Sol-gel deposition of oxide-ion conducting thin films ; Liquid precursors to hafnium and tantalum carbides

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999.Includes bibliographical references.I. The deposition of thin films of the BiMeVOx oxygen ion conducting ceramics was studied. The sol-gel precursor solution included a soluble form of bismuth acetate, a vanadium alkoxide, and the acetate or alkoxide of the dopant metal (Me). Copper-doped films were spincoated onto nonporous quartz substrates and pyrolyzed. These were initally defect-free, but became agglomerated on heating at higher temperatures. The use of a number of different additive compounds was tried, but did not greatly improve the behavior of the films on quartz substrates. These films, when deposited onto platinum-coated substrates, remained defect-free to all temperatures. Niobium-doped films remained defect-free on quartz substrates at all heating temperatures. The reasons for these behaviors are examined. Copper-doped films were deposited defect-free onto porous alumina substrates. The structure of a single-molecule bismuth-vanadium precursor in the sol-gel solution is suggested. II. Liquid precursors to refractory transition metal carbides were produced via both organometallic and metal alkoxide starting materials. These precusors were pyrolyzed under inert atmosphere and found to convert to the metal carbide, plus excess carbon, between 1100 °C and 1500 °C. The use of Grignard reagents to functionalize (chloromethyl)silylterminated carbosilane dendrimers was investigated briefly. The syntheses were plagued by long reaction times and low purities, contrary to the behavior expected for the (chloromethyl)silyl group. Reasons for this behavior are discussed.by Jennifer Woodbridge Pell.Ph.D

The RNA-binding proteins Zfp36l1 and Zfp36l2 act redundantly in myogenesis.

BACKGROUND: Members of the ZFP36 family of RNA-binding proteins regulate gene expression post-transcriptionally by binding to AU-rich elements in the 3'UTR of mRNA and stimulating mRNA degradation. The proteins within this family target different transcripts in different tissues. In particular, ZFP36 targets myogenic transcripts and may have a role in adult muscle stem cell quiescence. Our study examined the requirement of ZFP36L1 and ZFP36L2 in adult muscle cell fate regulation. METHODS: We generated single and double conditional knockout mice in which Zfp36l1 and/or Zfp36l2 were deleted in Pax7-expressing cells. Immunostained muscle sections were used to analyse resting skeletal muscle, and a cardiotoxin-induced injury model was used to determine the regenerative capacity of muscle. RESULTS: We show that ZFP36L1 and ZFP36L2 proteins are expressed in satellite cells. Mice lacking the two proteins in Pax7-expressing cells have reduced body weight and have reduced skeletal muscle mass. Furthermore, the number of satellite cells is reduced in adult skeletal muscle and the capacity of this muscle to regenerate following muscle injury is diminished. CONCLUSION: ZFP36L1 and ZFP36L2 act redundantly in myogenesis. These findings add further intricacy to the regulation of the cell fate of Pax7-expressing cells in skeletal muscle by RNA-binding proteins

Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment

Kidney function and cancer risk: an analysis using creatinine and cystatin C in a cohort study

Background: We examined whether an increased risk of cancer incidence and death is associated with kidney function and albuminuria and whether the risk is more readily identified when kidney function is estimated using cystatin C. Methods: Participants were from UK Biobank (recruitment spanning 2007–2010), excluding those with a prior diagnosis of cancer. Estimated glomerular filtration rate (ml/min/1.73m2) was calculated using creatinine (eGFRcr), cystatin C (eGFRcys) and creatinine-cystatin C (eGFRcr-cys). Cox proportional hazards models tested associations between eGFR, urinary albumin:creatinine ratio (uACR) and cancer incidence and death. Findings: In 431,263 participants over median follow-up of 11.3 (IQR 10.6–12.0) years, there were 41,745 incident cancers and 11,764 cancer deaths. eGFRcys was most strongly associated with cancer incidence and death (HR 1.04 (95% CI 1.03–1.04) and 1.06 (1.05–1.07) per 10 ml/min/1.73m2 decline, respectively). eGFRcr was not associated with either outcome (incidence: HR 1.00 (1.00–1.01); death: HR 0.99 (0.98–1.01) per 10 ml/min/1.73m2 decline). Relative to eGFRcys>90 or uACR<3 mg/mmol, eGFRcys60–89 (HR 1.04 (95% CI 1.02–1.07)), eGFRcys<60 (HR 1.19 (1.14–1.24)) and uACR≥3 mg/mmol (HR 1.09 (1.06–1.12)) were associated with higher risk of incident cancer. eGFRcys60–89 (HR 1.15 (1.10–1.21)); eGFRcys<60 (HR 1.48 (1.38–1.59)) and uACR≥3 mg/mmol (HR 1.17 (1.11–1.24)) were associated with cancer death. Interpretation: Excess risk of cancer incidence and cancer death is more readily captured in early chronic kidney disease by eGFRcys than by current measures. The association between kidney function, uACR and cancer death in particular is concerning and warrants further scrutiny

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Stratigraphy, structure and metamorphism of Hadrynian strata in the southeastern Cariboo Mountains, B.C.

Bibliography: p. 173-185.Approximately 750 square kilometers of the Southeastern Cariboo Mountains near Thunder River were mapped in detail. The Semipelite-Amphibolite and Middle Marble divisions of the Horsethief Creek Group crop out in that region. They are overlain by the Upper elastic Division of the Horsethief Creek Group which grades upwards into Kaza Group lithologies. The Semipelite-Amphibolite Division is in excess of 500 m thick, with its base not exposed within the study area. The Middle Marble Division varies greatly in thickness, with a maximum thickness of 300 m. Approximately 3800 m of Kaza Group section were measured. The Kaza Group is overlain by slates of the Isaac Formation. Earlier workers correlated the Kaza Group with the basal division of the Horsethief Creek Group and with the Middle Miette Group. In light of the findings in the Thunder River area these correlations cannot all be correct. The Horsethief Creek Group underlies the grits of the Kaza Group. The Kaza Group is still considered correlative with the Middle Miette Group. Shales and carbonates overlie both the Middle Miette and Kaza groups. The strata in the Southeastern Cariboo Mountains were subjected to two major phases of folding during the Jura-Cretaceous Columbian Orogeny. The earliest phase resulted in west facing nappe structures. Fl folds are best developed at deep structural and stratigraphic levels. In the highest stratigraphic units studied there are no Fl folds or Sl schistosity developed. F2 folds are northwest plunging, upright to overturned and characterized by a crenulation cleavage. The F2 folds are conical but can only be recognized as such when mapped for large distances parallel to their trace. Metamorphism in the area ranges from sub-biotite to sillimanite grade. The metamorphic peak is synkinematic with D2. At the sillimanite isograd, sillimanite, kyanite and staurolite all coexist. Pressures and temperatures of 4.7 kb and 530 C were estimated for samples from the sillimanite isograd using garnet-biotite geothermometery and garnet-plagioclase geobarometry. The west-side-down North Thompson River Fault, separates the Cariboo Mountains from the Monashees to the east. Pressures and temperatures of 6.0kb and 655 C were estimated for samples from the sillimanite isograd in the Monashee Mountains. This pressure difference (in excess of 1kb) suggests that there is approximately 4 km of vertical displacement on the North Thompson River Fault