Publications by authors named "David Nicholls"

In a recent publication, Hernansanz-Agusti̒n et al. propose that a sodium gradient across the inner mitochondrial membrane, generated by a Na/H activity integral to Complex I can account for half of the mitochondrial membrane potential. This conflicts with conventional electrophysiological and chemiosmotic understanding.

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Objectives: The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires appraising the cost effectiveness of existing pharmacological interventions against TB to identify key drivers of cost effectiveness and value and guide pharmaceutical innovation and novel drug regimen development.

Methods: Studies were identified from a search of six database: MEDLINE MEDLINE-In Process, MEDLINE Epub Ahead of Print, EMBASE, Cochrane Database of Systematic Reviews, and Econlit in July 2022.

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Objective: To describe the trends in remission rates among RA patients in the OPAL dataset, spanning from 2009 to 2022, and provide insights into the effectiveness of evolving RA management approaches in real-world clinical settings.

Methods: Patients with a physician diagnosis of RA and at least 3 visits between 1 January 2009 and December 2022 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 117 Australian rheumatologists. Demographics, disease history, prescribed medications and proportions of patients in Disease Activity Score 28-joint count C-reactive protein (DAS28CRP)) categories (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)) were described.

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As the initial crisis of the COVID-19 pandemic recedes, healthcare decision makers are likely to want to make rational evidence-guided choices between the many interventions now available. We sought to update a systematic review to provide an up-to-date summary of the cost-effectiveness evidence regarding tests for SARS-CoV-2 and treatments for COVID-19. Key databases, including MEDLINE, EconLit and Embase, were searched on 3 July 2023, 2 years on from the first iteration of this review in July 2021.

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Critical physiotherapy has been a rapidly expanding field over the last decade and could now justifiably be called a professional sub-discipline. In this paper we define three different but somewhat interconnected critical positions that have emerged over the last decade that share a critique of physiotherapy's historical approach to health and illness, while also diverging in the possibilities for new forms of practice and thinking. These three positions broadly align with three distinctive philosophies: approaches that emphasize lived experience, social theory, and a range of philosophies increasingly referred to as the "posts".

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Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation.

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Physiotherapists interested in the profession's future have turned in recent years to historical evidence to understand how the physical therapies were practiced before the advent of modern healthcare. However, studies to date suggest that their practice was largely confined to social elites, and those from working-class or poor populations rarely, if ever, experienced them. To test this theory further, this study focuses on British sailors during the Napoleonic wars (1803-1815).

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Following life-cycle assessment (LCA) methodology, this study presents a state-level estimation of embodied carbon of wood products harvested in 2019 from California and subsequently processed, manufactured, transported, used, and disposed at the end-of-life (EoL). In a conventional static approach to LCA, all GHG emissions were aggregated and considered to occur at year 0 of the given time horizon (500 years in this study) and used a static characterization factor (CF). In dynamic LCA, GHG emissions occurring in different years were considered, and their global warming impact (GWI) was determined using a time-dependent CF over the selected time horizon of 500 years.

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Introduction: There is a paucity of data on how patient characteristics may affect the long-term durability of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA). This study therefore aimed to investigate CZP durability and reasons for discontinuation over 5 years between different subgroups of patients with RA.

Methods: Data were pooled from 27 clinical trials in RA patients.

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Exactly 50 years ago, I was a post-doc in the laboratory of Olov Lindberg in Stockholm measuring fatty acid oxidation by mitochondria isolated from thermogenic brown adipose tissue, when we noticed a curious nonlinearity in the respiration rate. This initiated a convoluted chain of experiments revealing that the mitochondria were textbook demonstrations of the then novel and highly controversial "chemiosmotic hypothesis" of Peter Mitchell and that thermogenesis was regulated by a proton short-circuit, mediated by a 32 kDa "uncoupling protein," UCP1, activated by fatty acid. This review is a personal account of the research into the bioenergetics of isolated brown adipocytes and isolated mitochondria, which led, after fifteen years of investigation, to what is still accepted as the "canonical" UCP1-mediated mechanism of nonshivering thermogenesis, uniting whole animal physiology with mitochondrial bioenergetics.

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Brown adipose tissue is specialized for non-shivering thermogenesis, combining lipolysis with an extremely active mitochondrial electron transport chain and a unique regulated uncoupling protein, UCP1, allowing unrestricted respiration. Current excitement focuses on the presence of brown adipose tissue in humans and the possibility that it may contribute to diet-induced thermogenesis, countering obesity and obesity-related disease as well as protecting cardio-metabolic health. In common with other tissues displaying a high, variable respiration, the tissue possesses a creatine pool and mitochondrial and cytosolic creatine kinase isoforms.

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A deep learning aided optimization algorithm for the design of flat thin-film multilayer optical systems is developed. The authors introduce a deep generative neural network, based on a variational autoencoder, to perform the optimization of photonic devices. This algorithm allows one to find a near-optimal solution to the inverse design problem of creating an anti-reflective grating, a fundamental problem in material science.

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We present an efficient numerical method for simulating the scattering of electromagnetic fields by a multilayered medium with random interfaces. The elements of this algorithm, the Monte Carlo-transformed field expansion method, are (i) an interfacial problem formulation in terms of impedance-impedance operators, (ii) simulation by a high-order perturbation of surfaces approach (the transformed field expansions method), and (iii) efficient computation of the wave field for each random sample by forward and backward substitutions. Our perturbative formulation permits us to solve a sequence of linear problems featuring an operator that is deterministic, and its LU decomposition matrices can be reused, leading to significant savings in computational effort.

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How, and how much, physiotherapists should touch in practice is once again being debated by the profession. COVID-19 and people's enforced social isolation, combined with the growth of virtual technologies, and the profession's own turn away from so-called "passive" therapies, has placed therapeutic touch once again in an uncertain position. The situation is more ambiguous and uncertain because, despite its historical importance to the profession, physiotherapists have never articulated a comprehensive philosophy of touch, taking-for-granted its seeming obviousness as either a bio-physical or inter-subjective phenomenon.

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Movement has always been central to physiotherapy practice and theory. But physiotherapists have largely focused on forms of human bodily movement governed by the neuro-mechanical body system in illness or injury. Many other forms of movement exist though, and we argue here that the exploration of these other movements might give physiotherapists new language, concepts, and tools, to guide its adaptation to forms of healthcare that are becoming increasingly complex, diverse, and inclusive.

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Article Synopsis
  • * The Cambridge COVID-19 Testing Centre (CCTC) was established in April 2020 through partnerships with AstraZeneca, GlaxoSmithKline, and the University of Cambridge, aiming for a testing capacity of 22,000 tests per day.
  • * The CCTC enhanced laboratory processes using internal metrics and new technologies, such as Heat Inactivation of samples and a Direct to PCR protocol, which improved efficiency and eliminated the RNA extraction step.
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Objectives: As healthcare systems continue to respond to the COVID-19 pandemic, cost-effectiveness evidence will be needed to identify which tests and treatments for COVID-19 offer value for money. We sought to review economic evaluations of diagnostic tests and treatments for COVID-19, critically appraising the methodological approaches used and reporting cost-effectiveness estimates, using a "living" systematic review approach.

Methods: Key databases (including MEDLINE, EconLit, Embase) were last searched on July 12, 2021.

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Large river systems, such as the River Ganges (Ganga), provide crucial water resources for the environment and society, yet often face significant challenges associated with cumulative impacts arising from upstream environmental and anthropogenic influences. Understanding the complex dynamics of such systems remains a major challenge, especially given accelerating environmental stressors including climate change and urbanization, and due to limitations in data and process understanding across scales. An integrated approach is required which robustly enables the hydrogeochemical dynamics and underpinning processes impacting water quality in large river systems to be explored.

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Graphene has transformed the fields of plasmonics and photonics, and become an indispensable component for devices operating in the terahertz to mid-infrared range. Here, for instance, graphene surface plasmons can be excited, and their extreme interfacial confinement makes them vastly effective for sensing and detection. The rapid, robust, and accurate numerical simulation of optical devices featuring graphene is of paramount importance and many groups appeal to Black-Box Finite Element solvers.

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Background: Global environmental change is fundamentally altering the composition and functioning of our planetary ecosystem. Effectively presenting the largest threat to the health of present and future generations, these changes and their health impacts are forcing us to think and practice healthcare in much broader terms than ever before.

Objective: In this article, we provide an early outline for a radically otherwise, yet strangely familiar, environmental physiotherapy developed through a succession of carefully developed arguments.

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The convergence of large datasets, increased computational power, and enhanced algorithm design has led to the increased success of machine learning (ML) and artificial intelligence (AI) across a wide variety of healthcare professions but which, so far, have eluded formal discussion in physiotherapy. This is a concern as we begin to see accelerating performance improvements in AI research in general, and specifically, an increase in competence within narrow domains of practice in clinical AI. In this paper we argue that the introduction of AI-based systems within the health sector is likely to have a significant influence on physiotherapy practice, leading to the automation of tasks that we might consider to be core to the discipline.

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In this Viewpoint, I argue that we may be at an inflection point in the course of the physical therapy profession. The current debate over "active" and "passive" therapies highlights once again how much physical therapy practices reflect shifting cultural and social attitudes. Calls for less passive management of musculoskeletal conditions and more self-management reflect the neoliberal desire for autonomous, entrepreneurial, endlessly resilient, and self-sufficient subjects who will shift the burden of health care from the state to the individual.

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