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Drug coated balloons in percutaneous coronary intervention: how can computational modelling help inform evolving clinical practice?
Get PDFDrug-coated balloons (DCB) represent an emerging therapeutic alternative to drug-eluting stents (DES) for the treatment of coronary artery disease (CAD). Among the key advantages of DCB over DES are the absence of a permanent structure in the vessel and the potential for fast and homogeneous drug delivery. While DCB were first introduced for treatment of in-stent restenosis (ISR), their potential wider use in percutaneous coronary intervention (PCI) has recently been explored in several randomized clinical trials, including for treatment of de novo lesions. Moreover, new hybrid techniques that combine DES and DCB are being investigated to more effectively tackle complex cases. Despite the growing interest in DCB within the clinical community, the mechanisms of drug exchange and the interactions between the balloon, the polymeric coating and the vessel wall are yet to be fully understood. It is, therefore, perhaps surprising that the number of computational (in silico) models developed to study interventions involving these devices is small, especially given the mechanistic understanding that has been gained from computational studies of DES procedures over the last two decades. In this paper, we discuss the current and emerging clinical approaches for DCB use in PCI and review the computational models that have been developed thus far, underlining the potential challenges and opportunities in integrating in silico models of DCB into clinical practice
Using natural experiments to evaluate population health and health system interventions: new framework for producers and users of evidence
Get PDFNatural experiments are widely used to evaluate the impacts on health of changes in policies, infrastructure, and services. The UK Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) have published a new framework for conducting and using evidence from natural experimental evaluations. The framework defines key concepts and describes recent advances in designing and planning evaluations of natural experiments, including the relevance of a systems perspective, mixed methods, and stakeholder involvement. It provides an overview of the strengths, weaknesses, applicability, and limitations of the range of methods now available, and makes good practice recommendations for researchers, funders, publishers, and users of evidence
The immacallam and the Ulster Cycle
No full textTwo Old Irish Ulster Cycle works – one a complete tale, the other an episode within a larger work – bear the label immacallam in one of their manuscript witnesses; in each case the witness dates from the twelfth century . The works in question are Immacallam in Dá Thuarad and the section of Recension I of Táin Bó Cúailnge known as Imacallaim na Mórigna fri Coin Culaind. This essay explores why these works were perceived to share a genre identity, and asks how they can nuance our understanding of what the label immacallam signified in medieval Irish literary culture
Socio-structural and direct health challenges related to illness management among patients with type 2 diabetes in Kenya and Tanzania during the COVID-19 pandemic: a qualitative inquiry
Get PDFDuring COVID-19, people with type 2 diabetes (T2D) experienced increased vulnerability, including severe COVID-19 complications, disruptions in diabetes management, and social isolation. These aspects were heightened in many sub-Saharan African countries, such as Kenya and Tanzania, where healthcare systems already face critical challenges in coping with increasing non-communicable diseases (NCDs). Little is known about how people with T2D in these countries managed their diabetes or how the different approaches to COVID-19 control (Kenya imposed lockdown and curfew, whereas Tanzania adopted less strict measures) impacted their T2D management. This qualitative study aimed to compare the accounts of T2D patients in both countries to examine similarities and differences in the illness management challenges they faced during the COVID-19 pandemic.Semi-structured interviews were conducted with 52 patients (Kenya, n=22; Tanzania, n=30), and the transcripts were analyzed thematically. Despite different COVID-19 control measures, patients in both countries faced similar direct health challenges, such as difficulties accessing diabetic consultations and treatment, but they also experienced distinct socio-structural challenges. Direct health challenges included difficulties in accessing diabetic consultations and treatment, limited availability of diabetic medicine at health facilities and mental health distress. These were exacerbated by socio-structural challenges, many of which pre-dated COVID-19 but intensified during the pandemic. These included closure of diabetic clinics in Dar es Salaam, business instability, financial difficulties, health insurance challenges, higher food prices impacting patients’ adherence to T2D dietary recommendations (in both countries), and price inflation of diabetic medicine and test kits (in Kenya). Together, these challenges led to patients practicing self-medication, missing doses and resulted in poor blood sugar control. People with T2D in Kenya and Tanzania have described similar illness management challenges. In both countries, future contingency planning is essential to ensure adequate routine management of T2D and to improve access to care in emergency situations. Affordable comprehensive health insurance, economic support, and psychosocial services are required to increase patient resilience and support the health and wellbeing of people with T2D
SmartOracle: generating smart contract oracle via fine-grained invariant detection
No full textAs decentralized applications (DApps) proliferate, the increased complexity and usage of smart contracts have heightened their susceptibility to security incidents and financial losses. Although various vulnerability detection tools have been developed to mitigate these issues, they often suffer poor performance in detecting vulnerabilities, as they either rely on simplistic and general-purpose oracles that may be inadequate for vulnerability detection, or require user-specified oracles, which are labor-intensive to create. In this paper, we introduce SmartOracle, a dynamic invariant detector that automatically generates fine-grained invariants as application-specific oracles for vulnerability detection. From historical transactions, SmartOracle uses pattern-based detection and advanced inference to construct comprehensive properties, and mines multi-layer likely invariants to accommodate the complicated contract functionalities. After that, SmartOracle identifies smart contract vulnerabilities by hunting the violated invariants in new transactions. In the field of invariant detection, SmartOracle detects 50% more ERC20 invariants than existing dynamic invariant detection and achieves 96% precision rate. Furthermore, we build a dataset that contains vulnerable contracts from real-world security incidents. SmartOracle successfully detects 466 abnormal transactions with an acceptable precision rate 96%, involving 31 vulnerable contracts. The experimental results demonstrate its effectiveness in detecting smart contract vulnerabilities, especially those related to complicated contract functionalities
Demographic and regional disparities in U.S. adult mortality due to cutaneous lupus erythematosus: insights from a CDC wonder analysis (1999–2020)
No full textNo abstract available
Reassessing pancreatectomy in diffuse congenital hyperinsulinism: a tale of two brothers with homozygous KCNJ11 variants
Get PDFCongenital hyperinsulinism (CHI) is a rare but serious disorder characterized by a dysregulated increase in insulin secretion, leading to hypoglycemia. Existing literature on CHI highlights the importance of early recognition and maintenance of blood glucose levels, due to the risk of neurological damage posed by uncorrected hypoglycemia. The cases presented highlight the treatment of 2 brothers who developed neonatal hypoglycemia due to diffuse CHI resulting from homozygous KCNJ11 variants. These cases demonstrate the challenges in maintaining normoglycemia in cases of CHI through medical and surgical therapies. The older sibling, Brother 1, underwent pharmacological treatment and a near-total pancreatectomy at 2.5 months. The outcomes of his treatment highlight the limitations of pancreatectomy in the management of diffuse CHI, as he experienced challenges such as continued hypoglycemic episodes and eventual development of diabetes. Brother 2 was managed with pharmacological therapies and a long-term feeding regimen via gastrostomy. At 6 years he was able to maintain normoglycemia with weaning of octreotide therapy. This paper contributes to our understanding of how to best manage diffuse CHI by emphasizing the limitations and adverse long-term outcomes of pancreatectomy—namely ongoing hypoglycemia and development of diabetes and pancreatic exocrine insufficiency
Segmentation and gender wage disparities in the early industrial workforce: Insights from Arkwright's Lumford Mill, 1786–1811
Get PDFThis article examines the gender wage gap and wage setting in the early cotton spinning factories of the industrial revolution, with a specific focus on Richard Arkwright's Lumford Mill in Bakewell, Derbyshire. The research links workers from the mill's wage books with parish baptism records to estimate ages and construct age–wage profiles in the spinning department. Findings show a significant gender wage gap emerging in adulthood, with women's wages stagnating while men advanced to higher-paying roles such as overseers, indicating limited advancement for women. However, there is little evidence of gender wage discrimination among child workers. The gendered segmentation of the spinning workforce towards adulthood was the main cause of the wage gap. The analysis also reveals that weekly wage rates for children increased annually until adulthood. In rural mills such as Arkwright's, attracting labour was crucial. Yearly wage increases incentivized loyalty and ensured workforce stability, despite potential mismatches between wages and worker productivity
Mechanical signatures and models of the bone marrow niche
Get PDFThe bone marrow is a complex tissue with distinct cellular and mechanical heterogeneity, serving as the primary site for haematopoiesis. Under certain conditions, such as on the onset of mutations to healthy cells or alterations to the environment, the bone marrow can also become the origin of haematological malignancies, often characterized by uncontrolled self-renewal of hematopoietic stem cells, overproduction of immature progeny and remodelling of the tissue microenvironment. This remodelling alters the composition and mechanics of the extracellular matrix (ECM), facilitating the proliferation and metastasis of leukaemic cells. The elastic and dissipative properties of the ECM are hallmarks of both health and disease progression in different tissues. However, studying the mechanical properties of bone marrow is difficult owing to inaccessibility in situ. Advanced three-dimensional bioengineered models offer a way to recapitulate the mechanical properties of the bone marrow, but it remains challenging to incorporate the elastic and viscous components. Understanding the physiological and disease-specific mechanical ECM signatures is crucial for advancing bone marrow research and for developing therapeutics. In this Review, we explore the structure–function relationship of the bone marrow, emphasizing its complex mechanical behaviour, and discuss the bioengineered models that recapitulate the mechanical properties in the healthy and diseased bone marrow niche, stressing the importance of replicating ECM physiological and pathological mechanical signatures in the future
Relative magnetic helicity under turbulent relaxation
Get PDFMagnetic helicity is a quantity that underpins many theories of magnetic relaxation in electrically conducting fluids, both laminar and turbulent. Although much theoretical effort has been expended on magnetic fields that are everywhere tangent to their domain boundaries, many applications, both in astrophysics and laboratories, actually involve magnetic fields that are line-tied to the boundary, i.e., with a non-trivial normal component on the boundary. This modification of the boundary condition requires a modification of magnetic helicity, whose suitable replacement is called relative magnetic helicity. In this work, we investigate rigorously the behaviour of relative magnetic helicity under turbulent relaxation. In particular, we specify the normal component of the magnetic field on the boundary and consider the ideal magnetohydrodynamic limit of resistivity tending to zero in order to model the turbulent evolution in the sense of Onsager’s theory of turbulence. We show that relative magnetic helicity is conserved in this distinguished limit and that, for constant viscosity, the magnetic field relaxes in a weak, time-averaged sense to a magnetohydrostatic equilibrium
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