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The status of risk factors and disease remains a disputed question in the theory and practice of medicine and healthcare, and so does the related question of delineating disease boundaries. I present a framework based on Bernard Lonergan’s account of emergent probability for differentiating (1) generically distinct levels of systematic function within organisms and between organisms and their environments and (2) the methods of functional, genetic, and statistical investigation. I then argue on this basis that it is possible to understand disease in terms of biological or higher intra-level dysfunction, risk factors—including genetic risk factors—in terms of statistical inter-level conditioning of a given stage or developmental sequence of systematic functioning, and the empirical boundaries of disease in terms of the limits of both functional categorization (from an epistemic standpoint) and upper-level integration of lower-level processes and events (from an ontological standpoint).

The safe and effective management of pain is a critical healthcare and societal need. The potential for misuse and addiction associated with opioids, nephrotoxicity, and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use, as well as acute liver injury from paracetamol (ApAP) overdose, are unresolved challenges. To address them, we developed a non-opioid and non-hepatotoxic small molecule, SRP-001. Compared to ApAP, SRP-001 is not hepatotoxic as it does not produce N-acetyl-p-benzoquinone-imine (NAPQI) and maintains hepatic tight junction integrity at high doses. SRP-001 has comparable analgesia in pain models, including the complete Freund’s adjuvant (CFA) inflammatory von Frey. Both induce analgesia via N-arachidonoylphenolamine (AM404) formation in the midbrain periaqueductal grey (PAG) nociception area, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways, including the endocannabinoid, mechanical nociception, and fatty acid amide hydrolase (FAAH) pathways. Both regulate the expression of key genes encoding FAAH, 2-AG, CNR1, CNR2, TRPV4, and voltage-gated Ca2+ channel. Interim Phase 1 trial results demonstrate SRP-001’s safety, tolerability, and favorable pharmacokinetics (NCT05484414). Given its non-hepatotoxicity and clinically validated analgesic mechanisms, SRP-001 offers a promising alternative to ApAP, NSAIDs, and opioids for safer pain treatment.

Lockdowns were widely used to reduce transmission of COVID-19 and prevent health care services from being overwhelmed. While these mitigation measures helped to reduce loss of life, they also disrupted the everyday lives of billions of people. We use data from a survey of Singaporean citizens and permanent residents during the peak of the lockdown period between April and July 2020 to evaluate the social and economic impacts of Singapore’s COVID-19 mitigation measures. Over 60% of the population experienced negative impacts on their social lives and 40% on household economics. Regression models show the negative economic impacts were influenced by socio-economic and demographic factors that align with underlying societal vulnerabilities. When dealing with large-scale crisis’ like COVID-19, slow-onset disasters, and climate change, some of the burdens of mitigation measures can constitute a crisis in their own right – and this could be experienced unevenly by vulnerable segments of the population.

The 2015 Nepal earthquakes devastated the Kathmandu Valley and exposed the challenges of conserving andrestoring architectural heritage in historic urban neighborhoods damaged by disasters, while also trying to rapidly rebuild houses, revitalize livelihoods, and reduce vulnerabilities to future hazards. In this paper we use quantitative and qualitative data to investigate how traditional housing was transformed during the post-earthquake reconstruction of four historic neighborhoods in the Kathmandu Valley. We assess how traditional housing stock in these neighborhoods was transformed by a combination of the direct impact of the earthquake; the enforcement of seismic-resistant modern building technology; the costs and logistics of rebuilding; and the priorities of local residents. Our findings indicate that the enforcement of seismic safety building codes and the expense of incorporating traditional architectural elements led to notable changes to the tangible cultural heritage of Kathmandu's historic urban neighborhoods, but likely also improved seismic safety., International Journal of Disaster Risk Reduction, 86, ISSN:2212-4209

Skin and wound blotting are non-invasive techniques used to sample the skin and wound surface chemistry, whereby a nitrocellulose membrane is applied to an intact or broken cutaneous surface to detect biomarkers. However, there has been no comprehensive review of the evidence for the techniques used and data obtained to date. The primary aim of this study was to review the utilities of surface blotting for the diagnosis and prognosis of physiological, pre-disease, and pathological states. The secondary aim was to summarise the procedural steps. A systematic literature search was conducted on 9 July 2021 using Medline, Embase, and Google Scholar databases. Investigators used McMaster's Critical Review Form for Quantitative Studies to assess quality, then performed a narrative synthesis reporting according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-five studies were reviewed. Eighteen studies were of good quality, and seven were of moderate quality. These studies conducted skin and wound blotting on 176 animals and 1546 humans. Studies reported physiological and pathological states for diagnosis and prediction of conditions, including skin tears, wound healing, biofilm detection, and skin barrier function. The four steps for blotting are surface preparation, blot preparation, application and removal of blot, and analysis. This review demonstrates that blotting can determine the skin and wound surface chemistry using a versatile and reproducible technique. However, future research is needed to validate the technique and skin biomarkers identified.

This study presents a distinctive type of Muslim gravestone found on the northern coast of Sumatra, Indonesia, that dates to the 15th century. These grave markers, locally known as plang-pleng, pro...

On 12 November 1970, the Bhola Cyclone swept across the southern districts of East Pakistan, killing over 300,000 people. Small islands were swept away and dead bodies of humans and cattle lay strewn across the devastated landscape. Following the news of the destruction, journalists, students, artists, and political workers rushed to the affected area with basic relief supplies, without waiting for the Military Law Administration (MLA) to intervene. The cyclone's occurrence just three weeks prior to the first general elections in Pakistan added a new dimension to the already simmering political crisis. The extensive media coverage of the disaster brought the pitiful state of infrastructural development and lack of governance in East Pakistan under local and global scrutiny. The cyclone and the corresponding issues soon became embroiled within the larger political demand for regional autonomy. The MLA came under attack from sections of East Pakistan's politicians, press, and public, as well as international political actors, for its poor disaster governance. This article uses the Bhola Cyclone of 1970 as the lens to explore the complex interconnections between environmental disasters and a key issue of governance. While the Bhola Cyclone has been a subject of recent discussions, this article uses a disaster-politics analytical framework to understand the disaster's role in the subsequent political turbulence and the emergence of Bangladesh. Ministry of Education (MOE) National Research Foundation (NRF) Published version

Our team has previously built a ~7500 year tsunami history for the northern patch of the Sunda Megathrust. However, the paleo-tsunami history south of Aceh province and the 2004 rupture patch remains poorly understood. We conducted geological investigation to better define the boundaries of rupture patches along the Megathrust. We utilized satellite imagery to pinpoint potential sites likely to archive evidence of paleo tsunami inundations and co-seismic land-level change. Due to the continuing Covid-19 pandemic and restrictions, our researchers from Singapore, and USA could not travel to Indonesia. However, because of the longstanding close collaboration between the Earth Observatory of Singapore and Syiah Kuala University, Banda Aceh, Indonesia, the project continued to progress. The Syiah Kuala University team investigated nearly 20 sites between Banda Aceh in the northern patch of the of Sumatra Megathrust and Padang in the south. Several sites preserved probable paleo-tsunami sediments. The paleo-tsunami sediments were identified from anomalous layers of sand in low energy environments where they would not normally occur, such as mangroves, coastal lowlands, and/or swales. Here we present results of litho-, bio- and chronostratigraphical analysis from Susoh as well as preliminary information from sites along the coastline between Meulaboh and Padang. From Susoh we described stratigraphy from a series of cores to a depth of 4.75 m. The top 2.5 meters was dominated by muds typical of estuarine or tidal flat settings, but it is interrupted by three pulses of sandy muds. At 2.55 m we encountered a 0.2 m thick layer of course sand, underlain by a 0.5 m thick mangrove peat with a gradual transition into organic sandy muds and sands. Pollen analysis from the fine-grained organic layers indicate they were formed in a mangrove environment. Radiocarbon dating of the organic macrofossils from the mangrove peat indicate the tsunami event occurred post 1850 cal. yrs BP. Our research continues to improve our understanding of the Sumatran Megathrust.

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After considering two of Pellegrino's papers that address the relation between philosophy of medicine and medical ethics, I identify several overarching problems in his account that revolve around his self-described essentialism and the lack of a systematic attempt to relate clinical medicine to biomedicine and public health. I address these from the critical realist position of Bernard Lonergan, who grounds both metaphysics and ethics on the normative structure of human inquiry and seeks to understand historical development, such as we are witnessing in health science and health care, in terms of the dynamic structure of the human good. I conclude that Lonergan's generalized empirical method and hierarchical account of world order provide a potentially dynamic framework on which to build a more comprehensive philosophy of medicine than one whose foundations rest primarily on a phenomenology of the clinical encounter and the telos of medicine.

Significance We demonstrate that a tsunami in the late 14th century CE destroyed coastal sites along a critical part of the maritime Silk Road and set in motion profound changes in the political economy of Southeast Asia. Our results provide a precise chronology of settlement and trade along a historically strategic section of the Sumatran coast and are robust physical evidence for the rise of the Aceh Sultanate. Tragically, coastal areas impacted by the late 14th century tsunami were devastated by the 2004 Indian Ocean tsunami. This makes our findings relevant to debates about hazard mitigation and risk reduction. This example shows that archaeological, historical, and geological data are relevant in discussions about the long-term sustainability of communities exposed to geological hazards., Archaeological evidence shows that a predecessor of the 2004 Indian Ocean tsunami devastated nine distinct communities along a 40-km section of the northern coast of Sumatra in about 1394 CE. Our evidence is the spatial and temporal distribution of tens of thousands of medieval ceramic sherds and over 5,000 carved gravestones, collected and recorded during a systematic landscape archaeology survey near the modern city of Banda Aceh. Only the trading settlement of Lamri, perched on a headland above the reach of the tsunami, survived into and through the subsequent 15th century. It is of historical and political interest that by the 16th century, however, Lamri was abandoned, while low-lying coastal sites destroyed by the 1394 tsunami were resettled as the population center of the new economically and politically ascendant Aceh Sultanate. Our evidence implies that the 1394 tsunami was large enough to impact severely many of the areas inundated by the 2004 tsunami and to provoke a significant reconfiguration of the region’s political and economic landscape that shaped the history of the region in subsequent centuries.

The Maldives Heritage Survey was established to document cultural heritage vulnerable to human and environmental threats in the Maldives. An open-access online database is being produced to inform academic studies, support heritage-management plans and create a permanent archive of digital heritage resources.

The 2004 Indian Ocean Tsunami tragically underscored the practical implication of understanding the Sumatran subduction zone and its tsunami potential. Further paleo-tsunami research is needed to fully inform the assessment of future tsunami hazards for coastal regions of the Indian Ocean. However, the Covid-19 pandemic has severely limited the ability of many international teams to conduct field investigations of paleo-tsunami sites in Southeast Asia. In collaboration between Syiah Kuala University in Indonesia and Nanyang Technological University in Singapore our team has been investigating the paleo-tsunami history of Sumatra for more than 10 years. This year, in order to facilitate training of junior staff at Syiah Kuala University we recorded a number of coring, sampling and sediment description videos combined with virtual workshops. Written material, as well as regular meetings via zoom, have made co-ordination of fieldwork possible. We also uploaded all data to cloud services immediately following fieldwork to allow everyone in the project to have access to it quickly. This data now consists of more than 500 photographs, field description files, and field reports.Previously our efforts have concentrated along the northern half of the Aceh province, which was devastated by the 2004 Indian Ocean Tsunami. Over the past 12 months, we have extended our field research ~250 km southwards along the western coastline of Sumatra. Despite the pandemic, we have been able to investigate 4 new coastal wetland sites and identify between 1 and 5 potential paleo-tsunami layers at each site at depths of 1.7 to 4.5 m. More than 50 samples of the sediments have been sampled and are currently being analyzed to confirm their marine origin and the chronology of the events they represent.