Top-down Strategy Research Articles

Co-creation and community engagement in implementation research with vulnerable populations: a co-creation process in China.

Background Top-down implementation strategies led by researchers often generate limited or tokenistic community engagement. Co-creation, a community engagement methodology, aims to create a shared leadership role of program beneficiaries in the development and implementation of programs, and encourages early and deep involvement of community members. We describe our experience using a four-stage co-creation approach to adapt and implement a sexually transmitted diseases (STD) testing intervention among men who have sex with men (MSM) in China. Methods We adapted a four-stage approach to co-creation. First, we conducted a needs assessment based on our prior work and discussions with community members. Second, we planned for co-creation by establishing co-creator roles and recruiting co-creators using both stratified convenience and opportunistic sampling. Third, we conducted co-creation via hybrid online/in-person focus groups (four multistakeholder groups and four MSM-only groups). Finally, we evaluated validity of the co-creation process through qualitative observations by research staff, analyzed using rapid qualitative analysis, and evaluated co-creator experience through post-discussion survey Likert scales and open-ended feedback. Results Needs assessment identified the needs to adapt our STD intervention to be independently run at community-based and public clinics, and to develop explanations and principles of co-creation for our potential co-creators. In total, there were 17 co-creation members: one co-creation lead (researcher), two co-chairs (one gay influencer and one research assistant), eight MSM community members, four health workers (two health professionals and two lay health workers) and two research implementers and observers. Co-created contents for the trial included strategies to decrease stigma and tailor interventions to MSM at public STD clinics, strategies to integrate STD testing services into existing community-led clinics, and intervention components to enhance acceptability and community engagement. Our evaluation of validity identified three main themes: challenges with representation, inclusivity versus power dynamics and importance of leadership. Surveys and free responses suggested that the majority of co-creators had a positive experience and desired more ownership. Conclusion We successfully adapted a structured co-creation approach to adapt and implement an STD testing intervention for a vulnerable population. This approach may be useful for implementation, and further research is needed in other contexts and populations.

Recent advances in cell membrane-coated porphyrin-based nanoscale MOFs for enhanced photodynamic therapy

Porphyrins-based nanoscale metal-organic frameworks (nMOFs) has been widely utilized to kills tumor cells by generating cytotoxic reactive oxygen species (ROS). However, porphyrin based nMOFs (por-nMOFs) still face challenges such as rapid immune clearance and weak tumor targeting. Researchers have discovered that using a top-down biomimetic strategy, where nMOFs are coated with cell membranes, can promote long blood circulation, evade the reticuloendothelial system, and improve cancer cell targeting, thereby significantly enhancing the photodynamic therapy (PDT) effect of nMOFs. This review summarizes the recent work on different cell membranes-coated por-nMOFs for enhanced tumor PDT. This review details the changes in physicochemical properties, enhanced homotypic cancer cell-selective endocytosis, improved tumor tissue targeting, and increased cytotoxicity and effective in vivo tumor suppression after the nMOFs are wrapped with cell membranes. Additionally, this review compares the biological functions of various types of cell membranes, including cancer cell membranes, red blood cell membranes, aptamer-modified red blood cell membranes, and hybrid membranes from the fusion of cancer and immune cells. The review highlights the enhanced immunogenic cell death function when using hybrid membranes derived from the fusion of cancer and immune cell membranes. By summarizing the augmented PDT effects and the combined antitumor outcomes with other therapeutic modalities, this review aims to provide new insights into the biomedical applications of por-nMOFs and offer more references for the preclinical application of porphyrin-based photosensitizers.

An Analysis of the Effectiveness of the Fetša Tlala Initiative on the Food and Nutrition Security of Women Smallholder Farmers in Limpopo Province, South Africa

The Fetša Tlala Initiative is one of the development projects which were designed to contribute towards the achievement of the South African National Development Plan, 2030. The objective of the research was to analyse the effectiveness of the Fetša Tlala Initiative on the food and nutrition security of women smallholder farmers residing in Semaneng village, Limpopo Province, South Africa. The reason for focusing on women smallholder farmers was that whilst there has been research undertaken on the effectiveness of the Fetša Tlala Initiative, there has not been a study that focuses exclusively on women’s perspectives about the Initiative. The study, thus, sought to break exploratory ground about the effectiveness of the Fetša Tlala Initiative from the viewpoint of women smallholder farmers. The study, thus, adopted a qualitative research design in the form of an exploratory case study. Data were collected using a semi-structured interview guide from 16 participants who were purposefully selected. Face-to-face interviews were conducted and then reflected upon using an inductive thematic analysis. Results of the research indicated that the food security initiative had mixed results. On the positive side, and consistent with one objective of the broader Fetša Tlala Initiative, agricultural inputs increased amongst the women smallholder farmers, which assisted them to boost their yields and improve household food security. The Initiative also empowered the women smallholder farmers by strengthening their collective resilience in the face of adversities they encountered during the project. Notwithstanding these successes, the research findings also indicate that the effectiveness of the Initiative was reduced because of the inconsistent institutional support provided by the appointed Fetša Tlala Initiative project managers. The inconsistent institutional support represented a top-down planning and management strategy premised upon a centralised decision-making model. As a consequence of this style of planning and management, the beneficiaries could only respond by building localised resilience to the challenges. Such agency from the beneficiaries suggests that future Fetša Tlala projects might benefit from a decentralised decision-making planning and management strategy, that is inclusive of the project beneficiaries from the outset. The paper recommends continuation of the Fetša Tlala Initiative with emphasis on transforming the institutional support so that future beneficiaries are included in decision making processes from the inception phases through to completion of projects. Key words: Community resilience, Empowerment, Household food security, Resource constraints, Rural development

Recycling Sulfur-Poisoned Pd Catalysts via Thermal Atomization for Semi-Hydrogenation of Acetylene.

Palladium catalysts are highly efficient for a variety of chemical industrial processes but are prone to being affected by poisons during practical application. Sulfur is one of the major poisons in Pd-based catalysts. The recycling of deeply poisoned Pd species like Pd sulfides is challenging due to the strong Pd-S bond. Herein, we proposed a top-down strategy to degrade Pd sulfides and create Pd single-atom sites simultaneously by one-step thermal atomization. Pd4S model nanoparticles were successfully converted to Pd single-atom sites supported on nitrogen and sulfur-codoped carbon (Pd1/N, S-C) after loading them on ZIF-8 and thermal treatment. PdZn intermediates were formed during the atomization process. Density functional theory revealed that the formation of PdZn helped the generation of vacancies adjacent to metal nanoparticles, which prompted the atomization process. This strategy can be facilely applied to the atomization of sulfur-poisoned commercial Pd/C, which shows the potential for recycling commercial catalysts. The optimal Pd1/N, S-C catalyst showed good activity and much enhanced selectivity than Pd4S for the semi-hydrogenation of acetylene.

Urea/Thiourea Imine Linkages Provide Accessible Holes in Flexible Covalent Organic Frameworks and Dominates Self-Adaptivity and Exciton Dissociation.

Unraveling the robust self-adaptivity and minimal energy-dissipation of soft reticular materials for environmental catalysis presents a compelling yet unexplored avenue. Herein, a top-down strategy, tailoring from the unique linkage basis, flexibility degree, skeleton electronics to trace-guest adaptability, is proposed to fill the understanding gap between micro-soft covalent organic frameworks (COFs) and photocatalytic performance. The thio(urea)-basis-dominated linkage within benzotrithiophene-based COFs induce the framework contraction/swelling (intralayer micro-flexibility) in response to tetrahydrofuran or water. Adaptability of micro-flexible thiourea-COF with pore hydrophilicity not only contributes to the favorable mass transfer, but also enhances the accessible redox active sites, culminating in nearly 100% removal of micropollutant with low-energy dissipation in wastewater. The incorporating urea/thiourea into imine linkage facilitates polarization reduction and exciton dissociation within skeleton wall, inducing strong localization for holes. This transformation facilitates interchain charge transport and unbalanced distribution conducive to oxidative holes-mediated micropollutant decomposition.

Task-switching mechanisms under methamphetamine cravings: sex differences in cued and voluntary task-switching.

This study explored the effects of task-switching type and sex on the task-switching ability of methamphetamine abstainers, as well as the differences in brain mechanisms under drug cravings under drug cravings using near-infrared spectroscopy. Craving-inducing videos were used to arouse 20 methamphetamine abstainers (including 10 men), whose switching ability was then assessed using voluntary and cued task-switching exercises. During task-switching under methamphetamine cravings, the activation of the premotor cortex (PMC), supplementary motor area (SMA), frontal eye field (FEF), and dorsolateral prefrontal cortex (DLPFC) in women was significantly stronger than in men, while the activation of FEF in men was significantly stronger than in women. Voluntary task-switching induced stronger FEF activation than cued task-switching. During the latter, women exhibited stronger activation in the anterior prefrontal cortex (aPFC) than men. Both men and women showed brain lateralization during task-switching under methamphetamine cravings. Men tended to adopt proactive control and use a top-down dominant strategy to start a new task. Women, however, tend to use a bottom-up strategy focusing on inhibiting old tasks and emotional switching. Moreover, in cued task-switching, the result shows women paid more attention to emotional processing than did men, which suggests that different task-switching training programs should be developed according to sex.

Influence of different sample preparation approaches on proteoform identification by top-down proteomics

Top-down proteomics using mass spectrometry facilitates the identification of intact proteoforms, that is, all molecular forms of proteins. Multiple past advances have lead to the development of numerous sample preparation workflows. Here we systematically investigated the influence of different sample preparation steps on proteoform and protein identifications, including cell lysis, reduction and alkylation, proteoform enrichment, purification and fractionation. We found that all steps in sample preparation influence the subset of proteoforms identified (for example, their number, confidence, physicochemical properties and artificially generated modifications). The various sample preparation strategies resulted in complementary identifications, substantially increasing the proteome coverage. Overall, we identified 13,975 proteoforms from 2,720 proteins of human Caco-2 cells. The results presented can serve as suggestions for designing and adapting top-down proteomics sample preparation strategies to particular research questions. Moreover, we expect that the sampling bias and modifications identified at the intact protein level will also be useful in improving bottom-up proteomics approaches.

Carbon offsets compatible with the Paris Agreement to limit global warming: Call for a direct action

The societal commitment to combat climate change is reflected in the Paris Agreement with the primary focus to mitigate climate change by reducing or limiting greenhouse gas emissions. To facilitate the achievement of emission reduction targets, innovative carbon crediting and offsetting mechanisms have been developed. These mechanisms enable stakeholders to offset their emissions by using carbon offset credits if needed. These carbon offset methodologies can be classified into two main categories. The first category involves directly reducing greenhouse gas emissions from the environment through green and emission-capturing solutions, such as reforestation and carbon capture and storage. The second category focuses on achieving a relative reduction in carbon emissions by using or investing in technologies with lower carbon intensity compared to business-as-usual practices, such as renewable energy. The reduction achieved in this second category is assumed to be equivalent to not emitting the calculated amount of emissions. However, both categories generally do not address the emissions' sources directly. This study introduces a third approach by proposing the creation of a carbon offset market at the emissions' source, offering a novel way to directly tackle the origins of carbon emissions. This approach aims to prevent emissions from being released in the first place, directly addressing the source of emissions. It aligns with the precautionary principle, which advocates for proactive measures to prevent harm. This approach should not be confused with the non-consumption approach, which is a top-down strategy focused on reducing demand. Instead, it is a bottom-up approach that seeks to reduce the supply of emissions. This study developed a four-step methodology for implementing a carbon offset market at the source, starting with fixing fossil fuel extraction per producer, then fixing the profit margin per unit of extraction, then calculating the carbon content per unit of fossil fuel, and finally creating a carbon offset market at the source where one can offset their carbon footprint by paying an amount equivalent to the profit from fossil fuel extraction to the producer in exchange for a reduction in an equivalent amount of fossil fuel extraction. It also offers insights into emission reductions potential through this approach, along with cost calculations per unit of reduction based on historical records, literature data, and statistical databases. The main advantage of the proposed approach is its bottom-up focus on reducing the supply of emissions, which leads to tangible and quantifiable reductions in real time. This method eliminates potential loopholes in traditional methodologies, ensuring that the reductions are both immediate and verifiable.

Enhancing the effectiveness of heat adaptation strategies through citizen science-based outdoor thermal comfort

Urbanization and intensifying climate change expose populations in cities to escalating heat stress and associated health risks. Mitigating these challenges require comprehensive assessments that combine quantitative and qualitative data to develop effective heat wave response strategies and policies. Previous research has primarily focused on thermal sensation measured by individual biometrics within specific locations. However, limitations in data collection across large areas often lead to the neglect of the influence of diverse urban environments. This may disregard the importance of regional variations and citizen engagement in formulating effective heat wave mitigation strategies. This study explored the impact of heat wave frequency and intensity across various urban spatial types and assessed thermal sensation vote (TSV) among residents of Suwon City using a citizen science approach. Temperature measurements and subjective heat sensations were collected over a three-year period using homemade temperature sensors. The analysis investigated thermal sensation differences across spatial types—open high rise, open low rise, compact mid-rise, urban park, and lake park—utilizing boxplots, and examined TSV variations by age using the R program localized smoothing methodology. Results indicate significant variations in TSV across different urban areas, particularly when temperatures exceeded 32 °C. The TSV was highest in the lake park areas (average thermal sensation vote +3.5) and was comparatively lower in the open high-rise and open low-rise areas (average thermal sensation vote +2.0). A significant age-related trend was observed, with the highest TSV reported by the 19–30 age group. Heat sensitivity appeared to decrease among participants aged 41 and over. These findings highlight the limitations of traditional top-down heatwave response strategies, which may not adequately account for spatial variations and individual experiences. Conversely, a bottom-up approach that leverages citizen science can inform the development of tailored and proactive strategies that consider a region's specific conditions.

Exploring the Relationship between Top-Down and Bottom-Up Strategies in Listening

Exploring the Relationship between Top-Down and Bottom-Up Strategies in Listening

Porous silicon/carbon composites as anodes for high-performance lithium-ion batteries

Silicon anodes are promising for use in lithium-ion batteries. However, their practical application is severely limited by their large volume expansion leading to irreversible material fracture and electrical disconnects. This study proposes a new top-down strategy for preparing microsize porous silicon and introduces polyacrylonitrile (PAN) for a nitrogen-doped carbon coating, which is designed to maintain the internal pore volume and lower the expansion of the anode during lithiation and delithiation. We then explore the effect of temperature on the evolution of the structure of PAN and the electrochemical behavior of the composite electrode. After treatment at 400 -, the PAN coating retains a high nitrogen content of 11.35%, confirming the presence of C―N and C―O bonds that improve the ionic-electronic transport properties. This treatment not only results in a more intact carbon layer structure, but also introduces carbon defects, and produces a material that has remarkable stable cycling even at high rates. When cycled at 4 A g−1, the anode had a specific capacity of 857.6 mAh g−1 even after 200 cycles, demonstrating great potential for high-capacity energy storage applications.

An Overview of Transdisciplinary and Bottom-up Approach for Urban Resilience: The Case of Turkey

While top-down strategies have traditionally dominated urban planning in Turkey, recent shifts towards participatory practices and project-based policies have aimed to involve citizens in decision-making processes. Nevertheless, in the case of Turkey, these participatory models are inadequate for effectively addressing resilience. This article therefore discusses the role of participatory processes in creating resilient cities, as well as how to strengthen transdisciplinary (TR) and bottom-up approaches to urban participation in Turkish urban contexts. The article presents a theoretical framework that connects TR and bottom-up approaches based on existing literature, practices, and planning policy examples. It argues that TR approaches complement bottom-up approaches to urban governance by enhancing urban and social resilience, strengthening local communities, and reducing urban inequalities. Urban planning efforts that promote collaboration, incorporate multiple perspectives, and involve local communities in decision-making processes can address complex urban issues while also fostering long-term sustainability and resilience. This approach not only instills a sense of ownership and empowerment among urban residents but also leverages knowledge and skills to generate more effective and sustainable solutions. By creating a framework that promotes long-term education and citizenship awareness, urban governance can sustain urban resilience in a more viable manner over the long term in Turkey.

Evaluating the Robustness of Transfer Learning with Recipes on Small Data– Using Data of Birds as an Example

Processing small data in machine learning often leads to challenges like low accuracy and overfitting. To address these issues effectively, it is essential to assess the integrity of the underlying problem. One effective approach to tackling such challenges is to adopt a top-down strategy, focusing on adjusting and creating a suitable framework. In this paper, various techniques will be employed to fine-tune the model for optimization. Experiments will be conducted on six distinct datasets to enhance the model’s accuracy and prevent overfitting.

An analytic traction-displacement model for a reinforcing ligament bridging a crack at an arbitrary angle, including elastic, frictional, snubbing, yielding, creep, and fatigue phenomena

A micromechanical model is developed that generates analytic expressions for the crack displacement vector u given an arbitrary far-field stress state σa for a crack that is bridged by an array of ligaments oriented at an arbitrary angle with respect to the crack plane. The model is applicable to various materials, e.g., fibrous ceramic composites, or polymer composites reinforced by stitches or z-pins or woven tows, and deals with interfacial friction, enhanced friction due to increased contact pressure (“snubbing”), and the possibility of ligament deflection enabled by yield or damage. The model also conveniently incorporates ligament failure and rate dependent phenomena (fatigue or creep). Adaptability of the model is enabled by the definition of a standard Reference Model, which generates analytic expressions for the crack displacement for given possible yield, ligament deflection, and friction and snubbing effects and is invariant for all geometrical and material choices. The switching on or off and the strengths of all phenomena are governed by assigning values to a handful of material parameters. The material parameters will generally be calibrated against data in a top-down strategy, the model thereby mapping material selection onto engineering fracture via the predicted bridging relationship u[σa]. The relationship u[σa] can depend strongly on bi-angular ligament orientation. Yield and deflection can change u[σa] qualitatively, e.g., by creating fracture surface contact even when σa includes substantial opening tension. Snubbing has significant effects, including possible stabilization of the pullout of a finite ligament. Since model output is computed via analytic expressions, its speed will support the model's use in large-scale material simulations or as constraining physical information in machine learning algorithms.

Engineering Microbial Consortia as Living Materials: Advances and Prospectives.

The field of Engineered Living Materials (ELMs) integrates engineered living organisms into natural biomaterials to achieve diverse objectives. Multiorganism consortia, prevalent in both naturally occurring and synthetic microbial cultures, exhibit complex functionalities and interrelationships, extending the scope of what can be achieved with individual engineered bacterial strains. However, the ELMs comprising microbial consortia are still in the developmental stage. In this Review, we introduce two strategies for designing ELMs constituted of microbial consortia: a top-down strategy, which involves characterizing microbial interactions and mimicking and reconstructing natural ecosystems, and a bottom-up strategy, which entails the rational design of synthetic consortia and their assembly with material substrates to achieve user-defined functions. Next, we summarize technologies from synthetic biology that facilitate the efficient engineering of microbial consortia for performing tasks more complex than those that can be done with single bacterial strains. Finally, we discuss essential challenges and future perspectives for microbial consortia-based ELMs.

Bottom-up construction of defective TiO2 microspheres with hierarchical architectures and controlled crystallites for visible-light photocatalysis

Defect-engineering of TiO2 materials has emerged as an effective strategy to enhance the light adsorption and improve the photocatalytic activity under visible-light. However, the designing and fabricating of hierarchically structured TiO2 with controllable crystalline phases and stable structure defects is challenging and rarely reported. Herein, we present a novel bottom-up synthesis strategy to prepare defective TiO2 microspheres with hierarchical architecture and abundant phase junctions. The phase composition and defect concentration of the obtained TiO2 can be easily adjusted by regulating the amount of urea. Moreover, the formation mechanism of hierarchical defective TiO2 microspheres has been investigated. Notably, compared with the defective TiO2 prepared with traditional top-down strategies, more bulk Ti3+ and oxygen vacancies can be generated, which is crucial for the stability of materials. Such integration of unique hierarchical architecture, stable structure defects as well as abundant anatase/rutile phase junctions not only result in the narrowed band gap and improved visible-light absorption, but also allow the fast interfacial electron transfer and better charge separation, leading to enhanced photocatalytic activities in RhB degradation and hydrogen generation under visible light (λ>400 nm) irradiation.

Public Perception of the Food Estate Program of Cassava Cultivation as a Strategic Logistic Reserve in Realizing Regional Food Security in Gunung Mas Regency, Central Kalimantan

This research examines the implementation challenges of Indonesia’s Strategic Logistics Reserve Development Program (CLS), specifically focusing on cassava cultivation in Gunung Mas Regency. Launched as part of the 2020-2024 National Strategic Program (PSN), the initiative aims to address potential food security issues exacerbated by the COVID-19 pandemic, land degradation, and climate change. The program's primary goal is to develop food estates to enhance national food security. The study employs a mixed-methods approach, including interviews with key stakeholders, analysis of program documentation, and community surveys to assess the program’s effectiveness and impact. Key findings reveal significant obstacles, including policy misalignment, unsuitable land conditions for cassava, inadequate infrastructure, and a top-down implementation strategy that lacks local community involvement. Results indicate that while the program has led to some positive outcomes, such as job creation and increased food independence, it has also faced severe criticism. Issues such as suboptimal cassava growth, environmental damage, and socio-cultural impacts have led to negative public perceptions. The failure to issue a crucial Presidential Decree, poor inter-governmental coordination, and inadequate understanding of the program by local communities have compounded these challenges. Analysis suggests that the program’s shortcomings are due to a combination of regulatory delays, environmental mismatches, and insufficient stakeholder engagement. To address these issues, the research recommends a comprehensive evaluation of the program, restoration of damaged lands, enhanced community participation, and stronger environmental safeguards. Improved collaboration between central and regional governments and better alignment of policies and infrastructure are essential for the program’s success in achieving its food security objectives.

Distinct neural pathway and its information flow for blind individual's Braille reading

Natural Braille reading presents significant challenges to the brain networks of late blind individuals, yet its underlying neural mechanisms remain largely unexplored. Using natural Braille texts in behavioral assessments and functional MRI, we sought to pinpoint the neural pathway and information flow crucial for Braille reading performance in late blind individuals. In the resting state, we discovered a unique neural connection between the higher-order ‘visual’ cortex, the lateral occipital cortex (LOC), and the inferior frontal cortex (IFC) in late blind individuals, but not in sighted controls. The left-lateralized LOC-IFC connectivity was correlated with individual Braille reading proficiency. Prolonged Braille reading practice led to increased strength of this connectivity. During a natural Braille reading task, bidirectional information flow between the LOC and the IFC was positively modulated, with a predominantly stronger top-down modulation from the IFC to the LOC. This stronger top-down modulation contributed to higher Braille reading proficiency. We thus proposed a two-predictor multiple regression model to predict individual Braille reading proficiency, incorporating both static connectivity and dynamic top-down communication between the LOC-IFC link. This work highlights the dual contributions of the occipito-frontal neural pathway and top-down cognitive strategy to superior natural Braille reading performance, offering guidance for training late blind individuals.

PROPOSAL FOR AN EMBRYONIC MODEL TO PROMOTE SMART CITIES, IMPLEMENTED IN A BOTTOM-UP FORMAT, APPLIED TO THE AMAZON REGION

Environmental changes, many of which result from human negligence, have driven managers to adopt sustainable practices that adhere to the concept of Smart Cities, a concept that is becoming popular among administrators of Brazilian metropolises. This movement has been corroborated by ABNT standards and the federal government. However, in less developed regions such as Northern Brazil, where challenges are greater and resources are limited, traditional top-down urban development strategies such as BRTs have proven inefficient as initial solutions. This article investigates the feasibility of implementing projects for Smart Cities in the Amazon region given the scarcity of resources. It proposes an alternative bottom-up model titled Smart Launch, which is shown to be more viable for sustainable development in regions with these characteristics. The model recommends starting with smaller and more manageable projects that can be easily implemented without extensive bureaucracy or significant investments. Once established, the model can be quickly replicated and adapted in other locations. The case of the UsiPaz (Peace Plants) in Pará exemplifies the success of this approach and has been taken as a case study, showing significant reduction in violence rates and an increase in the sense of community belonging, as evidenced by qualitative research through semi-structured interviews with managers from three plants in different neighborhoods of the metropolitan region of Belém.

Human relevance of in vivo and in vitro skin irritation tests for hazard classification of pesticides

Background: Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations. One of the barriers to adoption of these methods in this sector is low concordance with results from the Draize rabbit test, particularly for chemicals within the mild to moderate irritation spectrum. Methods: This review compares and contrasts the extent to which available models used in skin irritation testing mimic the anatomy and physiology of human skin, and how each aligns with the known key events leading to chemically-induced adverse skin irritation and corrosion. Doing so fully characterizes the human relevance of each method. Results: As alternatives to the rabbit Draize test, several protocols using ex vivo, in chemico, and in vitro skin models are available as internationally harmonized test guidelines. These methods rely on a variety of models of human skin, including excised rodent skin, synthetic biochemical models of barrier function, cell culture systems, and reconstructed human tissue models. We find these models exhibit biological and mechanistic relevance aligned with human skin irritation responses. Further, recent retrospective analyses have shown that the reproducibility of the Draize test is less than 50% for mild and moderate responses, with many of the replicate predictions spanning more than one category (e.g., a moderate response reported in one study followed by a non-irritant response reported in another study). Conclusions: Based on this comparative evaluation, we recommend top-down and bottom-up testing strategies that use the most human relevant in vitro test methods for skin irritation and corrosion classification of pesticides and pesticide formulations. To further discriminate among mild and non-irritant formulations, optimization of a cytokine release protocol and subsequent analyses of reference formulation test results is recommended.