Chronic kidney disease, which is defined as having a reduced kidney function (estimated glomerular filtration rate (eGFR)) and/or signs of kidney damage (albuminuria), is highly prevalent in Western ...society and is associated with adverse health outcomes, such as cardiovascular disease. This warrants a search for risk factors of lower eGFR and higher albuminuria. Physical activity and sedentary behavior may be such risk factors.
To examine associations of physical activity (total, high, low), sedentary time and sedentary behavior patterns (breaks, prolonged bouts, average bout duration) with eGFR and albuminuria.
We examined these associations in 2,258 participants of the Maastricht Study (average age 60.1±8.1 years; 51.3% men), who wore an accelerometer 24h/day on 7 consecutive days. Associations with continuous eGFR and categories of urinary albumin excretion (UAE; <15 reference category, 15-<30, ≥30 mg/24h) were evaluated with linear regression analyses and multinomial logistic regression analyses, respectively.
After adjustment for potential confounders, each extra hour of total physical activity was associated with a more favorable kidney function (betaeGFR = 2.30 (95%CI = 1.46; 3.14)), whereas each extra hour of sedentary behavior was associated with a more adverse kidney function (betaeGFR = -0.71 (-1.08; -0.35)). Also, compared to individuals with the lowest levels of total physical activity, individuals with the highest levels had less kidney damage (OR15-<30mg/24h = 0.63 (0.41; 0.96), OR≥30mg/24h = 0.84 (0.53; 1.35). An extra hour of sedentary behavior was associated with more kidney damage (OR15-<30 mg/24h = 1.11 (1.01; 1.22), OR≥30 mg/24h = 1.10 (0.99; 1.22)). Further, a highly sedentary pattern was associated with a more adverse kidney function, but no association was seen with kidney damage.
Physical activity and sedentary behavior were associated with kidney function and kidney damage. Additionally, sedentary behavior patterns were associated with kidney function. Causal studies are required to examine whether this indeed implicates that prevention strategies should focus not only on increasing physical activity, but on reducing sedentary behavior as well.
Single-cell technologies have revealed the complexity of the tumour immune microenvironment with unparalleled resolution
. Most clinical strategies rely on histopathological stratification of tumour ...subtypes, yet the spatial context of single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize the tumour and immunological landscape of samples from 416 patients with lung adenocarcinoma across five histological patterns. We resolve more than 1.6 million cells, enabling spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. Using deep learning, we can predict with high accuracy those patients who will progress after surgery using a single 1-mm
tumour core, which could be informative for clinical management following surgical resection. Our dataset represents a valuable resource for the non-small cell lung cancer research community and exemplifies the utility of spatial resolution within single-cell analyses. This study also highlights how artificial intelligence can improve our understanding of microenvironmental features that underlie cancer progression and may influence future clinical practice.
Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. ...Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment
, yet many single-cell studies lack spatial context and rely on dissociated tissues
. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.
Summary Background Existing approaches for the screening and treatment of asymptomatic bacteriuria in pregnancy are based on trials that were done more than 30 years ago. In this study, we reassessed ...the consequences of treated and untreated asymptomatic bacteriuria in pregnancy. Methods In this multicentre prospective cohort study with an embedded randomised controlled trial, we screened women (aged ≥18 years) at eight hospitals and five ultrasound centres in the Netherlands with a singleton pregnancy between 16 and 22 weeks' gestation for asymptomatic bacteriuria. Screening was done with a single dipslide and two culture media. Dipslides were judged positive when the colony concentration was at least 1×105 colony-forming units (CFU) per mL of a single microorganism or when two different colony types were present but one had a concentration of at least 1×105 CFU per mL. Asymptomatic bacteriuria-positive women were eligible to participate in the randomised controlled trial comparing nitrofurantoin with placebo treatment. In this trial, participants were randomly assigned 1:1 to receive either nitrofurantoin 100 mg or identical placebo tablets, and were instructed to self-administer these tablets twice daily for 5 consecutive days. Randomisation was done by a web-based application with a computer-generated list with random block sizes of two, four, or six participants rendered by an independent data manager. 1 week after the end of treatment, they provided us with a follow-up dipslide. Women, treating physicians, and researchers all remained unaware of the bacteriuria status and treatment allocation. Women who refused to participate in the randomised controlled trial did not receive any antibiotics, but their outcomes were collected for analysis in the cohort study. We compared untreated and placebo-treated asymptomatic bacteriuria-positive women with asymptomatic bacteriuria-negative women and nitrofurantoin-treated asymptomatic bacteriuria-positive women. The primary endpoint was a composite of pyelonephritis with or without preterm birth at less than 34 weeks, analysed by intention to treat at 6 weeks post-partum. This trial is registered with the Dutch Trial Registry, number NTR3068. Findings Between Oct 11, 2011, and June 10, 2013, we enrolled 5621 women into our screening cohort, of whom 5132 were eligible for screening. After exclusions for contaminated dipslides and patients lost to follow-up, in our final cohort of 4283 women, 248 were asymptomatic bacteriuria positive, of whom 40 were randomly assigned to nitrofurantoin and 45 to placebo for the randomised controlled trial, whereas the other 163 asymptomatic bacteriuria-positive women were followed without treatment. The proportion of women with pyelonephritis, preterm birth, or both did not differ between untreated or placebo-treated asymptomatic bacteriuria-positive women and asymptomatic bacteriuria-negative women (6 2·9% of 208 vs 77 1·9% of 4035; adjusted odds ratio OR 1·5, 95% CI 0·6–3·5) nor between asymptomatic bacteriuria-positive women treated with nitrofurantoin versus those who were untreated or received placebo (1 2·5% of 40 vs 6 2·9% of 208; risk difference −0·4, 95% CI −3·6 to 9·4). Untreated or placebo-treated asymptomatic bacteriuria-positive women developed pyelonephritis in five 2·4% of 208 cases, compared with 24 0·6% of 4035 asymptomatic bacteriuria-negative women (adjusted OR 3·9, 95% CI 1·4–11·4). Interpretation In women with an uncomplicated singleton pregnancy, asymptomatic bacteriuria is not associated with preterm birth. Asymptomatic bacteriuria showed a significant association with pyelonephritis, but the absolute risk of pyelonephritis in untreated asymptomatic bacteriuria is low. These findings question a routine screen-treat-policy for asymptomatic bacteriuria in pregnancy. Funding ZonMw (the Netherlands Organisation for Health Research and Development).
•Most recent applications of nanofluids (NFs), from nanomedicine to renewable energies.•There are a large number of parameters that affect the thermal performance of NFs.•The superior k of NFs is the ...main attraction for the majority of the applications.•Identification of several challenges and potential solutions to accelerate the NFs translation.•Direct visualization devices are promising systems to solve thermal limitations of NFs.
The nanofluids (NFs) are known as a colloidal suspension where nanoparticles (NPs) are dispersed in conventional base fluids (BFs). This suspension has been frequently used to augment the heat transfer (HT) capacity of a fluid by studying their thermophysical properties. This review outlines the most recent advances on the NFs thermal properties and on their applications that are being used in different fields of engineering, ranging from nanomedicine to renewable energies. In the latter, several relevant advances have been achieved in mobility and propulsion with relevant application in defense and military technologies. Hence, specific applications of NFs in electronics cooling, heat exchangers, heat pipes, solar energy, nanomedicine, space technology, among others, have been reviewed and presented. Overall, the research performed in this subject has shown that several parameters can impact the thermal properties of the NFs including the BF, NPs size, concentration, shape and NPs fabrication procedures. In this review, the most relevant parameters are identified and debated, to provide guidance and inspire researchers to develop low cost NFs with high thermal properties. In addition, the models for predicting the specific heat, viscosity, thermal conductivity and density of NFs are listed and evaluated in a comprehensive way. Based on the results that the literature presents, there are still many models to be validated and explored. Finally, the challenges and several unresolved issues related to NFs flows are discussed and possible solutions are suggested to solve them.
Type 2 diabetes mellitus (T2DM) is a common chronic disease that disproportionally affects disadvantaged groups. People with a low socioeconomic position (SEP) have increased risk of T2DM and people ...with a low SEP and T2DM have higher HbA
-levels compared to people with T2DM and high SEP. The aim of this study is to analyze longitudinal socioeconomic differences in health-related functioning in people with T2DM.
Longitudinal data from 1,537 participants of The Maastricht Study with T2DM were used (32.6% female, mean (SD) age 62.9 (7.7) years). SEP was determined by baseline measures of education, occupation and income. Health-related functioning (physical, mental and social) was measured with the Short-Form Health Survey and the Impact on Participation and Autonomy survey (all scored from 0 to 100). Associations of SEP and health-related functioning were studied annually over a 10-year period (median (IQR) 7.0 (5.0) years, baseline 2010-2018) using linear mixed methods adjusting for demographics, HbA
-levels and lifestyle factors.
Participants with a low SEP had significantly worse health-related functioning compared to those with a high SEP. For example, participants with low income had lower scores for physical (-4.49CI -5.77;-3.21), mental (-2.61-3.78,-1.44) and social functioning (-9.76-12.30;-7.23) compared to participants with high income on a scale from 0 to 100. In addition, participants with a low education significantly declined more over time in mental (score for interaction education with time - 0.23-0.37;-0.09) and social functioning (-0.44-0.77;-0.11) compared to participants with high education. Participants with low and intermediate incomes significantly declined more over time in physical functioning (-0.17 -0.34, -0.01 and - 0.18 -0.36, 0.00) compared to participants with high income.
Among people with T2DM, those with a lower SEP had worse health-related functioning in general than people with a higher SEP. Additionally, people with T2DM and low education developed poorer mental and social functioning over time compared to people with T2DM and high education. People with T2DM and low or intermediate income declined more in physical functioning over time than those with high incomes. In addition to HbA
-levels and lifestyle patterns, more attention is needed for socioeconomic differences in health-related functioning for people living with T2DM.
INTRODUCTION
The retina may provide non‐invasive, scalable biomarkers for monitoring cerebral neurodegeneration.
METHODS
We used cross‐sectional data from The Maastricht study (n = 3436; mean age ...59.3 years; 48% men; and 21% with type 2 diabetes the latter oversampled by design). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency).
RESULTS
After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node degree, lower global efficiency, higher clustering coefficient, and higher local efficiency.
DISCUSSION
The retina may provide biomarkers that are informative of cerebral neurodegenerative changes in the pathobiology of dementia.
Context.
Extended and delayed emission around distant TeV sources induced by the effects of propagation of
γ
ray s through the intergalactic medium can be used for the measurement of the ...intergalactic magnetic field (IGMF).
Aims.
We search for delayed GeV emission from the hard-spectrum TeV
γ
-ray emitting blazar 1ES 0229+200, with the goal of detecting or constraining the IGMF-dependent secondary flux generated during the propagation of TeV
γ
rays through the intergalactic medium.
Methods.
We analysed the most recent MAGIC observations over a 5 year time span, and complemented them with historic data of the H.E.S.S. and VERITAS telescopes, along with a 12-year-long exposure of the
Fermi
/LAT telescope. We used them to trace source evolution in the GeV–TeV band over a decade and a half. We used Monte Carlo simulations to predict the delayed secondary
γ
-ray flux, modulated by the source variability, as revealed by TeV-band observations. We then compared these predictions for various assumed IGMF strengths to all available measurements of the
γ
-ray flux evolution.
Results.
We find that the source flux in the energy range above 200 GeV experiences variations around its average on the 14-year time span of observations. No evidence for the flux variability is found in the 1 − 100 GeV energy range accessible to
Fermi
/LAT. The non-detection of variability due to delayed emission from electromagnetic cascade developing in the intergalactic medium imposes a lower bound of
B
> 1.8 × 10
−17
G for the long-correlation-length IGMF and
B
> 10
−14
G for an IGMF of cosmological origin. Though weaker than the one previously derived from the analysis of
Fermi
/LAT data, this bound is more robust, being based on a conservative intrinsic source spectrum estimate and accounting for the details of source variability in the TeV energy band. We discuss implications of this bound for cosmological magnetic fields that might explain the baryon asymmetry of the Universe.
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