N = 201). The results show that design aesthetics has a positive influence on consumers’ purchase intention through perceived value and that Chinese traditionality moderates the indirect influence of perceived value. The contributions and implications are discussed.As a symbol of Chinese culture, the Palace Museum undertakes the mission of spreading Chinese culture. In recent years, through the innovative integration of traditional culture, the Palace Museum has provided a series of cultural and creative products to meet consumers’ personalized expectations, which has attracted wide attention from both academia and practice. Cultural and creative products, as one of the means of cultural dissemination by museums, affect the revenue and sustainable development of museums. Thus, it is of great significance to study how consumers arrive at the decision to purchase these products. This article explores the influence mechanism of design aesthetics on consumers’ purchase intention ( With the development of the economy, Chinese people are more likely to pursue quality of life and spiritual culture . As a plThe rapid development of the cultural and creative industry is not only meeting the spiritual and cultural needs of contemporary people but also improving the financial situation of museums themselves, which is important for their sustainable improvement. By promoting cultural products, museums can avoid financial struggles and enhance their surroundings and operating conditions , which iIf a museum intends to survive the fierce market competition, it needs to also survive severe challenges, such as resource constraints, fierce competition, and public concerns . In the The overwhelming acceptance of cultural and creative products by the public is reflected in their sales volume. Therefore, it is of great importance to study consumers’ intention to purchase cultural and creative products, which affects whether traditional culture can be transmitted in a lasting and far-reaching manner. Consumer purchase intention is the basis of consumer purchase behavior , and it In behavioral research, the concept of aesthetics was first proposed by Fechner . Its purCompared with business products, the cultural and innovative products of museums are viewed more as carriers of cultural expression rather than commodities. Therefore, when they are sold, consumers’ doubts are easily aroused, and this may weaken consumers’ purchase intention and hinder the development of cultural and creative industries. However, existing studies have pointed out that design aesthetics can significantly affect consumer behavior , and thaH1: Design aesthetics is positively correlated with consumers’ purchase intention.The notion of perceived value was first presented in Porter’s competitive advantage . ThereafIn this article, we endorse that perceived value performs a mediating function in the relationship between design aesthetics and consumers’ purchase intention. Existing literature suggests that although cultural and creative products can also be questioned by consumers when they are sold as commodities, design aesthetics can alleviate such feelings. On the one hand, design aesthetics can improve product functions , which cIn addition, based on the analysis of utility theory, perceived value is a trade-off between the benefits obtained from the transaction and the costs paid by consumers. No matter the consumption situation, the purchase purpose of consumers is to obtain maximum utility at the minimum cost. Therefore, under the condition of their own limited resources, consumers will first decide whether to buy goods based on their subconscious judgment of the utility of the goods. The higher the value of goods as perceived by consumers, the more willing they are to pay . Eggert H2: Perceived value mediates the relationship between design aesthetics and purchase intention.Chinese traditionality is a cultural variable that describes the fundamental cognition, concept, attitude, conduct and values below the impact of regular culture, and refers to the degree of personal identification with traditional Chinese values . Chinesevia the formation of cognition through the interpretation of culture , indicating good discriminative validity among the variables. The details are shown in Confirmatory factor analysis was performed using structural equation modeling (Amos 25.0), and the data fit indexes of the four-factor model met the fitting requirements , which adequately supports Hypothesis 1. Additionally, design aesthetics also has a positive relationship with perceived value , and perceived value is significantly correlated with purchase intention . Moreover, Chinese traditionality is positively related to design aesthetics , perceived value , and purchase intention .As shown in p < 0.001, Model 2), which supports Hypothesis 1. Model 4 added mediation variables based on Model 2, and the results of Model 4 displayed a significant mediating effect of perceived value on the relationship between design aesthetics and purchase intention . Although it was decreased for the regression coefficient of design aesthetics on consumers’ purchase intention , perceived value still had a significant impact on purchase intention . That is, perceived value partially mediates the influence of design aesthetics on purchase intention. Thus, Hypothesis 2 is supported.As shown in p < 0.001), proving the moderating effect of Chinese traditionality and verifying the inference of Hypothesis 4. In this study, the SPSS PROCESS macro was used to test the mediating effect of Chinese traditionality. According to the results obtained, in the context of low Chinese traditionality, the indirect effect of perceived value through the relationship among design aesthetics and purchase intention was non-significant . In the context of high Chinese traditionality, perceived value had a significant mediating effect between design aesthetics and purchase intention . This suggests that the mediating effect of perceived value is affected by different levels of Chinese traditionality. That is, the higher Chinese traditionality is, the stronger the mediating effect of perceived value. In addition, according to the index of moderated mediation, the indirect effect of perceived value between design aesthetics and purchase intention was significant . Therefore, Hypothesis 4 is supported.via perceived value and vice versa.Based on Chinese cultural background, this study concentrates on the cultural and creative products in the Palace Museum, which respond to the appeal of promoting traditional Chinese culture and provide a new way to improve consumers’ purchasing intention of cultural and creative products. Specifically, our study explores how design aesthetics affects consumers’ purchase intention of cultural and creative products through perceived value. The results show that design aesthetics has a positive influence on purchase intention; perceived value plays a mediating role between design aesthetics and purchase intention; Chinese traditionality not only moderates the relationship between design aesthetics and perceived value but also significantly moderates the mediating role of perceived value between design aesthetics and purchase intention. Specifically, the higher the level of Chinese traditionality in a consumer, the stronger the influence of design aesthetics on purchase intention This research has the following theoretical significance: First, design aesthetics is introduced into the cultural and creative industry to fill the gaps in previous studies and expand the theoretical research of design aesthetics. Existing studies on design aesthetics mainly focus on the field of fine arts and design, and few studies apply design aesthetics to the cultural industry. This study explores the influence mechanism of design aesthetics on consumers’ purchase intention, which is innovative to some extent.Second, it enriches and deepens theoretical research on Chinese traditionality. The previous research on the Chinese tradition typically focuses on management and explores the influence of Chinese traditionality on leadership style and employee performance. This study, however, introduces Chinese traditionality into the field of cultural entrepreneurship, explores the moderating role of Chinese traditionality in the consumer decision-making process—that is, when considering factors affecting consumers’ purchase intention, it is necessary to consider both product characteristics and cultural attributes.This study aims to explore how design aesthetics affects consumers’ purchase intention of cultural and creative products of the Palace Museum, and the research results can provide some practical enlightenment for practitioners and designers of cultural and creative products.Initially, product managers should be deeply aware that consumers focus on experiential consumption and are becoming increasingly fond of innovative products. Thus, product managers ought to pay more attention to the design aesthetics of cultural and innovative products, integrate Chinese traditionality into cultural and creative products and ensure that the products are innovative and unique. They can bring in interdisciplinary talents who no longer solely understand the history and culture of the museum collection but also have additional knowledge about the development and design of cultural and innovative products and can improve product characteristics, thereby meeting the needs of consumers.via such immersive and interactive courses, and the perceived value of products can be enhanced. This will lead to the purchase of more products and the realization of the sustainable development of museums.Moreover, when designing cultural and innovative products, designers should pay attention to the perceived value of the products, as it is only when consumers feel the products are valuable that they will purchase them. The following specific measures can be taken. The first is to combine culture with virtual reality technology to develop digital cultural and creative products with personalized experiences. Second, museums can launch DIY projects online and offline according to their collections, so consumers can participate in the production process of cultural and innovative products and further understand the value that the products represent. Third, museums can cooperate with colleges to set up behavior experiential courses such as craft making, situation simulation, and so on. Participants can acquire historic and cultural knowledge Finally, practitioners should strike a balance between innovation and the seriousness of the Chinese cultural tradition. Instead of excessively imitating traditional culture to meet the demand of consumers for personalized experience, managers should pay attention to Chinese tradition and develop designs and products based on historical facts. The cultural and innovative industry must and can only serve as “the icing on the cake” of museums. The original intention of spreading the traditional Chinese culture should be adhered to so that consumers can learn traditional Chinese culture in the process of happy shopping.Although this article supplements the research on consumers’ purchasing intention with some innovation and insights, it also has some limitations. First, the participants selected for this study are concentrated in some universities in eastern China. Although representative to a certain extent, the sample size may not be large enough, which may affect the universality of the results. As such, future studies could further expand the sample size. Second, this study focused on purchase intention rather than actual purchase behavior. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.YL developed the theoretical framework and worked on literature review and manuscript writing. JL developed the theoretical framework and worked on data collection and analysis. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The loss of mobility is a common trait in multiple health conditions  and is associated with reduced quality of life. In this context, being able to monitor mobility in the real world, is important. Until recently, the technology was not mature enough for this; but today, miniaturized sensors and novel algorithms promise to monitor mobility accurately and continuously in the real world, also in pathological populations. However, before any such methodology can be employed to support the development and testing of new drugs in clinical trials, they need to be qualified by the competent regulatory agencies . Nonetheless, to date, only very narrow scoped requests for regulatory qualification were successful. In this work, the Mobilise-D Consortium shares its positive experience with the European regulator, summarizing the two requests for Qualification Advice for the Mobilise-D methodologies submitted in October 2019 and June 2020, as well as the feedback received, which resulted in two Letters of Support publicly available for consultation on the website of the European Medicines Agency. Leveraging on this experience, we hereby propose a refined qualification strategy for the use of digital mobility outcome (DMO) measures as monitoring biomarkers for mobility in drug trials. The consequences of mobility loss are significant and wide reaching, leading to loss of independence and quality of life and being associated with future adverse events such as falls.The loss of Loss of mobility can take different forms for different diseases, which highlights the need to understand mobility not as a single variable but as a combination (pattern) of mobility constructs. For example, multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. MS affects different clinical domains including ambulation; gait is one of the most important and valued functions for patients with MS and its dysfunction is one of the main contributors to poor quality of life in such patients . ChronicThus, the Mobilise-D consortium selected MS, COPD, PFF and PD which despite different etiopathogenesis and disease presentation patterns, are all known to significantly impact patients' mobility. PFF produces a sudden and total loss of mobility in usually older patients , who then recover their locomotor function in variable degrees and at different speed. MS, which is usually diagnosed in people in their 20–40 s, is characterized by flares, and progresses quite heterogeneously between patients. PD is usually diagnosed in patients over 60 years old and tends to have a relatively steady progression. COPD, which is commonly misdiagnosed, may not be diagnosed until the disease is advanced, on average in people around 40 years old, and is known to have little impact on mobility in its early stages. Thus, these four diseases are a good sample of the wide range of modalities with which the loss of mobility manifests across diseases.As mobility can be a fairly vague concept, we propose the following definitions:Mobility—physical mobility, the ability to move freely and easily without a vehicle. Mobility can be evaluated in terms of capacity, patient's perception, and performance.- Mobility capacity—intensity with which the patient can perform an assigned motor task, as assessed within a clinical assessment.- Mobility perception—mobility as it is perceived by the patients themselves in their daily life; mainly assessed with questionnaires and diaries.- Mobility performance—mobility measured in the real world and over a sufficiently long period of time, for example with wearable digital devices.- Mobility disability—loss of mobility performance. Mobility Performance is a monitoring biomarker of the construct Mobility Disability. Mobility Capacity and Mobility Perception can be used as surrogate biomarkers of the construct Mobility Disability.- Mobility-related activities of daily living—ADL are those activities that allow an individual to live independently in a community. Of the seven ADL normally considered six are related to mobility: Bathing and Grooming, Dressing and Undressing, Meal Preparation and Feeding, Functional Transfers, Safe Restroom Use and Maintaining Continence, and Ambulation.- Digital mobility outcomes—DMOs are digitally measured outcomes used to assess an individual's mobility, e.g., in terms of gait spatiotemporal features, walking bout characteristics, and physical activity .- From the patients' perspective, mobility disability is the inability to perform activities of daily life, especially those repeated on a regular basis; ideally, we should monitor mobility in the real world, and over a sufficiently long period of time to capture all repeating patterns in the patient's lifestyle, so to notice such changes. However, to date there are no tools qualified by regulatory authorities to monitor mobility in the real world for sufficiently long time .Inertial Measurement Units (IMU) that integrate accelerometers, gyroscopes and magnetometers are in principle capable of measuring the position, velocity, and acceleration of the center of mass of a human body. IMUs became miniaturized enough to be wearable a while ago; however, the signal processing algorithms that quantify mobility outcomes from raw signals generated by the sensors are unreliable for subjects walking slowly, or with unusual gait patterns because of their health condition. The IMI-funded Mobilise-D consortium 1 is currThe second request for qualification advice which was submitted in June 2020, was also followed up with a Letter of Support summarizing our second submission in May 2021The rationale for seeking regulatory advice was related to a new methodology developed by the Mobilise-D consortium to quantify mobility performance over 7 consecutive days and in a real-world setting, using wearable sensors. The intention is to use the DMOs provided by this new methodology:- As disease-specific monitoring biomarkers to account for mobility performance in assessing the efficacy of new treatments for patients affected by COPD, MS, and PFF, in addition to PD patients as discussed in the initial Qualification Advice (EMA/CHMP/SAWP/128601/2020). These new monitoring biomarkers will complement those already in use, that account for a patient's perception of mobility  clinical endpoints that are more difficult, expensive, or time-consuming to use than the DMOs.The briefing book posed three key questions to EMA:1) Does the EMA agree that the clinical validation of the use of DMOs as disease-specific monitoring biomarker of mobility performance for each of the three additional diseases under consideration  is fit for purpose?2) Does the EMA agree that the clinical validation of the use of DMOs as potentially generic and disease-independent monitoring biomarkers of mobility performance for all four diseases under consideration  is fit for purpose?3) The Applicant plans to perform a 24-month observational study to support the validation of disease-specific DMOs in four disease areas and of disease-independent DMOs to assess the mobility performance of patients. Does the EMA agree with the study design (incl. patient characteristics), sample size, endpoints, and approach to evaluate responsiveness?For the clinical validation study, the Consortium proposed a 24-month longitudinal observational cohort study to be conducted in 17 sites located in 10 EU countries. The objective of the study is to identify and validate four disease-specific DMOs and a disease-independent DMO that can assess the mobility performance of the patient. The clinical validation study will use two technically validated devices and a suite of technically validated algorithms to quantify the DMOs. The study will enroll 2400 subjects with PD, COPD, MS and PFF, resulting in four different disease cohorts (with 600 participants in each). To have a generalizable clinical population, the 17 consortium partners provide a good geographical representation across Europe: the cohorts maximize variability in mobility difficulties, provide diverse representation of culture, age, gender, and health care services . The primary objective is to assess the capacity of DMOs to predict global and disease-specific clinical outcomes using relevant endpoints:- Global  endpoint: the Late-Life Functional Disability Index (LLFDI).- Disease-specific endpoints: fall frequency for patients with PD and MS; occurrence/rate of moderate to severe exacerbations for patients with COPD; and admission to care/nursing home following PFF.In addition to the general eligibility criteria valid across all cohorts that were selected to enhance subjects' compliance and adherence to the protocol and to minimize bias , disease-specific inclusion and exclusion criteria have been defined. This will help focusing on those subgroups of patients who would benefit most from the outcomes of the project, while maximizing inclusiveness , and further enables the stratification of subjects in disease severity subgroups , which is key in the proposed validation plan for all disease specific DMOs.The proposed clinical validation concept was that each DMO should be tested in terms of construct validity, predictive capacity, and ability to detect change in clinically relevant variables. The Consortium proposed to demonstrate construct validity by showing that DMOs correlate with related constructs, they distribute differently across known (sub)groups of patients expected to have a different mobility performance, and do not correlate with constructs that are not correlated with mobility . Following the same approach proposed for PD in the first qualification advice request, predictive capacity would be demonstrated by showing that DMOs predict widely accepted clinical endpoints for PFF, COPD and MS. Last, it was proposed to demonstrate that DMOs obtained within the Mobilise-D observational study can detect change by testing longitudinal validity against therapy changes and/or changes in health outcomes meaningful to patients and/or clinicians and calculating the minimal clinically important difference  using meaningful changes in constructs relevant to patients and clinicians as anchors (such as changes in SPPB score or change in LLFDI disability sub-score). The Consortium also proposed to try evaluating the responsiveness of DMOs using the observational study (by using changes in therapies required by the evolution of the disease), before resorting to interventional trials. For the purpose of comparing DMOs across diseases, we proposed to use the Late Life Function and Disability Instrument (LLFDI).The most important elements of the advice are:- EMA agreed on the distinction between mobility performance, mobility capacity, and mobility perception.- EMA agreed that the construct mobility performance could provide valuable additional information about mobility disability in the four diseases of interest.- EMA supported the overall clinical validation concept.- Since mobility performance has never been evaluated so far in a regulatory submission, there is no gold standard to be used. The measurements may or may not correlate with other known mobility outcomes such as mobility capacity or mobility perception.- EMA agreed that, if a MCID of disease specific outcomes is justified, the observational multicentre study may be adequate to identify the most appropriate DMO per disease in terms of its ability to detect change.- EMA considered the observational multicentre clinical study proposed by the Mobilise-D consortium as an important step toward the validation of DMOs, but only exploratory. With respect to the ability to detect change, EMA considered it necessary to evaluate responsiveness also with at least one interventional randomized clinical trial for each disease of interest.EMA working party experts believed that monitoring mobility performance in real world settings may provide an additional dimension of mobility, in addition to patient's mobility perception and mobility capacity across the four diseases. But the discussion revealed that it remains unclear which of these dimensions of mobility is perceived as most important by patient and health care professionals.1, 6MWT and exacerbations for COPD), were recognized as standards for the assessment of the disease status and progression. However, considering that many of these endpoints are themselves evaluations of mobility capacity or mobility perception, a certain degree of circularity was involved.The disease-specific endpoints proposed by the Mobilise-D consortium to validate the predictive capacity of the DMOs 1.3 Mobility performance1. MobilityHypothesis #1—New algorithms are available that provide accurate and reliable quantification of various DMOs to measure mobility performance in real life over a period of seven days using appropriate wearable IMU sensors.- Hypothesis #2— The loss of mobility performance is perceived by both patients and medical professionals as a very important aspect in all four diseases of interest . Thus, every treatment should be evaluated also on the effect it has on mobility performance, both in terms of efficacy  and safety .- Hypothesis #3—Selected DMOs when used as monitoring biomarkers of mobility performance are superior to other currently used biomarkers for mobility capacity or mobility perception when these are used as surrogate biomarkers for mobility performance.- The qualification of a new methodology/tool for drug development is organized like the testing of a scientific theory, in the Popperian sense. We start with a set of hypotheses to be tested, and then we propose a qualification plan to the regulatory agency where we will attempt the experimental falsification of each of these hypotheses. If the advice of the regulatory agency is supportive of the proposed qualification plan, and if the results of the experimental studies do not falsify any of the hypotheses, a qualification opinion can be requested, which if positive enables, from then on, the use of the new methodology/tool in any marketing authorization request, without any further scrutiny. Thus, it is important to state the hypotheses that the whole qualification process aims to test:Hypothesis #1 requires no further explanation.The need to provide evidence in support of hypothesis #2 has been stated in various documents from EMA and FDA. While all practitioners in our consortium agree that the ability of moving around in daily life is a key determinant of the quality of life of the patient, no regulatory evidence has been produced so far to support that this is indeed the case.The rationale behind hypothesis #3 is the following. There is confusion on how to appropriately measure mobility. Such confusion arises because until recently mobility performance could not be measured reliably and thus other biomarkers of mobility, such as mobility capacity and the patient's perception of mobility were used as surrogate biomarkers for mobility performance. However, this relation of surrogacy was rarely made explicit. Our hypothesis is that the DMOs measured with the Mobilise-D methodology will be better at monitoring mobility performance than other indicators such as mobility capacity and mobility perception, which are only surrogate biomarkers of mobility performance in the real world.For a defined context of use, the following qualification plan relies on a technical validation to validate hypothesis #1, a qualitative research program to validate hypothesis #2, and a clinical validation to validate hypothesis #3.The Mobilise-D DMOs are used for monitoring mobility in the regulatory evaluation of a new drug in diseases, where mobility disability is an important sign of the disease. Mobilise-D DMOs are used to confirm that the new drug causes a progression of mobility disability that is significantly slower than the placebo or comparator. Mobility disability is a secondary efficacy endpoint of the interventional RCT, as measured with the monitoring biomarker Mobilise-D DMO.The testing of hypothesis #1, relevant for all three proposed contexts of use, requires a detailed technical validation. The technical validation plan  was apprclinical meaningfulness of outcomes measures of mobility performance  as such clinical outcome. This is consistent with the idea that from a patient's perspective, mobility disability is the loss of specific MRADL in their daily life.Using the data collected in the observational study, we plan to demonstrate for the Mobilise-D DMOs construct validity and predictive capacity. With respect to the ability to detect change we will try to demonstrate longitudinal validity and calculate the MCID for each disease. Following the EMA advice, to evaluate responsiveness it will be necessary to test the DMOs in an interventional double-blind RCT for each disease of interest.Following the staged approach recommended by EMA, and thanks to the two qualification advices they provided, we now have a clear qualification plan. The next step is to present such qualification plan to the FDA through the CDER Clinical Outcome Assessment Qualification ProgramWhile recent technological improvements now enable to monitor mobility continuously and reliably, the regulatory qualification of digital mobility outcome measures to support labeling claims in the market authorization process has so far been limited.In this study, the Mobilise-D consortium summarizes its successful interaction with the European Medicines Agency that led to two publicly available Letters of Support on the use of Digital Mobility Outcomes as biomarkers of disease status and progression in four clinical indications.By sharing its positive experience and outlining a revised regulatory strategy resulting from the two Qualification Advices received, the Mobilise-D consortium aims to provide a valuable example and a potential starting point (regulatory strategy) for future requests for regulatory qualification.via mobility biomarkers derived from continuous recordings of wearable sensors.The regulatory strategy hereby outlined may inform future requests for marketing authorization of new drugs based on evidence gathered The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.This study is part of a large collaborative initiative, involving several members of the Mobilise-D consortium. MV, MT, WD, IK, SH, CM, BC, JG-A, CB, WM, TT, BS, GD, SC-R, and LR wrote the manuscript and performed the research. MV, WD, IK, SH, and LR designed the research. All authors contributed to the article and approved the submitted version.This work was supported by the Mobilise-D project that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 820820. This JU receives support from the European Union's Horizon 2020 research and innovation program and the European Federation of Pharmaceutical Industries and Associations (EFPIA). Content in this publication reflects the authors' view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained herein. CM was supported by the NIHR Sheffield Biomedical Research Center (BRC).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care (DHSC).


Traumatic Brain Injury (TBI) is one of the leading causes of injury related mortality in the world, with severe cases reaching mortality rates of 30-40%. It is highly heterogeneous both in causes and consequences, complicating medical interpretation and prognosis. Gathering clinical, demographic, and laboratory data to perform a prognosis requires time and skill in several clinical specialties. Machine learning (ML) methods can take advantage of the data and guide physicians toward a better prognosis and, consequently, better healthcare. The objective of this study was to develop and test a wide range of machine learning models and evaluate their capability of predicting mortality of TBI, at hospital discharge, while assessing the similarity between the predictive value of the data and clinical significance.The used dataset is the Hackathon Pediatric Traumatic Brain Injury (HPTBI) dataset, composed of electronic health records containing clinical annotations and demographic data of 300 patients. Four different classification models were tested, either with or without feature selection. For each combination of the classification model and feature selection method, the area under the receiver operator curve (ROC-AUC), balanced accuracy, precision, and recall were calculated.Methods based on decision trees perform better when using all features  but other models require prior feature selection to obtain the best results . Additionally, Random Forest and XGBoost allow assessing the feature's importance, which could give insights for future strategies on the clinical routine.Predictive capability depends greatly on the combination of model and feature selection methods used but, overall, ML models showed a very good performance in mortality prediction for TBI. The feature importance results indicate that predictive value is not directly related to clinical significance. Traumatic Brain Injury (TBI) is an extremely incident condition worldwide , accountPrevious studies revealed that early treatment is beneficial for TBI recovery. It is of great importance to conduct early interventions and treatment before secondary injury and brain deterioration happen. However, a precise prognosis of TBI outcome is difficult due to the high heterogeneity of the disease, i.e., a wide range of lesions  and affected areas of the brain  , 13. To Considering that TBI is often an emergency case, increasing efficiency in data analysis is important. Therefore, many previous studies were dedicated to developing outcome predictors based on machine learning (ML) algorithms , which hCRASH  and IMPATherefore, the defined goal is predicting mortality at discharge of pediatric patients with TBI, using demographic and clinical data as well as CT findings gathered during the patient stay at the hospital. To do so, a variety of models and feature selection processes are explored, to understand the dependence of prediction quality on the used features and model type and which combination of model and feature selection methods works best in this specific cohort of patients. Besides evaluating feature value for the prediction, the coherence with their clinical significance is also discussed in detail. A pediatric patient dataset was selected as the focus of this exploratory study because despite being less studied, it is utterly important to develop medical decision support tools for this group of patients as well. Pediatric TBI has been thoroughly studied but mostly from a clinical and epidemiological perspective –24. FromThe methods used in this study are summarized in The dataset used in this study is the Hackathon Pediatric Traumatic Brain Injury (HPTBI) dataset . It compThe highest portion of this cohort is infants under the age of 1 year old, as shown in A total of 96 features of different types, summarized in First, features related to the Functional Status Scale (FSS) were removed from the data since FSS could not be assessed for patients who perished. Therefore, they are not useful as there is a high correlation between mortality and missing data on these features.n binary variables, where n was the number of categories in that variable. Data were normalized by scaling each feature to have a unit norm. After the feature selection methods (Refer to Section 2.3), due to the high imbalance of the dataset and its smaller size, the data were oversampled using Synthetic Minority Oversampling Technique (SMOTE) (One Hot Encoding (OHE) was performed to transform categorical features into  (SMOTE) . With SMFeature selection allows us to decrease data dimensionality, hence reducing computation cost, by removing redundant features or features that contribute little to the predictive capability of the model.Three methods were tested, starting with a simple feature selection method, using the Koehrsen's Feature Selector (KFS) tool by Koehrsen . The firThen, Principal Component Analysis (PCA) and Independent Component Analysis (ICA) were tested to verify if these highly used methods in ML outperform the simpler first approach. PCA and ICA are two extremely different approaches to dimensionality reduction since they provide different feature spaces obtained from the data , 32. In In this study, a wide range of modest models was presented to establish baseline results and provide a foundation on which to improve. Four machine learning-based methods were implemented in this study, covering different strategies of learning and allowing a heterogeneous analysis of the data since there is no previous knowledge about TBI prediction in the pediatric cohort. For this reason, were implemented methods based on decision trees, neural networks, and clustering. Artificial Neural Networks are tested in this study as it is a highly used method for a variety of tasks, including TBI mortality prediction . KNN wasSince one of the objectives of this study is to quantify and qualify the predictive value of features, models such as Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) are useful , 33, as KNN and ANN present limitations when speaking of feature importance, which is one of the reasons that they are inherently harder to interpret. For KNN, the distance between clusters could be used to indirectly obtain feature importance, and for ANN, the weights of the nodes could also be used for similar purposes. However, the methods to achieve explanations for these models are another area of expertise  that falls out of the scope of such a preliminary study. Another approach to make these models more interpretable is to pair them with an external feature selection method, such as Koehrsen's Feature Selector as it is done in this study.Before training, 20% of the data is held out for the final testing. The remaining 80% is used for training. This proportion was chosen based on previous study . To traiThe choice of hyperparameters has always been a major focus of study in machine learning. It is extremely task and data specific which impedes data scientists to define a generalized feature selection method. In this study, a vast range of hyperparameters was tested, as seen in Usually, the best value is also the most frequent one, as seen in On the other hand, other parameters, usually discrete hyperparameters, like solver type and activation functions, are easier to define. For example, the most recommended solver used by ANN is LBFGS as it performs well in small datasets like ours. tanH is also clearly the best activation function for this dataset.Nevertheless, defining the best hyperparameters can be challenging but what is proposed here is to start with a wide range of values and test the models for a large number of trials, saving the best estimator in each trial. Then, we are able to pick the most often selected hyperparameters and remove the values that are not chosen often. After some iterations of this process, we will get a small range of values that gets similar performances but can run in much less time.The model comparison is summarized in The oversampling of the dataset provided far superior results than using the original unbalanced data. All model score results reported include this processing step prior to the training.Another important topic addressed is the predictive value of the features in this dataset. Feature importance computed by Koehrsen's feature selector is presented in Comparing From Quantitatively, feature importance values are low in both methods, especially after the top five, indicating that the predictive value of those less important features does not vary much. Nevertheless, the top features present feature importance two times higher than the fifth to tenth top features, which is a considerable difference.As previously stated, it is of the utmost importance for physicians to understand algorithm results, therefore, we must analyze the results from the clinical point of view. Regarding the feature importance results obtained by Koerhsen's Feature Selector , enteralThe feature importance results obtained by the RF model  are overIn all three methods, there is an unforeseen absence of the GCS, which is a very valuable indicator of the patient's state and it is standard practice in brain injuries . In an aThe unexpected absence of CT related features such as midline shift and brain swelling in the top 10 features can be related to the previously referred heterogeneity of the condition in pediatric patients, due to their still developing brains. The pre-conceived importance of CT-based features is mostly based on adult cases, but eventually, in a cohort of pediatric patients where the brain and skull are still not fully formed, the importance of these CT and brain related features may be changed, which is why they are not visible in the feature importance figures. Nevertheless, this interpretation would still require confirmation by other external validation studies, with different datasets and methods of feature importance.This study presents some limitations that were identified and the possible strategies for future work. The size of the datasets in healthcare usually suffers from the lack of massive collections, which has been slowing the progress and application of AI solutions in the medical field. In the current study, the size of the dataset used is namely one of the limitations. The dataset may not cover the heterogeneity of the population, and eventually, the learning model did not generalize enough to cope with the variabilities of the population. On other hand, the small size of the dataset limited the approach to be used. Deep learning methods were not applied, since they need massive data to be trained. Moreover, the dataset only contains pediatric patients, which is a less studied group of the population for TBI-related classification. For some ages, there are only a few cases, which do not allow to study the correlation between some variables and age. Finally, the dataset did not contain continuous data, which could be very useful for mortality prediction and allow the creation of novel classification models that take into consideration the time sequence.In this study, four machine learning methods were compared in terms of their ability to predict mortality after TBI. XGBoost seems to be the best performer of the tested models, achieving an AUC of 0.91, using no feature selection. The feature selector tool tested showed promising results for KNN and ANN, outperforming PCA and ICA. Decision tree-based methods performed better with no feature selection.The comparison between different combinations of machine learning models and feature selection tools allows us to conclude that feature selection can improve prediction quality, either through external feature selection methods paired with models like KNN or with decision-tree based models with inherent feature selection capability, like XGBoost. Besides, feature selection also introduces more comprehensibility to the methods, facilitating the comparison of predictive value and clinical significance.Regarding the feature importance, there are some differences between the expected clinically significant variables and important features for prediction, namely the absence in the top 10 of the GCS features and the CT-based features, which may be explained by the still developing brain and skull of pediatric patients, that causes a higher variety of outcomes in this cohort.Exploring a new cohort of patients portrays challenges such as dealing with smaller datasets and less literature to compare results. This entails further responsibilities such as exploring different methods instead of improving or building upon a more established methodology. Nevertheless, despite the exploratory nature of this study, the results obtained showed that machine learning methods can take advantage of the information in ICU data, allowing the prediction of mortality in TBI pediatric patients with high accuracy.Predictive tools can be helpful in the prognosis process by warning physicians about more critical cases and allowing them to adapt their medical care plan based on the severity of each case.Future study may focus on training and testing these models on bigger and multicenter datasets, making them more robust, but also, focused on the initial period of the ICU admission which is the most critical time window for prognosis. For example, using only the data from the first two days of admission, in order to make a faster prediction that can more carefully guide medical attention. Efforts can also be made toward predicting not only mortality but also the functionality of the patient after a certain amount of time, providing physicians information that can lead to more focused and overall better medical care.https://github.com/fouticus/hptbi-hackathon.Publicly available datasets were analyzed in this study. This data can be found here: GitHub, JF conducted the experiments, AI-based model development, and testing. JF, XL, HO, and TP performed the analysis of the results. JF wrote the first draft of the manuscript. JF and XL performed the clinical interpretation of the results. All authors reviewed the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Science recently described a series of articles with potential scientific misconduct (Science called out potential image manipulation in multiple articles, including one published in the Journal of Clinical Investigation in 2012 (Science story relayed many of the same details found in an April 18, 2022, New York Times piece (The journal sconduct , emphasies piece .Science and the New York Times focused primarily on the very serious topic of potential scientific misconduct. However, these articles only lightly touched upon the concept of short selling stock, and I believe this matter deserves more attention for its inherent conflicts of interest. Short selling entails borrowing shares of a stock, selling shares high, followed by buying shares back at a lower price and pocketing the difference. Short sellers profit from devaluing a stock. It is legal to devalue stocks using public statements, and short sellers will often use social media as a primary venue to make defamatory statements, expressed as opinions. This process is known as “short and distort.”The articles in JCI article. The email asserted image manipulation, stating that sender was “retained by a law firm to investigate a concern of scientific misconduct related to the development of a drug intended to treat Alzheimer’s disease.” In the summer of 2021, the stock price connected to the company testing simufilam soared, drawing the interest of short sellers. This company developing simufilam is featured among the most highly shorted stocks (New Yorker, two physician-scientists in 2021 worked with an attorney to petition the FDA to halt the clinical trials of simufilam (New Yorker and described in Compliance Weekly (In August 2021, the Journal was contacted by email about the 2012 d stocks , and by imufilam . The FDAe Weekly , 6.JCI paper. Although we cannot be certain, there now appear to be new “short and distorters.” A recent round of emails was sent simultaneously to multiple journals and editors, identifying 25 articles with potential problems and providing recommendations on how the journals should respond. Importantly, these accusatory emails do not identify any financial conflicts of interest on the part of the whistleblowers. The emails insist that an investigation begin within 24 hours and request that the journals update them on investigative progress. As an editor, I am expressing concern because this represents a new means of manipulating the scientific publishing industry.Throughout 2022, the Journal has been repeatedly contacted to comment on the 2012 JCI has been at the forefront in trying to detect image manipulation in its manuscripts. For more than a decade, the JCI has required full uncut gel and blot images as part of the submission process. Beginning in 2021, the JCI was among the first to use an artificial intelligence–driven software package to analyze all images prior to accepting a paper (JCI, we will act accordingly through expressions of concern or retractions. There are ongoing institutional investigations for some of the allegations outlined in Science, and as a journal we await the outcome.The  a paper , 8. FundJCI will always take seriously any allegations of misconduct or misrepresentation, but we will take the time needed to conduct a proper and thorough investigation. Going forward, whistleblowers, just like authors, editors, and referees, will be asked to inform us of recent, ongoing, and potential conflicts of interest. Financial conflicts of interest will be considered and weighed in any follow-up investigative actions and especially in any communication to the whistleblowers. We may independently seek to verify whistleblowers’ potential conflicts. We will limit what information we share with whistleblowers, since advanced notice of news reports positions short sellers to take advantage of shifts in stock prices. There is a time sensitivity to short selling, so we feel the best approach for any journal is to be deliberate and cautious, and to exert due diligence in investigating any allegations of scientific misconduct or data/image manipulation.What is a journal to do? The JCI may elect to express its concern to the US Securities and Exchange Commission or the Department of Justice.Last, if the Journal uncovers allegations made for the purposes of stock manipulation, with evidence of misinformation, the


Despite evidence-based proof that sexuality education enhances school-going adolescents’ sexual and reproductive health, the high number of teenage pregnancies and sexually transmitted infections, including HIV, among young people in the rural areas of South Africa suggests that the school-based sexuality education programme in the rural areas might have less influence on learners due to various contextual factors in these settings. This phenomenological study used nine focus group interviews to explore the experiences of 84 school-going adolescents regarding sexuality education offered in their schools, located in the rural areas of the King Cetshwayo District, in Kwazulu-Natal, South Africa. The participants were purposively sampled and the transcribed data from the interviews were thematically analysed. The study revealed that the sexuality information provided to learners did not improve their motivation or encourage behaviour to act on the information provided. Additionally, the results highlighted environmental factors in the research setting that influenced the effectiveness of the sexuality education programme. To enhance its effectiveness, a sexuality education enhancement model was developed using elements of the systems theory and modified information-motivation-behavioural skills model. The model identifies the input resources needed to address issues of information, motivation and skills as well as the influencing environmental factors. Adolescents; Information-motivation-behavioural skills model; Learner; Rural-based schools; Sexual and reproductive health; Sexuality education; Systems theory. GreenbeSeveral studies have shown that a well-implemented sexuality education is beneficial to learners. According to Despite these benefits, several studies noted that the positive influence of sexuality education on young people was mostly realised in urban and semi-urban areas, while its impact is limited among school-going adolescents in rural areas This prompted the researcher to conduct a study aimed to identify and describe the prevailing factors and determinants that could be hindering or enhancing the effectiveness of sexuality education at rural-based schools in King Cetshwayo District and what could be done to enhance the programme's effectiveness. The researcher conducted this study to explore the experiences of learners with regard to sexuality education being offered in their schools, because of the high rate of teenage pregnancy among school-going adolescents in the King Cetshwayo District, a rural area in KwaZulu-Natal, South Africa. The high prevalence of teenage pregnancy suggested that learners were engaging in unprotected sex, which also signifies that the sexuality education programme in these schools might not be effective. Guided by 2The IMB skills model is the theoretical framework that underpins this study. According to Furthermore, the constructs of the IMB skills model could guide teachers in curriculum planning, delivery and evaluation . In the 3According to The elements of the systems theory shown in  include 4The methodology for this study was done in two phases, namely situational analysis and model development.4.14.1.1This phenomenological study aimed to develop a model to enhance the sexuality education programme at schools in the rural areas of the King Cetshwayo District based on the analysis of school-going adolescents' lived experiences and perspectives regarding sexuality education offered at their schools. 4.1.2This study was conducted in nine public secondary schools located in the rural areas of the King Cetshwayo District, in the KwaZulu-Natal province, South Africa. The sexuality education curriculum is offered as part of Life Orientation, which is a mandatory subject at all the selected schools.4.1.3The researcher used a non-probability purposive sampling technique on Grade 10 and 11 learners in the public schools situated in the rural areas of the King Cetshwayo District. This study was conducted in 2020 and learners, who met the pre-set inclusion criteria, formed the sample for this study. The inclusion criteria include being a Grade 10 or Grade 11 learner, aged between 14 and 19 years, residing in the rural areas of the King Cetshwayo District, fluent speaker of either or both English and isiZulu languages and willingness to be audio recorded. In addition, the learner should be ready to sign an informed consent form, coupled with obtaining parental consent, to participate in the study. For this study, 84 participants, made up of 49 female learners and 35 male learners, took part in the focus group interviews. This sample size was guided by data saturation, which, according to 4.1.4The researcher used focus group interviews in the data collection process, which provided the researcher with rich information, because the participants freely narrated their experiences and perspectives. In addition, the focus group interviews provided the researcher with in-depth insights of sexuality education in the research setting. The focus group interviews took place at the selected schools, over five months, from March to July 2020. The researcher used a pilot study to refine the developed focus group interview guide that was used for mediation of the interview process. In line with Kvale’s (1996) interview guidelines, as cited in Additionally, the researcher recorded his reflections and observations on the data collection process, as well as participants’ non-verbal cues, with field notes. The focus group interviews and the analysis of collected data were done iteratively until data saturation was reached.4.1.5The researcher transcribed audio recorded data from nine focus group interviews, verbatim, into written text within two days. The nine transcripts obtained were kept in Microsoft Word format and were analysed using content analysis, as described by 4.1.6The researcher, guided by 4.1.7The researcher sought and obtained ethical clearance from the University of South Africa and Provincial Department of Basic Education, in KwaZulu-Natal, to conduct this study. The researcher explained the aim, nature and the potential benefits of the study thoroughly to the participants. Furthermore, the researcher affirmed participants’ rights of refusal to participate in the research and emphasised to the participants that their participation in the study was voluntary and they may withdraw their participation at any time, without any negative consequence.Before each focus group interview, the researcher obtained informed parental/guardian consent letters and assent forms from the participants, which were completed and signed by the parents/guardians and participants, respectively. To protect participants' identities, the researcher used pseudonyms in the transcripts and in the research reports. Furthermore, to enhance confidentiality, the researcher ensured the venues used for the group interviews were suitable, convenient and comfortable. While focus group interviews have peculiar challenges regarding anonymity, the researcher was guided by the approach of 4.2This phase of the research design focused on developing a model to enhance the delivery, implementation and effectiveness of the sexuality education programme in schools located in the rural areas of the King Cetshwayo District, KwaZulu-Natal. The development of the sexuality education enhancement (SEE) model was informed by the findings in the first phase of this study, which explored learners' experiences regarding sexuality education offered in their schools.The conceptual framework that underpins this study is the IMB skills model, which guided the researcher in the development of the SEE model. Additionally, the findings from a literature review and elements of the systems theory were utilised to develop this model. The elements of systems theory used to formulate the SEE model include environment, input, process and output. The researcher followed 4.2.1Concept analysis aims to give meaning to a particular construct or concept by identifying all relevant definitions and characteristics . McEwen 4.2.24.2.3According to The researcher described and interpreted participants' experiences and linked the study findings with reviewed literature. Additionally, the researcher adopted 4.2.4The Delphi technique is a process used to measure a group of experts' judgments in order to make decisions, forecasts or assessing priorities . In thisIn order to add rigour to the model evaluation process and further ensure trustworthiness, the researcher, guided by Chinn and Kramer’s (2015)’s modified criteria, shared the model with ten sexuality education teachers and five education experts for evaluation. The researcher utilised e-mail group and WhatsApp group chats to engage the reviewers for safety reasons due to the COVID-19 pandemic. This allowed the reviewers to share their perspectives and build consensual validation of the SEE model. The researcher compared the feedback from the teachers and education experts with the comments from the panel of expert reviewers. All the reviewers and evaluators felt that SEE model is user friendly, easily interpretable, relevant, adaptable to similar contexts and would positively enhance sexuality education programme in the research setting; thus, promoting adolescents' SRH and well-being.5The findings of this study revealed that the barriers to effective school-based sexuality education programme in the research setting are learner-centred, educator-centred and community-centred. It also emerged from the study that certain factors and practices are likely to enhance sexuality education effectiveness in the schools located in the research setting. In addition, the study findings revealed interventions that may improve the effectiveness of sexuality education programme among learners in the rural areas the King Cetshwayo District of KwaZulu-Natal. The detailed findings of the study are discussed in reference to the structure of the SEE model below.5.1The three constructs of the IMB skills model align with the key learning objectives of sexuality education proposed by International Technical Guidance on Sexuality Education, which include knowledge, attitude and skills building . In addi5.25.3The researcher utilised elements of the systems theory - made up of context, input, processes, output and outcome - in the development of the SEE model:5.3.1Context is the interrelated conditions in which a phenomenon exists or occurs  and it pThe SEE model is in line with the relevant Sustainable Development Goals , which is aimed at achieving universal access to SRH services, HIV prevention, quality education, gender equality, good health and total well-being of young people . Further5.3.2Input relates to the human, financial, physical and information resources needed to carry out the transformational process in a system . The fin5.3.2.1I do not think they are comfortable talking about some topics on sexuality. You can see it from the teachers' body language. They are not themselves because they don't go into details. They only teach us about disadvantages of sex like teenage pregnancy, diseases and so on. – The findings of the study showed the need for sexuality education teachers to undergo continuous professional training, which should be aimed at changing their attitudes and empowering them to be well grounded in the scientific facts that underpin sexuality education curricula as well as to improve their pedagogical competency. It was revealed from the lived experiences of the participants that some teachers were not comfortable and struggled with certain aspects of the sexuality education curriculum.Sometimes they (teachers) are not at ease, with a little bit of awkwardness here and there when you ask questions. We don't demonstrate these things in the class probably they weren't comfortable with that, yeah like how to put a condom on and so on. – LO teachers must not filter information during lessons. They must teach us everything as we get to the age of puberty. – It was further established that certain topics like contraception, sexual identities and sexual pleasure were skipped by the teachers, because they find them difficult to teach.This suggests that teachers should be continuously trained to acquire knowledge about the fundamental concepts of sexuality education curricula, ideology and pedagogy. In addition, it emerged from the analysis of research data that the Department of Basic Education needs to allocate more resources for training and workshops to build the capacity of sexuality education teachers in the study setting. This was supported by Some of our teachers are living with HIV, and some also suffer from guilty of what happened to them in their teenage years. Some of them have experienced teenage pregnancy and risky sexual practices so, when they are telling it to us, it is like they are blaming themselves. – They (the teachers) were not taught about their sexual life because the teachers of those days thought they were too young then but now they have to discuss everything with their learners which make them uncomfortable. So, I think they are not comfortable sometimes because they think they are exposing us to information that is not appropriate for us and that we may go and do ‘those things’. - This study further established that factors such as the teacher-learner age gap, religion, cultural background and health status, and educators’ experience can inhibit teachers’ motivation and commitment to deliver the sexuality education curriculum.The SEE model proposes training for educators that will boost their emotional, personal and social motivation regarding sexuality education programmes in their schools. These training programmes should address individual teacher's antecedents, perceptions, values and attitudes toward sexuality education, provide them with evidence-based information on the benefits of sexuality education, and address the identified personal biases, prejudices and discomfort in relation to the curriculum content of the sexuality education programme. This proposed SEE model is in line with the views of 5.3.2.2“We all come from different homes, and our parents taught us differently. Even our teachers see things differently. In the community, there is a traditional practice, which encourages learners, and teenagers to get married while they are still in school, and they are allowed to fall pregnant. This practice does not agree with what we learnt in Life Orientation, but it happens here in this community”. – Some of the churches and parents do not accept what the teacher taught us in sexuality education. They think we should not be learning about sex at school, andthey do not approve of it because it does not agree with their religion. Some people in the community also think we are being encouraged to have sex, abortion, and “practice” gay. – Besides the training of teachers, another significant finding that emerged from the study is the necessity to engage in multi-stakeholder collaboration in the study setting. It was noted from the analysis of research data that some parents and community actors, such as religious and cultural leaders, provided contradictory information and misinformation to school-going adolescents, which could undermine the key messages of the sexuality education curriculum.Some of our teachers are pastors too in their churches, and they think it is against their beliefs to discuss sexuality education with us. Some teachers think LO cannot change our behaviours no matter what they (teacher) do”. – Certain people in the community believe that using protection during sex is bad because they want skin to skin but if a condom is not used you are at risk of getting diseases. Some cultural practices here don't believe in the usage of condoms when having sex. – Apart from contradictory messages emanating from the community and learners' homes, the attitude of the teachers, community and parents, especially where there is disapproval of the sexuality education programme, can have a negative influence on learners’ motivation to engage in SRH-related behaviours and willingness to access SRH care and support services.Sex is trending in the community among young people, and friends are pulling each other into doing it. Some do not follow the teachings in Life Orientation because of peer pressure. If all the people in your circle are smoking or having boyfriends, you will feel the odd one out, and it may look like something is wrong with you if you do not join them. – The clinic is very far, and you cannot easily get free condoms too in the community. We are scared to speak about it to our parents or in the community because of the way you might be treated”. - Furthermore, the study found that peer pressure and lack of access to non-judgemental SRH care and services are likely to demotivate young people from acting on the information received during sexuality education.– The “blessers” are taking advantage of young boys and girls by buying them nice things and giving them money. Some parents even allow this to happen because they cannot provide for their children. This lack of social motivation may dissuade learners from initiating and maintaining SRH-related behaviours in the research setting. The study findings further indicated that socio-economic status, cultural norms and religious beliefs influence how learners receive school-based sexuality education and their attitude and motivation to act on the knowledge acquired during these sexuality education lessons.We end up not listening to our teachers because some believe in different cultures, and they are coming from different homes where they believe the things they are told by their parents. So what we do is to weigh things that we learnt from our teachers and things that we are taught by our family and come up with our conclusions”. – Additionally, the results indicate that some learners were inclined to rather follow their cultural beliefs when key messages that emanate from sexuality education do not align with cultural norms.Some cultural practices guard you to stay a virgin till you turn 21 years old or get married. It has a positive influence on sexuality education. My parents always say, get married first and then do those things. So, this helped me to be serious and wait for the right time and not to rush into things – In our community there are a lot of bad things that are happening. I have to focus at school and in sport because even sport teaches me many things. I have been learning about this sexual education with my team. I can say so”. – On a different note, this study revealed that parental support, rewards, as well as certain cultural beliefs, the activities of some religious organisations, provision of recreational facilities and access to friendly SRH services in the community could be enhancers of learners’ motivation to initiate and maintain positive SRH behaviours learnt in sexuality education.Therefore, the SEE model proposes that resources should be provided to collaborate on a continuous basis with key stakeholders such as Department of Basic Education district officials, parents, faith-based organisations, non-governmental organisations (NGOs), community leaders, learners and teachers to optimise the enhancers of sexuality education in the research setting and to address the stakeholder-related barriers to sexuality education. Likewise, the SEE model proposes that stakeholder engagement should stimulate local ownership of the sexuality education programme and promote socio-culturally acceptable ways of addressing stakeholders’ concerns. This study also highlights key areas of intervention in the research setting where input resources should be targeted and these inputs should include sexuality education campaigns, formation of help clubs, advocacy, eradication of poverty, and provision of information resources and infrastructure.5.3.2.3We need to raise awareness to educate the community as well. This will help make the parents look at the things differently from the one they used to do. These may help sexuality education to be more effective in our school” – Resources should be made available to build community awareness about the impact of sexuality education on adolescents’ well-being and to address misconceptions about sexuality education in the communities.The awareness campaigns on sexuality education should extend to all the stakeholders in the community and could be initiated, managed and funded by the Department of Basic Education, in collaboration with NGOs and the private sector.5.3.2.4Yes, we need to form groups in the community. To teach other people in the community about sexuality education, HIV, and to stay away from unprotected sex. – The schools and the local Department of Basic Education and NGOs should collaborate to form help clubs which are social groups in schools and in the community.This will likely enhance sexuality education among the learners and build social capital in the community. In addition, the help clubs will have defined goals and objectives to support school-based sexuality education programme. This may improve learners’ motivation and commitment to enact the skills learnt in the sexuality education programme; thus, enhancing their ability to attain SRH and well-being.5.3.2.5The school must have meetings with the community and our parents so that they will allow us to practice what we learnt in sexuality education at school. I think Life Orientation teachers should be more specific on this one. They must organize meetings with parents to teach parents not to feel afraid to talk to their sons about this sexual intercourse. – The school management teams should implement a programme in the school academic calendar that will facilitate collaboration between parents and sexuality education teachers in the research setting.This will empower parents to become active and constructive partners in school-based sexuality education. Furthermore, it will address concerns, misconceptions, misinformation and contradictory messages regarding sexuality education that emanate from learners’ homes.5.3.2.6The use of respected professionals, social influencers and opinion leaders, with relevant experiences to reinforce important messages of sexuality education, can shape the opinions and social attitudes of young people and other stakeholders about the sexuality education programme. This may create an enabling and supportive environment that will assist the programme to achieve its outcomes in the community and could promote its acceptance. The SEE model proposes that the Department of Basic Education, district office and school managers should allocate resources toward sexuality education advocacy in their annual plan and budget.5.3.2.7The government should help out with the people who live in poverty as this will reduce the number of people who are becoming prostitutes and getting pregnant” – The findings of the study indicate that addressing poverty in the research setting is critical to enhancing the effectiveness of the school-based sexuality education programme.The SEE model proposes that resources be allocated for the creation of community food bank and cash transfer programmes, which may potentially address household poverty, both in the short and long term. A collaborative effort between municipal authorities, NGOs, religious organisations, the private sector, the Department of Social Development, the Department of Basic Education and other relevant governmental agencies to address poverty could mitigate the negative impact that the socio-economic environment has on the effectiveness on the sexuality education programme.5.3.2.8While other studies have shown that availability of recreational and sporting facilities could enhance school-based sexuality education , this stThe SEE model proposes the provision of accessible, youth-friendly, non-judgmental and non-discriminatory SRH facilities, and recreational and sporting infrastructure as the input resources that will enhance the outcomes of the sexuality education programme. The local government authority should invest in sport and recreational facilities to engage young people in skills-building activities after school hours; thus, strengthening the effectiveness of sexuality education programme in the research setting.5.3.2.9They tell you that getting pregnant is not right, but they will not tell you how to avoid getting pregnant- Apart from lack of supportive infrastructure, this study found that stakeholders’ access to information resources on sexuality education could be improved upon. The findings of this study indicate that, while the educators and parents desired positive SRH outcomes for learners, they lacked capacity to provide them with the necessary knowledge and skills on how to achieve those outcomes.In addition to the scripted lessons and textbooks on sexuality education, the SEE model proposes that information and knowledge resources on sexuality education should be accessible to all stakeholders, using multiple sources like audio-visual resources, online portals, creative posters, informative pamphlets and other thematic activities that promote SRH and well-being of young people in the research setting. The local district offices of the Department of Basic Education can coordinate and provide these input resources.I think social media can also come in where maybe young people can be able to ask a sensitive and private question where confidentiality can be kept and all of that yes. – Furthermore, the model also proposes utilisation of social media platforms to promote access to sexuality education information resources. Social media is interactive and could be attractive to young people for accessing SRH-related information resources and details of locations of SRH services in the community without compromising their privacy and confidentiality.Additionally, social media platforms could be used for multi-stakeholder engagement initiatives and collaboration on the school-based sexuality education programme in the study setting.6The process refers to a mechanism that converts inputs into desired results. It consists of procedures or techniques that mediate the transition of inputs into outputs in systems theory . The SEEThe SEE model acknowledges, outlines and addresses key interrelated and interacting elements in the modified IMB skills model to enhance school-based sexuality education in the rural areas of the King Cetshwayo District. To access and utilise SRH care services and to develop complex skills for achieving sexual and reproductive health, young people need multiple information sources, and emotional, personal, and social motivation as well as the necessary objective and perceived skills. It emerged from the analysis of research data that there are learner-centred, educator-centred and community-centred factors that need to be addressed to enhance the school-based sexuality education programme in the study setting. Therefore, the overarching purpose of the SEE model's process unit is to use the input resources to address inhibiting environmental factors and to influence the information, motivation and behavioural skills of learners, educators and community actors positively regarding sexuality education. The SEE model predicts that the implementation of these processes will enhance the effectiveness of sexuality education in the schools in this research setting.6.1The SEE model's information process calls for the provision of scientifically accurate, evidence-based, age-appropriate, contextually relevant information resources and materials that should be made available to educators, learners, parents and community members. This implies that there should be continuous training, community engagement and provision of information resources to inform stakeholders about the sexuality education curriculum.6.2I believe that it all start in the mind, the mindset of a person. If they've told themselves that okay I'm a teenager I ‘wanna’ experience things, there is nothing you can do about that, that's my opinion. - The findings of this study revealed multiple reasons why learners sometimes do not act on the information they receive in the sexuality education programme. The results indicated that motivation plays a critical role in whether a well-informed learner will be inclined to act on information in the classroom. It emerged from data analysis that lack of personal and emotional motivation could prevent learners from acting on information received in sexuality education.To keep the stress out of ourselves we do things we should not do normally so that we can forget about our stress. When you are stressed, you may not even remember what you learnt in the class, you just want to feel good and that why we do such things like smoking, drugs and sex to forget. – “Many teenagers do it just to keep their friendship even thou they know that what they are doing is bad”. – Furthermore, this study established that providing learners with sexuality education information is not sufficient to achieve positive SRH behavioural changes; learners also have to be motivated. In addition, the results indicated that perceived lack of social support from both educators and peers, and the psychological status of learners have an impact on their motivation.Most of our teachers like to emphasize abstinence from sex than telling us how to protect ourselves. They judge very much even if you date a guy they judge you that you are so young. In some lessons, the teacher just wants to do all the talking and teach us what to do to be safe. – It was further noted from the study findings that providing learners with sport and recreational facilities, integrating certain cultural beliefs and accentuating the rewards of adopting positive choices could enhance their motivation to initiate and maintain positive SRH behaviours learnt in schools. Besides learners’ lack of motivation, the study findings revealed that a percieved lack of motivation on the part of some sexuality education teachers has prevented them from teaching the sexuality education curriculum in a comprehensive and professional manner, because the messages conflict with their personal antecedents and beliefs.Consequently, the SEE model's motivation process calls for sexuality education curriculum planners and teachers to focus on the motivation of learners to act on the sexuality education information received in the classroom that would improve their SRH. Similarly, the training and capacity-building resources for educators should target and address their motivation and attitude. Furthermore, the SEE process requires provision of infrastructure like recreational sports amenities and accessible, youth-friendly and non-judgemental SRH services to enhance young peoples' motivation to initiate and maintain positive SRH behaviours. The model's motivation process predicts that a well-informed and motivated adolescent is likely to act on the sexuality education knowledge received in the classroom.6.3The findings of this study revealed that there is a gap between the information provided to learners and the behavioural skills possessed by learners to act on the acquired information.As much as they are teaching us about these sexual life, we still become pregnant as teenagers. – The results of the data analysis further indicated that sexuality education lessons, in the research setting, focused more on sharing information, with little or no emphasis on cultivating the relevant and necessary behavioural skills.Therefore, the SEE model’s behavioural skills process advocates that all input resources should be harnessed to enhance educators and learners’ self-efficacy and objective abilities. The model demands that every input resource should focus on building the sexuality education-related skills of learners, educators and parents. Additionally, teachers' training should be designed to improve teaching and learning strategies around behavioural skills development. The SEE model argues that a well-informed, well-motivated educator requires the necessary pedagogical and behavioural skills to facilitate sexuality education teaching effectively and to achieve the desired behavioural outcomes in adolescents.6.4Within the community, life is difficult for young people, and there is a temptation to do things that will make you comfortable. Schoolgirls want to have sugar daddies from mining company, and this is common in our community. These behaviours may not agree with what we learnt in Life Orientation, but life is not fair. You have to survive and look after yourself. – The results indicated that there are environmental factors like poverty, cultural and religious norms, parental antecedents and community attitudes that influence the causal pathways of the constructs of the IMB skills model, which underpins the SEE model's processes in the study setting. Therefore, the environmental construct of the SEE processes seeks to create an enabling environment in order for the school-based sexuality education programme to be effective. The socio-economic status of learners may influence the motivation and behavioural skills constructs of the SEE model. The analysis of the research data revealed that learners, who came from poor homes, are more likely not to be motivated to act on knowledge received in classroom during sexuality education lessons, because they engage in transactional sexual activities for money and material gain.We have a problem with drugs, and learners have access to these drugs in the community. Alcohol abuse is common in the community –Nomcebo, female, 17 years old)Furthermore, the results from this study indicated that other social issues, such as substance abuse, have an influence on learners’ motivation and ability to act on sexuality education knowledge obtained in school. Learners, who engage in substance use, are likely to act contrary to the SRH information received in sexuality education.In addition, the study findings revealed that the quality of information provided to learners and the teachers' motivation to adhere to the curriculum contents are negatively impacted by their cultural background. Similarly, the research findings showed that the cultural antecedents of the learners influenced how they respond to the SRH knowledge acquired in school. The results also revealed that some teachers skipped key parts of the sexuality education curriculum, because it conflicted with their cultural beliefs. The study established that certain cultural practices in the community are likely to negatively impact learners’ SRH and well-being, regardless of the sexuality education knowledge provided in the classrooms.In addition, the study revealed that religious beliefs might have both a negative and a positive influence on learners regarding sexuality education. The study established that religious beliefs are likely to shape the views of parents, teachers, learners and the community, as a whole, towards the school-based sexuality education programme.The SEE model processes highlight the need to address environmental factors that influence sexuality education in the research setting. The model further asserts that the provision and processing of the allocated input resources, to address these environmental factors, will enhance sexuality education in the rural areas of the King Cetshwayo District.77.1The SEE model's feedback provides for a monitoring and evaluation process, whereby the model gathers information about its performance. According to •The accuracy and relevance of the sexuality education information provided to the learners.•If the contents of the curriculum and its implementation are comprehensive, inclusive, human rights-based, gender-sensitive and address gender-based violence.•If it focuses on providing adolescents with SRH information, building motivation and developing the SRH behavioural skills of learners.•If the programme creates awareness and engagement about influencing environmental factors that could impact sexuality education outcomes.•If sexuality education lessons are mediated by well-informed and well-motivated teachers, who are equipped with the necessary pedagogical and behavioural skills.•If curriculum implementation is guided by a balanced approach that promotes positive SRH habits and prevention of negative SRH outcomes.The objectives of the feedback's tools are to ascertain:8The SEE model consists of the following elements: a multi-level context ; input ; processes ; and output  as shown in 9The SEE model assumes that, if the necessary resources are allocated for the sexuality education programme in the study setting - to address issues relating to information, motivation, behaviour and the environment - then the quality of school-based sexuality education programme being offered will be enhanced, leading to improved overall SRH and well-being of school-going adolescents in the research setting. In addition, the SEE model assumes that the quality of the sexuality education information provided to learners, the processing of this information by learners, the motivation of learners and teachers, and the behaviour of learners are affected by the prevailing environmental contexts in the research setting. Furthermore, the model assumes that a well-informed, well-motivated learner, who possesses all the necessary behavioural skills provided by sexuality education would be more inclined to initiate and maintain positive SRH behaviours leading to positive SRH outcomes. Conversely, learners, who lack the relevant SRH information, motivation and the necessary behavioural skills, are unlikely to engage in positive SRH behaviours.10The SEE model implies that the school-based sexuality education programme in the study setting will be effective when identified input resources are made available and are utilised to provide accurate sexuality education information, build motivation, and cultivate the skills of learners to initiate and maintain positive SRH behaviours and outcomes. Furthermore, The SEE model calls for the sexuality education curriculum to be mediated and facilitated by well-informed, motivated and skilled educators.Another implication of the SEE model is that it calls on relevant stakeholders, such as policymakers in the Department of Basic Education, to recognise and address environmental factors that affect the effectiveness of school-based sexuality education in the research setting. This can be done through continuous professional development of the educators responsible for delivering the sexuality education programme. Therefore, the model implies that, when both teachers and learners are well informed, motivated and equipped with the necessary skills, and the interfering contextual factors were addressed, the sexuality education programme in the research setting will be effective and achieve its desired outcomes.In addition, the SEE model implies that the ultimate objective of the school-based sexuality education is to empower learners to achieve positive SRH outcomes and well-being. The SEE model calls for a paradigm shift among all the stakeholders, such as the Department of Basic Education policymakers, curriculum planners and educators, as well as parents, learners and other community actors, regarding school-based sexuality education in the research setting.11For this study, the researcher adopted a non-probability and purposive sampling technique in the selection of the participants. Therefore, learners, whose experiences and perspectives might be different from the study participants’ experiences, could have been left out of the study. In addition, this study left out the experiences and views of parents and educators, but explored only the lived experiences and perspectives of learners in the study setting. The data collection was conducted by the researcher who is an adult male, it is possible that the perceived gender of the interviewer to have impact on the honest response to the interview questions. Furthermore, part of the data collection process for this study took place during the COVID-19 pandemic; therefore, the anxiety among the learners, who participated in the study, might have affected how they shared their experiences and views. On this basis, the interpretation of these research findings should take into account these limitations.12The SEE model was developed from the findings of this study. The model development was guided and supported by the IMB skills model, using elements of the systems theory. The model supports all the critical factors regarding school-based sexuality education addressed at global, national and district levels. The basic components of the SEE model are input, a modified IMB skills-based process, output and feedback. The model upholds that scientifically accurate information, motivation and behavioural skills influence learners' abilities to initiate and maintain SRH and well-being. It advocates for the provision of input resources to address environmental factors that influence information, motivation, and the behaviour of school-going adolescents and teachers to enhance the quality and effectiveness of the sexuality education programme in the King Cetshwayo District, South Africa. The SEE model's ultimate goal is to empower learners to initiate, engage and maintain positive SRH behaviours and outcomes through an effective school-based sexuality education programme in the research setting.Ayobami Precious Adekola, Ph.D: Conceptualised and designed the study; collected the data; Analyzed and interpreted the data; Wrote the paper.Azwihangwisi Helen Mavhandu-Mudzusi, Ph.D: Supervised the study, analysed and interpreted the dataThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Data included in article/supp. material/referenced in article.The authors declare no conflict of interest.No additional information is available for this paper.