Corrigendum to: “Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis” [J Hepatol (2020) 241-251]

It has come to our attention that there are errors in the Table 2 of the original manuscript “Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis”. The Variance Explained for SNP rs738409 has been incorrectly reported as 0.9. The correct value is 0.29. The amino acid changes for SNPs rs111723834, rs58542926 and rs738409 have been incorrectly reported as A561G, I148M and E167K, respectively. The correct amino acid changes are R561Q, E167K and I148M, respectively. SNP rs4820268 variant type (synonymous) and amino acid change (D521D) have also been corrected. Please see the corrected Table 2 below. These errors have occured during manual editing of the table and do not affect the results and conclusions of this article. The authors would like to apologise for any inconvenience caused

Long-term effects of chronic light pollution on seasonal functions of European blackbirds (turdus merula)

Light pollution is known to affect important biological functions of wild animals, including daily and annual cycles. However, knowledge about long-term effects of chronic exposure to artificial light at night is still very limited. Here we present data on reproductive physiology, molt and locomotor activity during two-year cycles of European blackbirds (Turdus merula) exposed to either dark nights or 0.3 lux at night. As expected, control birds kept under dark nights exhibited two regular testicular and testosterone cycles during the two-year experiment. Control urban birds developed testes faster than their control rural conspecifics. Conversely, while in the first year blackbirds exposed to light at night showed a normal but earlier gonadal cycle compared to control birds, during the second year the reproductive system did not develop at all: both testicular size and testosterone concentration were at baseline levels in all birds. In addition, molt sequence in light-treated birds was more irregular than in control birds in both years. Analysis of locomotor activity showed that birds were still synchronized to the underlying light-dark cycle. We suggest that the lack of reproductive activity and irregular molt progression were possibly the results of i) birds being stuck in a photorefractory state and/or ii) chronic stress. Our data show that chronic low intensities of light at night can dramatically affect the reproductive system. Future studies are needed in order to investigate if and how urban animals avoid such negative impact and to elucidate the physiological mechanisms behind these profound long-term effects of artificial light at night. Finally we call for collaboration between scientists and policy makers to limit the impact of light pollution on animals and ecosystems

The outcome of bone graft surgery for nonunion of fractures of the scaphoid

Data on 806 patients undergoing bone graft surgery for a scaphoid fracture nonunion were retrospectively collected at 19 centres in the United Kingdom. Each centre contributed at least 30 cases. Sufficient data were available in 462 cases to study factors that influenced the outcome of surgery. Overall union occurred in at least 69%, and nonunion in at least 22%, with 9% of cases having ‘uncertain union status’. Union appeared to be adversely influenced by smoking and the time between acute scaphoid fracture and nonunion surgery, with adjusted odds ratios of 1.8 and 2.4, respectively, but neither achieved the pre-determined significance level of 0.003. The type of bone graft (vascular vs non-vascular; iliac crest vs distal radius) did not appear to influence outcome. Further large multicentre prospective studies with clear definitions of ‘union’ and other factors are needed to clarify whether modification of surgical technique can influence union

Clonal Haematopoiesis and Risk of Chronic Liver Disease

Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P \u3c 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). to assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P \u3c 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response

Analog modulation of spike-evoked transmission in CA3 circuits is determined by axonal Kv1.1 channels in a time-dependent manner

International audienceSynaptic transmission usually depends on action potentials (APs) in an all-or-none (digital) fashion. Recent studies indicate, however , that subthreshold presynaptic depolarization may facilitate spike-evoked transmission, thus creating an analog modulation of spike-evoked synaptic transmission, also called analog–digital (AD) synaptic facilitation. Yet, the underlying mechanisms behind this facilitation remain unclear. We show here that AD facilitation at rat CA3–CA3 synapses is time-dependent and requires long presynaptic depolarization (5–10 s) for its induction. This depolarization-induced AD facilitation (d-ADF) is blocked by the specific Kv1.1 channel blocker dendrotoxin-K. Using fast voltage-imaging of the axon, we show that somatic depolarization used for induction of d-ADF broadened the AP in the axon through inactivation of Kv1.1 channels. Somatic depolarization enhanced spike-evoked calcium signals in presynaptic terminals, but not basal calcium. In conclusion, axonal Kv1.1 channels determine glutamate release in CA3 neurons in a time-dependent manner through the control of the presynaptic spike waveform

A qualitative grounded theory study of the conceptions of clinical practice in osteopathy – A continuum from technical rationality to professional artistry

How practitioners conceive clinical practice influences many aspects of their clinical work including how they view knowledge, clinical decision-making, and their actions. Osteopaths have relied upon the philosophical and theoretical foundations upon which the profession was built to guide clinical practice. However, it is currently unknown how osteopaths conceive clinical practice, and how these conceptions develop and influence their clinical work. This paper reports the conceptions of practice of experienced osteopaths in the UK. A constructivist grounded theory approach was taken in this study. The constant comparative method of analysis was used to code and analyse data. Purposive sampling was employed to initially select participants. Subsequent theoretical sampling, informed by data analysis, allowed specific participants to be sampled. Data collection methods involved semi-structured interviews and non-participant observation of practitioners during a patient appointment, which was video-recorded and followed by a video-prompted reflective interview. Participants' conception of practice lay on a continuum, from technical rationality to professional artistry and the development of which was influenced by their educational experience, view of health and disease, epistemology of practice knowledge, theory-practice relationship and their perceived therapeutic role. The findings from this study provide the first theoretical insight of osteopaths' conceptions of clinical practice and the factors which influence such conceptions

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant