The impact and significance of tephra deposition on a Holocene forest environment in the North Cascades, Washington, USA

High-resolution palaeoecological analyses (stratigraphy, tephra geochemistry, radiocarbon dating, pollen and ordination) were used to reconstruct a Holocene vegetation history of a watershed in the Pacific Northwest of America to evaluate the effects and duration of tephra deposition on a forest environment and the significance of these effects compared to long-term trends. Three tephra deposits were detected and evaluated: MLF-T158 and MLC-T324 from the climactic eruption of Mount Mazama, MLC-T480 from a Late Pleistocene eruption of Mount Mazama and MLC-T485 from a Glacier Peak eruption. Records were examined from both the centre and fringe of the basin to elucidate regional and local effects. The significance of tephra impacts independent of underlying long-term trends was confirmed using partial redundancy analysis. Tephra deposition from the climactic eruption of Mount Mazama approximately 7600 cal. years BP caused a significant local impact, reflected in the fringe location by changes to open habitat vegetation (Cyperaceae and Poaceae) and changes in aquatic macrophytes (Myriophyllum spicatum, Potamogeton, Equisetum and the alga Pediastrum). There was no significant impact of the climactic Mazama tephra or other tephras detected on the pollen record of the central core. Changes in this core are potentially climate driven. Overall, significant tephra fall was demonstrated through high resolution analyses indicating a local effect on the terrestrial and aquatic environment, but there was no significant impact on the regional forest dependent of underlying environmental changes

Bowel ischaemia in COVID-19 infection: a scoping review protocol

Introduction: COVID-19 disease was declared as a pandemic by WHO since March 2020 and can have a myriad of clinical presentations affecting various organ systems. Patients with COVID-19 are known to have an increased risk of thromboembolism, including cardiovascular, pulmonary and cerebral ischaemic events. However, an increasing number of case studies have reported that COVID-19 infection is also associated with gastrointestinal ischaemia. This scoping review aims to collate the current evidence of COVID-19-related gastrointestinal ischaemia and raise awareness among healthcare professionals of this lesser known, but serious, non-pulmonary complication of COVID-19 infection. Methods: The proposed scoping review will be conducted as per the Arksey and O’Malley methodological framework (2005) the Joanna Briggs Institute methodology for scoping reviews. A systematic search will be undertaken on different databases including EMBASE, PubMed and MEDLINE. Two independent reviewers will screen titles, abstracts and full-text articles according to the inclusion criteria and extract relevant data from the included articles. Results will be presented in a tabular form with a narrative discussion. Ethics and dissemination: Ethical approval will not be required for this scoping review. This scoping review will provide an extensive overview of the association between COVID-19 infection and bowel ischaemia. Further ethical and methodological challenges will also be discussed in our findings to define a new research agenda. Findings will be disseminated through peer-reviewed publications and presentations at both national and international conferences

An immunotherapy survivor population: health-related quality of life and toxicity in patients with metastatic melanoma treated with immune checkpoint inhibitors

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Purpose The immune checkpoint inhibitors (ICIs) have resulted in subgroups of patients with metastatic melanoma achievinghigh-quality durable responses. Metastatic melanoma survivors are a new population in the era of cancer survivorship. The aimofthis study was to evaluate metastatic melanoma survivors in terms of health-related quality of life (HRQoL), immune-relatedadverse events (irAEs) and exposure to immunosuppressive agents in a large single centre in the UK.Methods We defined the survivor population as patients with a diagnosis of metastatic melanoma who achieved a durableresponse to an ICI and had been followed-up for a minimum of 12 months from initiation of ICI without disease progression.HRQoL was assessed using SF-36. Electronic health records were accessed to collect data on demographics, treatments, irAEsand survival. HRQoL data was compared with two norm-based datasets.Results Eighty-four metastatic melanoma survivors were eligible and 87% (N = 73) completed the SF-36. ICI-related toxicity ofany grade occurred in 92%of patients and 43%had experienced a grade 3 or 4 toxicity. Almost half (49%) of the patients requiredsteroids for the treatment of ICI-related toxicity, whilst 14% required treatment with an immunosuppressive agent beyondsteroids.Melanoma survivors had statistically significant lower HRQoL scores with regard to physical, social and physical rolefunctioning and general health compared with the normative population. There was a trend towards inferior scores in patientswith previous exposure to ipilimumab compared with those never exposed to ipilimumab.Conclusions Our results show that metastatic melanoma survivors have potentially experienced significant ICI-related toxicityand experience significant impairments in specific HRQoL domains. Future service planning is required to meet this population’sunique survivorship needs.Peer reviewe

The management of tubo-ovarian abscess - A retrospective analysis of a centre offering outpatient intravenous antibiotic therapy

Background Tubo-ovarian abscess (TOA) carries long-term sequale in women of reproductive age. Consensus of the optimal treatment of tubo-ovarian abscess remains lacking. The aims of this study are to identify risk factors predicting the need for early drainage and compare clinical outcomes of current management practices of TOA. Methods From 2015 to 2019, a retrospective cohort study of 92 women admitted to a tertiary centre for gynaecological surgery was performed. Patients with diagnosed TOA were classified into two groups: treatment with antibiotics only, and those receiving additional drainage. Primary outcomes included length of hospital stay (LoS), length of antibiotic treatment (LoA) and need for re-intervention. Results In this study, 52 women (56.5%) were successfully treated with first line intravenous antibiotics; 40 (43.5%) received surgical drainage. Significant predictors for successful medical treatment only include age 35 years, pyrexia ≥ 38°C and a TOA size > 6cm may independently predict the need for drainage of TOA. Early identification of these patients is imperative for timely surgical intervention to avoid prolonged hospitalisation, antibiotic usage, and patient morbidity. More work is required to identify whether early drainage may reduce length of hospital stay and antibiotic treatment, including identifying certain patient groups who most likely to benefit from outpatient antibiotic intravenous therapy

Diffusion Tensor Imaging for Diagnosing Root Avulsions in Traumatic Adult Brachial Plexus Injuries: A Proof-of-Concept Study

Cross-sectional MRI has modest diagnostic accuracy for diagnosing traumatic brachial plexus root avulsions. Consequently, patients either undergo major exploratory surgery or months of surveillance to determine if and what nerve reconstruction is needed. This study aimed to develop a diffusion tensor imaging (DTI) protocol at 3 Tesla to visualize normal roots and identify traumatic root avulsions of the brachial plexus. Seven healthy adults and 12 adults with known (operatively explored) unilateral traumatic brachial plexus root avulsions were scanned. DTI was acquired using a single-shot echo-planar imaging sequence at 3 Tesla. The brachial plexus was visualized by deterministic tractography. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for injured and avulsed roots in the lateral recesses of the vertebral foramen. Compared to healthy nerves roots, the FA of avulsed nerve roots was lower (mean difference 0.1 [95% CI 0.07, 0.13]; p < 0.001) and the MD was greater (mean difference 0.32 × 10−3 mm2/s [95% CI 0.11, 0.53]; p < 0.001). Deterministic tractography reconstructed both normal roots and root avulsions of the brachial plexus; the negative-predictive value for at least one root avulsion was 100% (95% CI 78, 100). Therefore, DTI might help visualize both normal and injured roots of the brachial plexus aided by tractography. The precision of this technique and how it relates to neural microstructure will be further investigated in a prospective diagnostic accuracy study of patients with acute brachial plexus injuries

Evaluation of methods and marker systems in genomic selection of oil palm (Elaeis guineensis Jacq.)

Background Genomic selection (GS) uses genome-wide markers as an attempt to accelerate genetic gain in breeding programs of both animals and plants. This approach is particularly useful for perennial crops such as oil palm, which have long breeding cycles, and for which the optimal method for GS is still under debate. In this study, we evaluated the effect of different marker systems and modeling methods for implementing GS in an introgressed dura family derived from a Deli dura x Nigerian dura (Deli x Nigerian) with 112 individuals. This family is an important breeding source for developing new mother palms for superior oil yield and bunch characters. The traits of interest selected for this study were fruit-to-bunch (F/B), shell-to-fruit (S/F), kernel-to-fruit (K/F), mesocarp-to-fruit (M/F), oil per palm (O/P) and oil-to-dry mesocarp (O/DM). The marker systems evaluated were simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs). RR-BLUP, Bayesian A, B, Cπ, LASSO, Ridge Regression and two machine learning methods (SVM and Random Forest) were used to evaluate GS accuracy of the traits. Results The kinship coefficient between individuals in this family ranged from 0.35 to 0.62. S/F and O/DM had the highest genomic heritability, whereas F/B and O/P had the lowest. The accuracies using 135 SSRs were low, with accuracies of the traits around 0.20. The average accuracy of machine learning methods was 0.24, as compared to 0.20 achieved by other methods. The trait with the highest mean accuracy was F/B (0.28), while the lowest were both M/F and O/P (0.18). By using whole genomic SNPs, the accuracies for all traits, especially for O/DM (0.43), S/F (0.39) and M/F (0.30) were improved. The average accuracy of machine learning methods was 0.32, compared to 0.31 achieved by other methods. Conclusion Due to high genomic resolution, the use of whole-genome SNPs improved the efficiency of GS dramatically for oil palm and is recommended for dura breeding programs. Machine learning slightly outperformed other methods, but required parameters optimization for GS implementation

T Cell-Intrinsic and -Extrinsic Contributions of the IFNAR/STAT1-Axis to Thymocyte Survival

STAT1 is an essential part of interferon signaling, and STAT1-deficiency results in heightened susceptibility to infections or autoimmunity in both mice and humans. Here we report that mice lacking the IFNα/β-receptor (IFNAR1) or STAT1 display impaired deletion of autoreactive CD4+CD8+-T-cells. Strikingly, co-existence of WT T cells restored thymic elimination of self-reactive STAT1-deficient CD4+CD8+-T cells. Analysis of STAT1-deficient thymocytes further revealed reduced Bim expression, which was restored in the presence of WT T cells. These results indicate that type I interferons and STAT1 play an important role in the survival of MHC class I-restricted T cells in a T cell intrinsic and non-cell intrinsic manner that involves regulation of Bim expression through feedback provided by mature STAT1-competent T cells

Analysis of Intracellular State Based on Controlled 3D Nanostructures Mediated Surface Enhanced Raman Scattering

Near-infrared surface-enhanced Raman spectroscopy (SERS) is a powerful technique for analyzing the chemical composition within a single living cell at unprecedented resolution. However, current SERS methods employing uncontrollable colloidal metal particles or non-uniformly distributed metal particles on a substrate as SERS-active sites show relatively low reliability and reproducibility. Here, we report a highly-ordered SERS-active surface that is provided by a gold nano-dots array based on thermal evaporation of gold onto an ITO surface through a nanoporous alumina mask. This new combined technique showed a broader distribution of hot spots and a higher signal-to-noise ratio than current SERS techniques due to the highly reproducible and uniform geometrical structures over a large area. This SERS-active surface was applied as cell culture system to study living cells in situ within their culture environment without any external preparation processes. We applied this newly developed method to cell-based research to differentiate cell lines, cells at different cell cycle stages, and live/dead cells. The enhanced Raman signals achieved from each cell, which represent the changes in biochemical compositions, enabled differentiation of each state and the conditions of the cells. This SERS technique employing a tightly controlled nanostructure array can potentially be applied to single cell analysis, early cancer diagnosis and cell physiology research

CLEC5A Regulates Japanese Encephalitis Virus-Induced Neuroinflammation and Lethality

CLEC5A/MDL-1, a member of the myeloid C-type lectin family expressed on macrophages and neutrophils, is critical for dengue virus (DV)-induced hemorrhagic fever and shock syndrome in Stat1−/− mice and ConA-treated wild type mice. However, whether CLEC5A is involved in the pathogenesis of viral encephalitis has not yet been investigated. To investigate the role of CLEC5A to regulate JEV-induced neuroinflammation, antagonistic anti-CLEC5A mAb and CLEC5A-deficient mice were generated. We find that Japanese encephalitis virus (JEV) directly interacts with CLEC5A and induces DAP12 phosphorylation in macrophages. In addition, JEV activates macrophages to secrete proinflammatory cytokines and chemokines, which are dramatically reduced in JEV-infected Clec5a−/− macrophages. Although blockade of CLEC5A cannot inhibit JEV infection of neurons and astrocytes, anti-CLEC5A mAb inhibits JEV-induced proinflammatory cytokine release from microglia and prevents bystander damage to neuronal cells. Moreover, JEV causes blood-brain barrier (BBB) disintegrity and lethality in STAT1-deficient (Stat1−/−) mice, whereas peripheral administration of anti-CLEC5A mAb reduces infiltration of virus-harboring leukocytes into the central nervous system (CNS), restores BBB integrity, attenuates neuroinflammation, and protects mice from JEV-induced lethality. Moreover, all surviving mice develop protective humoral and cellular immunity against JEV infection. These observations demonstrate the critical role of CLEC5A in the pathogenesis of Japanese encephalitis, and identify CLEC5A as a target for the development of new treatments to reduce virus-induced brain damage