163 research outputs found

    The spurious correlation between concentration and creatinine-corrected concentration in urine

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    The use of urinary analytes to monitor physiological processes relies on making the correct measurement. Three alternatives are commonly contemplated: concentration, creatinine-corrected concentration and excretion rate. Of these, the latter is the most reliable, but is perceived by some to be difficult to measure. This has led to the more frequent reliance on concentration and one of the justifications for this is the reported linear relationship between the concentration and the creatinine-corrected concentration. We show that this correlation is spurious in that the magnitude of the correlation coefficient depends on the ratio of the standard deviations of the creatinine and analyte concentrations. As an example urinary analyte we use pregnanediol (Pd) which is an important tool for women wishing to monitor their own fertility. Urinary Pd concentration is not a reliable substitute for creatinine-corrected Pd concentration or the Pd excretion rate

    Micro-CT yields high image quality in human fetal post-mortem imaging despite maceration

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    Background Current clinical post-mortem imaging techniques do not provide sufficiently high-resolution imaging for smaller fetuses after pregnancy loss. Post-mortem micro-CT is a non-invasive technique that can deliver high diagnostic accuracy for these smaller fetuses. The purpose of the study is to identify the main predictors of image quality for human fetal post-mortem micro-CT imaging. Methods Human fetuses were imaged using micro-CT following potassium tri-iodide tissue preparation, and axial head and chest views were assessed for image quality on a Likert scale by two blinded radiologists. Simple and multivariable linear regression models were performed with demographic details, iodination, tissue maceration score and imaging parameters as predictor variables. Results 258 fetuses were assessed, with median weight 41.7 g (2.6–350 g) and mean gestational age 16 weeks (11–24 weeks). A high image quality score (> 6.5) was achieved in 95% of micro-CT studies, higher for the head (median = 9) than chest (median = 8.5) imaging. The strongest negative predictors of image quality were increasing maceration and body weight (p < 0.001), with number of projections being the best positive imaging predictor. Conclusions High micro-CT image quality score is achievable following early pregnancy loss despite fetal maceration, particularly in smaller fetuses where conventional autopsy may be particularly challenging. These findings will help establish clinical micro-CT imaging services, addressing the need for less invasive fetal autopsy methods

    Fuel poverty in the cost of living crisis

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    Access to energy is being severely restricted by the cost of living crisis, with almost a quarter of households experiencing fuel poverty, despite existing interventions. Here we draw on a large body of evidence on fuel poverty to summarise likely effects on households this winter. We find there is urgent need for further bill support, energy efficiency and targeted advice for vulnerable households

    Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

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    Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < −2.5 standard deviation). Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherap

    Eating, heating or taking the bus? Lived experiences at the intersection of energy and transport poverty

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    Experiences of poverty can manifest in multiple aspects of everyday life, often in interlinking ways. One example is ‘double energy vulnerability’, where a household faces both energy poverty and transport poverty simultaneously. This can result in trade-offs, where prioritising one essential need (e.g., transport) makes accessing another impossible (e.g., heating). Such decisions are not easily made, and they can have distinct spatio-temporal characteristics. They can vary between space and time and across different household members, and result in stark inter- as well as intra-household differences. People with socio-demographic and contextual vulnerabilities are particularly at risk of experiencing double energy vulnerability. Based on 59 household interviews across the four nations of the United Kingdom, we provide novel, multi-nation empirical evidence on the lived experiences of double energy vulnerability, drawing on our themes; ‘being locked into infrastructure’, ‘facing high costs and low incomes’, ‘choosing between energy and transport’, and ‘missing out’. A cross-national lived-experiences approach sheds light on double energy vulnerability as a relational, contingent and ongoing phenomena, attending to everyday experiences and capacities. We provide suggestions for further research, such as further study of double energy vulnerability amongst refugees and migrants. We also highlight that the study of lived experiences can aid the recognition of how different forms of poverty intersect and how they need to be taken into account in the design of Net Zero policies

    Membrane binding of antimicrobial peptides is modulated by lipid charge modification

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    Peptide interactions with lipid bilayers play a key role in a range of biological processes and depend on electrostatic interactions between charged amino acids and lipid headgroups. Antimicrobial peptides (AMPs) initiate the killing of bacteria by binding to and destabilizing their membranes. The multiple peptide resistance factor (MprF) provides a defense mechanism for bacteria against a broad range of AMPs. MprF reduces the negative charge of bacterial membranes through enzymatic conversion of the anionic lipid phosphatidyl glycerol (PG) to either zwitterionic alanyl-phosphatidyl glycerol (Ala-PG) or cationic lysyl-phosphatidyl glycerol (Lys-PG). The resulting change in the membrane charge is suggested to reduce the binding of AMPs to membranes, thus impeding downstream AMP activity. Using coarse-grained molecular dynamics to investigate the effects of these modified lipids on AMP binding to model membranes, we show that AMPs have substantially reduced affinity for model membranes containing Ala-PG or Lys-PG. More than 5000 simulations in total are used to define the relationship between lipid bilayer composition, peptide sequence (using five different membrane-active peptides), and peptide binding to membranes. The degree of interaction of a peptide with a membrane correlates with the membrane surface charge density. Free energy profile (potential of mean force) calculations reveal that the lipid modifications due to MprF alter the energy barrier to peptide helix penetration of the bilayer. These results will offer a guide to the design of novel peptides, which addresses the issue of resistance via MprF-mediated membrane modification

    Community resilience to climate change: an evidence review

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    How is the resilience of communities to climate change in the UK currently understood and practised? The concept of community resilience to climate change in the UK has a diverse range of meanings and associated activities. This review of evidence and practice explores this varied and contested field to build the evidence base and help support the development of community resilience to climate change
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