Paleoclimates in Southwestern Tasmania during the Last 13,000 Years

Plant-sociological and climatic classification of the Australian Nothofagus cunninghamii rain forest provides the basis for a new, semiquantitative approach to interpretations of late-Quaternary paleoclimates from four pollen sequences in southwestern Tasmania. Varying proportions of rain-forest pollen types in the records were related to different modern rain-forest alliances and their specifc climatic regimes, such as Eastern Rain Forest, Leatherwood Rain Forest, and sclerophyllous, Subalpine Rain Forest. According to this interpretation, early Holocene climates were characterized by 1,600 mm annual precipitation and 10°C annual temperature, conditions substantially warmer and drier than previously thought. Maximum precipitation levels of 2,500 mm annually were not reached until 8,000 years B.P. A short-term cooling episode between 6,000 and 5,000 years B.P. led to the establishment of modern rain-forest distribution in western Tasmania, characterized either by a precipitation gradient steeper than before, or by greater climatic variability. To interpret paleoclimates from before 12,000 years B. P., when non-arboreal environments dominated in western Tasmanian bollen records, various modern treeless environments were studied in search for analogs. Contrary to earlier interpretations, late-glacial environments were not alpine tundra with a treeline at modern sea level, but steppe, with marshes or shallow lakes instead of the modern lakes. Climate was characterized by 50% less precipitation than today, resulting in substantial summer droughts. To explain such drastic precipitation decrease, the westerlies that dominate Tasmanian climate today must have been shifted polewards. This suggestion is supported by climate models that take Milankovitch-type insolation differences into account as well as sea-surface temperatures. Paleolimnological information based on diatom analyses support the general paleoclimatic reassessment

Modelling the potential for permafrost development on a radioactive waste geological disposal facility in Great Britain

The safety case for a geological disposal facility (GDF) for radioactive waste based in Great Britain must consider the potential impact on the repository environment of permafrost during the 1 million years following GDF closure. The depth of penetration of permafrost, defined as ground which remains at or below 0 °C for at least 2 consecutive years, has been modelled for a future climate that uses the climate of the last glacial–interglacial cycle as an analogue. Two future climates are considered; an average estimate case considered to be the best estimate of ground surface temperatures during the last glacial–interglacial cycle, and a cold estimate case considered to be an extreme cold, but plausible future climate. Maximum modelled permafrost thicknesses across Great Britain range from 20 to 180 m for the average estimate climate and 180–305 m for the cold estimate climate. The presence of ice cover is an important determinant on permafrost development. Thick permafrost evolves during long periods of cold-based ice cover and during periods of ice retreat that results in ground exposure to very cold air temperatures. Conversely, warm-based ice has an insulating effect, shielding the ground from cold air temperatures that retards permafrost development. For a GDF at a depth greater than that predicted to be directly affected by permafrost, phenomena associated with permafrost, e.g., enhanced groundwater salinity at depth, will need to be taken into account when considering the impact on the engineered and natural barriers associated with a GDF

An evaluation of combined geophysical and geotechnical methods to characterize beach thickness

Beaches provide sediment stores and have an important role in the development of the coastline in response to climate change. Quantification of beach thickness and volume is required to assess coastal sediment transport budgets. Therefore, portable, rapid, non-invasive techniques are required to evaluate thickness where environmental sensitivities exclude invasive methods. Site methods and data are described for a toolbox of electrical, electromagnetic, seismic and mechanical based techniques that were evaluated at a coastal site at Easington, Yorkshire. Geophysical and geotechnical properties are shown to be dependent upon moisture content, porosity and lithology of the beach and the morphology of the beach–platform interface. Thickness interpretation, using an inexpensive geographic information system to integrate data, allowed these controls and relationships to be understood. Guidelines for efficient site practices, based upon this case history including procedures and techniques, are presented using a systematic approach. Field results indicated that a mixed sand and gravel beach is highly variable and cannot be represented in models as a homogeneous layer of variable thickness overlying a bedrock half-space

Distribution modelling and statistical phylogeography: an integrative framework for generating and testing alternative biogeographical hypotheses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73644/1/j.1365-2699.2007.01814.x.pd

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

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; p5mg/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. Funding: UK Research and Innovation and National Institute for Health Research

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury

Long COVID and cardiovascular disease: a prospective cohort study

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known. Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors. Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health. Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86). Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need