Living with a changing climate: Holocene climate variability and socio-evolutionary trajectories, central Turkey

Collaborative studies between Quaternary scientists and archaeologists increasingly provide new and informative discussions about the nature and timing of cultural change and links with variation in the natural world (particularly climate). In the Eastern Mediterranean region, connecting the human past with palaeoclimate is an important research theme but the complex interactions between them are still poorly understood and past climate records have often been collected from regions distant from the human record. The thesis aims to derive a record of past climatic and environmental changes from lake sediment cores and synthesise this with archaeological data in order to reconstruct human-climate interactions at the regional scale. Annually laminated sediment data collected from Nar Gölϋ crater-lake and archaeological archives from the same region, Cappadocia (Turkey) allow problems of chronological uncertainty between records of the human past and palaeoclimatic archives, and spatially variable datasets to be addressed. New sediment cores collected from Nar Lake in 2010 cover the last ~14000 years based on varve counting and climate-stratigraphic correlation. The changing chemical composition of these sediments has been obtained using high-resolution Itrax XRF core scanning, mainly at 200μm resolution over 21.6m. Temporal differences in Ca and Sr are interpreted as a record of regional moisture levels, while Ti and Fe are elemental proxies that detail changes in catchment in-wash. These and other sedimentary data (e.g. total carbon analysis) document lake evolution from a predominately stable and moist early Holocene climate dominated by high authigenic Ca precipitation to a drier and less stable IV late Holocene dominated by increased authigenic Sr and Mg (and higher lake salinity levels). The most arid climatic conditions occurred during Bronze and early Iron Age times, but frequent and intense centennial-scale climatic shifts between wet and dry are also evidenced during the last 2600 years from Ca/Sr data. Peaks in Fe and Ti, along with Si, K and Rb indicate two distinct phases of increased sediment influx into Nar Lake, namely ~9200 to ~8000 yr. BP (ceramic Neolithic) and again – more importantly – during the last 2600 years (Iron Age and later). These appear to be related primarily to increased human impact on vegetation and soils in the lake-catchment, but volcanic activity and intense rainfall events and/or water deficits may also have played a role. To determine the degree to which climatic variability and cultural change are interlinked, the geochemical record from Nar Lake is correlated against long-term settlement histories which have been derived from systematic archaeological site survey and excavation data from Cappadocia. One of the key outcomes of the project is an examination of periods of climatic stability and instability which are identified by amplitudinal changes from the mean state using correlation of coefficient statistics on the Nar Lake geochemical record. This information about the predictability of climate has been coupled to data in settlement density and location within the resiliency model framework of Holling and Gunderson (2002). Together these data suggest that a series of four long-term adaptive cycles (Neolithic, Chalcolithic-Bronze Age, Iron Age-Classical, Byzantine-Ottoman) characterise the dynamic inter-play between people, climate and their environment. In each adaptive cycle, environmental change contributed (both positively and negatively) to community resilience, although at no point during the Holocene is climatic variability seen as the sole driver of societal change. There were times such as the post-Roman Dark Age (1300 to 1100 yr. B.P.) when increased climatic variability and environmental degradation may have heightened social vulnerability.Studentship awarded by SoGEES, Plymouth Universit

Ethno-geochemical and phytolith studies of activity related patterns: A case study from Al Ma'tan, Jordan

Understanding Neolithic sites in southwest Asia is often difficult because of the lack of preservation of organic remains and the effects of various taphonomic processes that alter the original record. Here, we use an ethnographic approach to test the potential of using plant phytoliths and geochemistry to aid our interpretation of southwest Asian Neolithic sites. Our study of a recently abandoned stone and mud constructed village in Jordan, shows that for certain activity types, phytoliths and geochemistry can help distinguish different construction methods and functions, particularly for burnt areas, animal use areas and where there has been the addition of a specific construction material. For features constructed from the same source materials distinctions are more problematic. Geochemical and phytolith proxies were individually effective in distinguishing activity areas and construction materials, but signals were diminished when the statistical analysis was run on both forms of evidence combined. It is therefore recommended that the data from plant phytolith and geochemical analyses are subject to separate statistical tests and that the two sets of results are used in combination to interpret archaeological sites and their uses

Examining Neolithic Building and Activity Areas through Historic Cultural Heritage in Jordan: A Combined Ethnographic, Phytolith and Geochemical Investigation

The INEA project (Identifying activity areas in Neolithic sites through Ethnographic Analysis of phytoliths and geochemical residues, https://research.bournemouth. ac.uk/2014/07/inea-project-2/) develops and applies a method that combines the analysis of plant remains (silica phytoliths) and geochemical residues to inform on construction methods and the use of space in recently abandoned historical villages and Neolithic settlements. It is a collaborative project based at Bournemouth University, in partnership with the Council for British Research in the Levant

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Using Phytolith, Geochemical and Ethnographic Analysis to Inform on Site Construction and Activities in the Neolithic of Southwest Asia:Case Studies from Wadi Faynan 16 and ‘Ain Ghazal, Jordan

This paper explores what can be learned about settlement construction and use in the southwest Asian Neolithic from phytolith, geochemical and ethnographic analysis. This period was targeted because, despite its importance, our understanding of building practices and use of space within settlements is sometimes limited. We chose the sites of WF16 and ‘Ain Ghazal as case studies and compared them with ethnographic samples of known origin from the similarly constructed 20th century village of Al Ma’tan, Jordan. We split our samples into different context categories for example middens, hearths and floors, and found that phytolith and elemental signatures are strongest for categories linked to construction practices rather than activities. Geology, age and the availability of local plant materials are shown to be key sources of signature variability. Fire contexts have particularly distinct activity signatures, which are heavily influenced by fuel choice yet are relatively analogous. We suggest that the use of micro-proxies such as phytoliths and geochemistry should be considered when sampling strategies are devised and integrated with other forms of archaeological evidence to enhance site interpretation

Follow-on rifaximin for the prevention of recurrence following standard treatment of infection with clostridium fifficile (RAPID): a randomised placebo controlled trial

©2018 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/gutjnl-2018-316794Background Clostridium difficile infection (CDI) recurs after initial treatment in approximately one in four patients. A single-centre pilot study suggested that this could be reduced using ’follow-on’ rifaximin treatment. We aimed to assess the efficacy of rifaximin treatment in preventing recurrence. Methods A multisite, parallel group, randomised, placebo controlled trial recruiting patients aged ≥18 years immediately after resolution of CDI through treatment with metronidazole or vancomycin. Participants received either rifaximin 400mg three times a day for 2weeks, reduced to 200mg three times a day for a further 2weeks or identical placebo. The primary endpoint was recurrence of CDI within 12 weeks of trial entry. Results Between December 2012 and March 2016, 151 participants were randomised to either rifaximin or placebo. Primary outcome data were available on 130. Mean age was 71.9 years (SD 15.3). Recurrence within 12 weeks was 29.5% (18/61) among participants allocated to placebo compared with 15.9% (11/69) among those allocated to rifaximin, a difference between groups of 13.7% (95% CI −28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6-month safety follow-up, nine participants died in each group (12%). Adverse event rates were similar between groups. Conclusion While ’follow-on’ rifaximin after CDI appeared to halve recurrence rate, we failed to reach our recruitment target in this group of frail elderly patients, so the estimated effect of rifaximin lacks precision. A meta-analysis including a previous trial suggests that rifaximin may be effective; however, further, larger confirmatory studies are needed.The trial was sponsored by the University of Nottingham, was coordinated from the Nottingham Clinical Trials Unit and was supported by the National Institute for Health Research Clinical Research Network

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Background Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients’ preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings Between June 16, 2014, and April 29, 2015, data from 22803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj –4·4%, 95% CI –5·5 to –3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj –2·6%, 95% CI –3·9 to –1·4) and the administration of reversal agents (1·23, 1·07–1·41; –1·9%, –3·2 to –0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj –0·3%, 95% CI –2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; –0·4%, –3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications