Earthquakes and sea-level change in Hokkaido, north-east Japan

This thesis details the results of an investigation into the pattern of relative sea-level (RSL) changes in north-east Hokkaido, Japan. The aim of the research is to better understand the importance of seismic and non-seismic processes in controlling spatial patterns of vertical land motions over a range of timescales. The main focus is on using salt-marsh sediments as a source of data to reconstruct RSL change during the current interseismic period, since c. 300 calibrated years before present (cal. yr BP). Previous research on the Pacific coast of Hokkaido suggests that this period is characterised by subsidence caused by strain accumulation on the locked part of the Pacific/North American plates. I apply foraminiferal-based methods of palaeoenvironmental reconstruction to develop, using transfer functions, quantitative reconstructions of RSL change at five sites in north-east Hokkaido. Contemporary foraminifera are zoned with respect to elevation and tidal inundation, and my preferred transfer function (a model that contains 87 samples and 24 taxa) has a prediction r2 of 0.75 and a root mean squared error of prediction of ± 0.32 m. I apply this transfer function to shallow fossil sediment sequences at five salt marshes and use a combination of 210Pb, 137Cs and tephra chronology to establish age models for the sequences. The reconstructions are consistent in demonstrating little net RSL change during the last 300-100 cal. yrs, with the exception of data from one site, Sarfutsu-toh, located on the northern tip of Hokkaido. Chronologies from two profiles developed on the Pacific coast record strong evidence for recent RSL rise since the mid-1980s, but during earlier periods of the 20th century reconstructed RSL was stable or falling. I compare my reconstructions with other direct and proxy records of land and sea-level motions. Previously published GPS and repeat levelling data indicates subsidence in south-east Hokkaido during the 20th century, although the spatial patterns and rates of change have varied. An unknown amount of this subsidence at the Kushiro tide gauge likely reflects anthropogenic activities associated with sediment compaction as well as mining-induced subsidence. An analysis of the tide-gauge records from Hokkaido show a more varied pattern of land motions, although they also confirm subsidence on the Pacific coast, close to the Kuril trench. A database of Holocene sea-level index points provides insights into longer-term millennial-scale trends in RSL. Data from six regions of Hokkaido demonstrate stable RSL close to present during the mid- and late Holocene; only the northern tip of Hokkaido (around Sarubetsu) is there evidence for a small mid-Holocene highstand of 1-3 m above present. Finally, a review of Pleistocene raised marine terrace data shows net uplift over the last c. 330 k yr, with two areas of particularly high uplift at Abashiri and on the Pacific coast near Kushiro. The evidence presented in this research demonstrates that it is incorrect to infer that the current interseismic period is characterised by subsidence. Overall, RSL has changed little in the last 300-100 cal. yrs. The subsidence recorded in the mid- and late 20th century on the Pacific coast of Hokkaido is not typical of the full interseismic period, nor can it have been sustained over Holocene or Pleistocene timescales. Limited data from previous earthquake cycles indicate that RSL was stable, rising or falling during previous interseismic intervals. These observations suggest that a representative ‘Hokkaido earthquake deformation cycle’ may not exist. Future research should better understand the controls of Quaternary volcanic activity on regional deformation patterns, and apply microfossil-based techniques to multiple earthquake cycles at sites to help define the spatial extent of land motions associated with different events

Effectiveness and implementation of lower-intensity weight management interventions delivered by the non-specialist workforce in postnatal women: a mixed-methods systematic review

Lower-intensity interventions delivered in primary and community care contacts could provide more equitable and scalable weight management support for postnatal women. This mixed-methods systematic review aimed to explore the effectiveness, implementation, and experiences of lower-intensity weight management support delivered by the non-specialist workforce. We included quantitative and qualitative studies of any design that evaluated a lower-intensity weight management intervention delivered by non-specialist workforce in women up to 5 years post-natal, and where intervention effectiveness (weight-related and/or behavioural outcomes), implementation and/or acceptability were reported. PRISMA guidelines were followed, and the review was prospectively registered on PROSPERO (CRD42022371828). Nine electronic databases were searched to identify literature published between database inception to January 2023. This was supplemented with grey literature searches and citation chaining for all included studies and related reviews (completed June 2023). Screening, data extraction and risk of bias assessments were performed in duplicate. Risk of bias was assessed using the Joanna Briggs Institute appraisal tools. Narrative methods were used to synthesise outcomes. Seven unique studies described in 11 reports were included from the Netherlands (n = 2), and the United Kingdom, Germany, Taiwan, Finland, and the United States (n = 1 each). All studies reported weight-related outcomes; four reported diet; four reported physical activity; four reported intervention implementation and process outcomes; and two reported intervention acceptability and experiences. The longest follow-up was 13-months postnatal. Interventions had mixed effects on weight-related outcomes: three studies reported greater weight reduction and/or lower postnatal weight retention in the intervention group, whereas four found no difference or mixed effects. Most studies reporting physical activity or diet outcomes showed no intervention effect, or mixed effects. Interventions were generally perceived as acceptable by women and care providers, although providers had concerns about translation into routine practice. The main limitations of the review were the limited volume of evidence available, and significant heterogeneity in interventions and outcome reporting which limited meaningful comparisons across studies. There is a need for more intervention studies, including process evaluations, with longer follow-up in the postnatal period to understand the role of primary and community care in supporting women’s weight management. Public Health Wales was the primary funder of this review

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

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Investigation of SARS-CoV-2 faecal shedding in the community: a prospective household cohort study (COVID-LIV) in the UK

Background SARS-CoV-2 is frequently shed in the stool of patients hospitalised with COVID-19. The extent of faecal shedding of SARS-CoV-2 among individuals in the community, and its potential to contribute to spread of disease, is unknown. Methods In this prospective, observational cohort study among households in Liverpool, UK, participants underwent weekly nasal/throat swabbing to detect SARS-CoV-2 virus, over a 12-week period from enrolment starting July 2020. Participants that tested positive for SARS-CoV-2 were asked to provide a stool sample three and 14 days later. In addition, in October and November 2020, during a period of high community transmission, stool sampling was undertaken to determine the prevalence of SARS-CoV-2 faecal shedding among all study participants. SARS-CoV-2 RNA was detected using Real-Time PCR. Results A total of 434 participants from 176 households were enrolled. Eighteen participants (4.2%: 95% confidence interval [CI] 2.5–6.5%) tested positive for SARS-CoV-2 virus on nasal/throat swabs and of these, 3/17 (18%: 95% CI 4–43%) had SARS-CoV-2 detected in stool. Two of three participants demonstrated ongoing faecal shedding of SARS-CoV-2, without gastrointestinal symptoms, after testing negative for SARS-CoV-2 in respiratory samples. Among 165/434 participants without SARS-CoV-2 infection and who took part in the prevalence study, none had SARS-CoV-2 in stool. There was no demonstrable household transmission of SARS-CoV-2 among households containing a participant with faecal shedding. Conclusions Faecal shedding of SARS-CoV-2 occurred among community participants with confirmed SARS-CoV-2 infection. However, during a period of high community transmission, faecal shedding of SARS-CoV-2 was not detected among participants without SARS-CoV-2 infection. It is unlikely that the faecal-oral route plays a significant role in household and community transmission of SARS-CoV-2

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination