Political power and the development of the GB renewable heat incentive

This is the final version of the paper. Available from BIEE via the link in this record.A transformation of the UK’s heat system is required to ensure that the goals of sustainable and secure energy are met. This transformation could require a complete shift away from fossil fuels to primarily renewable sources of heat. Like in any transformation, social and political power is likely to be an important factor. This paper documents research which has focussed on the sociopolitical power of actors to affect policy and regulation in the area of UK sustainable heat policy. It draws on theory from the sociological literature around socio-political power and literature around lobbying to examine the GB renewable heat incentive policy. It shows that while there have been numerous attempts to influence GB heat policy, these attempts are limited in their success and unpicking the role actors versus evidence is extremely difficult. The research also shows the methodological complexity of examining political influencing

A transformation to sustainable heating in the UK: risks and opportunities for UK heat sector businesses

This is the final version of the article. Available from UKERC via the link in this record.This is working paper 2/3 from the Heat, Incumbency and Transformations (HIT) project.This working paper considers the risks and opportunities posed to UK heat sector businesses by a potential transformation towards a low-carbon heat system in the UK. It is an output from the Heat, Incumbency and Transformations (HIT) project which is part of the UK Energy Research Centre programme. The HIT project is investigating the idea of incumbency, considering what the term means, how it is present in the UK’s heat sector and what the implications of incumbency are for the UK’s potential transformation from a high carbon heat system to a low-carbon heat system. The previous working paper developed a working definition of incumbency (Lowes et al., 2017). This working paper forms the second phase of the project, exploring who the incumbents are in the UK heat system and the implications of the potential transformation for incumbents.UKERC is funded by The Research Councils UK Energy Programme

Incumbency in the UK heat sector and implications for the transformation towards low-carbon heating

This is the final version of the article. Available from UKERC via the link in this record.This is working paper 3/3 from the Heat, Incumbency and Transformations (HIT) project.This paper forms the last of three working papers published by the Heat, Incumbency and Transformations (HIT) team. The project investigated issues surrounding the decarbonisation of heating, which is increasingly seen as a priority by energy policy makers. It considers the move towards low carbon heating from the perspective of incumbency, a topic which has received only limited focus. Prior research has suggested that incumbent businesses can have both positive and negative influences on decarbonisation. There are examples of large companies investing in low carbon energy and driving change but there are also examples of incumbents trying to resist change therefore slowing or blocking decarbonisation. This paper focuses on what the policy implications of incumbency in the UK heat sector are for the decarbonisation of UK heat. The paper reports on a large number of interviews with experts working across the UK heat sector. This evidence is further built on using grey sources of literature and data.UKERC is funded by The Research Councils UK Energy Programme

Incumbency and the transformation towards low carbon heating in the UK – Implications for policy

This is the final version of the article. Available from UKERC via the link in this record.This briefing paper summarises the key policy implications from the last of three working papers published by the Heat Incumbency Transitions Team. This research has investigated the role and behaviour of heat market ‘incumbents’ in relation to the decarbonisation of heat.UKERC is funded by The Research Councils Energy programme

Apilimod Inhibits the Production of IL-12 and IL-23 and Reduces Dendritic Cell Infiltration in Psoriasis

Psoriasis is characterized by hyperplasia of the epidermis and infiltration of leukocytes into both the dermis and epidermis. IL-23, a key cytokine that induces TH17 cells, has been found to play a critical role in the pathogenesis of psoriasis. Apilimod is a small-molecule compound that selectively suppresses synthesis of IL-12 and IL-23. An open-label clinical study of oral administration of apilimod was conducted in patients with psoriasis. Substantial improvements in histology and clinical measurements were observed in patients receiving 70mg QD. The expression of IL-23p19 and IL-12/IL-23p40 in skin lesions was significantly reduced in this dose group, with a simultaneous increase in IL-10 observed. A decrease in the levels of TH1 and TH17 cytokines/chemokines in skin lesions followed these p19 and p40 changes. In parallel, a reduction in skin-infiltrating CD11c+ dendritic cells and CD3+ T cells was seen, with a greater decrease in the CD11c+ population. This was accompanied by increases in T and B cells, and decreases in neutrophils and eosinophils in the periphery. This study demonstrates the immunomodulatory activity of apilimod and provides clinical evidence supporting the inhibition of IL-12/IL-23 synthesis for the treatment of TH1- and TH17-mediated inflammatory diseases

Global maps of the magnetic thickness and magnetization of the Earth’s lithosphere

International audienceWe have constructed global maps of the large-scale magnetic thickness and magnetization of Earth's lithosphere. Deriving such large-scale maps based on lithospheric magnetic field measurements faces the challenge of the masking effect of the core field. In this study, the maps were obtained through analyses in the spectral domain by means of a new regional spatial power spectrum based on the Revised Spherical Cap Harmonic Analysis (R-SCHA) formalism. A series of regional spectral analyses were conducted covering the entire Earth. The R-SCHA surface power spectrum for each region was estimated using the NGDC-720 spherical harmonic (SH) model of the lithospheric magnetic field, which is based on satellite, aeromagnetic, and marine measurements. These observational regional spectra were fitted to a recently proposed statistical expression of the power spectrum of Earth's lithospheric magnetic field, whose free parameters include the thickness and magnetization of the magnetic sources. The resulting global magnetic thickness map is compared to other crustal and magnetic thickness maps based upon different geophysical data. We conclude that the large-scale magnetic thickness of the lithosphere is on average confined to a layer that does not exceed the Moho

Shedding Light on The Role of Keratinocyte-Derived Extracellular Vesicles on Skin-Homing Cells

Extracellular vesicles (EVs) are secretory lipid membranes with the ability to regulate cellular functions by exchanging biological components between different cells. Resident skin cells such as keratinocytes, fibroblasts, melanocytes, and inflammatory cells can secrete different types of EVs depending on their biological state. These vesicles can influence the physiological properties and pathological processes of skin, such as pigmentation, cutaneous immunity, and wound healing. Since keratinocytes constitute the majority of skin cells, secreted EVs from these cells may alter the pathophysiological behavior of other skin cells. This paper reviews the contents of keratinocyte-derived EVs and their impact on fibroblasts, melanocytes, and immune cells to provide an insight for better understanding of the pathophysiological mechanisms of skin disorders and their use in related therapeutic approaches

INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy

Supplementary Material: The supplementary material is available in the electronic version of this article: https://doi.org/10.3233/JND-210871.Copyright © 2022 The authors. Background X-linked myotubular myopathy (XLMTM) is a life-threatening congenital myopathy that, in most cases, is characterized by profound muscle weakness, respiratory failure, need for mechanical ventilation and gastrostomy feeding, and early death. Objective We aimed to characterize the neuromuscular, respiratory, and extramuscular burden of XLMTM in a prospective, longitudinal study. Methods Thirty-four participants 16 hours/day); 20% required non-invasive support (6–16 hours/day). Median age at tracheostomy was 3.5 months (95% CI: 2.5, 9.0). Thirty-three participants (97%) required gastrostomy. Thirty-one (91%) participants had histories of hepatic disease and/or prospectively experienced related adverse events or laboratory or imaging abnormalities. CHOP INTEND scores ranged from 19–52 (mean: 35.1). Seven participants (21%) could sit unsupported for≥30 seconds (one later lost this ability); none could pull to stand or walk with or without support. These parameters remained static over time across the INCEPTUS cohort. Conclusions INCEPTUS confirmed high medical impact, static respiratory, motor and feeding difficulties, and early death in boys with XLMTM. Hepatobiliary disease was identified as an under-recognized comorbidity. There are currently no approved disease-modifying treatments.The INCEPTUS and ASPIRO studies are sponsored by Astellas Gene Therapies

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome