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Biomarker concentrations in white and British Indian vegetarians and non-vegetarians in the UK Biobank
No full textBackground: Prospective studies have shown differences in some disease risks between vegetarians and non-vegetarians, but the potential biological pathways are not well understood.
Objective: We aimed to assess differences in concentrations of biomarkers related to disease pathways in people with varying degrees of animal foods exclusion.
Methods: The UK Biobank recruited 500,000 participants aged 40-69 years (54.4% women) throughout the United Kingdom in 2006-2010. Blood and urine were collected at recruitment and assayed for more than 30 biomarkers related to cardiovascular diseases, bone and joint health, cancer, diabetes, renal disease, and liver health. In cross-sectional analyses, we estimated adjusted geometric means of these biomarkers by six diet groups (regular meat eaters, low meat eaters, poultry eaters, fish eaters, vegetarians, vegans) in 466,058 white British participants, and two diet groups (meat eaters, vegetarians) in 5535 British Indian participants.
Results: We observed differences in the concentrations of most biomarkers, with many biomarkers showing a gradient effect from meat eaters to vegetarians/vegans. Of the largest differences, compared with white British regular meat eaters, white British vegans had lower C-reactive protein (adjusted geometric mean 1.13; 95% confidence interval 1.03, 1.25 versus 1.43; 1.42, 1.43 mg/L); lower low-density lipoprotein cholesterol (LDL-C, 3.13; 3.07, 3.20 versus 3.65; 3.65, 3.65 mmol/L); lower vitamin D (34.4; 33.1, 35.9 versus 44.5; 44.4, 44.5 nmol/L); lower serum urea (4.21; 4.11, 4.30 versus 5.36; 5.36, 5.37 mmol/L); lower urinary creatinine (5440; 5120, 5770 versus 7280; 7260, 7300 µmol/L); and lower gamma glutamyltransferase (23.5; 22.2, 24.8 versus 29.6; 29.6, 29.7 U/L). Patterns were mostly similar in British Indians, and results were consistent between women and men.
Conclusions: The observed differences in biomarker concentrations, including lower C-reactive protein, lower LDL-C, lower vitamin D, lower creatinine and lower gamma glutamyltransferase concentrations in vegetarians and vegans may relate to differences in future disease risk
Light rail
No full textLight rail describes a range of urban rail transit systems running largely on exclusive rights of way within city centers and between city centers and their suburbs. Light rail is different from, though shares similar characteristics with other transit modes such as buses and heavy rail. Following mid-20th century decline of streetcars, light rail emerged in the 1970s as a response to growing traffic congestion and efforts to draw people and investment back into city centers. Light rail is a leading sustainable transport mode renowned for its high service speed, frequency, safety, and reliability. Light rail is recognized for its potential to facilitate and enhance urban (re)development to boost economic growth and property values. Light rail can help to improve environmental quality and social equity though the latter is a largely neglected part of light rail research
3D chromatin architecture and epigenetic regulation in cancer stem cells
No full textDedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics. Cancer development and progression are demarcated by transcriptional dysregulation. In this article, we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation, with an emphasis on 3D chromatin architecture. Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics. We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics
A powerful subvector Anderson Rubin test in linear instrumental variables regression with conditional heteroskedasticity
No full textWe introduce a new test for a two-sided hypothesis involving a subset of the struc tural parameter vector in the linear instrumental variables (IVs) model. Guggenberger et al. (2019), GKM19 from now on, introduce a subvector Anderson-Rubin (AR) test with data-dependent critical values that has asymptotic size equal to nominal size for a parameter space that allows for arbitrary strength or weakness of the IVs and has uniformly nonsmaller power than the projected AR test studied in Guggenberger et al. (2012). However, GKM19 imposes the restrictive assumption of conditional ho moskedasticity. The main contribution here is to robustify the procedure in GKM19 to arbitrary forms of conditional heteroskedasticity. We first adapt the method in GKM19 to a setup where a certain covariance matrix has an approximate Kronecker product (AKP) structure which nests conditional homoskedasticity. The new test equals this adaption when the data is consistent with AKP structure as decided by a model se lection procedure. Otherwise the test equals the AR/AR test in Andrews (2017) that is fully robust to conditional heteroskedasticity but less powerful than the adapted method. We show theoretically that the new test has asymptotic size bounded by the nominal size and document improved power relative to the AR/AR test in a wide array of Monte Carlo simulations when the covariance matrix is not too far from AKP
Facile and fast transformation of nonluminescent to highly luminescent metal–organic frameworks: acetone sensing for diabetes diagnosis and lead capture from polluted water
No full textMetal–organic frameworks (MOFs) stand as one of the most promising materials for the development of advanced technologies owing to their unique combination of properties. The conventional synthesis of MOFs involves a direct reaction of the organic linkers and metal salts; however, their postsynthetic modification is a sophisticated route to produce new materials or to confer novel properties that cannot be attained through the traditional methods. This work describes the postsynthetic MOF-to-MOF transformation of a nonluminescent MOF (Zn-based Oxford University-1 material [Zn-BDC, where BDC = 1,4-benzene dicarboxylate] (OX-1)) into a highly luminescent framework (Ag-based Oxford University-2 material [Ag-BDC] (OX-2)) by a simple immersion of the former in a silver salt solution. The conversion mechanism exploits the uncoordinated oxygen atoms of terephthalate linkers found in OX-1, instead of the unsaturated metal sites commonly employed, making the reaction much faster. The materials derived from the OX-1 to OX-2 transformation are highly luminescent and exhibit a selective response to acetone, turning them into a promising candidate for manufacturing fluorometric sensors for the diagnosis and monitoring of diabetes mellitus. Our methodology can be extended to other metals such as lead (Pb). The fabrication of a polymer mixed-matrix membrane containing OX-1 is used as a proof-of-concept for capturing Pb ions (as pollutants) from water. This research instigates the exploration of alternative methodologies to confer MOFs with special aptitudes for photochemical sensing or for environmental applications such as water purification
Uniform Hölder-norm bounds for finite element approximations of second-order elliptic equations
No full textWe develop a discrete counterpart of the De Giorgi–Nash–Moser theory, which provides uniform Hölder-norm bounds on continuous piecewise affine finite element approximations of second-order linear elliptic problems of the form −∇⋅(A∇u)=f−∇⋅F with A∈L∞(Ω;Rn×n) a uniformly elliptic matrix-valued function, f∈Lq(Ω), F∈Lp(Ω;Rn), with p>n and q>n/2, on A-nonobtuse shape-regular triangulations, which are not required to be quasi-uniform, of a bounded polyhedral Lipschitz domain Ω⊂Rn
Matlab code for retrospective MRA undersampling optimization for Compressed Sensing reconstruction: Optimization of Undersampling Parameters for 3D Intracranial Compressed Sensing MR Angiography at 7 Tesla
No full textMatlab code for the retrospective undersampling section of "Optimization of Undersampling Parameters for 3D Intracranial Compressed Sensing MR Angiography at 7 Tesla", by Matthijs de Buck, Peter Jezzard, and Aaron Hess (Oxford, 2021).
Requires the BART toolbox (https://mrirecon.github.io/bart/) and the ESPIRiT-vdPoisMex tool by M. Lustig (https://people.eecs.berkeley.edu/~mlustig/Software.html) to run. Code was written in Matlab R2019a
Altered RNA splicing initiates the viral mimicry response from inverted SINEs following type I PRMT inhibition in triple-negative breast cancer
No full textChildren's experiences of welfare in modern Britain
No full textThe history of childhood and welfare in Britain through the eyes of children. Children’s Experiences of Welfare in Modern Britain brings together the latest research as provided by the state, charities and families from 1830 to 1980. Demonstrating how the young were integral to the making, interpretation, delivery and impact of welfare services, the chapters consider a wide range of investments in young people’s lives, including residential institutions, emigration schemes, hospitals and clinics, schools, social housing and familial care. Drawing upon thousands of personal testimonies, including a wealth of writing by children themselves, the book shows that we can only understand the history and impact of welfare if we listen to children’s experiences
Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial
No full textBackground
Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications.
Methods
In this UK-based, primary care, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomisation: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analysed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis. The trial is registered with ISRCTN, ISRCTN86534580.
Findings
The first participant was recruited to PRINCIPLE on April 2, 2020. The azithromycin group enrolled participants between May 22 and Nov 30, 2020, by which time 2265 participants had been randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI −0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI −1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azothromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19.
Interpretation
Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK