmitas, utilitas, et venustas’ or ‘firmness, commodity and delight’ in De architectura, referred to as The Ten Books on Architecture, have long been core measures of successful design and placemaking ..88].3D tree simulation is an area of research for many disciplines from the gaming industry, defence, hydrology catchment management to agroforestry ,90. WhilIn recent work, we combined these 3D high polygon tree models within a precinct model, to develop a performance-based visual-functional street design approach ,90. ThatIntegrate and assess existing and proposed urban form (building massing) for shadow and visualisation;Integrate different proposed approaches to storm water control measure (SCM) modelling and subsequent flood inundation implications;Link flood inundation area maps with appropriate tree species choices for projected flood conditions (flood tolerant or non-flood tolerant species for in-flood and not-in-flood conditions);Calculate shadow projections for different times of day and different days of the year;Link projected shadow maps of built urban form with appropriate tree species choices for projected shadow conditions to maximise tree-shade in summer and minimise tree-shade in winter (evergreen or deciduous for in-shade and not-in-shade conditions);Provide rapid visualisation of light levels of streetscape designs;Provide rapid visualisation of streetscape condition-responsive street tree designs with 3D trees for visual aesthetic consideration.Selecting trees to address the criteria of SCM, summer thermal comfort and winter light access, all while offering minimal disruption to aesthetic principles in higher density urban renewal projects, is a challenging problem that requires balance and compromise. Development of performance-based design approaches that intersect traditional visualisation with ecosystem service calculation and spatially explicit decision analysis is critical ,93. To oOur aim was to develop and test a green infrastructure and urban-renewal simulation for street tree decision-making that moderates between the demands for stormwater management, sunlight and aesthetics.The method for this study builds on the Spatio-temporal Design Decision Support System approach by White and Langenheim, expanding their previous model for assessing solar exposure in existing built form conditions for both visual analysis and tree shade quantification ,90.The model employs the functionality of gaming and animation industry software (Autodesk 3dsMax™) with a solar metric sun-system and advanced processing of three-dimensional polygon-dense ‘proxy object’ three-dimensional trees  to simulate large scenes such as forests).(1)Spatializing built form planning controls as an accurate 3D (precinct) model.(2)Utilizing the solar metric sun system within the precinct model to assess both summer solar exposure and winter overshadowing of streets (proposed and retained built form only), output as conditions or ‘presence’ maps.(3)Integration of flood modelling output as ‘presence of’/‘absence of’ conditions maps.(4)Selection of indicative tree species suitable for intersections of conditions or co-conditions .(5)Use of 3D high polygon visually accurate tree models to represent the above species selection in the precinct model, with their occurrence in the model controlled by the ‘presence of’/‘absence of’ conditions or co-conditions maps.This model comprises five components:This same model can be used to generate shade maps that are ‘rendered out’, using a texture baking technique that captures shadows on a surface . These sFlood scenario 01: ‘Land subject to inundation’, and Flood scenario 02: ‘Road-based integrated water management’.To test the effectiveness, we have applied our approach on a test case in inner Melbourne, Australia. We chose a complex major urban renewal project with distinct flooding as well as micro-climatic challenges of heat in summer and cold in winter. To test the flexibility of our approach, we considered two different proposals for SCM that have been under consideration by the local government—The overall test case application process involved 11 steps:Site model construction (ensemble simulation) see ;Application of the solar preservation model see ;Extension of the solar preservation model to include floods see ;Flood scenario 01: ‘Land subject to inundation’;Flood scenario 02: ‘Road-based integrated water management’;Procedural presence–absence multi-conditions maps  see :Flood sDevelop tree selection criteria based on the four co-conditions see ;Create sets of proxy-object scatters over the street network categorised by width and orientation see ;Adjustment to achieve summer shading criteria see ;Visualisation of streetscape designs—multi scale visual impact renderings see ;Fit indicative tree species suitable for the conditions criteria see ;Visualising tree selections for iterative storm-water management scenarios see ;Light level analysis for expressing summer shading outcomes see ;The test case site, Arden-Macaulay, a major urban renewal project with distinct flooding as well as micro-climatic challenges of heat in summer and cold in winter, is located in the inner north of Melbourne, Australia. In this development, the proposed ‘street wall’, (or zero lot development), will have a substantial impact on both summer shade and winter overshadowing of streets. Our first requirement was to quantify to where, and at what time of day, the proposed built form would overshadow the streets in winter, so as to ascertain when solar preservation would be possible.We constructed a 3D digital model of the site, spatialising the written proposed building envelopes (built-form) outlined in the Arden-Macaulay Structure plan and the C190 planning scheme ,95. The We integrated high-quality existing 3D building models of the LGA of City of Melbourne combined with land parcel maps and street centre lines from PSMA Australia Limited 2016, street casements from Vicmap Property 2017, and water bodies and flood extent from Melbourne Water corporation and City of Melbourne Urban Forest data, which are available to researchers through the Australian Urban Research Infrastructure Network (AURIN). The models of the currently existing site buildings adjacent to the renewal precinct were supplied in ‘geo chunks’  for each suburb within the Local Government Area (LGA). These were amalgamated into a single model from which the focus area could be selected. As the site has several heritage-registered buildings, we began by classifying the building models into three groups  . HeritagUsing a solar metric sun system allows accurate building shadow renderings to be produced for any time of the day and day of the year. We rendered summer and winter shadow maps for the three primary pedestrian peak times associated with mixed used development: morning 8:00–9:00, mid-day 12:00–13:00, and afternoon 15:30–17:30 . From thThe next step was to bring the storm water management plans and the building shadow plans into a single comparable georeferenced raster map format. This required 2D renderings of storm water management simulations output from external flood modelling programs as described by Tomkins and Lange . This isprocedural presence–absence conditions maps. The intersections of different co-conditions result in specific criteria for tree planting   allows textures to wrap onto complex geometry with three-dimensional surfaces). The four conditions can be combined into a single material by assigning them different ‘material ID’s. This procedural process allows any changes to the flood map (such as extent) or the overshadowing map  to be updated by simply replacing or plugging a different storm-water management scenario (flood map) or shade map into the initial map slots.In the site model we tested two flood scenarios against the 12:30 mid-winter building overshadowing condition, demonstrating how the model allows iteration of intensively different proposals. We created two black and white images, one for two potential storm water management strategies (referred to as flood scenarios) described below and shown in Flood scenario 01: ‘Land subject to inundation’: No new control measures are implemented for the current extent of 1 in 100 year flooding of the site  in the Melbourne Planning Scheme) [ Scheme)   or allowed to occur (over white). Tree models on three of the four concurrently occurring tree models will be suppressed, leaving only a single tree model visible per tree position available. presence–absence map.The lines of proxy-object tree model scatters ‘sample’ the pixel colour of their underlying conditions Nyssa sylvatica (Black Tuplo tree) as it is both deciduous and has high transpiration rates. This condition is also uncommon in Melbourne with its weather patterns of long dry periods, and thus species expected to survive and perform as needed in these locations would require access to additional water resources. In a real-world application, species ‘fitting’ would require coordination with tree managers or municipal arborists and would include planning for irrigation infrastructure.The next part of the process allowed for adjustment of the tree locations to meet positioning requirements for optimal summer shade provision to the streetscapes. This process required the fitting of specific tree species to each of the co-conditions to inform geometric proportions and growth habit requirements of trees to be planted in the precinct. For instance, the co-condition of ‘allow winter sun + does not occur in a place that requires high rates of transpiration’ would best suit a species that is deciduous, and given Australia’s climatic conditions, is tolerant to extended periods of drought. The process of fitting species to the resulting conditions brought into focus how restrictive even this limited number of performance criteria is for tree selection. For instance, the condition of ‘in flood, not shade’, would best be fitted to a species that constantly transpires to assist in clearing retention systems and that is also deciduous to preserve available winter sun to the street. This combination of characteristics is likely a biological anomaly as deciduous trees do not transpire while dormant. For this condition we selected the indicative Once indicative tree species were fitted to the tree selection criteria, their geometric proportions were used to inform the position of the property boundary offset lines, into the best possible tree location available in each category of street (width and orientation) for producing summer shade at mid-day over the cycle path and or footpath. Due to the building development proposal , options for the position of the trees were limited to two, either in the footpath or in the road reserve.The next part of the process was the output of visual material for decision-support and community consultation forums. Full visual impact renders  can be output at multiple scales from the model.http://max.klanky.com/plugins.htm, accessed on 1 February 2018) to simulate indicative mixed-use building forms.To allow the building models generated from the planning guidelines to appear less abstract  we used two scripts: ’Vu-normalise spline’ to divide the spline geometry evenly to give the appearance of façade window and door articulation, and Tom Hudson’s ‘Greeble’  can be seen switching over to Fraxinus pennsylvanica, (red over-toned tree model) as the street runs past the oval and comes into the condition of dry + not overshadowed by buildings. scenario 2:road-based storm water management at this same point, the tree species switches instead from Pinus strobus to Nyssa sylvatica, responding to the underlying co-conditions map of the road-based detention basins, that continue through the length of the street. scenario 1) and on the right (scenario 2). scenario 2, road-based storm water management, as flood conditions are more controlled than in scenario 1.Angophora costata model occurs in response to the map of a dry and overshadowed condition. However, in flood scenario (2), where flood conditions continue through the length of the street, trees planted in the road are different from those in the footpath as they must tolerate inundation. In scenario (2) there is more longitudinal symmetry, with species changes most affected by their position in the road to achieve the summer shading objective. At the streetscape level, the visual impact of these different storm-water management scenarios can be assessed in detail. Finally, In this paper we presented a visual-functional street treescape design decision approach for moderating between conflicting tree criteria for stormwater control, sunlight and visual impact, using ensemble simulation, co-conditions presence/absence mapping and 3D high polygon tree modelling. This approach is particularly useful in the initial stages of design of urban renewal sites where limitations of existing street networks and flood conditions must be addressed through integrated design of green infrastructure.The approach outlined in this paper treats trees, which have previously been considered an expensive ornamental element in streets, as critical urban infrastructure. By integrating our non-siloed approach to early stages of a treescape design process, it is possible to make early decisions about their placement, species and form, all crucial traits for meeting sustainability and environmental goals in cities ,101.Our non-siloed approach departs from traditional street tree decision making, where trees are often the last consideration, fitted into spaces left between driveways, above and below ground utilities and traffic visibility requirements, and where species are selected on the basis of tradition and other visual criteria such as neighbourhood character or resident preference by putting them at the forefront of street design.The aspects of street tree selection the approach can work with are the preservation of streetscape solar access in winter, ‘optimisation’ of shade in summer for cyclists and pedestrians, and maximisation of evergreen trees for flood adaptation. The environmental performances required of trees in urban development for these criteria are often conflicting, meaning that conscious and deliberate choices and trade-offs will need to be made that are informed by spatial constraints, flood modelling outputs, built form regulations and accurate solar conditions. In addition, the approach allows for the instantaneous update of tree quantities required for each co-condition type.scenario 2: Road-based storm water management, the opposite occurs. Street tree species, responding to the controlled flood map for the road surface, remain relatively constant along the length of the street (changing only in response to light conditions) while across the street, due to the different tree positioning for achieving the summer shading objective, species change. This visual departure is particularly apparent in flood scenario 01, where the underlying co-conditions cause trees to change type, mid street section (see The visualisation output from this decision model demonstrates how tree decisions based on these functional criteria may lead to quite different aesthetic experiences on streetscapes from the traditional symmetrical plantings of the 19th century, though some symmetries still occur. In scenario 1: Land subject to inundation, several changes occur along the length of the street but are often symmetrical across the street. In tion see . If treeIn this study we constructed 3D building models from written guidelines, which raised questions about the environmental performance of these future buildings, their impact on the quality of the streetscape and how they interact with provision of space for trees and flood infrastructure. By spatialising these written building form regulations, we were able to bring these three aspects of urban renewal into simultaneous, equitable and iterative consideration, potentially allowing the design of green infrastructure to inform building proposals in future cities, rather than post-operatively applied as a last moment consideration.Once the model is constructed it is capable of rapid and flexible iteration, resulting in significant time savings when responding to building proposals or flood projection changes. The input conditions maps make it simple to change and immediately update the streetscape design, including total number of each species, thus informing tree growers of the quantity of future trees required to survive and thrive in conditions that deliver green infrastructure. The selection of tree species for their specific flood moderating functions is complex and enabling preliminary criteria through this modelling approach should have a profound impact on grower’s species selections.While the modelling presented in this study expands on prior work and includes mutliple factors not previously considered together simulatinaiously, there are many other factors that could be considered and potentially integrated into the system in the future. This model was set up with static trees as objects rather than living, growing subjects. In future research, other aspects that impact tree growth could be added such as soil conditions and light level growth impact, as well as age of trees and expected growth rates to show change over time as sapplings grow to full-sized trees.There may be potential for the model to also add the calculation of carbon capture, as well as the potential for improving air quality. Lower vegetation might also be considered in the model, such as low-level shrubs and grasses used in rain gardens, which can be used to clean storm water coming from roads, flitering out heavy metals before entering waterways .Another aspect that is worthy of consideration is the compatibility of urban street trees with the promotion of active travel modes including walking and cycling . While tThis iterative data feedback process could be adapted to different environmental conditions and criteria in different locations. Adoption of the approach has the potential for improving design processes and integrating the science of nature-based solutions into governance and land use planning for urban renewal. Further to this, the model can be used for testing the integrated performance of other systems such as bike path locations and safety measures in flood conditions and has the potential to fulfil the role that urban design frameworks currently occupy.Our multi-criteria modelling approach makes a significant contribution to the arsenal of urban designers, planners and landscape architects in their pursuit of smarter streetscape design decisions that respond to complex spatial, cultural and climatic urban challenges, and maximises the benefits of trees in green infrastructure.


Economic evaluation studies demonstrate the value of money in health interventions and enhance the efficiency of the healthcare system. Therefore, this study reviews published economic evaluation studies of public health interventions from 26 Middle East and North Africa (MENA) countries and examines whether they addressed the region's major health problems.PubMed and Scopus were utilized to search for relevant articles published up to June 26, 2021. The reviewers independently selected studies, extracted data, and assessed the quality of studies using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.The search identified 61 studies. Approximately half  were conducted in Israel and Iran. The main areas of interest for economic evaluation studies were infectious diseases , cancers , and genetic disorders . Five (8%), 39 (64%), 16 (26%), and one (2%) studies were classified as excellent, high, average, and poor quality, respectively. The mean of CHEERS checklist items reported was 80.8% (SD 14%). Reporting the structure and justification of the selected model was missed in 21 studies (37%), while price and conversion rates and the analytical methods were missed in 21 studies (34%).The quantity of economic evaluation studies on public health interventions in the MENA region remains low; however, the overall quality is high to excellent. There were obvious geographic gaps across countries regarding the number and quality of studies and gaps within countries concerning disease prioritization. The observed research output, however, did not reflect current and upcoming disease burden and risk factors trends in the MENA region. The purposes of health interventions are not only to diagnose, treat, or relieve diseases but also to prevent and protect against illnesses . InterveDespite its current limited role in policy decision-making, the number of HE articles published in the Middle East and North Africa (MENA) countries has recently increased and begun to attract the interest of policy-makers to inform priority-setting toward achieving universal health coverage (UHC) in many countries . SimilarFurthermore, the burden of diseases and their background risk factors in the MENA region have shifted dramatically in the past decades, with wide variation across countries –11. The Based on this background, this study aims to systematically review the characteristics and critically assess the quality of economic evaluation studies on public health interventions in MENA countries. It also aims to examine whether the economic evaluation studies have addressed the major health problems and are suitable for policy decision-making in the region. The findings of this study may support existing evidence for better allocating healthcare and research resources in the region.This review was reported following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement .The researchers searched the literature in PubMed and Scopus for relevant articles published since databases inception up to June 26, 2021. The search strategy involved combining terms for public health interventions and economic evaluations using the Boolean ‘AND’, ‘OR’, and ‘NOT’ operators. The term "public health" was purposefully broad, and the authors expected that it would incorporate a wide array of interventions in the field. Search terms used involved the combination of the following Medical Subject Heading (MeSH) terms and keywords:  OR  OR (Exercise [MeSH]) OR (smoking cessation [MeSH]) OR (Mass Screening [MeSH]) OR (prevention [Title/Abstract]) OR (tobacco control [Title/Abstract]) OR (Public Policy [MeSH]) AND (cost [MeSH]) OR  OR  AND (Middle East [MeSH]) OR (North Africa [MeSH]) OR (Djibouti [Title/Abstract]) OR (Mauritania [Title/Abstract]) OR (Pakistan [Title/Abstract]) OR  OR (Sudan [Title/Abstract]) OR  NOT (vaccine [MeSH]) OR (vaccination [MeSH]) OR (immunization [MeSH]) OR (immunization program [Title/Abstract]) OR (immunoprophylaxis [Title/Abstract]). The search was restricted to journal articles, studies of human subjects, and studies written in the English language.Economic evaluation studies  of public health interventions available in full text, published in English, and about at least one country in the MENA region were included in this review. In this study, the researchers adopted the comprehensive definition of the MENA region , which iStudy selection was performed independently by two reviewers (MAN and SS) according to the exclusion and inclusion criteria; first by title, followed by abstract, and finally by full-text screening. Discrepancies were resolved by discussion and consensus with another reviewer (MT). Then, identified studies were screened independently by two reviewers (MAN and MAAR) to extract (1) general information ; (2) methodological characteristics ; (3) source of input parameters . In addition, the source of funding, result and conclusion, cost-effectiveness threshold, and types of included costs were also extracted. Any disagreements were resolved in discussion with another reviewer (MT).The methodological and reporting quality of each included economic evaluation study was assessed by two independent reviewers . Disagreement was resolved by discussion and consensus with the third reviewer (MT). Studies were assessed for their quality of reporting by their compliance with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement . StudiesEndNote X8 software was utilized for duplicate removal. All data extracted from the final list of included studies were entered into a pre-designed data extraction form in Microsoft Excel 2013 spreadsheet. Data synthesis involved stratifying and summarizing the evidence by intervention type, appraising the economic evaluation methods used to assess interventions, and presenting the cost-effectiveness outcomes. Then, descriptive statistics were used with percentages, mean, standard deviation (SD), and median to display the results of extracted data and evaluated items obtained in this review.In total, 849 studies were identified following the initial search . The removal of 69 duplicates resulted in 780 remaining articles. Title and abstract screening resulted in the removal of 623 papers and left 157 potentially relevant studies for full article text screening. Finally, 61 studies –81 were This review identified economic evaluation studies on screening programs  , 79–81 aGeographically, this review identified 18 studies 30%) from Israel % from Is, 80, 81,.Table Against applicable CHEERS items of each study, 21 studies (37%) did not explicitly mention the modeling approach and did not provide the model structure (item 15). Data on the quantities and unit costs of the resources used, the methods of currency conversion and the exchange rates item 14), the description of the analytical methods supporting the evaluation (item 17), and the perspective (item 6) were missed in 21 studies (34%). Similarly, 21 studies (64%) did not specify whether they dealt with heterogeneity (item 21), as shown in Table , the desThis review identified a heterogeneous body of literature on economic evaluations of different public health interventions in MENA countries, dominated by several screening programs . In addition, the number of published studies has been growing over time, particularly after 2013, and appears to be generated only in a few countries: Israel, Iran, Egypt, and Pakistan, contributing to 38 studies or 62% of the economic evaluation studies across all MENA countries. However, the number of published economic evaluation studies identified in this review remains very low and might not truly reflect the research efforts in the region. In this case, the actual number of economic evaluation studies on public health interventions might be higher in this region as studies are more likely to be written in local languages for submission to local authorities. Also, unlike economic evaluations of pharmaceutical products and vaccines, economic evaluation studies on public health interventions do not attract industry sponsorship; therefore, the chance of their publication is limited.Consequently, this review found that the number of economic evaluation studies on public health interventions was lower than economic evaluation studies on diagnostic and therapeutic interventions 69 studies)  but high9 studiesFirst is a geographical gap; there was a complete absence of economic evaluation studies from several high-income countries , middle-income countries , and low-income countries (Sudan and Yemen). In these countries, HE and HTA studies are not mandatory in decision-making , there is room to improve the overall quality of HE studies in this region. Utilizing locally-generated epidemiological data, unit cost of health service, effectiveness and utility data, model calibration and validation, dealing with skewed and missing data, and testing the robustness of results are all warranted. It is also required to explicitly describe the modeling approach and provide the model structure, mention the currency conversion methods and the exchange rates, report the perspective, and deal with heterogeneity. It is noteworthy that the number and quality of economic evaluation studies conducted in countries where HE academic programs, national HE guidelines, and HTA agencies exist  tend to be much better than studies performed in countries where HE academic programs and guidelines are still inexistent.As revealed by this study’s results, more than half of the studies conducted in the region  were performed in 3 countries , where HTA and HE had formal roles in the decision-making process , 19. Bes. Similarly, a recently published review article indicated that the overall estimated pooled prevalence of hypertension in MENA was 26% and is estimated to double by 2025 [. Another recent study indicated that smoking prevalence was 62.7% and 27.5% among adult men and women in some MENA countries, respectively. These rates ranked among the highest worldwide [This study’s results showed that the economic evaluation studies were conducted for the following diseases: infectious diseases , cancers , genetic disorders , CVDs , and other disease domains including maternal diseases, back pain, malnutrition, gestational diabetes mellitus, and mental diseases . The observed research output did not adequately reflect the current and upcoming disease burden and risk factors trends in the MENA region. Currently, several MENA countries have some of the highest rates of NCD-risk factors, such as high blood pressure, obesity, physical inactivity, tobacco use, and high intake of salt, sugar and fats . Likewis by 2025 . Anotherorldwide .On the other hand, MENA countries have witnessed many infectious disease outbreaks, such as polio outbreaks  and cholera outbreaks (Iraq and Yemen). Highly pathogenic and serious viral infections like hepatitis B and hepatitis C are also still an important risk of morbidity and mortality and pose a real threat to some MENA countries like Egypt. Similarly, malaria, hepatitis A virus, Chikungunya, dengue fever, cholera, diphtheria, Leishmaniasis, measles, and Rift Valley fever constitute major health, social, and economic challenges for several MENA countries , 91.By the end of the study identification process, the researchers could find only one economic evaluation study on public health interventions to control and prevent COVID-19 . Given tNotably, there was a complete absence of economic evaluation studies on interventions targeting specific realms, such as physical inactivity, alcohol drinking, occupational health, and mental health. Previous global systematic reviews on economic evaluations of occupational health interventions also revealed no single study from the MENA region and a very limited number from other regions, indicating a great need for further research in these domains , 95. AnoMoreover, it is noteworthy that the researchers observed that most public health interventions were significantly cost-effective or even cost-saving. Even low-intensity public health interventions can have strong positive effects on the population’s health in less developed countries and may positively impact the possibility of reducing poverty and boosting economic indicators and living standards. In this sense, a public health system that responds to the health need is a facilitator of human development since components of human capital, such as health and education, are positively correlated with the quality of the public health system . It is aFurther, the findings of this review reflect a misperception of the role of public health in communities. In this region, as in other parts of the world, the political nature of policy-making processes is apparent where policy-makers tend to advocate for curative interventions and invest in building large hospitals and medical cities as they perceive it as the best way to foster health and well‑being. However, the healthcare system has other tasks with prevention, health promotion, health education, and early disease detection even before one becomes ill and requires a hospital visit . Thus, tOn the other side, disease burden is commonly seen as an important criterion for low- and middle-income countries (LMICs) in national decision-making to prioritize research directions –104. WhiThis study is the first systematic review of economic evaluations of public health intervention in the MENA region, highlighting under-studied disease areas to fill these clear gaps. Although the strengths of this study lie in its rigorous and systematic search strategy, broad time horizon (database inception onwards), geographic coverage of all 26-MENA countries, and the quality assessment of included studies, this study has some limitations. First, it has been difficult to include all that constitutes a ‘public health intervention’ due to terminology diffusion. As such, the researchers had limited the search to the abovementioned terms. Second, the search was limited to studies published in English identified from the two main databases: PubMed and Scopus. Hence, this review did not include technical reports, HE, HTA, and other grey literature written in local languages. Concerning this, it can be argued that government institutions may perform more economic evaluation studies, but as in some other regions, they may not choose to publish their results due to the political environment in which the decision-making process remains largely secretive with limited transparency . HoweverThe number of economic evaluation studies on public health interventions conducted in MENA countries has increased in the past years; however, this number was still very limited, indicating that economic evaluation evidence is not widely used to guide public health decisions in the MENA region. Geographic gaps across countries in the region were also identified concerning the number of economic evaluation studies. In addition, this review found that the number of economic evaluation studies did not align with disease domains with the highest burden and the most prevalent risk factors in some countries. It suggested that MENA governments should prioritize the disease domains and innovative interventions when funding economic evaluation studies to reflect the health burden in the region better. Although the overall quality of the reviewed studies was good—more than two-thirds of them were of high to excellent quality—and were potentially useful for policy decision-making, the limited number of studies in high- and low-income countries and the transferability issues across jurisdictions since MENA region consisted of heterogeneous countries suggested that the existing economic evaluation evidence might not be sufficient to informed policy decision-making in the wider range of the region. The commitment to adopting economic evaluation evidence for public health policy decision-making and developing economic evaluation evidence on major disease burdens are also clearly warranted for efficient public health resource allocation in the MENA region. To facilitate this, national HE guidelines and institutionalizing HTA policy should be established in all countries.


High medicine prices contribute to increasing cost of healthcare worldwide. Many patients with limited resources in sub-Saharan Africa (SSA) are confronted with out-of-pocket charges, constraining their access to medicines. Different medicine pricing policies are implemented to improve affordability and availability; however, evidence on the experiences of implementations of these policies in SSA settings appears limited. Therefore, to bridge this knowledge gap, we reviewed published evidence and answered the question: what are the key determinants of implementation of medicines pricing policies in SSA countries?We identified policies and examined implementation processes, key actors involved, contextual influences on and impact of these policies. We searched five databases and grey literature; screening was done in two stages following clear inclusion criteria. A structured template guided the data extraction, and data analysis followed thematic narrative synthesis. The review followed best practices and reported using PRISMA guidelines.Of the 5595 studies identified, 31 met the inclusion criteria. The results showed thirteen pricing policies were implemented across SSA between 2003 and 2020. These were in four domains: targeted public subsides, regulatory frameworks and direct price control, generic medicine policies and purchasing policies. Main actors involved were government, wholesalers, manufacturers, retailers, professional bodies, community members and private and public health facilities. Key contextual barriers to implementation were limited awareness about policies, lack of regulatory capacity and lack of price transparency in external reference pricing process. Key facilitators were favourable policy environment on essential medicines, strong political will and international support. Evidence on effectiveness of these policies on reducing prices of, and improving access to, medicines was mixed. Reductions in prices were reported occasionally, and implementation of medicine pricing policy sometimes led to improved availability and affordability to essential medicines.Implementation of medicine pricing policies in SSA shows some mixed evidence of improved availability and affordability to essential medicines. It is important to understand country-specific experiences, diversity of policy actors and contextual barriers and facilitators to policy implementation. Our study suggests three policy implications, for SSA and potentially other low-resource settings: avoiding a ‘one-size-fits-all’ approach, engaging both private and public sector policy actors in policy implementation and continuously monitoring implementation and effects of policies.PROSPERO CRD42020178166The online version contains supplementary material available at 10.1186/s13643-022-02114-z. Over the past decade, the cost of accessing safe and quality healthcare has increased rapidly globally, attributed largely to the high prices of medicines . AdditioVarious medicine pricing policies exist to regulate supply of essential medicines . These pThe implementation of medicine pricing policies is influenced by multiple contextual barriers or facilitators of implementation approaches and processes. The facilitators include increased competition, skilful negotiations, pragmatic supply management and bulk purchasing . MedicinMost medicine pricing policies have been implemented in high-income countries, but there is paucity of empirical data/evidence on implementation policies in LMICs, especially sub-Saharan Africa (SSA). Understanding medicine pricing policy implementation is particularly important as implementation of these policies can be a major challenge in LMICs where many patients with extremely limited resources need to provide out-of-pocket payments, thus impeding their access to medicines and putting them at further risk with increasing prices , 22. OthWhich medicines pricing policies have been implemented in SSA and what are their key elements?How have these policies been implemented ?Which key facilitators and barriers affected implementation of medicines pricing policies and how?What were the effects of medicines pricing policies with regard to reducing prices and improving access to medicines?With this backdrop, we conducted a systematic review on available medicine pricing policies in SSA, their implementation processes, contextual influences and impacts on prices and access to essential medicines. We addressed the main question: what are the key determinants of implementation of medicines pricing policies in sub-Saharan African countries? The review addressed four interrelated questions:This review is aimed particularly at health policy analysts, healthcare professionals, implementation science scholars and decision-makers who are engaged in improving access to medicines in LMIC settings.The review was conducted as part of a study on ‘Improving equitable access to essential medicines in Ghana through bridging the gaps in implementing medicines pricing policy, which involved collaboration between University of Ghana, Ghana Health Services and University of Leeds, with funding from the National Institute for Health Research (NIHR), UK’. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement . The revThe literature search was initially run in April 2020 to identify studies covering implementation of medicine pricing policies in SSA. We updated and re-ran the searches on 25th May 2021 in Ovid MEDLINE(R) ALL 1946 to May 24, 2021, Embase (Ovid) 1996 to 2021 week 20; Global Health (Ovid) 1973 to 2021 week 20, Web of Science Core Collection, Scopus (Elsevier B.V) and African Index Medicus  Global Health Index Medicus). We also searched for grey literature in the Institutional Repository for Information Sharing (WHO)  and the Search strategies were developed using the major concepts: sub-Saharan African countries, medicine pricing, medicine policy and implementation. Database subject headings and free text words to search titles and abstracts were identified by the information specialist and project team members. The search terms and strategy were peer reviewed by a senior information specialist using the PRESS Checklist . The seaThe results of the database searches were stored and de-duplicated in an EndNote X9 library. Further relevant studies were added by citation searching of the included studies from the following reviews , 23–26.A screening decision flowchart was agreed within the review team, which followed inclusion and exclusion criteria , quasi-experimental studies, cross-sectional and cohort studies) and reviews in English or French possessing the following criteria:Opinion pieces, commentary or conceptual/theoretical publicationsPolicy analyses which focused solely on the agenda-setting and development stagesConducted two plus years prior to 2000 but published after 2000 as this predates the MDG and Sustainable Development Goals (SDG) agendaIn languages where we were unable to resource translation or where full text was unavailableWe excluded studies that were as follows:French articles were screened, translated and data extracted by native French speakers on the research team. Screening was conducted in two stages using the review management software Rayyan . The firyes (present), no (absent), unclear (insufficient information) or not applicable [. The checklist criteria were not modified but interpreted flexibly to reflect our focus on the implementation of medicines pricing policies. As a result, the overall scores or results were presented narratively to reflect the presence (yes) or otherwise (no) of which of the domains.Quality assessment on the included studies was performed independently by two researchers  using the relevant critical appraisal checklists from the Joanna Briggs Institute to assess the methodological quality of the eligible studies. Where discrepancies existed, two other reviewers were consulted . Three quality assessment tools for cross-sectional analytical studies, cohort studies and qualitative studies from the Joanna Briggs Institute tools were used. For the analytical cross-sectional quality assessment, eight domains were assessed as ‘Yes (present), No (absent), Unclear (insufficient information) or Not Applicable’ . The cheplicable . The cheTwo authors  extracted the data from all the 31 studies using a Microsoft Word template. The forms were designed to include publication details ; medicines pricing policy ; the policy implementation approach ; and any facilitators and barriers to policy implementation and their effects. Extracted data were coded in identifying the main themes emerging as shown in Table Due to the heterogeneous nature of medicines pricing policies, and the countries involved, we conducted a thematic narrative synthesis of the data , which fn = 57) because the intervention of interest was not present, population (n = 5), study type (n = 28) such as commentary and theoretical publication, publication type (n = 4) and background article (4) or duplicate (2), not SSA (n = 3), and these are detailed in the PRISMA flow diagram  use of private distribution outlets and networks and (b) use of government’s regulatory frameworks. Three studies , 58, 60 The second approach involved the use of regulatory frameworks to guide the sale and distribution of medicines , 65, 67.overnment [wholesalers [retailers [manufacturers [donor agencies [professional bodies [community members [public and private health facilities [A total of 22/31 studies highlighted seven groups of policy actors who were involved in policy implementation. These comprised the following: gvernment , 66, 68,lesalers , 46, 65,etailers , 46, 47,acturers , 65, 68,agencies , 49, 51,l bodies , communi members  and publcilities , 65, 67.None of the studies reported on the use of evidence to inform implementation as well as monitoring and evaluating implemented policies, although few studies (2/31) explicitly described evidence use in informing the design of medicine pricing policies. Where it was reported, evidence was sourced from review of pharmaceutical pricing policies  and a WHMultiple contextual facilitators and barriers to the implementation of the medicine pricing policies in sub-Saharan Africa were identified in this review. These were across the micro , meso  and macro  levels Table . Five stThree studies cited education and awareness creation where prescribers and users were aware of the medicines and therapies under the new medicine pricing policy as facilitators of successful medicine pricing policies , 48, 56.Introduction of government subsidies and exemptions of generic medicines contributed to a decline in the prices of medicines at facility level in Mali . PoolingThe review showed that the use of national essential medicine lists by health facilities was a facilitator of the implementation of reimbursement schemes in Ghana . Other fMedicine pricing policies sought to achieve two main aims: (a) control or reduce the prices of medicines and (b) improve access to essential medicines. Some studies reported separate effects on medicine prices , 62, 66 Overall, implementation of the different medicine pricing policies largely suggests a reduction in the prices of medicines. The results of the review showed that implementation of the tiered pricing (segmented pricing based on targeted markets), voluntary licensing (removing of regulatory barriers) and generic policy (promoting prescribing generic medicines) in seven different countries across Africa led to reductions in generic direct-acting antivirals (DAA) from US $1200 to between US $684 and US $750, i.e. the generic medicines were 40% cheaper than the originator prices . HoweverFifteen studies reported evidence of policy effect on improved availability and affordability to essential medicines , 65, 69.This systematic review sought to identify medicines pricing policies implemented in SSA, how these were implemented, which contextual facilitators and barriers affected policy implementation and how effective were these policies. The review revealed 13 different medicine pricing policies reflecting four domains, targeted public subsidies, regulatory framework and direct price control, generic medicine policies and purchasing policies, were implemented across SSA between 2003 and 2020. The medicines pricing policies were implemented in less than half (22/46) of SSA countries. The main implementation approaches involved the use of regulatory frameworks and private distribution outlets and networks. The review showed key actors involved in policy implementation were government, wholesalers, manufacturers, retailers, professional bodies, community members and private and public health facilities. The use of evidence to inform policy implementation was not reported in any of the included studies. Key barriers to policy implementation identified included limited awareness about policies, frequent stock out, lack of capacity to regulate implementation and lack of price transparency in external reference pricing process, whereas key facilitators included existing national essential medicine policy environment, strong political will and support from development partners. Evidence on effectiveness of implemented policies on reducing prices and improving access to medicines was mixed. Reductions in prices were reported only in some studies. There was evidence that implementation of medicine pricing policy led to improved availability and affordability to essential medicines.The categories of medicine pricing policies identified in this study are similar to what were previously reported, which also highlight predominant focus on regulatory measures or direct price control . AlthougThe use of generic medicines as a strategy to reduce prices and ensure improved access was widely employed in SSA, and the effect on price and expenditure favours the use of quality-assured generic medicines . A revieAlthough information on the role of actors was provided in the studies reviewed, the actors’ interests, agendas, relative powers and networking arrangements such as alliance building were missing. This information can be revealed through stakeholder analyses –79 and iThe review showed slightly more reported barriers than facilitators to implementation of medicine pricing policies. This may reflect researchers’ bias in revealing more constraints in their investigations , 85, thoThe ultimate goal of medicine pricing policies is to ensure low and affordable medicine prices as revealed in our review. This finding is in line with another study from Asia which found similar price reductions following implementation of generic medicine pricing policy in Indonesia . The autSome policies, however, did not have any effect on the prices of medicine , 54, 58.Implementation of medicine pricing policies can be mediated by different contextual facilitators or barriers. Our review has highlighted that key contextual barriers comprised weak enforcement or regulatory mechanisms, the absence of essential medicines list and the role of foreign exchange currency fluctuations. On the other hand, facilitators included raising awareness about implementation, existence of subsidies, use of essential medicine lists, establishing a fixed profit margin or percentage for manufacturers and the pivotal roles of supportive donor agencies and international policies and interventions. A study in China also revealed contextual barriers such as lack of enforcement of pricing regulations and policies, with authors encouraging strong governance structures and legal frameworks to ensure enforcement . The monThis study also reported on the effectiveness of the medicine pricing policies in SSA. Our review showed that some medicine pricing policies have the potential to improve access to essential medicines , 69, 88,The findings from this review contribute to the field of policy analysis. Specifically, the taxonomies of the categories of policies  and actor groups  involved in implementation and the distinction of micro, meso and macro levels context, which mirrors other policy studies , 90, 91.This review suggests three implications for improving implementation of medicine pricing policies in SSA, which can also be applied to other health policies in LMICs more generally. First, four broad groups of policy options are available for reducing medicine pricing: targeted public subsidies, regulatory frameworks and direct price controls, generic medicine policies and purchasing policies. However, it is important to design and apply the country-specific implementation mechanisms to avoid a ‘one-size-fits-all’ approach. Second, different stakeholders from both the public and private sectors can play important roles in the design and implementation of medicine pricing policies. Inclusive policy processes which allow representation of multiple voices of policy actors are, therefore, imperative to ensure sustainability of policy implementation, pooling of resources and collective ownership and acceptance. This is particularly pertinent to medicines pricing, given that the private (for profit) sector plays a major role in pharmaceutical manufacturing and distribution, but it is also important to encourage participation of underrepresented not-for-profit groups such as civil society organizations, in health policy processes. Third, it is important to continuously monitor and evaluate the implementation approaches and emerging effects of these policies, something which our review observed was generally lacking. This can represent an opportunity for enhancing the culture of evidence-informed decision-making within government agencies, as well as closer partnerships between government agencies and research organizations.We call for more research on medicine pricing policy implementation, covering three areas. First, more studies need to examine the role of evidence in the design and implementation of medicines pricing policies. The increased interest and attention on evidence-informed policy and planning decisions , 92–95 cWe acknowledge the following limitations. First, the review focused on studies conducted in SSA, but we acknowledge variation in income status, socio-economic contexts and healthcare systems across countries. Different contexts inevitably affected how medicine pricing policies were implemented and their outcomes. As a result, we were guided by the generally limited contextual information included in the reviewed studies and resisted making too many assumptions and inferences based on our knowledge of the different countries. We also suggest that experimental studies could report more robust and less biased results, as compared to the reported studies in this review which were largely cross-sectional with limited follow-up. Second, we conducted comprehensive searches in a range of health science, global health and multidisciplinary databases to capture all SSA medicines pricing literature, and although we may have missed some potentially relevant studies by not including specific pharmaceutical databases such as International Pharmaceutical Abstracts, we believe that full articles of most of these abstracts would have been captured from at least one of the databases, and this omission is not expected to miss studies that could likely change the magnitude, direction or conclusions of this review. Third, given the different study designs employed, sample sizes and outcome measures, we faced a challenge to analytically compare the outcomes or effects of the policies on the prices and access to essential medicines. This notwithstanding, we feel our analysis provides a useful taxonomy of types of medicines pricing policies and highlights implementation approaches to inform future policy, practice and research.The implementation of medicine pricing policies in SSA focused on four policy options: targeted public subsidies, regulatory framework and direct price control, generic medicine policies and purchasing policies. Implementation of these policies in SSA shows some mixed evidence of improved availability and affordability to essential medicines, and it is important to understand country-specific experiences, diversity of policy actors and contextual barriers and facilitators to policy implementation. Our study suggests three policy implications for improving implementation of medicines pricing policies in SSA: avoiding ‘one-size-fits-all’ approach, engaging both private and public sector policy actors in policy implementation and continuously monitoring implementation and effects of policies. Future studies can usefully examine interests, influences, relative powers and coalition formation of policy actors during implementation of medicine pricing policies.Additional file 1. African Index Medicus (AIM).Additional file 2. Screening flowchart.Additional file 3. Quality assessment of included studies.


From large ventral pleats of humpback whales to nanoscale ridges on flower petals, wrinkled structures are omnipresent, multifunctional, and found at hugely diverse scales. Depending on the particulars of the biological system—its environment, morphology, and mechanical properties—wrinkles may control adhesion, friction, wetting, or drag; promote interfacial exchange; act as flow channels; or contribute to stretching, mechanical integrity, or structural color. Undulations on natural surfaces primarily arise from stress-induced instabilities of surface layers  during growth or aging. Variation in the material properties of surface layers and in the magnitude and orientation of intrinsic stresses during growth lead to a variety of wrinkling morphologies and patterns which, in turn, reflect the wide range of biophysical challenges wrinkled surfaces can solve. Therefore, investigating how surface wrinkles vary and are implemented across biological systems is key to understanding their structure–function relationships. In this work, we synthesize the literature in a metadata analysis of surface wrinkling in various terrestrial and marine organisms to review important morphological parameters and classify functional aspects of surface wrinkles in relation to the size and ecology of organisms. Building on our previous and current experimental studies, we explore case studies on nano/micro-scale wrinkles in biofilms, plant surfaces, and basking shark filter structures to compare developmental and structure-vs-function aspects of wrinkles with vastly different size scales and environmental demands. In doing this and by contrasting wrinkle development in soft and hard biological systems, we provide a template of structure–function relationships of biological surface wrinkles and an outlook for functionalized wrinkled biomimetic surfaces. From large ventral pleats on the throats of humpback whales to fine scale ridges on flower petals, a variety of wrinkle-like surface patterns exist at highly diverse length scales in nature. In addition to the environment and species involved, the location, size, and morphological complexity of surface wrinkles determine their function and ecological role. Therefore, understanding the functional morphology of surface wrinkles across biological systems will not only assist in establishing organismal structure–environment links, but also in laying out morphological rules for diverse technical applications.In this work, we explore the structure–function relationships of surface wrinkles from various terrestrial and aquatic organisms from an ecomorphological viewpoint. First, we briefly describe the mechanical aspects of wrinkle formation, distinguishing between soft and hard biological systems . We then investigate structure–function aspects of biological wrinkled surfaces in relation to the size and ecology of organisms in a broad-scale metadata analysis of the literature. To illustrate the diverse interrelation of formation, development, and function in wrinkled biological systems, we then discuss three case studies based on our previous work on plant surfaces and preliminary data from our ongoing work on bacterial biofilms and basking shark filter structures. Taken together, we outline structure–function rules for biological surface wrinkles and provide an outlook for the targeted design of functionalized biomimetic surfaces .X and Y (X and thick gray substrate Y), the latter pre-stretched before the fabrics are bonded together. In this case, wrinkles will automatically emerge upon release of the stress in material X; in fact, this process of “self-shaping” is currently of great interest to the textile industry for the formation of 3D surfaces . In any bilayer system with a thin outer layer and thick inner substrate, an in-plane strain mismatch between these components due to compressive forces may induce mechanical instabilities, leading to the formation of wrinkles. Out-of-plane deformations of the system arise when bending becomes energetically favorable compared to compression. The structural effects of this mismatch in strain can be intuitively understood by considering two fabrics, surfaces . AlternaIn these structural formation processes, the wavelength and amplitude of the evolving wrinkles depend on the material properties and structural aspects of the components such as layer-to-layer rigidity ratio and layer thickness . For exaX and Y in While biological tissues aren't the stretched and bonded textiles described in the previous section, the fundamental mechanisms of wrinkle formation are the same. The layered materials Translating the general concepts in Although generally less explored, wrinkle-like ornamentations can also be found in some hard tissues, most notably the surfaces of some seed coats , mollusc shells , and many vertebrate teeth, spines, and denticles (most studied in fishes and reptiles). Wrinkles in these tissues are not always only a surface phenomenon: in teeth, sculptured surfaces can be the result of folding of both the outer (enamel) and inner (dentin) layers together, or of just one of those layers, meaning wrinkled tissue patterning is sometimes invisible on the tooth's surface .Formation of wrinkles in these materials is temporally restricted, since the hard nature of the tissues involved make their morphologies comparatively static  . Since sThe growth processes described above, coupled with the available diversity of plant and animal tissue structures and material properties, create a wide palette of wrinkle types in natural systems. As the wrinkles are often on exposed surfaces, the manifold wrinkle morphologies and size scales therefore offer a massive library for understanding natural solutions for surface-environment interactions. And yet, while there has been much success in identifying the structure and function of surface wrinkles in individual biological systems, unified (eco)morphological principles still need to be synthesized and articulated. Characterizing the diversity of wrinkled surface architectures and their function across taxa will provide pathways to evaluate the correlation between material properties and surface morphology and to establish organismal structure–environment links. These pursuits will, in turn, inform diverse disciplines, while concomitantly demanding interdisciplinary perspectives into the material science, developmental biology, and ecology and evolution of natural wrinkled surfaces.We believe that key to a deeper understanding of the mechanistic bases of wrinkle development and evolution in biological systems is inquiry into the materials and the processing conditions see  involvedR software environment  to generate scatterplots comparing body size and wrinkle size as a function of organ and function  wrinkle size and shape—height, spacing or aspect ratio, sharpness of the wrinkles, (ii) density, (iii) orientation, (iv) complexity or patterns of wrinkles, and (v) type of wrinkling instability e.g., . To begifunction –D. In thThe metadata analysis demonstrates that surface wrinkles occur in a wide range of extinct and extant taxa with length scales spanning several orders of magnitude of organism size  and wrinkle size , exhibiting diverse functions that vary with body size, wrinkle size, and environment. In some organs, for example on skin, wrinkles are broadly distributed, occurring in a wide range of wrinkle and body sizes . For insAlthough the distribution of scatterplot data surely reflects some sampling bias on our part , the general lack of functional data , and inevitable bias from the available literature , our graphs of wrinkle–organism size space, across natural systems, provide a potential framing of the pathways and perhaps constraints involved in the evolution and adaptation of wrinkled structures. Our results provide a first compendium of surface wrinkle size-versus-function and are valuable in studying the influence of (wrinkle) structure on ecological interactions in a wide range of organisms. We are currently expanding this dataset and refining our organ/function categories to maximize our ability to resolve clear structure–function relationships. Phylogenetic relationships, tissue material properties  and environmental associations will also be considered in this expanded analysis, as these also clearly influence wrinkle functions. For instance, the wrinkles of attachment organs have been proposed to provide adhesion in both terrestrial and aquatic organisms , whereasBacillus subtilis  that are exchanged at the interfaces . WhereasE. coli biofilms grown at solid/air interface  are common on various plant organs such as leaves, flower petals, sepals, and stems, with length scales ranging from 100 nm to 1 μm, and with morphologies varying depending on location and species , and mayArabidopsis thaliana, daisy, Kalanchoe blossfeldiana, and Eustoma grandiflorum, Hevea brasiliensis  are the second largest fish and, like their relatives whale sharks and devil rays, are planktivorous suspension feeders. Filter feeding evolved multiple times independently in sharks and rays , our simulations suggest even fine-scale wrinkles have potential for significant local flow control. Our future CFD analyses will incorporate measurements from physical experiments to determine the extent to which raker surface wrinkling—even at a microstructural scale—may impact particle retention efficiency for the basking shark's massive biological filter. These results combined with anatomical and material data from rakers and raker arrays therefore, also represent valuable natural prototypes for inspiring large-scale dynamic industrial filters or lightweight yet robust filaments with interlocking and/or hydrodynamic cross sections .Using broad scale meta-analysis of literature and case studies, we demonstrate the huge diversity and structure–function aspects of biological surface wrinkles in a wide range of extinct and extant organisms  and 3. FBeyond characterizing the morphological and functional diversity of natural wrinkles, we believe, a grand challenge in the study of wrinkled biological surfaces  is determining the degree to which “structures” in different systems are adaptations that were selected for versus being “merely” byproducts of growth and/or physics . Key to disentangling this and the factors impelling wrinkle formation is building time into comparative analyses, exploring the ontogenetic development of wrinkles , as well as the evolution of wrinkled systems in the context of organismal ecology. In this regard, we believe our metadata analysis can function much like a material selection chart , providiGiven the need to resolve, at multiple scales, wrinkle form–function relationships and the factors shaping them, we hope our work will act to spur more fluid multidisciplinary interactions, such as between biologists  and material scientists  . The casicac079_Supplemental_FileClick here for additional data file.


To investigate the role of standard patients (SPs) and examiners as assessors for scoring in the dental objective structured clinical examination (OSCE) system and to evaluate the scoring differences between them.We developed the doctor-patient communication and clinical examination station in the OSCE system. The examination time of this station was 10 min, and the examination institution wrote the script and recruited SPs. A total of 146 examinees who received standardized resident training at the Nanjing Stomatological Hospital, Medical School of Nanjing University between 2018 and 2021 were assessed. They were scored by SPs and examiners according to the same scoring rubrics. Subsequently, the SPSS software was used to analyze the examination results of different assessors and evaluate the consistency.The average score of all examinees provided by SPs and examiners was 90.45 ± 3.52 and 91.53 ± 4.13, respectively. The consistency analysis showed that the intraclass correlation coefficient was 0.718, which was indicative of medium consistency.Our findings showed that SPs could be used directly as assessors, as they could provide a simulated and realistic clinical setting and create favorable conditions for comprehensive competence training and improvement for medical students. Objective structured clinical examination (OSCE), a multi-station clinical skill examination, is an approach used for assessing the clinical competence of medical students , 2. ThisA doctor-patient communication and clinical examination station are important in the OSCE used to conduct standardized and systematic training for healthy individuals to help them pose as standard patients (SPs). Furthermore, SPs can accurately present actual clinical problems and imitate the symptoms of the corresponding cases, including body movements, pain degree, facial expressions, self-report of symptoms in the medical history, and so on. The examinees establish a correct diagnosis based on SP’s medical history, conditions, and symptoms. During the examination, SP principally takes the role of a patient who “has medical history and undergoes physical examinations.” Also, a well-trained SP can act as an examiner to assess examinees’ performance and even guide them. Thus, the recruitment of SP allows dental school students to practice communication skills and obtain patients’ feedback .Compared with other assessment methods, the “objectification” and “structuration” of OSCE can well simulate real clinical settings and achieve consistency in assessment contents. However, OSCE requires numerous examiners and other examination personnel to develop detailed pre-exam plans during the actual implementation. The limitations related to examination time, space, and the lack of relevant examination staff are the common factors affecting the promotion and implementation of OSCE , 7. WhetThe present study aimed to construct a suitable doctor-patient communication and clinical examination station, improving the rating scale and pre-exam training. The SP undertook the role of an examiner, providing feedback and guidance to the examinees, thus achieving an environment similar to clinical practice and reducing the involvement of a large number of examiners in the OSCE . In the present study, the scoring differences between SPs and stomatological examiners were assessed based on a 4-year resident midterm evaluation.The present study was approved by the Institutional Review Board of Nanjing Stomatological Hospital, Medical School of Nanjing University (No. NJSH-2022NL-074). The OSCE system was used for the midterm assessment of 146 residents in the aforementioned hospital between 2018 and 2021. These residents were in the second year of standardized resident training and completed basic theoretical courses and 1 year of clinical practice during the examination. An SP and an examiner scored all examinees according to the same scoring rubrics, who wrote brief feedback on the rating scale for each examinee. The study was conducted in strict accordance with the requirements of the Declaration of Helsinki. The participation was voluntary, without any compensation or incentive. Both confidentiality and anonymity were guaranteed for all participants. Participating residents filled out an informed consent form.The OSCE assessment system has been used for dental teaching evaluation since 2016. The OSCE had eight stations; the third was the doctor-patient communication and clinical examination station. SP was required to assess students’ doctor-patient communication and clinical examination competencies and whether the students could perform standardized receptions. The SPs were also required to comprehensively and accurately record the medical history based on chief complaints, make a possible diagnosis, and determine further examination and treatment plans in combination with the clinical examination results. Meanwhile, the students’ communication skills, such as appearance, attitude, and language expression during clinical reception, as well as inquiry of patients, diagnosis and treatment decisions, disease prognosis, diagnosis and treatment costs, and similar, were assessed , the assessment is more likely to be conducted through remote video or picture recording. However, previous studies showed that encounters with SP may cause anxiety among examinees, which was a stress-related response , 21. In The limitations of the present study included a small sample size of students and examiners and a shorter observation time; hence, the conclusions cannot be generalized. More SPs should be used as assessors and instructors in the educating medical students in the future.The present study demonstrated excellent scoring consistency between SPs and examiners, suggesting that using SPs directly as assessors was feasible after comprehensive and detailed pre-exam training and a well-designed rating scale. They can be used for teaching assessment and usual teaching and training, as well as to provide simulated and realistic clinical settings, thus creating favorable conditions for the comprehensive competence training and improvement of medical students.


Group Name: Watussi Study GroupBackground: A positive safety climate is an important precursor of safe care outcomes. However, only limited evidence supports the association of low surgical-site infection (SSI) rates and positive safety climate. We investigated the role that perceptions of SSI prevention measures play for both safety climate level and strength as a subjective norm, that is, the social pressure perceived to perform the prevention measures, commitment to observe SSI prevention measures despite other situational pressures, and the level of knowledge about the prevention measures. Methods: The safety climate scale of the Safety Attitudes Questionnaire and 3 scales assessing subjective norm, commitment, and knowledge were used. All items were translated and retranslated from German to French and to Italian. All translated scales were pretested for understandability. Operating room (OR) personnel in 54 Swiss acute-care hospitals were surveyed, resulting in 2,769 analyzed responses with data aggregated on the hospital level. Two regression analyses were conducted: one using the percentage of positive responses per hospital as a safety climate level indicator, and another using the standard deviation of the safety climate ratings per hospital as a safety climate strength indicator. As independent variables, the hospital means of subjective norm, commitment, and knowledge were investigated and appropriately adjusted for number of respondents and sample composition. Results: The sample consisted of 1,495 nurses (54%) and 1,101 physicians (40%). Commitment and subjective norm were significant predictors  of safety climate level, in the expected positive direction, but KNOW was not ; for safety climate strength, only COM was significant p < 0.001 . Conclusions: The extent to which OR personnel were committed to perform the measures, such as timely administration of antibiotics, was associated with their safety climate rating level and strength. Thus, the rather general safety climate assessments are related to more specific safety behaviors necessary to achieve good outcomes such as low infection rates. Subjective norm was related to safety climate level only, indicating that in work environments with a good safety climate, the perceived social pressure to adhere to infection prevention measures may be higher. Knowledge about SSI prevention had no significant impact on safety climate, pointing to future research regarding the role of education in implementing prevention measures. Investigating how attitudes and knowledge about measures to prevent specific patient safety outcomes furthers our understanding of the role of safety climate in patient safety improvement.Funding: NoDisclosures: None


This study aimed to systematically review the literature on the associations between birth spacing and developmental outcomes in early childhood (3–10 years of age). Studies examining the associations between interpregnancy intervals and child development outcomes during and beyond the perinatal period have not been systematically reviewed.We searched Ovid/MEDLINE, Global Health, PsycINFO, EMBASE, CINAHL Plus, Educational Source, Research Starters, ERIC, Scopus, PubMed, Social Science Research Network database, and ProQuest's Social Sciences Databases for relevant articles published between 1 January 1989 and 25 June 2021. Studies published in English, conducted in populations residing in high-income countries with any measure of birth spacing, and child development outcomes among children aged <10 years were included. Two authors independently assessed the eligibility of studies and extracted data on the study design, setting and population, birth spacing, outcomes, and results.The search yielded 1,556 records, of which seven studies met the inclusion criteria. Five of these seven studies used birth intervals as the exposure measure. Definitions of exposure differed between the studies. Three studies reported an association between short birth spacing and poorer child development outcomes, and two studies reported an association between long birth spacing and poorer child development outcomes.Currently, limited evidence suggests that the adverse effects of sub-optimal birth spacing are observable beyond infancy. The early childhood period is a time of rapid growth and development of skills and abilities. Early life experiences strongly mediate childhood development, and the development undertaken during this period forms the basis for future achievements. Variations in development and developmental inequalities that occur during this period can significantly impact the later life outcomes of children , 2. In pmaternal depletion hypothesis. The definition of maternal depletion syndrome traditionally states that the cumulative effect of successive pregnancies and lactations results in a worsening of maternal nutritional status  intervals between pregnancies and adverse pregnancy and birth outcomes for mothers and infants ; yet it l status –19. Altel status . Sub-optl status , 21–23. l status –31. Thusl status , 32.The concept of optimizing birth spacing has been widely discussed in the literature; the World Health Organization recommends interpregnancy intervals (IPIs) of approximately 2–3 years to reduce infant and child morbidity and mortality . HoweverCurrently, there is no standardized definition for short or long IPIs . Short IWhether there is a significant biological risk for adverse pregnancy outcomes associated with pregnancy intervals is important to establish as birth spacing and unplanned pregnancy rates can be controlled. To date, systematic reviews and meta-analyses have reported that sub-optimal IPIs are associated with an increased risk of adverse prenatal and perinatal health outcomes , 36, 37;We conducted a systematic review of the literature related to birth spacing and child development outcomes, as guided by the minimum evidence-based set of items for reporting in systematic reviews outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . The sysWe conducted electronic searches in Ovid/MEDLINE, Global Health, PsycINFO, EMBASE, CINAHL Plus (EBSCO), Educational Source, Research Starters, ERIC, Scopus, PubMed, Social Science Research Network database, and ProQuest's Social Sciences Database . We inclEligible studies were all observational studies that investigated the effects of an interval preceding the younger sibling's birth on child development outcomes of the younger child for children aged less than 10 years. For this review, we included studies using measures of birth spacing defined as either: (1) interpregnancy intervals, defined as the time between the birth of the older sibling  and the conception of the immediately subsequent pregnancy; or (2) birth intervals (or age-gap), defined as the time between the birth of the older sibling and the birth of the immediately subsequent sibling. This review assessed the five development domains most commonly used to define school readiness among children: (1) cognition and general knowledge; (2) language; (3) social knowledge and competence; (4) emotional health; and (5) physical wellbeing and motor development .Articles were excluded based on the following exclusion criteria: (1) articles published prior to 1989; (2) dissertations, conference papers, case studies, editorials, newspaper articles, and other forms of popular media; (3) articles published in languages other than English; (4) articles that contained “child (and/or) infant mortality” in the title; (5) articles for which the age of outcome assessment for the study cohort was more than 10 years of age; and (6) articles for which the study population comprised of children with developmental disabilities, including autism spectrum disorder, intellectual disability, based on the assumption that these outcomes have a large genetic basis.biological clock . Th. Th64). We developed a narrative description of the study characteristics and results for all the included studies. To generate pooled effect estimates for each outcome, a random-effects meta-analysis using the inverse variance method  to explon = 146), 1,324 studies were excluded after the initial title and abstract screening (n = 72), were a report or commentary (n = 3), did not report on child development outcomes (n = 3), and if the effect of birth spacing was assessed for the index child (n = 1).The search produced a total of 1,556 records. After removing duplicates ; however, no association was reported between the age gap between siblings and lower language skill scores of the younger sibling . Sujan et al.  were associated with an increased risk of children being classified as developmentally vulnerable on the Language and Cognitive Skills (school-based) domain of the AEDC   were more likely to score higher on school performance compared with children born after longer birth intervals (>31 months) . The othTwo additional studies reported that short birth spacing [birth intervals of <24 months  and IPIsFindings from studies examining the associations between long birth spacing were mixed. Havron et al.  reportedDifferences in results between the studies may be attributable to differences in sample size and the adjustment variables used in the adjusted models. The studies that reported the greatest effect sizes , 72, 74 Nathens et al.  comparedExisting studies have assessed a range of child development outcomes with respect to birth intervals. Compared with IPIs, birth interval measures have an inherent bias  as this Our review identified a need for further research investigating the effects of birth spacing, particularly IPIs, on child development outcomes. The categorization of measures of birth spacing was inconsistent, with the definitions of birth spacing between siblings varying significantly across the studies included in this review. Only two studies adjusted for paternal risk factors , 71, andEvidence from this review, albeit limited, is suggestive of potential adverse effects of both short and long birth spacing between successive pregnancies on childhood development beyond infancy. However, additional studies which adhere to the World Health Organization's recommendations of IPIs of 18–23 months are required to better establish the potential association between IPIs and early childhood development outcomes.