Towards a novel carbon device for the treatment of sepsis

Sepsis is a systemic inflammatory response to infection in which the balance of pro- andanti-inflammatory mediators, which normally isolate and eliminate infection, is disrupted[1]. Gram negative sepsis is initiated by bacterial endotoxin release which activatesmacrophages and circulating monocytes to release TNF and IL-1β followed by IL-6 andother inflammatory cytokines [2]. As the disease progresses, an unregulatedinflammatory response results in, tissue injury, haematological dysfunction and organdysfunction. Severe sepsis, involving organ hypoperfusion may be further complicatedby hypotension that is unresponsive to adequate fluid replacement, resulting in septicshock and finally death [3].Despite improvements in anti-microbial and supportive therapies, sepsis remains asignificant cause of morbidity and mortality in ICUs worldwide [4]. The complexity ofprocesses mediating the progression of sepsis suggests that an extracorporeal devicecombining blood filtration with adsorption of a wide range of toxins, and inflammatorymediators offers the most comprehensive treatment strategy. However, no such deviceexists at present. A novel, uncoated, polymer pyrolysed synthetic carbon device isproposed which combines the superior adsorption properties of uncoated activatedcarbons with the capacity to manipulate porous structure for controlled adsorption oftarget plasma proteins and polypeptides [5]. Preliminary haemocompatibility andadsorptive capacity was assessed using a carbon matrix prototype

Conformal proper times according to the Woodhouse causal axiomatics of relativistic spacetimes

On the basis of the Woodhouse causal axiomatics, we show that conformal proper times and an extra variable in addition to those of space and time, precisely and physically identified from experimental examples, together give a physical justification for the `chronometric hypothesis' of general relativity. Indeed, we show that, with a lack of these latter two ingredients, no clock paradox solution exists in which the clock and message functions are solely at the origin of the asymmetry. These proper times originate from a given conformal structure of the spacetime when ascribing different compatible projective structures to each Woodhouse particle, and then, each defines a specific Weylian sheaf structure. In addition, the proper time parameterizations, as two point functions, cannot be defined irrespective of the processes in the relative changes of physical characteristics. These processes are included via path-dependent conformal scale factors, which act like sockets for any kind of physical interaction and also represent the values of the variable associated with the extra dimension. As such, the differential aging differs far beyond the first and second clock effects in Weyl geometries, with the latter finally appearing to not be suitable.Comment: 25 pages, 2 figure

Health care's response to climate change: a carbon footprint assessment of the NHS in England

Background: Climate change threatens to undermine the past 50 years of gains in public health. In response, the National Health Service (NHS) in England has been working since 2008 to quantify and reduce its carbon footprint. This Article presents the latest update to its greenhouse gas accounting, identifying interventions for mitigation efforts and describing an approach applicable to other health systems across the world. Methods: A hybrid model was used to quantify emissions within Scopes 1, 2, and 3 of the Greenhouse Gas Protocol, as well as patient and visitor travel emissions, from 1990 to 2019. This approach complements the broad coverage of top-down economic modelling with the high accuracy of bottom-up data wherever available. Available data were backcasted or forecasted to cover all years. To enable the identification of measures to reduce carbon emissions, results were disaggregated by organisation type. Findings: In 2019, the health service's emissions totalled 25 megatonnes of carbon dioxide equivalent, a reduction of 26% since 1990, and a decrease of 64% in the emissions per inpatient finished admission episode. Of the 2019 footprint, 62% came from the supply chain, 24% from the direct delivery of care, 10% from staff commute and patient and visitor travel, and 4% from private health and care services commissioned by the NHS. Interpretation: This work represents the longest and most comprehensive accounting of national health-care emissions globally, and underscores the importance of incorporating bottom-up data to improve the accuracy of top-down modelling and enabling detailed monitoring of progress as health systems act to reduce emissions. Funding: Wellcome Trust

Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms

OBJECTIVE: To provide clinical data on a cohort of 6 patients with massive expansion (>200 CAG repeats) of spinocerebellar ataxia type 2 (SCA2) and investigate possible pathways of pathogenesis using bioinformatics analysis of ATXN2 networks. METHODS: We present data on 6 patients with massive expansion of SCA2 who presented in infancy with variable combinations of hypotonia, global developmental delay, infantile spasms, and retinitis pigmentosa. ATXN2 is known to interact with a network of synaptic proteins. To investigate pathways of pathogenesis, we performed bioinformatics analysis on ATXN2 combined with known genes associated with infantile spasms, retinitis pigmentosa, and synaptic function. RESULTS: All patients had a progressive encephalopathy with autonomic dysfunction, 4 had retinitis pigmentosa, and 3 had infantile spasms. The bioinformatics analysis led to several interesting findings. First, an interaction between ATXN2 and SYNJ1 may account for the development of retinitis pigmentosa. Second, dysfunction of postsynaptic vesicle endocytosis may be important in children with this progressive encephalopathy. Infantile spasms may be associated with interactions between ATXN2 and the postsynaptic structural proteins MAGI2 and SPTAN1. CONCLUSIONS: Severe phenotype in children with massive expansion of SCA2 may be due to a functional deficit in protein networks in the postsynapse, specifically involving vesicle endocytosis

Gemini Principles

Up to 30% of annual spend across the built environment is lost in inefficiencies related to poor quality data1. This is seen in lost productivity due to underperforming economic and social infrastructure. Effective information management will enable better decisions, leading to financial savings, improved performance and service, and better outcomes for business and society per whole-life pound. To make this possible an information management framework is necessary. This paper seeks to build consensus on foundational definitions and guiding values – the Gemini Principles – and to begin enabling alignment on the approach to information management across the built environment.Funded by the Centre for Digital Built Britai

Neuroscience, Ethics, and National Security: The State of the Art

Military involvement and research in neuroscience generates unique ethical, legal, and social issues that require careful elucidation and consideration in order to align the potentially conflicting needs of national defense, public interest, and scientific progress

Health care's response to climate change: a carbon footprint assessment of the NHS in England

Background Climate change threatens to undermine the past 50 years of gains in public health. In response, the National Health Service (NHS) in England has been working since 2008 to quantify and reduce its carbon footprint. This Article presents the latest update to its greenhouse gas accounting, identifying interventions for mitigation efforts and describing an approach applicable to other health systems across the world. Methods A hybrid model was used to quantify emissions within Scopes 1, 2, and 3 of the Greenhouse Gas Protocol, as well as patient and visitor travel emissions, from 1990 to 2019. This approach complements the broad coverage of top-down economic modelling with the high accuracy of bottom-up data wherever available. Available data were backcasted or forecasted to cover all years. To enable the identification of measures to reduce carbon emissions, results were disaggregated by organisation type. Findings In 2019, the health service's emissions totalled 25 megatonnes of carbon dioxide equivalent, a reduction of 26% since 1990, and a decrease of 64% in the emissions per inpatient finished admission episode. Of the 2019 footprint, 62% came from the supply chain, 24% from the direct delivery of care, 10% from staff commute and patient and visitor travel, and 4% from private health and care services commissioned by the NHS. Interpretation This work represents the longest and most comprehensive accounting of national health-care emissions globally, and underscores the importance of incorporating bottom-up data to improve the accuracy of top-down modelling and enabling detailed monitoring of progress as health systems act to reduce emissions. Funding Wellcome Trust