Biobanks and human genomics applications are key for understanding health, disease and heredity in Africa and globally. Growing interest in these technologies calls for strengthening relevant legal, ethical and policy systems to address knowledge disparities and ensure protection of society, while supporting advancement of science. In Zimbabwe there is limited understanding of ethical, legal, and societal issues (ELSI) for biobanking and genomics. The Genomics Inheritance Law Ethics and Society (GILES) initiative was established in 2015 to explore the current status and gaps in the ethical and legal frameworks, knowledge among various stakeholders, and to establish capacity for addressing ELSI of biobanking and genomics as applied in biomedical and population research, and healthcare. The project was conducted over a countrywide geographical region and established one of the most comprehensive studies for ELSI of human biobanking and genomics in Africa. This paper outlines the strategy undertaken during the implementation of the GILES initiative and discusses the importance of such an initiative for characterisation of ELSI of human biobanking and genomics in Zimbabwe and Africa. Linked to biobanking, advances in technology are enabling large-scale biochemical and genomic analysis, generating substantial amounts of data of personal and health relevance with ethical implications for communities and populations6. Although the benefits of human biobanking and genomics applications are well recognised, ethical, legal and social challenges arise alongside unclear regulations and policies, and limited understanding among research scientists, healthcare professionals and the wider public7. In particular, African countries are faced with a growing need for the application of genomics in medicine and research. African genomics and population data are drawing regional and global interests as they add rich genomic background diversity to existing efforts to fully understand human genomic variation. This plays an important role in biomarker identification, improving disease diagnostics, and development of targeted therapies, which take into account interplay of environmental and demographic factors8. However, the nature of biobanking and genomics gives rise to ethical and social issues at personal and population level. Therefore, there is urgent need to understand the current status, gaps and needs to build capacity for appropriately applying these technologies at the national, regional and international level. The main objective of this article is to describe the strategy and experiences of the Genomics Inheritance Law Ethics and Society (GILES) initiative aimed at understanding ethical, legal and societal issues (ELSIs) in human biobanking and genomics. In this article we build upon the rationale for addressing ELSIs in Africa using Zimbabwe as an example of a country with less advanced structures for human biobanking and genomics and where ELSIs are poorly understood among professional and community groups. We highlight challenges and opportunities observed during the implementation of the project and outline potential locally tailored approaches for comprehensive characterization and capacity building for ELSIs of human biobanking and genomics in Africa.Biobanks of human biospecimen collections are key resources for understanding individual and population diversity, and are integral to healthcare research, medical care, and drug discovery11. This and other ongoing initiatives create the need for anticipating and addressing emerging issues in human genomics notably: increased biobanking activities, whole genome sequencing, genome wide association studies, large scale databases and bioinformatics. Researchers in Zimbabwe are actively contributing to this initiative, and other related continent-wide consortia whereby associated ethical, legal, and societal issues (ELSI) remain under-explored. For example, despite the expectations of the international collaborative projects in the cross-border storage of human biospecimens and depositing of research results in consortia databases for access by scientists locally and abroad, differing terms and norms which are likely to present barriers to access and use are not well addressed. In addition, the uni-directional flow of samples and data out of Africa has created a sense of exploitation and distrust and the African genomics research community are playing a leading role in addressing such concerns and limitations as they become more likely to occur13.Recently, several consortia have embarked on projects to characterize African population genomics. The largest consortium is the Human Heredity and Health in Africa (H3Africa) program, which is focused on supporting biobanking and collaborative genomics research for understanding population genomic diversity in relation to disease susceptibility, diagnosis and association with environmental factors14. Such activities were established with limited knowledge and expertise about ELSIs and create a basis for strengthening the current structures for human biobanking and genomics sciences oversight.In Zimbabwe, human biospecimen collections or biobanks have largely focused on infectious diseases research, national surveillance programs, disease outbreaks and molecular diagnostic applications. In this work, we acknowledge the existence of biobanks both in their rudimentary and advanced form, and the potential for their samples to be used for a wider variety of human genomics applications than for which they were originally collected. To date, the Biobank and Pharmacogenetics Database of African Populations is the only openly reported resource, which marked a significant step in multi-national collaborative biobanking efforts, and was designed for the study of variations associated with drug response in AfricaCYP2B6, which were associated with decreased drug clearance, and thereby increasing risk of side effects such as depression and other neuropsychiatric complications17. Clinical trials to assess the possibility of reducing dose and cost-effectiveness of pharmacogenetics-based prescriptions are underway. The benefit of such examples of translational research cannot be underestimated and more clinical research involving biobanking and genomics is highly anticipated in the near future. As more awareness builds among researchers, healthcare professionals and policymakers, the applications of biobanking, genomics research and bioinformatics will increase bringing to light the deficiencies in the current ELSI framework in Zimbabwe.Although biobanking and genomics are still in their infancy in Zimbabwe, growing interest and participation of local researchers in international collaborative consortia promises new avenues for research and medical solutions important to public health. For example, a local pharmacogenetics-based study indicated that the prescribed use of the anti-HIV drug efavirenz may result in severe side effects among patients due to highly prevalent variants in the gene encoding the drug metabolising20.In the wider community, individual and society beliefs, practices and perceptions influence participation in biospecimen collection for human genomics. As with most African countries, Zimbabwe is undergoing socio-economic and cultural as well as religious transitions, which impacts on beliefs and practices towards health research involving biobanking. In Africa, blood sample collection is a major area of concern among community and religious groups, and may be viewed by many as part of “witchcraft”21. While Zimbabwe is undergoing constitutional reforms, scientific and technological advances, protection of researchers and participants may become more compromised. Ethico-legal consequences and risks of psychosocial harm, stigma and genetic discrimination also need to be addressed. These challenges present an opportunity for Zimbabwean researchers to contribute to the growing debate on ELSI of and development of appropriately tailored frameworks in line with various ongoing initiatives to build capacity for addressing and regulating current end emerging issues for biobanking, human genomics applications and data sharing in Africa.Zimbabwe is a landlocked country in the Southern African region with a population of approximately 15 million inhabitants. Being centrally located, Zimbabwe provides a major link for trade and migration, and access to a diverse ethnic and highly literate populationDriven by the need to understand the current status and to determine needs for building capacity and harmonised guidelines for addressing ELSI of biobanking and human genomics in Zimbabwe, the Genomics Inheritance Law Ethics and Society (GILES) initiative was launched in 2015. The strategy involving steps to establish empirical evidence for ELSI regulations and knowledge-based participation in biobanking and human genomics for research and healthcare is shown inPrior to the development of data collection tools and fieldwork, the research team held meetings to determine key issues regarding biobanking and human genomics in Zimbabwe. The topics of genomics and biobanking, although commonplace, may appear daunting and too advanced among researchers in Zimbabwe due to various reasons including limitations in graduate and advanced training programmes. The interdisciplinary nature of ELSI research in topics which are cross-cutting in health, biomedicine and society, motivated a team of experts from diverse backgrounds was necessary and included bioethics, genomics, medicine, psychology, psychiatry, biomedical sciences and sociology. The majority of the GILES team were novices in the subjects of biobanking and genomics and associated ethical issues. Therefore, informational sessions led by the key investigators formed part of the project implementation strategy to ensure good understanding of the subject topics under study.The GILES project employed a multi-methods approach, which included document reviews and an explorative qualitative study with targeted informant interviews and focus group discussions to understand the ELSIs and governance of biobanking and human genomics for health research and clinical applications in Zimbabwe. The qualitative method was used to establish subjective experiences of participants regarding biobanking and genomics as a basis for development of more focused studies and theoretical framework in future. The study was conducted in six provincial regions namely – Harare, Bulawayo, Mashonaland East, Manicaland, Matabeleland North and Matabeleland South . The sitThe health authorities are instrumental to accessing communities for research in Zimbabwe. We sought permission from the Ministry of Health and Child Care to engage with healthcare workers and members of the communities through local clinics and hospitals. Social scientists from the GILES project team guided the interviews and discussions.With the fast pace of advanced technologies such as large scale biobanking, next generation sequencing and genomics, the current ethical review and regulatory structures may be inadequate in upholding ELSI requirements which ensure human subject protection while optimising research in Zimbabwe. To understand how ELSI are addressed and regulated in Zimbabwe and how they are used to govern biobanking and genomics for human health research and clinical applications, desk reviews of legal and policy documents, and regulatory instruments were conducted. In total, 76 documents were reviewed inclusive of the Zimbabwe Constitution, regulations, policies, national guidelines and guideline documents from institutions which collect biospecimens for research or clinical diagnostics use. Content analysis was used to determine the presence and absence of information or guidelines regarding the collection, storage, exportation and analysis of biological specimens and data, biospecimen and data sharing, data security and consent.All human subject research protocols are submitted for review, approval and registration through institutional and the national research ethics committee at the Medical Research Council of Zimbabwe (MRCZ). This provided a rich source of materials to analyse, as a proxy for the current practices among researchers in addressing ELSIs of biobanking and genomics by reviewing protocols, which involve human subjects and biospecimen collection/biobanking and genetics/genomics. In total, 200 protocols submitted to MRCZ for review from 2010 to 2016 were reviewed using a checklist. The 200 protocols were identified through the review of the Research Proposal register and electronic database maintained by MRCZ starting with recent submissions and moving backwards in time. At the time of the study, the register contained about 1600 entries. As this was the first time to conduct such a study, a preliminary assessment of research protocols by the ethics experts of the research team determined that there was poor consistency in the manner in which ELSIs were addressed in projects undertaking biospecimen collections and genetic or genomic analysis. Therefore a key objective in the GILES initiative was to generate empirical evidence to understand the needs for developing updated guidance for ELSI of human biobanking and genomics for researchers and ethics committees. We analysed content from the research protocols regarding ELSIs such as consent, privacy and confidentiality protections, community consultation and engagement, biorepositories , data sharing and security, informed consent features, descriptions of risks and benefits, long-term storage and implementation of sample disposal plans.23. Ethical issues such as stigma, informed consent, privacy and confidentiality are emerging in the use and sharing of genetic information. A call for increased publications describing perceptions of the diverse African researchers, ethics committees and communities regarding genomics25, resonates on the key aim of the GILES project in characterising the broad range of knowledge, attitudes and perceptions about biobanking and genomics, and the rationales behind them. We targeted research scientists and healthcare workers who collect biospecimens which are used or have potential to be used for human genomics research or clinical diagnosis. The wider community represented prospective donors of biospecimen collection and participants in genetic or genomic analysis. The qualitative study approach was deemed appropriate at this exploratory stage. Applying a combination of in-depth interviews (IDIs) and focus group discussions (FGDs) allowed for an understanding of the meaning people give to their experiences particularly for terminologies, which may be less familiar generally. The research team held various workshops to develop consensus on the terminologies for use during the development of IDI and FGD guides. The process entailed generating ideas, recording the ideas, discussing the ideas, voting on the ideas, translation of items and triangulation. For effective communication with the individuals and communities around Zimbabwe, the guides were developed in English language and translated into local languages Shona and Ndebele. Topic guides and prompt statements were used to explore general issues about biobanking of biospecimens and their use in genomic analysis in healthcare and research. In-Depth Interviews were conducted among 31 individuals consisting of 3 spiritual and religious leaders, 11 researchers, 5 regulatory and ethics experts, 9 health service providers, 2 policymakers and 1 journalist. A total of 15 Focus Group Discussions were conducted among healthcare workers and community members from 6 provincial region  in Zimbabwe. This was achieved through a multi-disciplinary approach involving research scientists, health and academic professionals and community members. The GILES initiative is innovative in being the first to address ELSI regarding the human genomics resources for health research and application in Zimbabwe. This was enriched by using a comprehensive methodology encompassing desk reviews and interviews and by involving a diverse research team of biomedical scientists, clinicians, public health and ethics experts and social scientists. Further comprehensive descriptions of findings will be reported separately.Zimbabwe is a country that is experiencing growth in genomic research and biobanking and yet ELSI of human bioresources and genomics are inadequately applied and poorly understood. Growing interest in the application of genomics in medicine and diagnostics implies that there is a need for a paradigm shift in the education and training of researchers, health professionals and the public on ELSI of biobanking and human genomics. The GILES initiative will culminate in strengthening capacity through education, training and community engagement. We envisage the use of local beliefs, perceptions and folklore in developing tools, which can provide more efficient means for research participant recruitment, awareness and consent processes for biobanking and genomics research. Capacity building will empower students, faculty and health professionals, researchers, regulatory authorities, public health scientists and the wider public. In the future, workshops will be conducted to develop recommendations, which will be availed to institutional review boards, research ethics committees, regulatory bodies and government in order to tailor the ELSI framework which protects and empowers research participants, researchers and health professionals while advancing biobanking and human genomics in Zimbabwe and the African region.13. The GILES initiative presents an example, which may be used to conduct such explorative work in other African countries. It is also among a select few studies in Zimbabwe and Africa, which have employed an inclusive approach for exploring the needs for future development of an evidence-based ELSI framework. This will provide opportunities for education, community engagement and capacity building for tailored ethical frameworks appropriate for African communities.Anecdoctally, there is limited understanding of ELSI implications for genomic research and healthcare in Zimbabwe, a situation which may apply across the continent. The experiences in implementation of the GILES initiative and preliminary observations suggest a need for more thorough localised ELSI research projects in Africa to accommodate the diversity of cultural norms and levels of capacity in use of biobanking and human genomics technologies. This reiterates calls for the development of more tailored national and regional guidelines, which support the inevitable and growing nature of collaborative biobanking and genomics researchThe views expressed in this article are those of the author(s). Publication in AAS Open Research does not imply endorsement by the AAS.The GILES study was approved by the Joint Research Ethics Committee (JREC) at Parirenyatwa Central Hospital, and College of Health Sciences at University of Zimbabwe Reference: number 06/15. Additionally, the study was reviewed and approved by the national research ethics Committee at the Medical Research Council of Zimbabwe Reference number: MRCZ/A/2051). Prior to the focus group discussions and in-depth interviews, written informed consent was obtained from all participants. All participants were given pseudonyms to use instead of their names for confidentiality purposes. Permissions to conduct interviews and document reviews were obtained from the heads of the relevant institutes and organisations. Permission to engage with community members and health care staff was obtained from the Ministry of Health and Child Care as we used health centres to recruit community participants. Further permission was obtained from the community leaders from the respective communities.No data is associated with this article. First, I would like to thank you for the opportunity of reviewing this paper. The authors have addressed the comments that were requested of them to my satisfaction. I recommend that the manuscript be indexed.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Thanks for giving me an opportunity to review both the revised article and the author responses to the issues that were raised during the initial review. I have reviewed both the revised article and author responses. The authors have responded adequately to the issues I had raised during the initial review. Therefore, I am happy to approve this version of the article for indexing. Best wishes, Francis.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. This manuscript presents interesting and novel primary data about views and opinions of research participants interviewed in a qualitative study nested within the Genomics Inheritance Law, Ethics and Society (GILES) initiative in Zimbabwe. The study appears to have been well designed and executed, but additional details about the structure of the manuscript, which should include the following order: background/introduction, objectives, methods, results/findings, discussion of the findings, recommendations and conclusions are needed. Additionally, this manuscript should have been classified as a research article and not as an open letter since it reports on findings of the qualitative study.The objectives of the empirical study should be articulated in the manuscript.The methods section should explain how the qualitative data from the in-depth interviews (IDIs) and Focus Group Discussions (FGDs) was processed and analyzed.The results section could benefit from a substantial organizational overhaul with an eye towards enhancing the clarity of the central message of the manuscript including direct quotations from research participants. Finally, enhancing the emphasis on key study findings that are novel, exciting, and have direct implications for addressing ethical, legal and societal issues (ELSI) for bio-banking and genomics in Africa  is important. This manuscript has much to teach the bio-baking and genomics research community, but would benefit from revisions as follows:I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Thank you for reviewing our article. We have addressed the comments as indicated in bold below. This includes clarification of the objectives of the article as an Open letter providing an overview of the GILES initiative. More detailed manuscripts for the various results of the project are currently underway.Reviewer 2– The objectives of the article have been clarified to fit with expectations for the classification.This manuscript presents interesting and novel primary data about views and opinions of research participants interviewed in a qualitative study nested within the Genomics Inheritance Law, Ethics and Society (GILES) initiative in Zimbabwe. The study appears to have been well designed and executed, but additional details about the structure of the manuscript, which should include the following order: background/introduction, objectives, methods, results/findings, discussion of the findings, recommendations and conclusions are needed. Additionally, this manuscript should have been classified as a research article and not as an open letter since it reports on findings of the qualitative study. This manuscript has much to teach the bio-baking and genomics research community, but would benefit from revisions as follows:– This has been revised to emphasise the main aim of the paper as well as the main aims of the GILES Initiative.1.      The objectives of the empirical study should be articulated in the manuscript. – As indicated in the main aim of the paper which was to describe the strategy and experiences of the GILES initiative. Detailed reports and results will be published in separate research manuscripts which will also provide more details on methods including management of qualitative data..2.      The methods section should explain how the qualitative data from the in-depth interviews (IDIs) and Focus Group Discussions (FGDs) was processed and analyzed– In line with the above the paper has been revised to emphasise its main aim in providing an overview of the strategy of the project, and experiences of the researchers. Detailed reports and results will be published in separate research manuscripts which will also provide more details on the study methods adopted for the different components of the GILES study.3.      The results section could benefit from a substantial organizational overhaul with an eye towards enhancing the clarity of the central message of the manuscript including direct quotations from research participants. Finally, enhancing the emphasis on key study findings that are novel, exciting, and have direct implications for addressing ethical, legal and societal issues (ELSI) for bio-banking and genomics in Africa is important.  describes the strategy undertaken for the development and implementation of the GILES project and discusses the importance of such an initiative for characterisation of ELSI of human biobanking and genomics in Zimbabwe and Africa”. However the way it is written  is more inclined towards reporting the experiences of the GILES project.In the abstract it is stated that the paper “The GILES project employed a multi-methods approach, which included document reviews and an explorative qualitative study with targeted informant interviews and focus group discussions to understand the ELSIs and governance of biobanking and human genomics for health research and clinical applications in Zimbabwe”. But it seems the paper is presenting more of the experiences of the GILES project than an explorative qualitative study. The voice of the respondents is conspicuously missing. I think the main problem is with the rationale of this paper. I suggest that the introduction be revised and the precise objective of this paper be clearly articulated. Otherwise it is confusing in its current form.“ELSI regulations”; “There exist gaps in the current guidelines and policies for addressing ELSI of biobanking and genomics in Zimbabwe”. Later on in the same paragraph the authors state “Content analysis will determine the presence and absence of information or guidelines regarding the collection, storage, exportation and analysis of biological specimens and data, biospecimen and data sharing, data security and consent.” It sounds like the content analysis is not yet done. Then, what is this paper reporting? Desk review? “Desk review of “legal and policy documents, and regulatory instruments” is vague. It is indicated that protocols were also reviewed. Which protocols? Protocols of which research? For which time period; since MRCZ was established? Etc. It is thus not clear which exact documents from MRCZ were reviewed. The documents should be explicitly stated and references cited where applicable.Knowledge, attitudes and practice of ELSI of biobanking and genomics” section is presented in present tense; is it a preamble? If so, was it from literature? Provide reference citation. Are these study findings? The first paragraph of the “Application of ELSI in research projects” section indicates that FGDs and in-depth interviews were conducted however, how this was done is not clearly articulated. The last paragraph of this section talks about community engagement and there seems to be a disconnect with the preceding sections. Please include a bridging statement.“At this point it difficult to tell whether this paper is presenting the experiences of the GILES project or perceptions and views of individual participants? It is a bit confusing to the reader.Let this paper be revised to present the results of the desk review and experiences of the GILES project.The limited understanding of ELSI applications for genomic research and healthcare in Zimbabwe is a situation, which also applies across the continent”. It is not clear whether this statement is derived from the results or it’s from literature?“Overall, the presentation of this paper is a bit confusing.I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Thank you for reviewing our article. We have addressed the comments as indicated in bold below. This includes clarification of the objectives of the article as an Open letter providing an overview of the GILES initiative. More detailed manuscripts for the various results of the project are currently underway.Reviewer 1Overall, the presentation of this paper is a bit confusing.describes the strategy undertaken for the development and implementation of the GILES project and discusses the importance of such an initiative for characterisation of ELSI of human biobanking and genomics in Zimbabwe and Africa”. However the way it is written is more inclined towards reporting the experiences of the GILES project. – This has been well noted and the abstract has been refined and inclined towards reporting of the strategy undertaken and experiences of the project.1.      In the abstract it is stated that the paper “The GILES project employed a multi-methods approach, which included document reviews and an explorative qualitative study with targeted informant interviews and focus group discussions to understand the ELSIs and governance of biobanking and human genomics for health research and clinical applications in Zimbabwe”. But it seems the paper is presenting more of the experiences of the GILES project than an explorative qualitative study. The voice of the respondents is conspicuously missing. I think the main problem is with the rationale of this paper. I suggest that the introduction be revised and the precise objective of this paper be clearly articulated. Otherwise it is confusing in its current form. – The objective of the paper has been revised both in abstract and in the Introduction. We have also indicated that the key aim was to describe the strategy and that detailed methodology of the various activities and their results will be reported in separate research manuscripts.2.      “ELSI regulations”; “There exist gaps in the current guidelines and policies for addressing ELSI of biobanking and genomics in Zimbabwe”. Later on in the same paragraph the authors state  “Content analysis will determine the presence and absence of information or guidelines regarding the collection, storage, exportation and analysis of biological specimens and data, biospecimen and data sharing, data security and consent.” It sounds like the content analysis is not yet done. Then, what is this paper reporting? Desk review? – This paragraph has been updated. As indicated above this manuscript summarises the methods and more details will be obtained in the full manuscripts which are underway.3.       “– As indicated above this manuscript summarises the methods and more details will be obtained in the full manuscripts which are underway. We have however provided clarification regarding the protocols reviewed.4.      Desk review of “legal and policy documents, and regulatory instruments” is vague. It is indicated that protocols were also reviewed. Which protocols? Protocols of which research? For which time period; since MRCZ was established? Etc. It is thus not clear which exact documents from MRCZ were reviewed. The documents should be explicitly stated and references cited where applicable. Knowledge, attitudes and practice of ELSI of biobanking and genomics” section is presented in present tense; is it a preamble? If so, was it from literature? Provide reference citation. Are these study findings? – This has been revised and references provided.5.      The first paragraph of the “Application of ELSI in research projects” section indicates that FGDs and in-depth interviews were conducted however, how this was done is not clearly articulated. The last paragraph of this section talks about community engagement and there seems to be a disconnect with the preceding sections. Please include a bridging statement. – This section has been revised to reflect the objective of the paper which aimed at providing an overview of the project, summarise activities undertaken and their rationale.6.      “– The former is correct. The revisions have highlighted the main aim of the paper describing strategy taken for the project, focusing on rationale and experiences of the research team.7.      At this point it difficult to tell whether this paper is presenting the experiences of the GILES project or perceptions and views of individual participants? It is a bit confusing to the reader. – Please refer to points above reading the main aim of the paper at this stage. As an open letter, the paper does not take the format of a research article. – Paper has been revised accordingly in line with above comments. 8.      Let this paper be revised to present the results of the desk review and experiences of the GILES project.The limited understanding of ELSI applications for genomic research and healthcare in Zimbabwe is a situation, which also applies across the continent”. It is not clear whether this statement is derived from the results or it’s from literature?– This sentence has been revised. The point is that more ELSI research is required and also more understanding and awareness about ethical issues in these advanced technologies is needed. This applies across all regions of the African continent where these technologies are only starting to be applied, and each country would need to tailor interventions appropriate to their settings.9.      “


Colon cancer is one of the common cancers and a major reason for cancer-related deaths with reported metastasis to the lungs and liver. Metastasis to inguinal lymph nodes from the adenocarcinoma of the colon is very rare and needs to be managed distinctly. We present a case of moderately differentiated adenocarcinoma of colon confirmed pathologically in an elderly male patient with locally extensive malignancy with involvement of the right-sided inguinal lymph nodes. Colon cancer is well known for its metastatic capacity . In mostTo our knowledge, there are six case reports of colon cancer with inguinal lymph nodes metastases -5, althoA 59-year-old male presented to the family practitioner complaining of melena, abdominal discomfort, weight loss, loss of appetite for one month, and right inguinal swelling. Then, he was referred to the gastroenterologist for a colonoscopy which showed a splenic flexure annular mass Figure  80 cm awAfter complete workup, the patient was referred to our service to perform an excisional biopsy of the right inguinal lymph node. Excision was done and the pathology report revealed the presence of metastatic moderately differentiated mucinous adenocarcinoma of colorectal origin. No further surgical intervention was offered to the patient as the multidisciplinary team decision of the Tumor Board labeled him as a metastatic disease that warrants palliative chemotherapy.Retrospective studies and the Saudi Cancer registry noted an increase in colon cancer in Saudi Arabia over the past decade and distant metastasis was diagnosed in about 28.4% of patients at the presentation of which rectal cancers account for 41% -10. It i Our case is of a patient with locally advanced disease with a right inguinal lymph node metastases. It is considered to be an extremely rare incidence -5. The m However, ours seems to be the first case to originate from the splenic flexure. We believe that the hypothesis of direct abdominal wall invasion is true to our case due to the fact of the presence of peritoneal deposits.We have encountered an extremely rare case that constitutes a challenge to the treating surgeon. A case of locally advanced colonic adenocarcinoma with peritoneal deposits and right inguinal lymphadenopathy. Further evidence is of utmost significance in order to support a certain plan of care since the management of such conditions varied drastically between different case reports.


In many countries, housing is used for wealth accumulation and provides financial security in old age. We tested the hypothesis that household wealth, measured by housing quality and ownership of durable assets, would increase with age of the household head.We conducted a survey of household heads in 68 villages surrounding Mtwara town, Tanzania and recorded relevant demographic, housing and social characteristics for each household. The primary analysis assessed the relationship between age of the household head, quality of the house structure and socio‐economic score (SES) using multivariate analysis. Principal Components Analysis (PCA) was used as a data reduction tool to estimate the social‐economic status of subjects based on relevant variables that are considered as proxy for SES.P < 0.0001), wattle and daub walls  and corrugated iron roofs . Wealth accumulation in the villages included in the study tends to be an inverted V‐relationship with age. Housing quality and SES rose to a peak by 50 years and then rapidly decreased. Households with a large number of members were more likely to have better housing than smaller households.Of 13 250 household heads were surveyed of whom 49% were male. Those at least 50 years old were more likely to live in homes with an earth floor (86%) compared to younger household heads (80%; Housing plays a critical role in wealth accumulation and socio‐economic status of a household in rural villages in Tanzania. Households with a head under 50 years were more likely to live in improved housing and enjoyed a higher SES, than households with older heads. Larger families may provide protection against old age poverty in rural areas. Assuring financial security in old age, specifically robust and appropriate housing would have wide‐ranging benefits. The way households accumulate wealth across nations, social classes and generations are profoundly different. In industrialised countries, wealth generally increases with age and occupation, usually in the form of savings and home ownership, sufficient for the period after retirement , 21. PenLand ownership in Tanzania is a mix of public and private as in many other countries, yet the legal situation is complex. According to the Land Act of 1999 , land inThe traditional basic rural African house is a single storey structure with an earth floor, walls built of earth and clay, either as mud blocks or plastered onto a stick frame (wattle and daub), and a thatched roof . VariatiThere is currently little information about the relationship between wealth, as assessed by housing quality, and the age of the household head. Here we tested the hypothesis that the accumulation of wealth during life would follow the model of high‐income countries and result in older household heads having better quality houses than younger household heads. This is highly relevant today since sub‐Saharan Africa has the highest population growth rate in the world  and withth [The economy of Tanzania is the second‐largest in the East African Community and the tenth‐largest in Africa. Tanzania is largely dependent on agriculture for employment, accounting for about half of the employed workforce. The economy has been transitioning from a state‐directed, command economy to a market economy since 1985 . Althougth .2 in size and in 2012 had a population of 1 270 854 [th highest GDP per capita of 31 regions of Tanzania [The study area is in rural Mtwara , an administrative region of Tanzania that shares its south border with Mozambique. Mtwara region is approximately 16 710 km 270 854 . In MtwaTanzania .The studies were approved by the Tanzanian NIMRI ethics review board (Ref. NIMR/HQ/R.8a/Vol. IX/2924). Each respondent provided individual, signed, informed consent; illiterate participants provided a fingerprint countersigned by a literate witness.Data were collected as part of the baseline assessment of a large housing study (NCT04529434). A team of researchers visited all houses and compounds in 68 villages surrounding Mtwara town. Villages were selected based on the proximity to the town and road access, which is critical for the delivery of building construction materials. The self‐identified household heads were interviewed in the assumption that s/he is most knowledgeable about family wealth and other household issues. The household head provided data his or her own house only. A household was here defined as a person or a group of people, related or unrelated, who live together and share a common source of food. A house is a residence where the family is currently living. The household head is responsible for making decisions within the household, often s/he is also the main provider of the household. A census was conducted in every village, during which time household heads were interviewed, houses were inspected, photographed and geo‐located. A structured form was used to collect demographic and socio‐economic information Appendix . The ass2 value was obtained when the cut off was 50 years. A quadratic regression was fitted to confirm the break point which was 49.9 (≈50) years. Respondents under 18 years (n = 19) were excluded from the analysis as they are unlikely to be the true household head and the reliability of responses was, at times, questionable. Poor housing was defined as a house with all of the following criteria an earth floor, mud walls, thatched roof, no electricity and no tap water. For the purposes of this study the ‘younger age group’ was defined as aged 18 to 50 years and the ‘older age group’ from 51 to 98 years, based on visual inspection of the SES/age relationship. A logistic regression model was used to assess the relationship between age group and (younger vs. adults) and modern housing defined as a house with concrete/tiles floor, brick walls and metal roof. Significance test was performed at 1% significance level due to multiple comparisons. Analyses were performed in Stata 15.The primary analysis aimed to assess the relationship between age of the household head, quality of the house structure and socio‐economic score (SES). A Principal Components Analysis (PCA) method was used as a data reduction tool to estimate the social‐economic status of subjects based on relevant variables that are considered as proxy for SES. The housing related variables education level, type of floor, type of walls, type of roof, number of sleeping rooms, type of kitchen, type of toilet, electricity and ownership of durable assets were used in the PCA to estimate the SES. The first principal component was used to construct the model for predicting the socio‐economic score for each respondent as it contains the most information among the PCA factors , 22. TheP < 0.0001). 68% of the older respondents were married which is lower compared to 75% of the younger respondents (P < 0.0001). And almost all (94%) of the older respondents were farmers which is higher compared to 86%, younger respondents (P < 0.0001). 41% and 32% of the households had 3 or 4 rooms, respectively. Those that had only 2 rooms accounted for 20% of the total.The study was conducted in 68 villages in Mtwara region, Tanzania between April and August 2019. Of 14 600 villagers approached by study staff 1331 (9%) respondents were excluded because their age was not recorded and 19 (0.1%) were excluded because they were under 18 years , and wattle and daub constructions . The frequency of thatched roofs was lower among the older than younger respondents . The most frequently used type of toilet (85%) was a pit latrine with an earth floor irrespective of the age of the household head. The three most common water sources were a community well (43%), water collected from a lake or river (16%), or a public tab (11%). 49% of the younger respondents had access to electricity but only 42% of the respondents at least 50 years. Older respondents were less likely to own durable assets like cell phones ; television , motorbikes  and bicycles .Older household heads were more likely to live in homes with an earth floor (86%) compared to younger household heads  and there was negative relationship between SES and age in older household heads (r = −0.87)  Figure . HousehoThe respondents reported that their households included between 6 and over 20 members. The age distributions of the reported household members as illustrated in Figure We found that wealth accumulation in the study villages peaks and levels off by age 50 years, after which it decreases precipitously. Households with a head under 50 years were more likely to live in improved housing and enjoyed a higher socio‐economic status. Households with a large number of members were more likely to have better housing compared to smaller households. These observations suggest that the poverty‐related problems faced by residents of the area are most severe among the elderly living on their own.Most people in the study villages work in agriculture. The nature of work is highly demanding and takes its toll on the health of the workers. By the time they are 60 years most people find it hard to continue demanding physical work. Households that depend in large part on the income of the household head experience a decrease in income once the head reaches such an age. Maintaining a basic wattle and daub home is labour‐intensive. An earth floor needs to be swept several times daily, mud walls need to be repaired at least after each rainy season, otherwise the walls collapse Figure . Thatchede facto household. Third, not all assets could be checked, and it is possible that land ownership and ownership of durable assets are overstated. We believe these limitations are outweighed by the strengths of the study, which includes its reliance on original primary data and the reporting of the house structure by direct observation.Our study has several limitations. First, as mentioned earlier the economy of Tanzania has undergone profound changes over the last 40 years including a transition from command to market economy. This leaves the theoretical possibility that people reaching adulthood during this transition remained economically disenfranchised while the following generation benefitted from the opening of economic opportunities. This scenario suggests that wealth or more precisely the relative poverty of the people over 50 is fixed. Our study design, a survey at a single point in time cannot distinguish whether wealth in study sites is fixed or dynamic. But based on the experience of the investigators it seems more likely that wealth is dynamic and directly correlates with the income capacity from labour which declines with age. Second while the housing structures can be directly observed for other information, we have to rely on the respondents’ information. This may explain the surprisingly large number of reported household members. As the respondents were asked about the members belonging to the household family members who have left the villages long ago and show no inclination to return any time soon were still included. The reported number of household members has to be understood as the ideal household as imagined in the mind of the respondent and not the The findings of this study provide an explanation for the preference of large households and big families which have resulted in the rapid population expansion in many parts of Africa. It seems likely that in many rural African villages the only protection against old age poverty is the hope that younger household members will eventually take care of the household. We are currently exploring new housing constructions for rural Africa that aside from providing a healthy environment, will be more durable compared with the current local standard. It is likely that a long‐lasting structure may contribute towards protection against old age poverty by assuring a safe refuge for the ageing members of a household.Appendix S1 SHT2 ELIGIBILITY SURVEY – structured questionnaire.Click here for additional data file.


The size change in this area was due to the increase of the quantities of water production that continued to increase as the oil and gas fields reached maturity. The 2019 Landsat satellite imagery reveals a drastic shrinkage in the area of the lake attributed to the suspension of the produced water pumping as well as the cycle of evaporation that resulted to the water led to a limited volume of water remaining in the lake.The study area, which is part of the Sirt sedimentary basin in the north-central part of Libya, is characterized by natural resources of important environmental value that need special attention as they are threatened by many human activities. The focus of this study was mainly on the production of high-resolution maps of oil-contaminated surfaces, and the series time maps of events resulting from oil pollution using multi temporal satellite data and validation of the results. Digital image processing techniques were used on satellite-based sensing, whether optical or radar data, which proved to be a cost-effective way to collect information on the volume of lake water, and to assess the depth and concentration of pollution in the study area rich in lakes taken from different periods (1972 to 2006). The area of the oil-contaminated lake, called produced water, was calculated from the 1972 Landsat MSS digital satellite imagery data and was about 1.8 km It is usually time consuming and more expensive, especially when applied to large or inaccessible areas. It has been found that the use of satellite images can cover large areas simultaneously and periodically in a non-destructive manner with lower costs and shorter time, and thus be a viable alternative to traditional methods based on the ground5.Oil pollution in producing fields located mainly on land is often monitored by sampling of soil, water, atmosphere, and plants, to determine if they are contaminated with oil10. In addition to11 who applied SIR-C/X synthetic aperture radar (SAR) data to determine oil lakes, surface roughness variation and vegetation distribution. Consequently to minimize the cost and save time, remote sensing technique in addition to GIS analysis must be first utilized before any other traditional methods.Multispectral remote sensing involves the acquisition of visible, near infrared, and short-wave infrared images in several broad wavelength bands are proving invaluable in developing environmental monitoring capabilities. It has become clear no doubt that when these techniques are used, they are very well suited on a large scale in the world, especially in many projects and studies to describe and provide invaluable information on the state of the oil pits (lakes) and oil-contaminated surfacesFor the sake of confidentiality of the information, the oilfield name and exact location will not be given instead it will be mentioned as a study area located in Sirt sedimentary basin at the central north part of Libya Fig.  which is12. It is by far the largest secondary source or waste stream associated with oil and gas production. This makes managing the water produced and its environmental impacts a huge challenge for the oil industry and environmental experts.Produced water can be defined as water present with oil or gas in ground formations and brought to the surface14 and have a chronic impact on ecosystems and humans affected by soil pollution of shallow surface and shallow aquifers as well.The produced water Fig.  is a polThe main objective of this study is to determine the size and depth of the lake and the amount of concentration of pollutants inside the lake utilizing satellite-based sensing.In addition, satellite data has been used for several dates of oil pollution events using indicators of change with multiple time images over the past decades.The focus of this study was mainly on the production of high-resolution maps of oil-contaminated surfaces, and the series time maps of events resulting from oil pollution using multi temporal satellite data and validation of the results.Preliminary study of the satellite images and identify areas of possible oil contamination were vectorized in ArcGIS and entering attribute information in the application ArcMap.Perform reconnaissance of produced water body extension, depth, and locate the data on GIS to produce multi- GIS layers of the available dataIdentify latitude, longitude  of the polluting features.Verify the direction of flow and assess their impact on the surrounding areas.The satellite imagery contains all bands has been used to classify produced water bodies according to different features: i.e., extension, and depth.Different time series aerial and satellite imagery have been used as a base for this and used to extract features relevant to this study.In order to predict the future extension of the disposal lake, topographical map of the study area has been constructed. To achieve this goal the available different dataset such as the SRTM obtained elevation data on a near-global scale to generate the most complete high-resolution digital topographic database of Earth supported by local topographical maps.Through this work, the following procedures were carried out:The satellite images of the study area were created using a variety of digital image processing techniques to enhance three separate satellite images from different dates in the period 1972–2006 and combine them into a single composite image. The results provide a dramatic view of the lake extension.Acquisition and processing of different remote sensing data.Generation of digitally enhanced satellite images to show time series of changes to the produced water lake of the study area.The used images were geographically corrected using digital image processing and geo-referenced to the same projection.The images have been transferred to Arc-GIS software to produce the accurate boundary delineation of the produced water body.The lake from the image were digitized and cut to perform the classification.Generating of time series maps of the studied lake for different years.Construction of the final maps and analyzes changes of polluted areas with the data of the previous years.The following main components have been covered this part of study:The geological study of any area affected by oil pollution is very important in identifying the consequences of that pollution on the rock layers below or around the lake. Despite the shrinking of the produced water from these lakes, they have left their surfaces in the form of dark formations saturated with oil materials, which completely changed the characteristics of the rock in terms of porosity and cohesion, and will result in future morphological changes. Although this is outside the framework of this study which is concerned with the extension, expansion and volume of water of the lake during several years.15. Maradah Formation is made up of two members . The size of the lake when measured from satellite image was about 1.8 kmThe studied lake is visible in the images as black pools. Satellite imagery helped reduce the costs of mapping these pools and quantify the level of lake expansion. The sand and gravel on the land's surface combined with oil and soot to form a layer of hardened “tar Crete” over the boundary of the area.2 since 1972.Figure 2.In 1988, the study area has been imaged by SPOT satellite image of XS mode registers light in three narrow bands  at a nominal ground resolution of 20 m. In this image Fig.  the mainAccording to this image the other lakes can be easily identified although the southern lake which located near to field camp has partially disappeared by smoke, while the one that located in the east of the field camp seems to start drying and disappearing except the Eastern boundary where still covered by water.2.Figure The other lakes can also be still easily identified where the southern lake which located near to field camp is appearing bounded in the north by a flame with arising smoke from some field wells.While the lake is located in the east of the field camp seems to be almost dried and disappeared except a small part in the western boundary which is still covered by water.2 to become about 10.7 km2.Figure 2 to 6 km2 and may be attributed to peak field production during that time.Figure The graph shows the effects of fluctuation in the amount of multi-year pumping (1972–2006) and subsequent return to more favorable pumping conditions.Figure 2 with a depth from 5 to 8 m while the shallowest area is about 0.6 km2 with a depth less than 2 m.This classified map reveals that the shallowest areas located at the margins of the lake with a depth of less than 2 m which increases gradually into the south central part of the lake coloured in dark blue with a depth of more than 8 m. The graph illustrates the different sizes with different depths where the largest area of the lake is about 4.2 kmThe use of topographic map shows that the terrain of the study area ranges from 120 to 240 m above sea level Fig. . The sam2.In 1972 the size of the lake when measured from satellite image was about 1.8 km2.1978 the lake has risen from 1.8 to reach to 6 km2.In 1988 the study area has been imaged by SPOT satellite image and the size of the lake was expanded into 8 km2.2004 the size of the lake was expanded into about 10 km2 to become about 10.7 km2.2, while the less shallow areas and not exceed 2 m deep covered an area of about 0.6 km2.Depths of less than two meters which represent shallow areas are located on the edge of the lake and this depth gradually increases as we head to the south-central part of the lake, which appears in dark blue with a depth of more than 8 m. The lake is characterized by difference in size or depths where areas with depths between 5 and 8 m is the largest area in the lake by about 4.2 kmThere is a possibility of expansion of the lake into the east rather than to the west.2 to 6 km2, likely due to topographical factors by flooding the eastern lake and flowing horizontally into the west.This study shows that the increase in the lake occurred mainly to the north-east and south-west, the greatest between 1972 and 1978, where the size of the lake grew significantly from approximately 1.8 kmThe volume of the lake can be measured in a certain time by multiplying the area with the average depth at that time. At 2006 the volume of the lake was as follows:So, the total volume of the lake during 2006 is:The volume of the oil slick: The result of a calculation using parameters recorded during the detection (remote sensing instruments) and observation  of related circumstances and conditions is only an estimation; for the existing quantity.In 2006, the lake was most likely expanded more to the west and the whole size increased by about 0.7 km The oil appearance as black tends to follow a pattern as shown in Fig. This study is demonstrating lake clarity, expansion, in case of obtaining altitude information (predictable depth) can be estimated over very large areas via satellite data this level of detail is one of the benefits of this techniques.mentclasspt{minimaWe should take in account that as a result of the resolution limitation of the image which generally 15 m the small areas of less than 15 m which possibly covered with oil will appear within the overall area the image. The overall area calculations should be ‘adjusted’ to take into account the areas which characterized by clear water within the main body of the slick.Usually the crude oil is characterizing by the difference in their optical density where black oils block shows all the wavelengths to the same degree but even then there are different ‘kinds of black’, while residual fuels can block all light passing through, even in thin layers. Therefore areas were measured by drawing a polygon around the detected slick and the overall length and width have been measured and estimated visually Fig.  as follo2 multiplied by the estimated depth of 2 cm to get an estimated volume of 2080 m3 multiplied by 1000 to convert to litres and divided by average of 159 to convert to barrels.The most probable zone consists of five crude oil slick areas (yellow colour) detected by satellite imagery equal to 2.08 kmThen the probable total volume of accumulated crude oil is:2, with an average depth of 0.5 cm. therefore the oil volume will be:The less probable zone consists of six crude oil slick area (violet) equal to 0.522 kmSo that the total expected oil quantity (at least) = 261.635 + 16.415 = 278.050 barrel of oil.However we should keep in mind that these quantities of oil often does not remain on the surface of the Lake, but moving and accumulate on the shores (margins) of the Lake. It is due to the wind forces and this has been measured by taking several samples along the shores of the lake as well as many meters away and showing the soil around the lakes (about 20 m from the edge of the lakes) is certainly affected as a result of produced water depositing.The impact has been recognized and ensured by both, visual observations and the results of the analyses obtained for produced water and soil nearby lakes. Therefore we do not expect to get the full amounts mentioned in case we decided to retrieve it as crude oil.2 compared to 10.7 km2 in 2006.Once this analysis has been concluded and the advice to the company owns the field to minimize the volume of this type of pollutants by reducing the amount of pumping produced water to this lake. A Landsat 8 OLI + TIRS (2019) of composed bands  to reach a resolution of 15 m as RGB was used which showed that the size of the lake decreased drastically and left just around 3443 km3 that measured in this time by multiplying the area with the average depth which estimated as 0.5 m compared with 54,750 m3 of water that was present in the lake during year 2006. This result is because we implement the same method for lake area multiplied by the approximate average depth of 5 m at that time. This decrease is about 32% of the volume of water that covered the lake. This is evident by the interpretation of the Landsat satellite image, through which the following conclusions were reached as shown in Fig. 2 whilst the water volume is about 831.5 m3 and the variation in the blue colour difference from very dark (1.1) to light (1.2) is due to the depth and amount of water which mixed slightly with oil.The size of remaining water less polluted by oil, which appears in blue colour is only about 1.663 km2 and the water volume is about 890 m3 of the total amount of water that was present in the lake previously.As for the area of water mixed with oil, it does not exceed (2), which shows as black colour towards of the polluted lakes has become only 1.78 kmThe areas shown in white (3) are the remainder of the amount of salts deposited in the center of the lake and on the edges.It is mostly sediments of soil mixed with oil (4) has been dried and appear in the satellite image in brown to light brown inside the lake.Whilst the surrounding of the lake (edges), which appears in dark brown colour (5) is the remainder of the soil, which is predominantly the concentration of oil pollutants, which occurred by pushing water currents by wind for these pollutants to settle on the edge of the lake.As for the volume of the remaining water of the area of produced water quantity inside the lake, it does not exceed 1721.5 mFrom this standpoint can be used to stop the pumping for certain periods, especially in areas characterized by high temperature, such as the study area, which contributes to the drying of the lake by evaporation of water and remains only solid substances harmful to the environment and then can be removed at the final stage.By reviewing the classification map of the main components of the lake under study, the distribution of depths in their sizes was identified.2 with a depth of 5–8 m, whereas the least shallow area is about 0.6 km2 and a depth of less than 2 m.The classified map shows that the shallowest areas are located at the margins of the lake, which is less than two meters deep and gradually rising in the south-central part, which appears in dark blue with a depth of more than 8 m. While the same map shows the different sizes of depths where the largest area of the lake, which is about 4.2 kmA polygon drawing method was used to measure areas affected by oil pollution and the overall length and width have been measured and estimated visually where we found that the most probable zone consists of five crude oil slick areas with the probable total volume of accumulated crude oil of 261.635 barrel of oil while the less probable zone of accumulated crude oil is 16.415 barrel of oil, therefore the total expected oil quantity is about = 261.635 + 16.415 = 278.050 barrel of oil.If the lake manages to a rise more elevation, the proper future extension of the lake will be in eastern side of the lake rather than the western side which it will may reach to the field facilities. This because the eastern side of the lake is lower in elevation than the western side.It is clear from this study that if we stop the pumping for certain periods, especially in areas characterized by high temperature, such as the study area, which contributes to the drying of the lake by evaporation of water and remains only solid substances harmful to the environment and then can be removed at the final stage.This is evident by the interpretation of the Landsat satellite image, which showed this decrease is about 32% of the lake area compared that was present during year 2006.From this study, it concludes that satellite images have proven successful in this form of monitoring and assessment, especially in places with broad geographical areas, and that we have been able to obtain the following results:


One possible approach how to economically facilitate gene expression profiling is to use the L1000 platform which measures the expression of ∼1,000 landmark genes and uses a computational method to infer the expression of another ∼10,000 genes. One such method for the gene expression inference is a D–GEX which employs neural networks.We propose two novel D–GEX architectures that significantly improve the quality of the inference by increasing the capacity of a network without any increase in the number of trained parameters. The architectures partition the network into individual towers. Our best proposed architecture — a checkerboard architecture with a skip connection and five towers — together with minor changes in the training protocol improves the average mean absolute error of the inference from 0.134 to 0.128.Our proposed approach increases the gene expression inference accuracy without increasing the number of weights of the model and thus without increasing the memory footprint of the model that is limiting its usage. The oriInferring the full profile is a large-scale machine learning task that is computationally challenging as the target dimension is much higher than the input dimension . A novelHowever, the model with TAAFs  still usArtificial neural networks are a powerful tool and lead to state-of-the-art results in various fields such as computer vision , speech recognition and machine translation. They are also commonly used in biology –11. Our The original D–GEX is actually a family of nine, similar architectures; a D–GEX network consists of one to three densely connected hidden layers with 3,000, 6,000, or 9,000 neurons in each layer with the hyperbolic tangent as the activation function . Due to The extension of the D–GEX  significmulti-column deep neural network (MCDNN)  for the CR–D–GEX with 5 towers and  for the D–GEX with TAAFs [A Wilcoxon signed-rank test was used for pairwise comparison of individual models. The test was used to compare the means of MAEs of individual samples (which are assumed to be independent) at a significance level 1 score of the prediction of the set of differentially expressed (DE) genes compared to the DE genes from the ground truth data found for the same sampled dataset. Then we have calculated the pairwise differences in the F0.5,F1,F2 scores, accuracy, and Matthews correlation coefficient (MCC) for both models. The distribution of values and the pairwise differences of F1 and MCC is shown in Figs. F0.5,F1,F2 scores, accuracy, and MCC) were statistically significant for all tested sample sizes when using the Wilcoxon signed-rank test as all the p–values were <10−8. To provide interpretation for the observed pairwise differences in F1 score, the typical scenario was that CR–D–GEX with 5 towers reported much fewer false positive differentially expressed genes than TAAFo, sometimes at the cost of a very small increase in false negatives. Obviously, the advanced architectures can reasonably improve differential gene expression analysis and better approximate the gene sets reached with the original gene expression data. The improvement most strongly manifests for small sample sets, where even small changes in gene expression values may result in significant gene set changes.While the checkerboard architecture has statistically significantly lower prediction error than the D–GEX with TAAFs , the praThe experimental results suggest that the introduction of Checkerboard and Tower architectures results in statistically significant improvement in the gene expression inference. At the same time, this improvement manifests in the practical gain when finding differentially expressed genes. We believe that this leads to new state-of-the-art results. Even though we are using a different normalization technique than other works , 29, 30,−6). We have also indirectly checked the practical significance of the improvement for the task of finding differentially expressed genes — our proposed model led to a statistically significant increase in the F1 score for different sample sizes (12 – 160). The best performing CR–D–GEX architecture allows better gene expression inference from the L1000 platform compared to the original CR–D–GEX. We have also hypothesized that the optimal number of towers for all tested architectures is such that the width of a layer in a tower is close to the width of the output layer and that the checkerboard architecture allows for lower error compared to the tower architecture while keeping the number of parameters constant.Gene expression profiling was made cheaper by the usage of L1000 platforms and using computational techniques to infer the expression of the target genes. The quality of the inference was improved by the D–GEX  and its There are several directions in which this work will be expanded. Since the optimal number of towers for each architecture was different, one of the direction is to determine the relationship between the optimal number of columns and the used architecture. Other directions include a generalization of the checkerboard architecture — the checkerboard architecture divided each layer in each tower into halves and reconnected those in a certain pattern; however, dividing the layers into multiple folds and using more complex reconnection patterns might lead to networks with better performance and thus further improving the gene expression inference.


With aerodynamics research being primarily focused on drag and lift mitigation strategies till date, engrossed attention has not been received by the event of numerous accidents caused due to negotiation of turns at high speeds by formula and motorsport cars. We present an unexplored and innovative concept of variable side-flap mechanism with a peculiar orientation for introducing three components of forces in the event of turning. Numerical simulations have been performed at two notorious slant angle configurations of the generic ground vehicle body, namely 25° and 35°. In order to analyse the inception of variable forces and flow changes introduced by the flap mechanism, RANS modelling has been performed on nine cases of flap angles from 10° to 90° at six instances of Reynolds numbers between  The problem exists in the case when such cars have to negotiate turns and twisty sections on the racetrack. Centrifugal force acting on a car is directly proportional to the square of velocity during turn negotiation, and consequently, drivers need to slow their cars down in order to not lose stability. They rely on the downforce generated by front and rear wings and tire friction for successfully negotiating the turn. While Formula 1 wings and tires generate massive amounts of downforce and friction, respectively, several cases of accidents have been reported till date wherein, the drivers lost control of their vehicles while negotiating sharp bends. While such incidents pose a direct threat to life and property, implementation of design additions specifically focused on turn negotiation and the dynamics involved for mitigation has received scant attention. Motivation can be sought from some of the provoking studies conducted so far.The automotive industry has received a significant amount of attention from researchers worldwide in improving the aerodynamic characteristics of various classes of vehicles, starting from high-speed motorsport cars to heavy load carriers. With the advancement in computational facilities, it has now become possible for simulating the proposed design changes and modifications before arriving at the final design that can be implemented. One of the few objectives of research has been in reducing drag and lift forces associated with the vehicles in motion. This has led to some remarkable aerodynamic designs that we see nowadays in the motorsports industry. Motorsport cars are subject to very high speeds, as a result of which, they experience tremendous amount of lift forces. Front and rear wings are fitted on these cars that generate downforce in order to maintain the overall stability at high speedset al.3. Now known after the name of the researcher, Ahmed body is a simplified model that represents ground vehicles. Ahmed et al.3 proposed a design of a bluff body which could serve the purpose of studying and analysing the external aerodynamics of ground vehicles. As shown in Fig. et al. Geometry of this body enables the flow to remain attached towards the front, in accordance with the concept of favourable pressure gradient in vehicular aerodynamics, while preserving the scope of studying intricate details of flow over the rear slant, offering relevance to hatchbacks and fastbacks. Although there is a significant amount of literature available that provides insight into the complex flow phenomena taking place on the rear portion of the ground body, some observations regarding the vortical structures being formed may be pointed out here5. Vortical structures resulting due to the presence of a rear slant angle have both spanwise and longitudinal components. The region at and near the centre of rear sloping angle is known as backlight. Longitudinal vortices emanate from the two C-pillars, travelling along the backlight region located at the rear of the vehicle. Besides, due to boundary layer separation taking place at the backlight region, some airstreams rush in for compensating the pressure gradients thus resulting in spanwise wake region vortices. Pressure drag caused due to the rear slant plays a significant role in determining the total drag on Ahmed body6. An observation specific to the case with 25° of slant angle is that a detachment zone is formed at the beginning of the backlight region and a subsequent reattachment zone is formed at the surface of the slant before reaching the trailing edge which results in a separation bubble. Previous studies show the complexities involved in capturing the flow phenomena taking place at the backlight region with a slant angle of 25° 10. The C-pillar vortices keep becoming more pronounced with an increase in slant angle. However, failure of the separation bubble to reattach was observed at 35° of slant angle, causing the longitudinal vortices to burst. Above a critical angle of 30°, the flow fully detaches over the slant due to the adverse pressure gradient.Majority of the available literature points towards studies carried out on a simplified bluff body, first introduced by Ahmed 7 who conducted experimental studies on the Ahmed body in an LSTM low-speed wind tunnel using Hot Wire Anemometry (HWA) and Laser Doppler Anemometry (LDA) measurements.There have been other experimental studies as well14. The realizable k-ε eddy-viscosity turbulence model has been used in the present work for numerically modelling the flow physics associated with the computational geometries of our concept. Detailed insights on the selection of the turbulence model, validation with experimental data and grid dependence study have been presented in the Methods section.Realizing the fact that merit of numerical modelling and simulation lies in the accuracy with which it is able to predict complex flow characteristics taking place in the wake and backlight region, baseline studies conducted in the present work have been benchmarked with the work of Lienhart and Becker23. Ahmed’s car model serves to be a useful tool for testing innovative concepts before performing tests on real-life cars or models. For the first time, a computational study of an unconventional idea of employing a side-flap spoiler – whose angle from the surface depends on steering input from the driver – for enhancing safety and driving dynamics, and its effect on the external aerodynamics of a ground vehicle body when compared to baseline case is being presented. The objective of this study is to evaluate the potential benefits and flaws of introducing active aerodynamics with the help of the said flap so that it could act as a motivation and starting point for more future studies. When the vehicle is moving on a straight-line path, the flaps remain in the retracted position, and during turn negotiation, they open at an angle based on steering input and the direction (left or right) the car is turning in. Numerical simulations have been performed to model a case where an Ahmed body negotiates a rightward turn. The left flap opens in this case, and the orientation of the same is such that it should induce three components of forces viz., drag force, downforce and inward centripetal force. One of the primary objectives of this work is to demonstrate the introduction of a downward force component which would lead to an increment in stability at winding sections. Secondly, while drag force reduction is one of the prime objectives in vehicle aerodynamics research, an increment in the same at curve negotiations would result in an air resistance, thus reducing the required braking effort. We aim to study how the theoretical proposition of inward force addition by our flap fares when investigated together with the effect of flow changes introduced by the same. Simulations have been performed at length-based Reynolds number values ranging from 1.98 × 106 to 2.98 × 106 for flap angles ranging between 10° and 90° from the surface, in steps of 10°, thus accruing a dataset of 108 cases. Success with the present proposition would prove to be a life-saving innovation which will not only enhance the driver’s safety but would also convalesce the loss of balance and stability at the most winding sections of race circuits. It may also be added that with improvement in road and transit systems globally, this concept has the potential to prove as being beneficial to private and commercial vehicles as well during instances of over-speeding at mild turns on highways, based on the design of the vehicle.There have been numerous studies on active and passive methods of drag and lift modification strategies having a direct or indirect impact on fuel savings and overall ride stability at high speedsLf of the flap is equivalent to diagonal length D of Ahmed body. Fillet of radius 0.1 m has been provided on the spanwise corner and 0.01 m radii each on the connection between top and bottom face as well as on the rear corner, in order to deter the generation of strong vortices since while a vortex is expected to form because of an added protrusion from the side, sharp corners would make its generation even stronger.The Ahmed body and flap with all their principal dimensions are depicted in Fig. et al.24 who used a blockage ratio of 1% in their study. The domain extents in our work have been set according to the studies of Guilminaeu25 and Lanfrit26. Length of domain towards the front face and rear face of the geometry is equivalent to approximately 3 L and 5 L respectively. Length of domain towards the two sides and top of the geometry is equivalent to 2 L, which gives a blockage ratio of 1.1%. Turbulence intensity at the inlet of the domain is less than 1%, comparable to that used in the wind tunnel study by Lienhart and Becker7.Computational domain setup and domain discretization play an important role in the accuracy of numerical results. One encounters the terminology of blockage ratio when dealing with closed domain aerodynamics, which refers to the ratio of frontal area of object to the frontal area of wind tunnel. The effect of blockage ratio on results produced in vehicle aerodynamics studies has been well compiled and documented by Keogh k-ε RANS modelling. Meile et al.14 investigated the variation in drag coefficient (CD) with Reynolds number (Re) up to 2.78 × 106 and presented a curve fit of their results with those of Ahmed et al.3 and Bayraktar et al.5. In the present case, on considering a variation of CD with Re for various flap angles at the two slant angles separately, a maximum variation of 1% was observed within the given range of Re. As per the terminology defined by Roshko27 and comparing our results with the curve fit presented by Meile et al.14, our investigated cases with realizable k-ε RANS turbulence modelling happen to lie in the transcritical range whereas this range of Re falls in the transitional regime for a simple Ahmed body without side flaps . Plots of percentage increment in CD and its variation with flap angle are shown in Fig. CD and Re because drag coefficient is a measure of wind resistance possessed by a vehicular body. Here we instead see a non-linear relationship between CD and Re. It may be concluded from this ambiguity in CD and Re relationship that increase in the frontal area due to the addition of side flap is not the sole cause of drag modification. There are other factors at play that govern this relationship. It would be seen in the upcoming paragraphs that vortex generation due to hindrance in the flow from side flap causes significant changes in the flow phenomena taking place at backlight and wake region which contribute to the non-linear relationship shown in Fig. Numerical results have been compiled for flap angles ranging from 10° to 90° in steps of 10° at six values of Reynolds numbers between entclass1pt{minimaentclass1pt{minimaIt is worthwhile to discuss the advantages that drag addition brings about in the event of turn negotiation. We have already seen in the previous sections how research in vehicle aerodynamics has been focused towards drag reduction and making the designs more streamlined. While environmental considerations and stringent norms imposed by authorities support this direction of research, speaking of which, new drag reduction measures are need of the hour, turning manoeuvres is where variable drag addition might help. This could be explained as follows. When a vehicle travelling at high speed has to negotiate a winding section, the driver first applies brakes to slow down the car to a safe limit of speed depending on various factors such as banking angle, car weight and centre of gravity. The reason behind doing this is to maintain stability considering the centrifugal force trying to push the car outwards. As soon as the turn is made, the driver again accelerates and moves forward. The intensity of this problem heightens when we consider the case of formula cars that travel at straight-line speeds of more than 300 kmph and slow down to around 100 to 150 kmph at sharp hairpin bends, which warrants a significant amount of braking effort. In other words, it is desirable to add resistance components right before an event of turn negotiation. From Fig. CL) of a vehicle is one of the sole objectives that this study holds. Figure CL with Re suggests that there is a net decrement in lift coefficient right from the case of 10° of flap angle for both slant angle configurations. Figure CL in 35° slant case as compared to the 25° slant case. This is primarily because of the fact that 25° baseline case has a high lift coefficient of the order of 0.35 whereas 35° baseline case has a reasonably low lift coefficient of the order of 0.0114.The decrement in overall lift coefficient , a study considering two slant angles cases of the Ahmed body provided grounds for concept validation and proof of potential. Drag coefficients were seen to increase with flap angle meaning that there is a greater amount of wind resistance-generated braking at tighter turns, correlating with an equivalent decrement in braking effort on driver’s part and enhancing the aspect of safety at the same time. Lift coefficients were seen to decrease with increase in flap angle. This resulted in an increment in downforce acting on the vehicle body with a direct impact on stability at bending sections. Interestingly due to weight transfer during turns, the downforce increment would result in more friction at outer wheels which as well, need it the most in order to maintain stability. While the flap was being able to generate an inward Z-force component, the investigated net effective Z-force component of the Ahmed body with flap was pointing towards the outward centrifugal direction due to flap-induced vortex generation. This factor holds significant potential for improving driving dynamics during cornering due to the oversteering approach applied by experienced drivers of motorsport cars. The tendency to oversteer would as well be along the lines of efforts made by modern motorsport teams in intentionally incorporating oversteering characteristics in their chasses.25 performed a comparative analysis of the performance of modelling techniques on an Ahmed body with 25° and 35° of slant angles respectively. It was reported that RANS modelling is fairly proficient in capturing all the flow properties of external flow past an Ahmed body having a slant angle of 35° due to the absence of a characteristic detachment and reattachment bubble in the backlight region. However, owing to the factor of presence of the talked about separation bubble in case of 25° of slant angle, all the eddy-viscosity turbulence models suffered in accurately capturing the same, although the drag coefficients were in satisfactory agreement with the experimental values of Lienhart and Becker7. Large-eddy simulations (LES) were found to be most nearly predicting the results when compared with experimental observations. Kranjovic and Davidson4 were among the first researchers to perform large eddy simulation on the peculiar case of Ahmed body having 25° of slant angle. Although LES was able to capture the complex flow phenomena, it did so at steep computational costs. Following the superior results provided by LES technique, several researchers have focused on a variety of nuances of complex turbulent flows being predicted by LES and its variations31. Realizing the high computational costs involved with LES, relatively less expensive, yet accurate modelling techniques have evolved and been researched upon in recent times which involve the use of partially averaged Navier Stokes (PANS) modelling and hybrid-RANS modelling34. Although such techniques present an advantage over LES in terms of computational cost-effectiveness, RANS modelling performs fairly in capturing the C-pillar vortices and wake region recirculations accurately, as seen in the past, alongside satisfactory prediction of drag and lift coefficients, which could be used for understanding a novel concept in hand within the lowest simulation runtime.A plethora of numerical studies have been performed on the Ahmed body, some of which investigate the accuracy of various turbulence models while some investigate the changes in flow phenomena induced by addition of active or passive flow control devices. Reynolds averaged Navier Stokes (RANS) modelling is one of the widely used turbulence modelling techniques by researchers, primarily because of the low computational costs involved. At the same time, it exhibits compromised accuracy in case of highly separated flows, but a calculation of the ratio between cost and accuracy provides motivation to use this technique for initial investigations of a concept in hand. GuilminaeuL to the rear, 0.5 L to the front, height of 0.8 L from ground and 0.45 L towards the sides, where L denotes car length. The other two bounding boxes provided a higher degree of refinement than the previous one in the wake and underbody regions. Element sizes near the wall were set according to y+ criterion of more than 30 up to 150 and non-equilibrium wall function approach was applied for modelling near-wall flow phenomena. While many of the numerical studies conducted on Ahmed body comply with y+ values being in the viscous sublayer of the wall, a recent work by Tian et al.23 highlights the use of y+ values in log-law region for obtaining accurate drag predictions.Two categories of the simulation were performed in this study, one using the baseline case of Ahmed body without flaps and the other involving flaps fixed on Ahmed body, both for 25° and 35° of slant angles. Hybrid meshing technique was used in which the domain was discretized using hexahedral elements in the region of boundary layers and ground, and polyhedral elements elsewhere. Using polyhedral elements proved to be advantageous as they reduced the number of elements thus ensuring faster solution runtime, alongside providing faster convergence in fewer iterations. We monitored the closeness of drag coefficients obtained from our numerical model setup with experimental ones and found a disagreement of about 10% with the coarsest grid. As a result, grid refinements were performed for which three bodies of influence were introduced. One enclosed the car model with extents of 1 k-ε turbulence model. Shih et al.35 presented a new formulation for the k-ε eddy viscosity model, which was quite different from the standard k-ε model. The realizable model is based on a new dissipation rate equation and eddy viscosity formulation36. The governing equations of the realizable k-ε model, are presented below  remains identical to standard and RNG k-ε models, the difference lies in turbulence dissipation rate (ε) relationship. There is no generation of turbulent kinetic energy in the production term of turbulence dissipation rate formulation. In addition, the destruction term in denominator never vanishes thus negating the possibility of singularity even if the turbulent kinetic energy vanishes or becomes less than zero. The changes implemented in this eddy viscosity model lead to a better representation of spectral energy transfer. It was found that the realizable k-ε model performed better for separated flows as compared to standard k-ε and this fact provides motivation for its use in present study.Literature suggests that RANS modelling successfully predicts flow phenomena for the case of 35° of slant angle but struggles in doing so for the 25° case. Due to the low computational costs involved in eddy viscosity RANS modelling, when compared with large-eddy simulations, we decided to check the accuracy of drag coefficient prediction of baseline case and further perform a grid dependence test using the low  for turbulent kinetic energy, turbulent dissipation rate and turbulent viscosity were kept as 0.8 for the first 100 iterations post which, the URF for turbulent viscosity was changed to 0.98.As suggested by KelecyCD values creates base for performing an investigation for validity of our innovative concept proposal. Using the solver parameters discussed above and grid sizing settings finalized upon, we performed a test case simulation on baseline cases of 25° and 35° of slant angles separately and compared the results with the experimental data of Lienhart and Becker7. CD predicted by the chosen grid was within 4% and 4.8% of accuracy with experimental CD for 25° case and 35° case respectively.We chose three grids with approximately 1.8, 2.4 and 3 million elements for 25° slant case in the full domain and found a disagreement of about 0.3% between drag coefficients predicted by the fine and medium grids respectively, thus leading to the selection of a grid with 2.4 million elements. Moving on to the case of 35° slant, we chose four grids consisting of approximately 1.2, 2.2, 3.2 and 4.1 million elements and found a significant disagreement of about 1.2% between drag coefficients predicted by the medium and fine grids. The percentage difference between drag coefficient values predicted by latter of the two grids was 0.22%, thus leading to our choice of grid consisting of 3.2 million elements. As accounted for extensively in the literature, we found that the selected RANS model setup was able to predict the backlight separation zone for 35° slant quite effectively, but same was not true for 25° slant. Nevertheless, the ability of our numerical model to closely predict Supplementary information.