Effects of Volcanic Eruption Source Parameters on Radiative Forcing and Sulfate Deposition

Explosive volcanic eruptions can inject sulfur dioxide (SO2) into the stratosphere, which forms stratospheric sulfate aerosol that can significantly impact the climate. The radiative forcing of an eruption depends on several eruption source parameters: the mass of SO2 emitted, the latitude and the emission height. However, the combined effects of these parameters are not well understood. Reconstructions of historic volcanic radiative forcing, which are essential for understanding the role of volcanism on climate variability, are derived from ice core sulfate records, but rely on relationships between ice sheet deposition, stratospheric aerosol burdens and radiative forcing from limited observations. The aim of this thesis is to understand the impact of explosive volcanic eruptions on radiative forcing and volcanic sulfate deposition. The role of individual and combined eruption source parameters are comprehensively investigated using interactive stratospheric aerosol models, perturbed parameter ensembles and statistical emulation. The results demonstrate that radiative forcing is primarily determined by the SO2 emission magnitude, is stronger for tropical eruptions and has a greater dependency on the injection height if the eruption is tropical. The ice sheet deposition is relatively independent of the injection height. The results reveal complex combined effects of the eruption parameters and illustrate the importance of explicitly simulating aerosol microphysical processes to determine aerosol mass, size and lifetime. A wide range of eruption-realisations is found that produce ice sheet deposition that is consistent with ice-core-derived estimates for historic eruptions in the last 2500 years. These eruptions have a range in time-integrated radiative forcing (> ~300 MJ m-2) that is not considered in reconstructions. Sulfate deposition differs considerably between models for the 1815 eruption of Mt. Tambora. The results suggest there is a large uncertainty in radiative forcing derived from ice cores. Consequently, the efficacy of volcanic radiative forcing derived from previous reconstructions may be incorrect

A reliance on human habitats is key to the success of an introduced predatory reptile

Understanding the success of animals in novel environments is increasingly important as human-mediated introductions continue to move species far beyond their natural ranges. Alongside these introductions, inhabited and agricultural areas are spreading, and correspondingly most animal introductions occur in populated areas. Commensal species which can live alongside humans by making use of specific conditions, structures, or prey, have a significant advantage. Introduced mammal species often use anthropogenic features in their environment and demonstrate a higher tolerance of human disturbance, but their importance remains understudied in ectotherms. The Aesculapian snake (Zamenis longissimus) is an ectotherm which has been introduced beyond the northern extremities of its natural range. To understand their persistence, we radio-tracked snakes daily over two active seasons, including high-frequency tracking of a subset of males. We investigated snake home range size using Autocorrelated Kernel Density Estimators (AKDE). Using AKDE-weighted Habitat Selection Functions we identified preferences for habitat features in a mosaic of habitats, and we used Integrated Step Selection Functions to further explore how these features influence movement. We revealed a particular preference for buildings in male snakes, while females preferred woodland. We demonstrate that the success of this ectothermic predator is likely tied to a willingness to use human features of the landscape

Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease

Plasma biomarkers for Alzheimer's disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. To define Alzheimer's disease with biomarkers rather than clinical assessment, we assessed prediction of research-diagnosed disease status using these biomarkers and tested genetic variants associated with the biomarkers that may reflect more accurately the risk of biochemically defined Alzheimer's disease instead of the risk of dementia. In a cohort of Alzheimer's disease cases (N=1439, mean age 68 years [SD=8.2]) and screened controls (N=508, mean age 82 years [SD=6.8]), we measured plasma concentrations of the 40 and 42 amino acid-long amyloid β fragments (Aβ40 and Aβ42, respectively), tau phosphorylated at amino acid 181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) using state-of-the-art Single molecule array (Simoa) technology. We tested the relationships between the biomarkers and Alzheimer's disease genetic risk, age at onset, and disease duration. We also conducted a genome-wide association study for association of disease risk genes with these biomarkers. The prediction accuracy of Alzheimer's disease clinical diagnosis by the combination of all biomarkers, APOE and polygenic risk score reached AUC=0.81, with the most significant contributors being ε4, Aβ40 or Aβ42, GFAP and NfL. All biomarkers were significantly associated with age in cases and controls (p<4.3x10-5). Concentrations of the Aβ-related biomarkers in plasma were significantly lower in cases compared with controls, whereas other biomarker levels were significantly higher in cases. In the case-control genome-wide analyses, APOE-ε4 was associated with all biomarkers (p=0.011- 4.78x10-8), except NfL. No novel genome-wide significant SNPs were found in the case-control design; however, in a case-only analysis, we found two independent genome-wide significant associations between the Aβ42/Aβ40 ratio and WWOX and COPG2 genes. Disease prediction modelling by the combination of all biomarkers indicates that the variance attributed to P-tau181 is mostly captured by APOE-ε4, whereas Aβ40, Aβ42, GFAP and NfL biomarkers explain additional variation over and above APOE. We identified novel plausible genome wide-significant genes associated with Aβ42/Aβ40 ratio in a sample which is fifty times smaller than current genome-wide association studies in Alzheimer's disease

Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease

Plasma biomarkers for Alzheimer’s disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. To define Alzheimer’s disease with biomarkers rather than clinical assessment, we assessed prediction of research-diagnosed disease status using these biomarkers and tested genetic variants associated with the biomarkers that may reflect more accurately the risk of biochemically defined Alzheimer’s disease instead of the risk of dementia. In a cohort of Alzheimer’s disease cases (N=1439, mean age 68 years [SD=8.2]) and screened controls (N=508, mean age 82 years [SD=6.8]), we measured plasma concentrations of the 40 and 42 amino acid-long amyloid β fragments (Aβ40 and Aβ42, respectively), tau phosphorylated at amino acid 181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) using state-of-the-art Single molecule array (Simoa) technology. We tested the relationships between the biomarkers and Alzheimer’s disease genetic risk, age at onset, and disease duration. We also conducted a genome-wide association study for association of disease risk genes with these biomarkers. The prediction accuracy of Alzheimer’s disease clinical diagnosis by the combination of all biomarkers, APOE and polygenic risk score reached AUC=0.81, with the most significant contributors being ε4, Aβ40 or Aβ42, GFAP and NfL. All biomarkers were significantly associated with age in cases and controls (p<4.3x10-5). Concentrations of the Aβ-related biomarkers in plasma were significantly lower in cases compared with controls, whereas other biomarker levels were significantly higher in cases. In the case-control genome-wide analyses, APOE-ε4 was associated with all biomarkers (p=0.011- 4.78x10-8), except NfL. No novel genome-wide significant SNPs were found in the case-control design; however, in a case-only analysis, we found two independent genome-wide significant associations between the Aβ42/Aβ40 ratio and WWOX and COPG2 genes. Disease prediction modelling by the combination of all biomarkers indicates that the variance attributed to P-tau181 is mostly captured by APOE-ε4, whereas Aβ40, Aβ42, GFAP and NfL biomarkers explain additional variation over and above APOE. We identified novel plausible genome wide-significant genes associated with Aβ42/Aβ40 ratio in a sample which is fifty times smaller than current genome-wide association studies in Alzheimer’s disease

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Exome sequencing identifies novel AD-associated genes

The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD

Abstracts from the NIHR INVOLVE Conference 2017

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LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

Researching COVID to Enhance Recovery (RECOVER) Adult Study Protocol: Rationale, Objectives, and Design

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options