Seeking answers through the pain

This article tells the story of the history and outcome of a 64-year-old woman who had suffered pain and other symptoms for over a decade. The woman thought nothing could be done to help her condition. The procedure that was eventually undertaken brought about a huge transformation in pain reduction and helped with mobility and posture. This operation came into being in relatively recent times and has revolutionised the treatment of people with hip-spine syndrome. The technique called an in-situ arthroplasty operation allows accurate restoring of leg length, together with restoring the natural alignment of hip structures. Experience Framework This article is associated with the Quality & Clinical Excellence lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens

A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non-hematopoietic toll like receptor 4 signalling and inhibits aortic aneurysms development

Objectives: The toll-like receptors (TLRs), including TLR4, have been shown to play a crucial role in vascular inflammatory diseases, such as atherosclerosis and aneurysm. The main goal of this study was to determine the potential of IAXO-102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental abdominal aortic aneurysm (AAA) development. Methods: Human umbilical vein endothelial cells (HUVEC) and Angiotensin II-induced experimental AAA development were our in vitro and in vivo models respectively. Western blotting, antibody array and ELISA approaches were used to explore the effect of IAXO-102 on TLR4 functional activity on two levels: modulation of TLR4-induced mitogen activated protein kinases (MAPK) and p65 NF-kB phosphorylation and expression of TLR4 dependent proinflammatory proteins. Results: Following activation of TLR4, in vitro/in vivo data revealed that IAXO-102 inhibited MAPK and p65 NF-kB phosphorylation associated with down regulation of the expression of TLR4 and TLR4 dependent proinflammatory proteins. Furthermore, IAXO-102 decreased Angiotensin II-induced aortic expansion, rupture and incidence of AAA. Conclusions: These results demonstrate the ability of IAXO-102 to negatively regulate TLR4 signalling and to inhibit experimental AAA development, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of AAA

Health Inequalities in Scotland: trends in deaths, health and wellbeing, health behaviours, and health services since 2000

Following a global pandemic and entering a cost-of-living crisis, concern around how health inequalities in Scotland have and will be impacted is considerable. This report synthesises a wide range of existing data and new analysis to establish the magnitude of the problem, where improvements or deterioration is evident and who is most affected. Over four detailed chapters, trends in social inequalities in health, health-related behaviours and, health and social care services in Scotland are presented

A failure of trust: resolving property disputes on cohabitation breakdown

This study tracked a sample of 29 separating cohabitants to explore how they dealt with property issues arising on the breakdown of their relationship, and interviewed 61 professional practitioners about how they handle such cases. Key findings include the significant risk of injustice arising from the complexity and unpredictability of the law; the difficulty of establishing convincing evidence to support or defend a claim; and the fear of costs. The authors conclude that the current law may serve to perpetuate rather than redress injustice and that reform is both justified and overdue

Analysis and design of a thrombectomy device by using simulation techniques

Purpose: In this work, we present the analysis, design and optimization of one experimental device recently developed in the UK, called the 'GP' Thrombus Aspiration Device (GPTAD). This device has been designed to remove blood clots without the need to make contact with the clot itself thereby potentially reducing the risk of problems such as downstream embolisation. Method: To obtain the minimum pressure necessary to extract the clot and to optimize the device, we have simulated the performance of the GPTAD analysing the resistances, compliances and inertances effects. We model a range of diameters for the GPTAD considering different forces of adhesion of the blood clot to the artery wall, and different lengths of blood clot. In each case we determine the optimum pressure required to extract the blood clot from the artery using the GPTAD, which is attached at its proximal end to a suction pump. Result: We then compare the results of our mathematical modelling to measurements made in laboratory using plastic tube models of arteries of comparable diameter. We use abattoir porcine blood clots that are extracted using the GPTAD. The suction pressures required for such clot extraction in the plastic tube models compare favourably with those predicted by the mathematical modelling. Discussion & Conclusion: We conclude therefore that the mathematical modelling is a useful technique in predicting the performance of the GPTAD and may potentially be used in optimising the design of the device

An investigation into the design of a device to treat haemorrhagic stroke

In this study, we present the design considerations of a device to assist in the potential treatment of hemorrhagic stroke with the aim of stopping blood from flowing out into brain tissue. We present and model three designs for the clinical scenarios when saccular aneurysms rupture in the middle cerebral artery in the brain. We evaluate and model these three designs using computer aided design software, SolidWorks, which allows the devices to be tested using finite element analysis and also enables us to justify that the materials chosen were suitable for potential use. Computational fluid dynamics modelling were used to demonstrate and analyse the flow of blood through the artery under conditions of normal and ruptured states. We conclude that our device could potentially be useful in the treatment of hemorrhagic stroke, and the modelling process is useful in assisting in determining the performance of our devices

Comparison of the Effectiveness of Three Methods of Recanalization in a Model of the Middle Cerebral Artery: Thrombus Aspiration via a 4F Catheter, Thrombus Aspiration via the GP Thromboaspiration Device, and Mechanical Thrombectomy Using the Solitaire Thrombectomy Device

Introduction. This paper compares different approaches to recanalization in a model of the middle cerebral artery (MCA). Methods. An occlusive thrombus (lamb's blood) was introduced into the MCA of a model of the cerebral circulation perfused with Hartmann's solution (80 pulsations/min, mean pressure 90 mm Hg). Three methods of clot retrieval were tested: thrombus aspiration via a 4F catheter (n = 26), thrombus aspiration via the GP thrombus aspiration device (GPTAD) (n = 30), and mechanical thrombectomy via the Solitaire Device (n = 30). Results. Recanalization rate was similar for all 3 approaches (62%, 77%, and 85%). Time to recanalization was faster with aspiration devices (41 SD 42 s for 4F and 61 SD 21 s for GPTAD) than with the Solitaire (197 SD 64 s P < .05 Kruksal-Wallis). Clot fragmentation was the same in the Solitaire (23%) and the GPTAD (23%), but higher with the 4F (53%, P < .05). Conclusion. In this model, thrombus aspiration was faster than mechanical thrombectomy, and similarly effective at recanalization. These results should be confirmed in vivo

Environmental Grain, Organism Fitness, and Type Fitness

Abstract Natural selection is the result of organisms&apos; interactions with their environment, but environments vary in space and time, sometimes in extreme ways. Such variation is generally thought to play an important role in evolution by natural selection, maintaining genetic variation within and between populations, increasing the chance of speciation, selecting for plasticity of responses to the environment, and selecting for behaviors such as habitat selection and niche construction. Are there different roles that environmental variation plays in natural selection? When biologists make choices about how to divide up an environment for the sake of modeling or empirical research, are there any constraints on these choices? Since diverse evolutionary models relativize fitnesses to component environments within a larger environment, it would be useful to understand when such practices capture real aspects of evolutionary processes, and when they count as mere modeling conveniences. In this paper, I try to provide a general framework for thinking about how fitness and natural selection depend on environmental variation. I&apos;ll give an account of how the roles of environmental conditions in natural selection differ depending the probability of being experienced repeatedly by organisms, and how environmental conditions combine probabilistically to help determine fitness. My view has implications for what fitness is, and suggests that some authors have misconceived its nature