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Impact of war and geopolitics on health in Palestine Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Life under occupation: the health and well-being of Palestinians Last updated: 27/11/25, 15:13 Published: 13/03/25, 08:00 Impact of war and geopolitics on health in Palestine This is article no. 1 in a series about global health injustices. Next article: Civil war in Sudan . Introduction Welcome to the Global Health Injustices Series, which will focus on critically examining the health inequalities and inequities faced by vulnerable populations within different countries and regions worldwide and even put forward actionable steps to improve their health and wellbeing. This series will begin with Palestine, as it has been an enduring crisis that should be addressed to include long-lasting benefits and outcomes for the Palestinians. Palestine: from a rich history to current occupation Palestine is a country in the Middle East (West Asia) mainly bordered by Israel. Palestine is unique in its various cultures and knowledge, moulded by multifaceted events and geopolitical shifts over centuries. The multidimensional cultural landscape of Palestine illustrates the impact of civilisations, such as the Romans, Byzantines, and Ottomans, who each had their religions, languages, and cultures, which still exist in various forms today. The resilience of the Palestinians is evident through their distinct traditions, art, food and environment, which are essential to their identity. With these testaments in mind, Palestinians are facing consistent strife because they are under constant occupation, blockade and cutting off of needed supplies carried out by Israel, as noted by several humanitarian and human rights non-governmental organisations (NGOs) like Amnesty International and Save the Children. These actions are facilitated by nations, notably the United States and the United Kingdom, through arms and weapons trade. Hence, the struggle for the Palestinians to have autonomy and freedom, among other human rights within their own homeland, is a consistent fight that requires ongoing international cooperation and solidarity. Geopolitics: its detrimental impacts on the Palestinians Given the currently divisive geopolitical landscape, it is essential to bring attention to the health outcomes of the Palestinian population, especially since at least half of them are children. A report from the Global Nutrition Cluster called “Nutrition Vulnerability and Situation Analysis / Gaza” had several key findings and tables (see Tables 1 and 2 ). Firstly, more than 90% of children less than a year old, along with pregnant and breastfeeding women, encounter high under-nutrition due to poverty. Another finding was that approximately 90% of children under five are impacted by at least one infectious disease, and 81% of households in Gaza lack clean and safe water. However, the authors noted limitations in their analysis, such as limited data sources because collecting it is difficult within the context of Gaza, and this was true for screening. Another report from the organisation Medical Aid For Palestinians (MAP), titled “Health Under Occupation” from 2017, discussed healthcare access and outcomes more broadly. For example, they noted that in 2016, up to one-third of patients’ permits to exit Gaza for healthcare access were either denied or delayed. Moreover, they stated that 40% of people in Gaza live below the poverty line. Given the recent geopolitical shifts in power, these findings from both reports will likely be higher now. This brings forthcoming uncertainty about whether the health outcomes of Palestinians will improve. In a recent qualitative study involving the views of Palestinian physicians in the West Bank, they shared their experiences of violence, threats of violence, issues with healthcare access for themselves and patients, financial difficulties to support their families, struggle to help their patients and limited access to education due to harsher life under occupation. Thinking more largely about emergency care in Palestine, one scoping review reported the depletion of healthcare resources such as medical equipment and medications. The authors even related how human rights violations and the destruction of the Palestinian healthcare system, including emergencies, have exacerbated outcomes; the most notable were stroke, myocardial infarction and traumatic injury, among other non-infectious diseases. Although the authors included this information from a human rights standpoint, they called for additional interventions and research to fill in and learn gaps within emergency care to enhance health outcomes for Palestinians. This review was published in 2022, and again, many geopolitical shifts in power have taken place within a few years. Therefore, it can be deduced that emergency care is drastically needed for the Palestinians; this is primarily compelled by the blockade in Gaza and occupation in the West Bank. Focusing on the mental health outcomes among Palestinians, they have become worse. In another scoping review, researchers focused on trauma among young Palestinian people in Gaza; the authors noted that events, such as exposure to devastation and violence, as well as the death or loss of friends and family, have contributed to mental health outcomes ranging from post-traumatic stress disorder (PTSD) to depression. Nevertheless, the authors stated that further qualitative research is vital to addressing gaps in knowledge and enhancing mental health outcomes among the Palestinian youth and the wider population. Connecting back to how the modern geopolitical landscape is very dynamic, the poorer mental health outcomes among Palestinians have conceivably increased. Urgent calls to action: recommendations from NGOs to upholding human rights Given all of these detrimental impacts on the health and wellbeing of Palestinians, there are recommendations from organisations, notably the United Nations (UN), for ways forward towards upholding the human rights of Palestinians: Immediately end all practices of collective punishment, including lifting its blockade and closures – and the “complete siege”- of Gaza, and urgently ensure immediate access to humanitarian and commercial goods throughout Gaza, commensurate with the immense humanitarian needs. Ensure that all Palestinians forcibly displaced from Gaza are allowed to return to their homes creating safe conditions and fulfil its responsibilities as an occupying Power in this regard. End the 56-year occupation of the Occupied Palestinian Territory, including East Jerusalem as part of a broader process towards achieving equality, justice, democracy, non-discrimination, and the fulfilment of all human rights for all Palestinians. These recommendations, among others mentioned in the report from the United Nations (UN) High Commissioner for Human Rights, were divulged in 2024; the year had been a challenging time, particularly in Gaza, due to the complete blockade of food, water and essentials like medical supplies; in addition to this, many explosives were dropped on Gaza, killing thousands of men, women and children. Finally, buildings, such as hospitals and homes, were destroyed. Conclusion: moving forward towards a equitable and equal future for Palestinians Reflecting on everything discussed in this article, the numerous injustices happening to Palestinians must not go on; they have been suppressed for nearly 75 years by governments and the mainstream media before receiving closer attention, examination and debate within Western society recently. Therefore, we need to take actionable steps by initiating more open discussions of justice and advocacy involving the voices of Palestinians, such as myself and others. Furthermore, it is crucial always to nudge those in positions of power worldwide to fulfil their responsibilities as civil servants and defend human rights for everyone. Both of these actions uphold the health and wellbeing of Palestinians living in Gaza and the West Bank, especially as enabling the recommendations from the UN and other NGOs. As for the wider international community, we must continue upholding human rights to maintain our health and wellbeing. In my next article, I will discuss Sudan because this population has also encountered many injustices, primarily the civil war that has been occurring since 2023. This has impacted the health and wellbeing of the Sudanese population, which requires thorough attention and discussion. Written by Sam Jarada Related articles: A perspective on well-being / Gentrification and well-being / Understanding health through different stances / Impacts of global warming on NTDs / Global health injustices- Bangladesh , Sri Lankan Tamils REFERENCES Human rights in Israel and the Occupied Palestinian Territory. Amnesty International. 2022. Available from: https://www.amnesty.org/en/location/middle-east-and-north-africa/middle-east/israel-and-the-occupied-palestinian-territory/report-israel-and-the-occupied-palestinian-territory/ Occupied Palestinian Territory. Save the Children International. 2024. Available from: https://www.savethechildren.net/occupied-palestinian-territory Nutrition Vulnerability and Situation Analysis / Gaza. 2024. Available from: https://www.nutritioncluster.net/sites/nutritioncluster.com/files/2024-02/GAZA-Nutrition-vulnerability-and-SitAn-v7.pdf HEALTH UNDER OCCUPATION. Medical Aid For Palestinians. 2017. Available from: https://www.map.org.uk/downloads/health-under-occupation---map-report-2017.pdf Husam Dweik, Hadwan AA, Beesan Maraqa, Taher A, Zink T. Perspectives of Palestinian physicians on the impact of the Gaza War in the West Bank. SSM - Qualitative Research in Health. 2024 Nov 14;6:100504–4. Available from: https://www.sciencedirect.com/science/article/pii/S2667321524001136 Rosenbloom R, Leff R. Emergency Care in the Occupied Palestinian Territory: A Scoping Review. Health and Human Rights. 2022 Dec;24(2):255. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9790939/ Abdallah Abudayya, Fugleberg T, Nyhus HB, Radwan Aburukba, Tofthagen R. Consequences of war-related traumatic stress among Palestinian young people in the Gaza Strip: A scoping review. Mental Health & Prevention. 2023 Nov 25;32:200305–5. Available from: https://www.sciencedirect.com/science/article/pii/S2212657023000478 M.I. Human rights situation in the Occupied Palestinian Territory, including East Jerusalem, and the obligation to ensure accountability and justice - Report of the United Nations High Commissioner for Human Rights - Advance unedited version (A/HRC/55/28) - Question of Palestine. United Nations. Available from: https://www.un.org/unispal/document/human-rights-situation-in-opt-unohchr-23feb-2024/ Project Gallery

Nanogels are tiny, water swollen polymer networks and encapsulate therapeutic agents Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Nanogels: the future of smart drug delivery Last updated: 17/07/25, 10:54 Published: 17/07/25, 07:00 Nanogels are tiny, water swollen polymer networks and encapsulate therapeutic agents Nanomedicine is a rapidly advancing field, with nanogels emerging as promising innovations for drug delivery applications. Nanogels are soft nanoscale hydrogels that are transforming how we deliver drugs and treat diseases. Whilst hydrogels themselves have long been used in biomedical applications such as tissue engineering and wound healing, their relatively larger sizes (above 100 micrometres) limits their ability to interact with cells and cross biological barriers. Nanogels, however, are thousands of times smaller, and offer unique advantages as a result. What are nanogels? Nanogels are tiny, water swollen polymer networks and are made up of crosslinked polymer chains to form a 3D matrix. Nanogels can encapsulate therapeutic agents inside their porous core shell structure. This swelling allowing nanogels to carry payloads, such as drugs, proteins, nucleic acids and these cargo materials are protected from degradation in the body whilst enabling controlled and targeted delivery. Due to their small sizes, nanogels can penetrate tissues and even enter cells, which overcomes the limitations faced with hydrogels. The surface of nanogels can also be engineered for specificity, to allow for precise targeting of drugs to receptors on diseased cells or inflamed tissues. Advantages over other nanocarriers Compared to liposomes and polymeric micelles, nanogels have a larger inner surface, which means they can carry more payload. The higher loading capacity improves the therapeutic efficiency whilst reducing the risks of side effects cause by off-target drug release. Nanogels also undergo the enhanced permeability and retention (EPR) effect - a phenomenon where the nanoparticles naturally accumulate in tumour or inflamed tissues due to leaky blood vessel, and as a result this improves drug delivery to targeted disease sites. Stimuli responsive ‘smart’ nanogels A key feature of nanogels is their stimuli responsiveness, or ability to act as ‘smart’ materials. The nanogels can be designed to respond to environmental triggers such as changes in pH, temperature, light, redox conditions, pressure and more. This responsiveness enables controlled release of drugs exactly when and where they are needed12. For example, thermoresponsive nanogels can change their structure at body temperature or when exposed to localised heating, making them ideal for applications like wound healing and cancer therapy. This controlled release prevents premature drug leakage, reduces systemic toxicity and overall improves the precision of the treatment. The future of nanogels in medicine Nanogels have huge potential as customisable drug delivery systems to target specific disease systems. They are biocompatible, stable, and have high drug loading capacities and are stimuli responsive; these properties combined make them a powerful tool in applications such as targeted drug delivery and gene therapy. As nanomedicine research progresses, nanogels are set to revolutionise healthcare with smarter, safer and more targeted therapies. Written by Saanchi Agarwal Related articles: Nanomedicine / Nanoparticles and diabetes treatment / Nanoparticles and health / Nanocarriers / Silicon hydrogel REFERENCES L. Blagojevic and N. Kamaly, Nanogels: A chemically versatile drug delivery platform, Nano Today, 2025, 61, 102645. F. Carton, M. Rizzi, E. Canciani, G. Sieve, D. Di Francesco, S. Casarella, L. Di Nunno and F. Boccafoschi, Use of Hydrogels in Regenerative Medicine: Focus on Mechanical Properties, Int. J. Mol. Sci. , 2024, 25 , 11426. N. Rabiee, S. Hajebi, M. Bagherzadeh, S. Ahmadi, M. Rabiee, H. Roghani-Mamaqani, M. Tahriri, L. Tayebi and M. R. Hamblin, Stimulus-Responsive Polymeric Nanogels as Smart Drug Delivery Systems, Acta Biomater. , 2019, 92 , 1–18. N. Rabiee, S. Hajebi, M. Bagherzadeh, S. Ahmadi, M. Rabiee, H. Roghani-Mamaqani, M. Tahriri, L. Tayebi and M. R. Hamblin, Stimulus-Responsive Polymeric Nanogels as Smart Drug Delivery Systems, Acta Biomater. , 2019, 92 , 1–18. A. Vashist, G. P. Alvarez, V. A. Camargo, A. D. Raymond, A. Y. Arias, N. Kolishetti, A. Vashist, P. Manickam, S. Aggarwal and M. Nair, Recent advances in nanogels for drug delivery and biomedical applications, Biomater. Sci. , 2024, 12 , 6006–6018. K. S. Soni, S. S. Desale and T. K. Bronich, Nanogels: an overview of properties, biomedical applications and obstacles to clinical translation, J. Control. Release Off. J. Control. Release Soc. , 2016, 240 , 109–126. A. Bordat, T. Boissenot, J. Nicolas and N. Tsapis, Thermoresponsive polymer nanocarriers for biomedical applications, Adv. Drug Deliv. Rev. , 2019, 138 , 167–192. K. S. Soni, S. S. Desale and T. K. Bronich, Nanogels: an overview of properties, biomedical applications and obstacles to clinical translation, J. Control. Release Off. J. Control. Release Soc. , 2016, 240 , 109–126. T. Alejo, L. Uson, G. Landa, M. Prieto, C. Yus Argón, S. Garcia-Salinas, R. de Miguel, A. Rodríguez-Largo, S. Irusta, V. Sebastian, G. Mendoza and M. Arruebo, Nanogels with High Loading of Anesthetic Nanocrystals for Extended Duration of Sciatic Nerve Block, ACS Appl. Mater. Interfaces , 2021, 13 , 17220–17235. S. V. Vinogradov, Nanogels in The Race for Drug Delivery, Nanomed. , 2010, 5 , 165–168. Project Gallery

Immunosenescence and related therapies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Ageing and its association with immune decline Last updated: 24/02/25, 11:28 Published: 20/02/25, 08:00 Immunosenescence and related therapies Introduction Ageing is a profoundly complex and integral part of human life. As pharmaceutical developments have occurred, introducing new medicines and therapies such as biologics and antibiotics within the last 100 years, research has begun to look at malignancy at a more macro scale. To be clear, while it has become easier to combat infectious diseases in recent times, the combating of diseases tied to our genetic composition is far more complicated, whether it be autoimmune diseases or onset conditions such as cases of dementia. Ageing is one such case of a process that is hard to combat because the mechanisms that cause it are diverse and currently not fully understood. Strides have been made under a concept known as senescence, which continues to enlighten researchers and the anti-ageing pharmaceutical industry. This article provides a short summary of what immunosenescence is and how we can utilise our understanding to develop therapies for human immunity. What is immunosenescence? Immunosenescence is the change from a healthy, active immune cell phenotype to one that is no longer conventionally active and begins to secrete inflammatory chemical messengers known as the senescence-associated secretory phenotype (SASP) ( Figure 1 ). A most important aspect of senescence is that a cell undergoes cell cycle arrest, meaning it cannot proliferate. You may now question why cells are programmed to senesce if the outcomes are detrimental to the host? It prevents the continued proliferation of old or damaged cells, including cells with uncontrolled proliferation (such as cancer cells). If we stop senescence altogether, we run the risk of accumulating damaged and/or mutated cells, increasing the chances of disease progression, such as through fibrosis and tumorigenesis, so specific targeting and dosage of drug interventions have to be considered. The immune system in particular, displays biological changes that are indicative of senescent progression. These include thymic involution (shrinking of the thymus associated with a decrease in T cell production), inflammaging (chronic inflammation associated with SASP), an increase in mitochondrial stress through metabolic changes, and an increase in differentiated memory T cells (EMRA T cells). Knowledge of these changes can give insight into potential mechanisms to target for therapeutics. Current and developing therapies for immunosenescence Given our expanding understanding of senescence, as of the time of writing, there are no clinically approved drugs for senescence specifically. The development of therapies for diseases such as cancer, heart disease and diabetes (diabetic patients tend to exhibit increased levels of cellular senescence owing to “accelerated ageing”) have been implicated with suppressing senescence. These drugs would be mTOR inhibitors such as Rapamycin, statins, P13K inhibitors, as well as immune checkpoint inhibitors for T cells, such as anti CTLA-4 PD-L1 and PD-L2, and the anti-diabetic metformin, which have all shown in vitro to be effective against high levels of senescent cells. There was also the development of the recent first senolytic drugs dasatinib and quercetin in 2015 that kill senescent cells selectively against non-senescent cells and stand to provide a proof of concept for targeting disease through senescent mechanisms. Conclusion The field of senescence is certainly one to keep an eye on, with a bibliometric analysis in 2023 showing an increase every year in the number of published papers ( Figure 2 ). It may be sooner rather than later that we see this become a trending topic of discussion for treating an array of disease states. Continuous research into specific immune cell subtypes (B, T and NK cells) and their relation to a decline in immunity in response to age can tell us more about potential therapeutic pathways or lifestyle choices that can improve the health of the immunocompromised elderly. One such example of this is Treg-mediated increased glucose consumption in the tumour microenvironment leading to an increase in cell senescence in effector T cells, suggesting that high sugar diets can accelerate tumorigenesis. Our understanding of ageing through senescence will help reduce the mortality rates of elderly groups in decades to come through knowing that mechanisms such as the SASP and altered immune cell function, which can promote disease states. Written by Yaseen Ahmad Related articles: Genetics of ageing and longevity / Accelerated ageing REFERENCES Henson, S.M. and Aksentijevic, D. (2021) ‘Senescence and type 2 diabetic cardiomyopathy: How young can you die of old age?’, Frontiers in Pharmacology , 12. doi:10.3389/fphar.2021.716517. Wang, R. et al. (2017) ‘Rapamycin inhibits the secretory phenotype of senescent cells by a NRF2-independent mechanism’, Aging Cell , 16(3), pp. 564–574. doi:10.1111/acel.12587. Henson, S.M. et al. (2012) ‘Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockade’, Immunology , 135(4), pp. 355–363. doi:10.1111/j.1365-2567.2011.03550.x. Islam, M.T. et al. (2023) ‘Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age’, Aging Cell , 22(2). doi:10.1111/acel.13767. Li, C., Liu, Z. and Shi, R. (2023) ‘A comprehensive overview of cellular senescence from 1990 to 2021: A machine learning-based bibliometric analysis’, Frontiers in Medicine , 10. doi:10.3389/fmed.2023.1072359. Herranz, N. and Gil, J. (2018) ‘Mechanisms and functions of cellular senescence’, Journal of Clinical Investigation , 128(4), pp. 1238–1246. doi:10.1172/jci95148. Li, L. et al. (2019) ‘TLR8-mediated metabolic control of human Treg function: A mechanistic target for cancer immunotherapy’, Cell Metabolism , 29(1). doi:10.1016/j.cmet.2018.09.020. Project Gallery

Arginine, the key to metabolic reprogramming in liver cancer Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Linking arginine and tumour growth: a breakthrough in cancer research Last updated: 20/02/25, 15:29 Published: 27/02/25, 08:00 Arginine, the key to metabolic reprogramming in liver cancer Unpicking the secrets of tumour growth: arginine, the key to metabolic reprogramming in liver cancer. We will look at how unleashing the power of arginine and elevating levels of this amino acid drive metabolic reprogramming and fuel tumour growth. Introduction In recent years, the field of cancer research has made significant progress in unravelling the complexities of this devastating disease. Scientists at the University of Basel have made a groundbreaking discovery regarding the role of the amino acid arginine in promoting tumour growth. Their findings shed light on the mechanisms underlying metabolic reprogramming in cancer cells and present new avenues for improving liver cancer treatment. Elevated levels of arginine: a surprising revelation An intriguing aspect of the study conducted by the researchers is the observation that tumour cells accumulate high levels of arginine despite producing less or none of this amino acid. Through careful analysis of liver tumour samples from both mice and patients, the team discovered that the tumour cells achieve this accumulation by increasing the uptake of arginine and suppressing its consumption. The role of arginine in tumorigenicity Upon further investigation, the scientists at the University of Basel found that high concentrations of arginine bind to a specific factor, triggering metabolic reprogramming in the tumour cells. This reprogramming, in turn, promotes tumour growth by regulating the expression of metabolic genes. The tumour cells revert to an undifferentiated embryonic cell state, enabling them to divide indefinitely. Immune system escape: a beneficial effect for tumour cells Another fascinating discovery made by the researchers is the role of arginine in aiding tumour cells in evading the immune system. Immune cells rely on arginine to function properly. By depleting arginine in the tumour environment, the tumour cells can escape immune surveillance. This finding opens up new possibilities for targeted therapies. Targeting the arginine-binding factor: a novel approach Instead of depleting arginine levels overall, which can have unwanted side effects, the scientists propose targeting the specific arginine-binding factor responsible for promoting metabolic reprogramming. By inducing the degradation of this factor, the researchers were able to prevent metabolic reprogramming in liver tumours. This approach offers a promising alternative to liver cancer treatment. Metabolic changes as biomarkers for early cancer detection Furthermore, the study suggests that metabolic changes, such as increased arginine levels, may serve as biomarkers for the early detection of cancer. Early detection is crucial for successful cancer treatment and patient survival. This finding provides hope for the development of non-invasive diagnostic methods that can detect elevated arginine levels. By measuring arginine levels in patients, these diagnostic methods can potentially identify liver cancer at an early stage. By identifying the elevated levels of arginine in liver tumour cells, these diagnostic methods could potentially use metabolic changes, such as increased arginine levels, as biomarkers for detecting cancer. Therefore, this would be crucial for successful cancer treatment and patient survival, as early detection allows for prompt intervention and improved outcomes. Conclusion The discovery of the role of arginine in driving metabolic reprogramming and promoting tumour growth opens up new avenues for liver cancer treatment. Additionally, the elevated levels of arginine observed in liver cancer patients suggest the potential for using arginine as a biomarker for non-invasive cancer detection. Further research is needed to explore the full potential of arginine as a diagnostic marker and to develop targeted therapies that exploit the metabolic vulnerabilities of cancer cells. With continued advancements in our understanding of cancer metabolism and the role of arginine in tumour growth, further research is needed to explore the full potential of arginine as a diagnostic marker and to develop targeted therapies that exploit the metabolic vulnerabilities of cancer cells. By studying the specific arginine-binding factor and its role in promoting metabolic reprogramming, scientists may be able to develop new treatments that selectively target tumour cells while minimising harm to immune cells that rely on arginine. Additionally, investigating the metabolic changes associated with increased arginine levels may lead to new biomarker designs for early cancer detection, which is crucial for successful treatment and patient survival. Written by Sara Maria Majernikova Related articles: Immune signals and metastasis / Cancer research treatment / Prostatate cancer treatment REFERENCE MOSSMANN, D., MÜLLER, C., PARK, S., RYBACK, B., COLOMBI, M., RITTER, N., WEISSENBERGE, D., DAZERT, E., COTO-LLERENA, M., NUCIFORO, S., BLUKACZ, L., ERCAN, C., JIMENEZ, V., PISCUOGLIO, S., BOSCH, F., TERRACCIANO, L. M., SAUER, U., HEIM, M. H. & HALL, M. N. Arginine reprograms metabolism in liver cancer via RBM39. Cell . DOI: https://doi.org/10.1016/j.cell.2023.09.011 Project Gallery

Unlocking the mystery of spinal disorders and paving the way for targeted therapies Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Unveiling the cancer magnet: vertebral stem cells and spinal tumour metastasis Last updated: 29/05/25, 10:46 Published: 24/04/25, 07:00 Unlocking the mystery of spinal disorders and paving the way for targeted therapies Introduction Researchers at Weill Cornell Medicine have discovered that the vertebral bones in the spine contain a unique type of stem cell that secretes a protein-promoting tumour metastasis. This protein, called MFGE8, plays a significant role in attracting tumours to the spine, making it more susceptible to metastasis when compared to other bones in the body. A new line of research on spinal disorders This groundbreaking study , published in the journal Nature, sheds light on the mechanisms behind the preference for solid tumours to spread to the spine. The findings open up a new line of research on spinal disorders, potentially leading to a better understanding and treatment of bone diseases involving the spine. Identifying vertebral stem cells The researchers began their study by isolating skeletal stem cells, which are responsible for bone and cartilage formation, from various bones in lab mice. Through gene activity analysis, they identified a distinct set of markers for vertebral stem cells. Further experiments in mice and lab-dish cell culture systems confirmed the functional roles of these stem cells in forming spinal bone. Unravelling the mystery of spinal tropism Previous theories attributed the spine's susceptibility to metastasis to patterns of blood flow. However, the study's findings challenged this long-standing belief. Animal models reproduced the phenomenon of spinal tropism, but the researchers discovered that blood flow was not the sole explanation. Instead, they found evidence pointing towards vertebral stem cells as the possible culprits. The role of MFGE8 The researchers discovered that spinal tropism is largely a result of the protein MFGE8, which vertebral stem cells secrete in greater quantities than other bone stem cells. Removing vertebral stem cells eliminated the difference in metastasis rates between spine bones and other long bones. Implications for cancer patients These findings have significant implications for cancer patients, particularly those at risk of spinal metastasis. The researchers are now exploring methods to block the activity of MFGE8, aiming to reduce the risk of tumour spread to the spine. By understanding the distinctive properties of vertebral stem cells, researchers hope to develop targeted treatments for spinal disorders. A new frontier in orthopaedics According to study senior author Matthew Greenblatt, the identification of these unique stem cells opens up a new subdiscipline in orthopaedics called spinal orthopaedics. Many conditions in this clinical category may be attributed to the properties of vertebral stem cells. Further research in spinal orthopaedics is needed to understand how these distinct properties of vertebral stem cells contribute to spinal disorders. The discovery of MFGE8, a protein secreted in higher amounts by vertebral stem cells, has shed light on the mechanism behind the preferential spread of tumours to the spine. By investigating methods to block MFGE8, researchers hope to reduce the risk of spinal metastasis in cancer patients. Additionally, the study findings highlight the importance of understanding the role of vertebral stem cells in bone diseases that primarily affect the spine. This new line of research may provide insights into the development of novel treatments for spinal disorders. Conclusion In conclusion, the study by researchers at Weill Cornell Medicine has shown that vertebral bones, which make up the spine, contain a particular type of stem cell that secretes a protein known as MFGE8. This protein plays a significant role in promoting tumour metastases, explaining why solid tumours often spread to the spine. The findings have opened up new avenues of research in understanding spinal disorders and may lead to the development of strategies for reducing the risk of spinal metastasis in cancer patients. Overall, this study highlights the importance of vertebral stem cells in contributing to spinal disorders and emphasises the need for further investigation in this field. Written by Sara Maria Majernikova Related articles: Cancer metastasis / Brain metastasis / Stem cells REFERENCE Sun, J., Hu, L., Bok, S. et al. A vertebral skeletal stem cell lineage driving metastasis. Nature 621, 602–609 (2023). https://doi.org/10.1038/s41586-023-06519-1 Project Gallery

The 14-day rule and stem cell-based embryo models Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Regulation and policy of stem cell research Last updated: 20/10/25, 14:40 Published: 23/10/25, 07:00 The 14-day rule and stem cell-based embryo models This is the last article (article no. 3) in a three-part series on stem cells. Previous article: The role of mesenchymal stem cells in regenerative medicine. Welcome to the final article in this series of three articles about stem cells. Article 1 was an overview of stem cells, and Article 2 focused on mesenchymal stem cells. In Article 3, I will look at the regulation and policy of stem cell research, which is important given the rapidly changing landscape of stem cell research. Introduction If used effectively, stem cells can be used in treating diseases, understanding human development, and more. For example, a recent paper published in September 2025 explains how scientists created embryos from human skin DNA, in an experimental process they named “mitomeiosis”. Here, the scientists attempted to force the egg cell to divide to remove half of its chromosomes so it could be fertilised like a normal egg cell. While mitomeiosis was unsuccessful in creating viable egg cells, new advancements like this raise ethical questions about the use of stem cells, especially those derived from embryos. As a result, policies and regulations must be created and followed to ensure stem cells are used ethically and appropriately. Two major topics in this policy landscape are the 14-day rule for using human embryos and the creation of Stem Cell-Based Embryo Model (SCBEM) frameworks. The 14-day rule One of the most widely known restrictions in the field of stem cells is the 14-day rule. The 14-day rule prohibits scientists from culturing human embryos in vitro (in the laboratory) beyond 14 days or the appearance of the primitive streak. The primitive streak is a developmental marker signalling the point at which an embryo is biologically individualised. The appearance of this streak also marks the beginning of gastrulation, which is when embryonic cells start differentiating into the three primary germ layers: endoderm, mesoderm, and ectoderm. A timeline of human embryo development from day 0 to day 14 is shown in Figure 1 to help visualise the different stages. In the UK, the 14-day rule is a law under the Human Fertilisation and Embryology (HFE) Act 1990 (as amended 2008) . These human embryos are either donated with consent for research purposes due to no longer being needed, are unsuitable for fertility treatments, or are embryos created explicitly from donated sperm and eggs for research purposes. However, scientific advances have meant that human embryo cultures have now become advanced, resulting in embryos being destroyed at the 14-day deadline due to the law. For example, in 2016, researchers developed new in vitro culture systems that allowed human embryos to be maintained in the lab up to the 12th and 13th day of development. This had previously not been possible. Unfortunately, the experiments had to be stopped because they were approaching the 14-day legal limit. Therefore, scientists have questioned whether the 14-day rule is still fit-for-purpose, and if not, how it could be amended in a way that still ensures ethical and appropriate use of these cells. A specific area of development that scientists do not have a lot of information on is the “black box” period, which includes the moment of gastrulation, happening around day 14-15. Having further knowledge of gastrulation could be used to improve the success rate of In Vitro Fertilisation (IVF), by helping scientists to understand possible causes of early miscarriage and implantation failure, and working to mitigate those. Because of this debate, the Nuffield Council on Bioethics has launched a project to better understand the arguments for and against extensions to the 14-day limit on human embryo research. The Council aims to use this project to provide decision-makers, such as policymakers, with the evidence they need to decide whether to extend the time limit. Regulating Stem Cell-Based Embryo Models (SCBEMs) There is also the development of SCBEMs to consider, as seen in Figure 2 . SCBEMs are also called embryoids or embryo models. They are complex, organised three-dimensional structures derived from pluripotent stem cells, which are cells that can differentiate into all cells in the human body. SCBEMs replicate certain features and processes of embryonic development, meaning they can provide new insights into stages of early human development that have been normally inaccessible to scientists. However, SCBEMs are not defined as embryos under existing laws, like the HFE Act 1990, meaning there is a policy and regulation gap covering these structures. To fill this gap, researchers recently created the first-ever UK guidelines for generating and using SCBEMs in research. The new SCBEM Code of Practice was published in July 2024 and has clear guidance and standards, increasing the transparency of research that will be conducted using SCBEMs. The Code requires that research have well-justified scientific objectives and adhere to an approved culture period, the minimum duration needed to achieve the scientific objective. For example, the Code prohibits the transfer of human SCBEMs into a human or animal womb. Furthermore, adherence to the Code requires that a dedicated SCBEM Oversight Committee be created to review and approve proposed work. An SCBEM Register is also needed to record information about successful applications. Both of these increase the transparency and openness of research using SCBEMs. Future of regulation and policy of stem cell research Given the rapid pace of development in stem cell research, policies and regulations must be created and followed to ensure ethical and appropriate use of these cells. The review by the Nuffield Council on Bioethics regarding the 14-day rule will be important in determining if the rule should be extended. The extension could allow scientists to study developmental stages such as gastrulation, currently part of the “black box” period of development occurring after 14 days. The creation of the UK's first-ever SCBEM Code of Practice in July 2024 has introduced guidelines to fill the existing policy gap, requiring research using these models to have well-justified scientific objectives, follow approved culture periods, and be reviewed by an Oversight Committee to ensure transparency and ethical use. However, there is a need for stronger regulations, as opposed to guidelines, for using SCBEMs, and it is an important example of where policy needs to continue to be developed. Written by Naoshin Haque Related articles: Animal testing ethics / How colonialism, geopolitics and health are interwoven Project Gallery

From the hull to the glass viewpoint- shortcuts in design Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The fundamental engineering flaws of the Titan Submersible Last updated: 03/04/25, 10:27 Published: 03/04/25, 07:00 From the hull to the glass viewpoint- shortcuts in design On June 18, 2023, the Titan submersible made headlines when the expedition to visit the wreck of the Titanic ended in tragedy. In the North Atlantic Ocean, 3,346 metres below sea-level, the underwater vessel catastrophically imploded along with its five passengers. Two years on, this article deep dives into the key points of failure in engineering and reflects on what we can learn from the fatal incident. The Titanic and OceanGate’s mission The Titanic wreck lies around 3800 metres below sea level in the North Atlantic Ocean, approximately 370 miles off the coast of Newfoundland, Canada. Since the wreckage was finally discovered in September 1985, over seven decades after the boat sank from an iceberg collision on the 15th of April 1912, less than 250 people have personally viewed the wreckage. Despite many discussions to raise the wreckage back to the surface, the complete Titanic structure has become too fragile after over a century underwater and will likely disintegrate completely over the next few decades. Hence, viewing the Titanic in person is only possible with an underwater vessel, a feat which has been achieved successfully since 1998 by a range of companies seating historians, oceanographers, and paying tourists. The Titan submersible is one such vessel developed by OceanGate Expeditions. Titan has been attempting dives to the Titanic wreck since 2017 and was first successful in 2021, when it went on to complete 13 successful dives. According to the passenger liability waiver however, this was only 13 out of 90 attempted dives (a 14% success rate), as a result of communication signal failures, structural concerns, strong currents, poor visibility, or logistical issues. On the many failed attempts, the mission was either cancelled or aborted before the Titan reached the depth of the Titanic wreck. Despite concerns raised by engineers, poor success rates in testing and simulation, as well as previous instances of the Titan spiralling out of control, OceanGate continued with their first planned dive of 2023, leading to its catastrophic implosion that claimed five lives. The Titan is the first fatality of a submersible dive to the Titanic. What went wrong: structural design When designing an underwater vessel to reach a certain depth, the body of the vessel called the hull, would need to be capable of withstanding an immense amount of pressure. For 10 metres of depth, the pressure on the submersible’s hull increases by one atmosphere (1 bar or 101kPa). To reach the wreck of the Titanic 3800 metres underwater would require the hull to withstand the pressure of over 38 MPa (see Figure 1 ). For perspective, this is around 380 times the pressure we feel on the surface and about 200 times the pressure of a standard car tyre. Over one square inch, this equates to nearly 2500kg. To withstand such high hydrostatic pressure, a submersible hull is normally constructed with high-strength steel and titanium alloys in a simple spherical, elliptical, or cylindrical shell. At this point we discover some of the key points of failure in the Titan. The Titan’s hull was made from Carbon Fibre Reinforced Plastic (CFRP), i.e., multiple layers of carbon fibre mixed with polymers. Carbon fibre is a high-tech and extremely desirable material for its tensile strength, strength-to-weight ratio, high chemical resistance, and temperature tolerance. The material has proven itself since the 1960’s in the aerospace, military, and motorsport industries, however the Titan was the first case of using carbon fibre for a crewed submersible. At first glance, the use of a carbon fibre hull suggests the advantage of significantly reducing the vessel's weight (50-75% lighter than titanium) while maintaining tensile strength, which will allow for a greater natural buoyancy. Without the need for added buoyancy systems, the hull would be able to hold space for more passengers at one time. As carbon fibre is cheaper than titanium and passengers pay $250,000 a seat, carbon fibre may appear to be a better business plan. However, although carbon fibre performs extremely well under tension loads, it has no resistance to compression loads (as with any fibre) unless it is infused with a polymer to hold the fibres together (see Figure 2 ). The polymer in the CFRP holding the fibres in alignment is what allows the material to resist compressive loads without bending by distributing the forces to all the fibres in the structure. This means the material is an isotropic: it is much stronger in the direction of the fibres than against (the same way wood is stronger along the grain). Therefore, individual layers of the CFRP must be oriented strategically to ensure the structure can withstand an expected load in all directions. A submersible hull intending to reach the ocean floor must withstand a tremendous compressive load, much higher than carbon fibre is typically optimised for in the aviation and automotive racing industries, and carbon fibre under such high compressive load is currently an under-researched field. Although it is likely possible for carbon fibre to be used in deep-sea vessels in the future, it would require rigorous testing and intensive research which was not done by OceanGate. Despite this, the Titan had apparently attempted 90 dives since 2017 and the repeated cycling of the carbon fibre composite at a high percentage of its yield strength would have made the vessel especially vulnerable to any defects reaching a critical level. Upon simple inspection, the Titan also raises other immediate structural concerns. Submersible hulls are usually spherical or slightly elliptical, which would allow the vessel to receive an equal amount of pressure at every point. The unique tube-shape of the Titan’s hull (see cover image) would not equally distribute pressure, and this issue was ‘addressed’ with the use of separate end-caps. The joints that attach the end-caps to the rest of the hull only introduced further structural weaknesses, which made the vessel especially vulnerable to collapsing from micro-cracks. The Titan’s glass viewpoint was another structurally unsound feature [Figure 3]. David Lochridge, the former director of OceanGate’s marine operations between 2015 and 2018 who was fired for raising concerns about the submersible’s safety features, claimed the company that made the material only certified its use down to 1300m (falling over 2000 metres short of the Titanic’s depth). The immense forces on materials without the properties to withstand the compressive pressure made the Titan’s failure inevitable. Cutting corners in the interest of business The foundation of the implosion’s cause was OceanGate’s insistence on cutting corners in Titan’s design to save time and money. The Titan was not certified for deep-sea diving by any regulatory boards and instead asked passengers to sign a waiver stating the Titan was ‘experimental’. As underwater vessels operate in international waters, there is no single official organisation to ensure ship safety standards, and it is not essential to have a vessel certified. However, many companies choose to have their ships assessed and certified by one of several organisations. According to The Marine Technology Society submarine committee, there are only 10 marine vessels capable of reaching Titanic level depths, all of which are certified except for the Titan. According to a blog post on the company website, OceanGate claimed the way that the Titan had been designed fell outside the accepted system - but it “does not mean that OceanGate does not meet standards where they apply”. The post continued that classification agencies “slowed down innovation… bringing an outside entity up to speed on every innovation before it is put into real-world testing is anathema to rapid innovation”. According to former engineers and consultants at OceanGate, the Titan’s pressure hull also did not undergo extensive full-depth pressure testing, as is standard for an underwater vessel. Carbon fibre - the primary material of the Titan’s hull - is extremely unpredictable under high compressive loads, and currently has no real way to measure fatigue. This makes it an unreliable and dangerous material to be used for deep-sea dives. OceanGate CEO Stockton Rush, who was a passenger on the Titan during its last fatal dive in 2023, described the glue holding the submersible’s structure together as “pretty simple” in a 2018 video, admitting “if we mess it up, there’s not a lot of room for recovery”. Having attempted 90 dives with a 14% success rate since 2017, it was inevitable that micro-cracks in the Titan from repeated dives, if not for the extremely sudden failure modes of carbon fibre composites, would result in the vessel's instantaneous implosion. On the 15th of July 2022 (dive 80), Titan experienced a "loud acoustic event" likely form the hull’s carbon fibre delaminating, which was heard by the passengers onboard and picked up by Titan's real-time monitoring system (RTM). Data from the RTM later revealed that the hull had permanently shifted following this event. Continued use of the Titan beyond this event without further testing of the carbon fibre - because the hull was ‘too thick’ - prevented micro-cracks and air bubbles in the epoxy resin from being discovered until it was too late. Another fundamental flaw lies in the Titan’s sole means of control being a Bluetooth gaming controller. While this is not an uncommon practice, especially in the case of allowing tourists to try controlling the vessel once it has reached its location, it is essential that there are robust secondary and even tertiary controls that are of a much higher standard. The over-reliance on wireless and touch-screen control, particularly one operating on Bluetooth which is highly sensitive to interference, was a dangerous and risky design choice. Although it was unlikely to have caused the implosion on its own, cutting corners in the electronics and controls of a vessel that needs to be operated in dangerous locations is irresponsible and unsafe. Submersibles operating at extreme depths require robust fail-safes, including emergency flotation systems and locator beacons. Again, OceanGate cut corners in developing Titan’s emergency recovery systems, using very basic methods and off-the-shelf equipment. In the event of catastrophic failure, the absence of autonomous emergency measures is fatal. With the extent of damage and poor design to the vessel’s carbon fibre hull, it was unlikely that even the most advanced emergency systems could prevent the magnitude of the implosion. Still, the carelessness displayed in almost every aspect of the submersible’s design was ultimately the cause of the fatal Titan tragedy. Conclusion In a 2019 interview, OceanGate’s former CEO Stockton Rush said: There hasn’t been an injury in the commercial sub industry in over 35 years. It’s obscenely safe because they have all these regulations. But it also hasn’t innovated or grown — because they have all these regulations. In the world of engineering, shortcuts can be catastrophic. Whilst risk-taking is undeniably essential to support innovation, Titan’s fatal tragedy was entirely preventable and unnecessary if the proper risk management techniques were employed. OceanGate had the potential to revolutionise the use of carbon fibre in deep-sea industries but consistently cutting corners and not investing in the required real-world testing, as well as the arrogance to ignore expert warnings, is what ultimately led to Titan’s story fatefully echoing the overconfidence of Titanic’s “she is unsinkable!”. Whilst regulations on submersibles tighten and research into carbon fibre is increased, it is important to take the fundamental cause of the tragic implosion as a wake-up call. Assumptions are deadly: trust the science, invest in the proper research, test every bolt, and never underestimate the ocean’s relentless power. Written by Varuna Ganeshamoorthy Related articles: Engineering case study- silicon hydrogel / Superconductors / Building Physics Project Gallery

In bones, neural communications, fertilisation and more Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The importance of calcium in life Last updated: 12/03/25, 16:45 Published: 10/04/25, 07:00 In bones, neural communications, fertilisation and more Did you know that the same mineral that gives your bones strength also helps to maintain your heartbeat and even plays a role in the very start of life? Calcium, the most abundant mineral in the human body, is primarily found in bones and teeth as calcium phosphate (Ca₃(PO₄)₂). But beyond its structural role, calcium ions are essential for nearly every biological function, from muscle contractions to nerve signalling. What makes calcium so versatile, while other minerals like iron, have far more limited roles? To truly understand its significance, we must explore its underlying chemical properties. Calcium and bones The calcium ion carries a 2+ charge allowing it to form stronger ionic bonds and interact strongly with negatively charged molecules like nucleotides and ATP. This makes it essential for energy transfer in cells. In comparison to monovalent ions like Na+ and K+, calcium, therefore, has a more significant charge density, increasing affinity for anions. However, the ion also has more shells than beryllium and magnesium in the same group (Group 2), contributing to reduced charge density. These properties are very crucial in determining the strength of Calcium compounds, as a high charge density may result in problems with toxicity and difficulty in the breakdown of the product. Calcium phosphate exists as hydroxyapatite in bones and teeth, giving them hardness and rigidity. Hydroxyapatite forms hexagonal crystals that are tightly packed, contributing to the dense, durable structure of bones. These crystals are organised into a matrix along collagen fibres, creating a composite material that combines rigidity (from hydroxyapatite) and flexibility (from collagen). The properties of hydroxyapatite make it uniquely suited for its roles in the body. Its hardness provides bones with the ability to resist deformation and compression, while its porous structure allows space for blood vessels, bone marrow, and the exchange of nutrients and waste. Osteoclasts break down the bone releasing calcium and phosphate ions while osteoblasts can reabsorb this calcium to reform bones in another area of the body, maintaining skeletal health and strength. Neural communication Imagine a relay race where one runner must pass the baton to the next for the race to continue. In a similar way, calcium ions act as messengers in the nervous system, triggering the release of neurotransmitters which allow nerve cells to communicate with each other. Upon experiencing a stimulus, sodium ions begin to enter neurones through voltage-gated sodium channels, causing depolarisation, which sends an electrical signal throughout the neurone that results in the opening of other sodium channels, carrying the electrical signal throughout the neurone until the signal reaches the axon terminal. When the action potential reaches the axon terminal, it triggers the opening of voltage-gated calcium channels in the membrane of the presynaptic neurone. Calcium ions from the extracellular fluid flow into the neurone due to the concentration gradient. This influx of calcium ions is a critical step in neural communication, as it directly facilitates the release of neurotransmitters stored in synaptic vesicles. This action helps to coordinate the strength and the timing of each heartbeat. Calcium ions bind to proteins on the surface of these vesicles, which enables the vesicles to fuse with the presynaptic membrane. This fusion releases neurotransmitters, such as acetylcholine, into the synaptic cleft—a tiny gap between the presynaptic and postsynaptic neurones. These neurotransmitters then bind to specific receptors on the postsynaptic neurone, leading to either an excitatory or inhibitory response. For example, acetylcholine often causes an excitatory response, such as muscle contraction or memory formation. Fertilisation Calcium ions are crucial for fertilisation, facilitating key events from sperm-egg interaction to the activation of embryonic development. When a sperm binds to the egg’s outer layer, calcium ions trigger the release of enzymes from the sperm, enabling it to penetrate the egg. Following the sperm-egg fusion, calcium ions are released within the egg, creating a wave-like signal. The rise in intracellular calcium levels in the egg has several critical effects triggers the cortical reaction, in which cortical granules – small vesicles located beneath the egg’s plasma membrane- release their contents into the space between the plasma membrane and the zona pellucida. The enzymes released during this reaction modify the zona pellucida, making it impermeable to other sperm. This process prevents polyspermy, ensuring that only one sperm fertilises the egg. This precise calcium signalling achieves successful fertilisation and the initiation of new life. Role of calcium in other organisms Calcium is a vital element essential for initiating and sustaining human life, but its importance extends far beyond the human body. Its role is not confined to animals as calcium is equally critical in the physiology of plants and fungi, where it contributes to a wide range of biological processes. In plants, calcium ions are used to form calcium pectate, a chemical used to strengthen the cell walls of the cell and make plant cells stick together. Additionally, calcium is vital for root development and nutrient uptake. It helps in the formation of root nodules in legumes, where nitrogen-fixing bacteria establish symbiotic relationships, and it influences the movement of ions across cell membranes to regulate nutrient transport. Furthermore, calcium oscillations play a crucial role in regulating the polarised growth of fungal hyphae, which are essential for environmental exploration and host infection. Hyphal growth is characterised by a highly localised expansion at the tip, requiring cytoplasmic movement and continuous synthesis of the cell wall. Calcium ions are central to these processes, functioning as dynamic signalling molecules. Calcium concentration is highest at the growing hyphal tip, forming a steep gradient essential for maintaining growth direction. This gradient is not static but oscillatory, with periodic fluctuations in cytosolic calcium levels. These oscillations arise from the interplay of calcium influx through plasma membrane channels like voltage-gated channels. These are critical for coordinating key processes at the hyphal tip. Calcium regulates vesicle trafficking by triggering the fusion of vesicles carrying enzymes with the plasma membrane. Additionally, calcium modulates the actin cytoskeleton, which provides tracks for vesicle transport and maintains the structural polarity of the hypha. Periodic calcium signals promote the dynamic assembly and disassembly of actin filaments, ensuring flexibility and responsiveness to physical barriers to mobility during growth. Through its oscillatory signalling, calcium enables the precise regulation required for hyphal growth and network formation. Conclusion In conclusion, calcium is a remarkably versatile element, playing vital roles across a diverse range of organisms. In humans and animals, it not only provides structural integrity through bones and teeth but also regulates critical physiological processes such as nerve signalling. Beyond animal systems, calcium is also essential in plants, where it strengthens cell walls and improves structure. In fungi, calcium oscillations are fundamental to hyphal growth, coordinating vesicle trafficking. From building bones to driving vital biological processes, calcium is a silent powerhouse in life. Its influence stretches across humans, plants, and even fungi. Its role is truly indispensable. Written by Barayturk Aydin Related articles: Bone cancer / Tooth decay REFERENCES Haider, A. et al. (2017) Recent advances in the synthesis, functionalization and biomedical applications of Hydroxyapatite: A Review, RSC Advances. Available at: https://pubs.rsc.org/en/content/articlehtml/2017/ra/c6ra26124h (Accessed: 24 November 2024). Splettstoesser, T. (2024) Action potentials and synapses, Queensland Brain Institute - University of Queensland. Available at: https://qbi.uq.edu.au/brain-basics/brain/brain-physiology/action-potentials-and-synapses (Accessed: 01 December 2024). Abbott, A., L. (2001) ‘Calcium and the control of mammalian cortical granule exocytosis’, Frontiers in Bioscience, 6(1), p. d792. doi:10.2741/abbott. Vaz Martins, T. and Livina, V.N. (2019) What drives symbiotic calcium signalling in legumes? insights and challenges of imaging, International journal of molecular sciences. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6539980/#:~:text=Currently%2C%20two%20different%20calcium%20signals,formation%20of%20the%20root%20nodule%2C (Accessed: 01 December 2024). Lew, R.R. (2011) ‘How does a hypha grow? the biophysics of pressurized growth in fungi’, Nature Reviews Microbiology, 9(7), pp. 509–518. doi:10.1038/nrmicro2591. Project Gallery

Establishing causation through Randomised Controlled Trials and Instrumental Variables Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Proving causation: causality vs correlation Last updated: 03/06/25, 13:43 Published: 12/06/25, 07:00 Establishing causation through Randomised Controlled Trials and Instrumental Variables Does going to the hospital lead to an improvement in health? At first glance, one might assume that visiting a hospital should improve health outcomes. However, if we compare the average health status of those who go to the hospital with those who do not, we might find that hospital visitors tend to have worse health overall. This apparent contradiction arises due to confounding – people typically visit hospitals due to existing health issues. Simply comparing these two groups does not tell us whether hospitals improve health or if the underlying health conditions of patients drive the observed differences. A similar challenge arises when examining the relationship between police presence and crime rates. Suppose we compare two cities—one with a large police force and another with a smaller police force. If the city with more police also has higher crime rates, does this mean that police cause crime? Clearly not. Instead, it is more likely that higher crime rates lead to an increased police presence. This example illustrates why distinguishing causation from correlation is crucial in data analysis, and that stating that two variables are correlated does not imply causation. First, let’s clarify the distinction between causation and correlation. Correlation refers to a relationship between two variables, but it does not imply that one causes the other. Just because two events occur together does not mean that one directly influences the other. To establish causation, we need methods that separate the true effect of an intervention from other influencing factors. Statisticians, medical researchers and economists have ingeniously come up with several techniques that allow us to separate correlation and causation. In medicine, the gold standard for researchers is the use of Randomised Controlled Trials (RCTs). Imagine a group of 100 people, each with a set of characteristics, such as gender, age, political views, health status, university degree, etc. RCTs randomly assign each individual to one of two groups. Consequently, each group of 50 individuals should, on average, have similar ages, gender distribution, and baseline health. Researchers then examine both groups simultaneously while changing only one factor. This could involve instructing one group to take a specific medicine or asking individuals to drink an additional cup of coffee each morning. This results in two statistically similar groups differing in only one key aspect. Therefore, if the characteristics of one group change while those of the other do not, we can reasonably conclude that the change caused the difference between the groups. This is great for examining the effectiveness of medicine, especially when you give one group a placebo, but how would we research the causation behind the police rate and crime example? Surely it would be unwise and perhaps unethical to randomise how many police officers are present in each city? And because not all cities are the same, the conditions for RCTs would not hold. Instead, we use more complex techniques like Instrumental Variables (IV) to overcome those limitations. A famous experiment using IV to explain police levels and crime was published by Steven Levitt (1997). Levitt used the timings of mayoral and gubernatorial elections (the election of a governor) as an instrument for changes in police hiring. Around election time, mayors and governors have incentives to look “tough on crime.” This can lead to politically motivated increases in police hiring before an election. Crucially, hiring is not caused by current crime rates but by the electoral calendar. So, by using the timing of elections to predict an increase in police, we can use those values to estimate the effect on crime. What he found was that more police officers reduce violent and property crime, with a 10% increase in police officers reducing violent crime by roughly 5%. Levitt’s paper is a clever application of IV to get around the endogeneity problem and takes correlation one step further into causation, through the use of exogenous election timing. However, these methods are not without limitations. IV analysis, for instance, hinges on finding a valid instrument—something that affects the independent variable (e.g., police numbers) but has no direct effect on the outcome (e.g., crime) other than through that variable. Finding such instruments can be extremely challenging, and weak or invalid instruments can lead to biased or misleading results. Despite these challenges, careful causal inference allows researchers to better understand the true drivers behind complicated relationships. In a world where influencers, media outlets, and even professionals often mistake correlation for causation, developing a critical understanding of these concepts is an essential skill required to navigate through the data, as well as help drive impactful change in society through exploring the true relationships behind different phenomena. Written by George Chant Related article: Correlation between HDI and mortality rate REFERENCE Steven D. Levitt (1997). “Using Electoral Cycles in Police Hiring to Estimate the Effect of Police on Crime”. American Economic Review 87.3, pp. 270–290 Project Gallery

VR in pain management, and mental health treatment Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The potential of virtual reality (VR) in healthcare Last updated: 27/03/25, 15:44 Published: 06/03/25, 08:00 VR in pain management, and mental health treatment Introduction The term 'extended reality' (XR) consists of three concepts: augmented reality, mixed reality and virtual reality (VR). The Oxford English Dictionary defines VR as a 'computer-generated simulation of a lifelike environment that a person can interact with in a seemingly real or physical way'. When you think of VR, you might think of headsets, goggles and gaming. However, you might not know that VR can have huge potential in healthcare as a non-pharmacological intervention. Research has shown that active VR, where patients interact and engage more with the virtual environment, becoming immersed, works better than passive VR, where patients just view content. In this article, I will look at the use of VR in two cases: for pain management and mental health treatment. VR for pain management VR-based treatments for pain management work by attention modulation, also known as focus-shifting, providing distraction analgesia (pain relief) by shifting a patient’s focus away from the pain to the virtual environment. To access the VR set-up, patients use a head-mounted display (HMD) and hardware. VR uses technology that stimulates the senses, particularly sight, sound, and touch, reducing the amount of pain a patient feels by changing the pain intensity; it is especially useful when a patient experiences sharp and sudden pain, including pain during labour or post-surgery. Additionally, VR changes how the brain processes pain by affecting the pain-control system, which includes regions like the periaqueductal grey (PAG) and the anterior cingulate cortex (ACC). Specifically for chronic pain (persistent pain that lasts for more than three months), VR can help patients develop techniques to manage their pain better over time, such as by improving their physical abilities, like moving their arms or legs more easily and improving their muscular endurance. For example, Merlot et al. (2023) found that for women with endometriosis-related pelvic pain who used Endocare (a VR software designed to reduce pain for those with endometriosis), women reported that it reduced pain intensity, with Endocare's maximum pain reduction being 51.58% compared to 27.37% in the sham control group. VR for mental health treatment VR-based treatments have also proven to be effective in treating mental health conditions, helping patients to manage conditions such as anxiety and depression. This is because they can replicate a negative environment within a controlled and safe VR setting, helping patients manage and confront their triggers. The Institute for Health Metrics and Evaluation has stated that as of 2019, 301 million people were living with an anxiety disorder, and 58 million of them (about 20% of those with anxiety) were children and adolescents. Regarding depression, the statistic was 280 million people, including 23 million (nearly 10% of those with anxiety) children and adolescents. For anxiety, VR-based treatments use exposure treatment, where patients are confronted with the stimuli, but the expected outcome does not occur. Repeating the exposure leads to patients’ anxiety decreasing over time since their perception of the stimuli leading to the feared outcome does not come true. For example, someone with a fear of heights would undergo VR-based exposure treatment where they would be exposed to heights. They would be guided through a learning process, and after multiple exposures, they would think of heights as being safe, leading to less fear of heights overall. For depression, VR-based treatments use behavioural activation so that individuals can reconnect with activities they enjoy. This can help patients develop and learn coping strategies, improving their mood and reducing depressive symptoms. VR-based treatments will be particularly helpful for children and adolescents. The statistics by the Institute for Health Metrics and Evaluation clearly show that a high percentage of those with mental health conditions are young people, and general research has shown that they will be less likely to seek professional help and receive appropriate care. VR could help this group by becoming a more appealing therapy method, especially through gamification, making children and adolescents more motivated and more likely to participate in treatment. This method would provide an immersive environment and could be a personalised form of therapy. Implications for the future It is important to note that there are still limitations stopping a wider roll-out of VR within healthcare. For example, VR can cause cybersickness, the virtual equivalent of motion sickness, resulting in nausea, disorientation, and headaches. In addition, within the use of VR for young people, more research needs to be conducted on whether gamified therapies are safe and effective. Nevertheless, these limitations can be mitigated. Technology is advancing rapidly, and newer hardware have a better field of vision and refresh rates of visual content. The VR environment is also being designed better, accounting for individual patient preferences. With further research, scientists can examine in more detail the factors that make VR-based therapies effective and implement them in a way that addresses ethical concerns and increases their effectiveness. Written by Naoshin Haque Related articles: Clinical scientist computing / Smart bandages / Emojis in healthcare Project Gallery