Palaeogeographic controls on climate and proxy interpretation

During the period from approximately 150 to 35?million years ago, the Cretaceous–Paleocene–Eocene (CPE), the Earth was in a “greenhouse” state with little or no ice at either pole. It was also a period of considerable global change, from the warmest periods of the mid-Cretaceous, to the threshold of icehouse conditions at the end of the Eocene. However, the relative contribution of palaeogeographic change, solar change, and carbon cycle change to these climatic variations is unknown. Here, making use of recent advances in computing power, and a set of unique palaeogeographic maps, we carry out an ensemble of 19 General Circulation Model simulations covering this period, one simulation per stratigraphic stage. By maintaining atmospheric CO2 concentration constant across the simulations, we are able to identify the contribution from palaeogeographic and solar forcing to global change across the CPE, and explore the underlying mechanisms. We find that global mean surface temperature is remarkably constant across the simulations, resulting from a cancellation of opposing trends from solar and palaeogeographic change. However, there are significant modelled variations on a regional scale. The stratigraphic stage–stage transitions which exhibit greatest climatic change are associated with transitions in the mode of ocean circulation, themselves often associated with changes in ocean gateways, and amplified by feedbacks related to emissivity and planetary albedo. We also find some control on global mean temperature from continental area and global mean orography. Our results have important implications for the interpretation of single-site palaeo proxy records. In particular, our results allow the non-CO2 (i.e. palaeogeographic and solar constant) components of proxy records to be removed, leaving a more global component associated with carbon cycle change. This “adjustment factor” is used to adjust sea surface temperatures, as the deep ocean is not fully equilibrated in the model. The adjustment factor is illustrated for seven key sites in the CPE, and applied to proxy data from Falkland Plateau, and we provide data so that similar adjustments can be made to any site and for any time period within the CPE. Ultimately, this will enable isolation of the CO2-forced climate signal to be extracted from multiple proxy records from around the globe, allowing an evaluation of the regional signals and extent of polar amplification in response to CO2 changes during the CPE. Finally, regions where the adjustment factor is constant throughout the CPE could indicate places where future proxies could be targeted in order to reconstruct the purest CO2-induced temperature change, where the complicating contributions of other processes are minimised. Therefore, combined with other considerations, this work could provide useful information for supporting targets for drilling localities and outcrop studies

Past East Asian monsoon evolution controlled by paleogeography, not CO2

The East Asian monsoon plays an integral role in human society, yet its geological history and controlling processes are poorly understood. Using a general circulation model and geological data, we explore the drivers controlling the evolution of the monsoon system over the past 150 million years. In contrast to previous work, we find that the monsoon is controlled primarily by changes in paleogeography, with little influence from atmospheric CO2. We associate increased precipitation since the Late Cretaceous with the gradual uplift of the Himalayan-Tibetan region, transitioning from an ITCZ-dominated monsoon to a sea breeze–dominated monsoon. The rising region acted as a mechanical barrier to cold and dry continental air advecting into the region, leading to increasing influence of moist air from the Indian Ocean/South China Sea. We show that, apart from a dry period in the middle Cretaceous, a monsoon system has existed in East Asia since at least the Early Cretaceous

Fully-Automated Analysis of Body Composition from CT in Cancer Patients Using Convolutional Neural Networks

The amounts of muscle and fat in a person's body, known as body composition, are correlated with cancer risks, cancer survival, and cardiovascular risk. The current gold standard for measuring body composition requires time-consuming manual segmentation of CT images by an expert reader. In this work, we describe a two-step process to fully automate the analysis of CT body composition using a DenseNet to select the CT slice and U-Net to perform segmentation. We train and test our methods on independent cohorts. Our results show Dice scores (0.95-0.98) and correlation coefficients (R=0.99) that are favorable compared to human readers. These results suggest that fully automated body composition analysis is feasible, which could enable both clinical use and large-scale population studies

Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting.

Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1. In vitro experiments showed that the basic patch on µ1 that interacts with the Nef acidic cluster also contributes to the binding of endogenous acidic cluster proteins. Surprisingly, µ1 mutant proteins lacking the basic patch and/or the tyrosine-based motif binding pocket could rescue the µ1 knockout phenotype completely. In contrast, these mutants failed to rescue Nef-induced down-regulation of MHC class I, suggesting a possible mechanism for attacking the virus while sparing the host cell

Walking cadence affects rate of plantar foot temperature change but not final temperature in younger and older adults.

This study examined the relationship between (1) foot temperature in healthy individuals and walking cadence, (2) temperature change at different locations of the foot, and (3) temperature change and its relationship with vertical pressures exerted on the foot. Eighteen healthy adult volunteers (10 between 30 and 40 years - Age: 33.4±2.4years; 8 above 40 years - Age: 54.1±7.7years) were recruited. A custom-made insole with temperature sensors was placed directly onto the plantar surface of the foot and held in position using a sock. The foot was placed on a pressure sensor and the whole system placed in a canvas shoe. Participants visited the lab on three separate occasions when foot temperature and pressure data were recorded during walking on a treadmill at one of three cadences (80, 100, 120steps/min). The plantar foot temperature increased during walking in both age groups 30-40 years: 4.62±2.00°C, >40years: 5.49±2.30°C, with the rise inversely proportional to initial foot temperature (30-40 years: R(2)=-0.669, >40years: R(2)=-0.816). Foot temperature changes were not different between the two age groups or the different foot locations and did not depend on vertical pressures. Walking cadence affected the rate of change of plantar foot temperature but not the final measured value and no association between temperature change and vertical pressure was found. These results provide baseline values for comparing foot temperature changes in pathological conditions which could inform understanding of pathophysiology and support development of evidence based healthcare guidelines for managing conditions such as diabetic foot ulceration (DFU)

Foot posture in people with medial compartment knee osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Foot posture has long been considered to contribute to the development of lower limb musculoskeletal conditions as it may alter the mechanical alignment and dynamic function of the lower limb. This study compared foot posture in people with and without medial compartment knee osteoarthritis (OA) using a range of clinical foot measures. The reliability of the foot measures was also assessed.</p> <p>Methods</p> <p>The foot posture of 32 patients with clinically and radiographically-confirmed OA predominantly in the medial compartment of the knee and 28 asymptomatic age-matched healthy controls was investigated using the foot posture index (FPI), vertical navicular height and drop, and the arch index. Independent t tests and effect size (Cohen's d) were used to investigate the differences between the groups in the foot posture measurements.</p> <p>Results</p> <p>Significant differences were found between the control and the knee OA groups in relation to the FPI (1.35 ± 1.43 vs. 2.46 ± 2.18, p = 0.02; <it>d </it>= 0.61, medium effect size), navicular drop (0.02 ± 0.01 vs. 0.03 ± 0.01, p = 0.01; <it>d </it>= 1.02, large effect size) and the arch index (0.22 ± 0.04 vs. 0.26 ± 0.04, p = 0.04; <it>d </it>= 1.02, large effect size). No significant difference was found for vertical navicular height (0.24 ± 0.03 vs. 0.23 ± 0.03, p = 0.54; <it>d </it>= 0.04, negligible effect size).</p> <p>Conclusion</p> <p>People with medial compartment knee OA exhibit a more pronated foot type compared to controls. It is therefore recommended that the assessment of patients with knee OA in clinical practice should include simple foot measures, and that the potential influence of foot structure and function on the efficacy of foot orthoses in the management of medial compartment knee OA be further investigated.</p

Facies Distribution, Sequence Stratigraphy, Chemostratigraphy, and Diagenesis of the Middle-Late Triassic Al Aziziyah Formation, Jifarah Basin, NW Libya

This study presents the depositional facies, sequence stratigraphy, chemostratigraphy and diagenetic evolution of the Middle-Late Triassic Al Aziziyah Formation, Jifarah Basin northwest Libya. Eight measured sections were sampled and analyzed. High-resolution stable carbon isotope data were integrated with an outcrop-based sequence stratigraphic framework, to build the stratigraphic correlation, and to provide better age control of the Al Aziziyah Formation using thin section petrography, cathodoluminescence (CL) microscopy, stable isotope, and trace element analyses. The Al Aziziyah Formation was deposited on a gently sloping carbonate ramp and consists of gray limestone, dolomite, and dolomitic limestone interbedded with rare shale. The Al Aziziyah Formation is predominantly a 2nd-order sequence (5-20 m.y. duration), with shallow marine sandstone and peritidal carbonate facies restricted to southernmost sections. Seven 3rd-order sequences were identified (S1-S7) within the type section. North of the Ghryan Dome section are three mainly subtidal sequences (S8-S10) that do not correlate to the south. Shallowing upward trends define 4th-5th order parasequences, but correlating these parasequences between sections is difficult due to unconformities. The carbon isotope correlation between the Ghryan Dome and Kaf Bates sections indicates five units of δ13C depletion and enrichment (sequences 3-7). The enrichment of δ13C values in certain intervals most likely reflects local withdrawal of 12C from the ocean due to increased productivity, as indicated by the deposition of organic-rich sediment, and/or whole rock sediment composed of calcite admixed with aragonite. The depletion of δ13C is clearly associated with exposure surfaces and with shallow carbonate facies. Heavier δ18O values are related to evaporetic enrichment of 18O, whereas depletion of δ18O is related to diagenesis due to freshwater input. Al Aziziyah Formation diagenetic events indicate: 1) initial meteoric and shallow burial; 2) three types of dolomite D1, D2 and D3 were most likely formed by microbial, seepage reflux and burial processes, respectively; and 3) diagenetic cements cannot be related to the arid, mega-monsoonal climate of the Triassic and most likely formed subsequently in a humid, meteoric setting

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