New onshore insights into the role of structural inheritance during Mesozoic opening of the Inner Moray Firth Basin, Scotland

The Inner Moray Firth Basin (IMFB) forms the western arm of the North Sea trilete rift system that initiated mainly during the Late Jurassic–Early Cretaceous with the widespread development of major NE–SW-trending dip-slip growth faults. The IMFB is superimposed over the southern part of the older Devonian Orcadian Basin. The potential influence of older rift-related faults on the kinematics of later Mesozoic basin opening has received little attention, partly owing to the poor resolution of offshore seismic reflection data at depth. New field observations augmented by drone photography and photogrammetry, coupled with U–Pb geochronology, have been used to explore the kinematic history of faulting in onshore exposures along the southern IMFB margin. Dip-slip north–south- to NNE–SSW-striking Devonian growth faults are recognized that have undergone later dextral reactivation during NNW–SSE extension. The U–Pb calcite dating of a sample from the synkinematic calcite veins associated with this later episode shows that the age of fault reactivation is 130.99  ±  4.60 Ma (Hauterivian). The recognition of dextral-oblique Early Cretaceous reactivation of faults related to the underlying and older Orcadian Basin highlights the importance of structural inheritance in controlling basin- to sub-basin-scale architectures and how this influences the kinematics of IMFB rifting

New onshore insights into the role of structural inheritance during Mesozoic opening of the Inner Moray Firth Basin, Scotland

The Inner Moray Firth Basin (IMFB) forms the western arm of the North Sea trilete rift system that initiated mainly during the Late Jurassic–Early Cretaceous with the widespread development of major NE–SW-trending dip-slip growth faults. The IMFB is superimposed over the southern part of the older Devonian Orcadian Basin. The potential influence of older rift-related faults on the kinematics of later Mesozoic basin opening has received little attention, partly owing to the poor resolution of offshore seismic reflection data at depth. New field observations augmented by drone photography and photogrammetry, coupled with U–Pb geochronology, have been used to explore the kinematic history of faulting in onshore exposures along the southern IMFB margin. Dip-slip north–south- to NNE–SSW-striking Devonian growth faults are recognized that have undergone later dextral reactivation during NNW–SSE extension. The U–Pb calcite dating of a sample from the synkinematic calcite veins associated with this later episode shows that the age of fault reactivation is 130.99  ±  4.60 Ma (Hauterivian). The recognition of dextral-oblique Early Cretaceous reactivation of faults related to the underlying and older Orcadian Basin highlights the importance of structural inheritance in controlling basin- to sub-basin-scale architectures and how this influences the kinematics of IMFB rifting

Singlet-triplet dephasing in radical pairs in avian cryptochromes leads to time-dependent magnetic field effects

Cryptochrome 4a (Cry4a) has been proposed as the sensor at the heart of the magnetic compass in migratory songbirds. Blue-light excitation of this protein produces magnetically sensitive flavin–tryptophan radical pairs whose properties suggest that Cry4a could indeed be suitable as a magnetoreceptor. Here, we use cavity ring-down spectroscopy to measure magnetic field effects on the kinetics of these radical pairs in modified Cry4a proteins from the migratory European robin and from nonmigratory pigeon and chicken. B1/2, a parameter that characterizes the magnetic field-dependence of the reactions, was found to be larger than expected on the basis of hyperfine interactions and to increase with the delay between pump and probe laser pulses. Semiclassical spin dynamics simulations show that this behavior is consistent with a singlet–triplet dephasing (STD) relaxation mechanism. Analysis of the experimental data gives dephasing rate constants, rSTD, in the range 3–6 × 107 s −1 . A simple “toy” model due to Maeda, Miura, and Arai [Mol. Phys. 104, 1779–1788 (2006)] is used to shed light on the origin of the time-dependence and the nature of the STD mechanism. Under the conditions of the experiments, STD results in an exponential approach to spin equilibrium at a rate considerably slower than rSTD. We attribute the loss of singlet–triplet coherence to electron hopping between the second and third tryptophans of the electron transfer chain and comment on whether this process could explain differences in the magnetic sensitivity of robin, chicken, and pigeon Cry4a’s

Using UAV-Based Photogrammetry Coupled with In Situ Fieldwork and U-Pb Geochronology to Decipher Multi-Phase Deformation Processes: A Case Study from Sarclet, Inner Moray Firth Basin, UK

Constraining the age of formation and repeated movements along fault arrays in superimposed rift basins helps us to better unravel the kinematic history as well as the role of inherited structures in basin evolution. The Inner Moray Firth Basin (IMFB, western North Sea) overlies rocks of the Caledonian basement, the pre-existing Devonian–Carboniferous Orcadian Basin, and a regionally developed Permo–Triassic North Sea basin system. IMFB rifting occurred mainly in the Upper Jurassic–Lower Cretaceous. The rift basin then experienced further regional tilting, uplift and fault reactivation during the Cenozoic. The Devonian successions exposed onshore along the northwestern coast of IMFB and the southeastern onshore exposures of the Orcadian Basin at Sarclet preserve a variety of fault orientations and structures. Their timing and relationship to the structural development of the wider Orcadian and IMFB are poorly understood. In this study, drone airborne optical images are used to create high-resolution 3D digital outcrops. Analyses of these images are then coupled with detailed field observations and U-Pb geochronology of syn-faulting mineralised veins in order to constrain the orientations and absolute timing of fault populations and decipher the kinematic history of the area. In addition, the findings help to better identify deformation structures associated with earlier basin-forming events. This holistic approach helped identify and characterise multiple deformation events, including the Late Carboniferous inversion of Devonian rifting structures, Permian minor fracturing, Late Jurassic–Early Cretaceous rifting and Cenozoic reactivation and local inversion. We were also able to isolate characteristic structures, fault kinematics, fault rock developments and associated mineralisation types related to these event

Light Induction of a Vertebrate Clock Gene Involves Signaling through Blue-Light Receptors and MAP Kinases

AbstractThe signaling pathways that couple light photoreception to entrainment of the circadian clock have yet to be deciphered. Two prominent groups of candidates for the circadian photoreceptors are opsins (e.g., melanopsin) and blue-light photoreceptors (e.g., cryptochromes). We have previously showed that the zebrafish is an ideal model organism in which to study circadian regulation and light response in peripheral tissues. Here, we used the light-responsive zebrafish cell line Z3 to dissect the response of the clock gene zPer2 to light. We show that the MAPK (mitogen-activated protein kinase) pathway is essential for this response, although other signaling pathways may also play a role. Moreover, action spectrum analyses of zPer2 transcriptional response to monochromatic light demonstrate the involvement of a blue-light photoreceptor. The Cry1b and Cry3 cryptochromes constitute attractive candidates as photoreceptors in this setting. Our results establish a link between blue-light photoreceptors, probably cryptochromes, and the MAPK pathway to elicit light-induced transcriptional activation of clock genes

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.The ACP is very grateful to all of its members who have expressed views on the development of the strategy and to the sponsors of our workshops and publications, especially Cancer Research UK and Macmillan Cancer SupportThis is the final version of the article. It was first available from Cancer Intelligence via http://dx.doi.org/10.3332/ecancer.2016.60

SmokeHaz: systematic reviews and meta-analyses of the effects of smoking on respiratory health

Background: Smoking tobacco increases the risk of respiratory disease in adults and children, but communicating the magnitude of these effects in a scientific manner that is accessible and usable by public and policymakers presents a challenge. We have therefore summarised scientific data on the impact of smoking on respiratory diseases to provide the content for a unique resource, SmokeHaz. Methods: We conducted systematic reviews and meta-analyses of longitudinal studies (published to 2013) identified from electronic databases, grey literature, and experts. Random effect meta-analyses were used to pool the findings. Results: We included 216 papers. Among adult smokers, we confirmed substantially increased risks of lung cancer (Risk Ratio (RR) 10.92, 95% CI 8.28-14.40; 34 studies), COPD (RR 4.01, 95% CI 3.18-5.05; 22 studies) and asthma (RR 1.61, 95% CI 1.07-2.42; 8 studies). Exposure to passive smoke significantly increased the risk of lung cancer in adult non-smokers; and increased the risks of asthma, wheeze, lower respiratory infections, and reduced lung function in children. Smoking significantly increased the risk of sleep apnoea, and asthma exacerbations in adult and pregnant populations; and active and passive smoking increased the risk of tuberculosis. Conclusions: These findings have been translated into easily digestible content and published on the SmokeHaz website (www.smokehaz.eu)

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification