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Prevalence of chronic kidney disease in the community in the United Kingdom in OxRen, a population-based cohort study
Background:
Chronic kidney disease (CKD) is a largely asymptomatic condition of diminished renal function, which may not be detected until advanced stages without screening.
Aim:
To establish undiagnosed and overall CKD prevalence using a cross-sectional analysis.
Design and Setting:
Longitudinal cohort study in UK primary care.
Method:
Participants aged ≥60 years were invited to attend CKD screening visits to determine whether they had reduced renal function (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 or albumin:creatinine ratio ≥3 mg/mmol). Those with existing CKD, low eGFR, evidence of albuminuria, or two positive screening tests attended a baseline assessment (CKD cohort).
Results:
A total of 3207 participants were recruited and 861 attended the baseline assessment. The CKD cohort consisted of 327 people with existing CKD, 257 people with CKD diagnosed through screening (CKD prevalence of 18.2%, 95% confidence interval [CI] = 16.9 to 19.6), and 277 with borderline/transient decreased renal function. In the CKD cohort, 54.4% were female, mean standard deviation (SD) age was 74.0 (SD 6.9) years, and mean eGFR was 58.0 (SD 18.4) ml/min/1.73 m2. Of the 584 with confirmed CKD, 44.0% were diagnosed through screening. Over half of the CKD cohort (51.9%, 447/861) fell into CKD stages 3–5 at their baseline assessment, giving an overall prevalence of CKD stages 3–5 of 13.9% (95% CI = 12.8 to 15.1). More people had reduced eGFR using the Modification of Diet in Renal Disease (MDRD) equation than with CKD Epidemiology Collaboration (CKD-EPI) equation in the 60–75-year age group and more had reduced eGFR using CKD-EPI in the ≥80-year age group.
Conclusion:
This study found that around 44.0% of people living with CKD are undiagnosed without screening, and prevalence of CKD stages 1–5 was 18.2% in participants aged >60 years. Follow-up will provide data on annual incidence, rate of CKD progression, determinants of rapid progression, and predictors of cardiovascular events
Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis
Background
Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection.
Methods
A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and
Results
Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p
Conclusions
The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women
Wandering in other worlds, talking with the spirits: choreographing a performative anthropology
Data for "Validity of Winkler's mattress model for thin elastomeric layers: Beyond Poisson's ratio"
Data created using MATLAB
Roadmap on emerging hardware and technology for machine learning
Recent progress in artificial intelligence is largely attributed to the rapid development of machine learning, especially in the algorithm and neural network models. However, it is the performance of the hardware, in particular the energy efficiency of a computing system that sets the fundamental limit of the capability of machine learning. Data-centric computing requires a revolution in hardware systems, since traditional digital computers based on transistors and the von Neumann architecture were not purposely designed for neuromorphic computing. A hardware platform based on emerging devices and new architecture is the hope for future computing with dramatically improved throughput and energy efficiency. Building such a system, nevertheless, faces a number of challenges, ranging from materials selection, device optimization, circuit fabrication, and system integration, to name a few. The aim of this Roadmap is to present a snapshot of emerging hardware technologies that are potentially beneficial for machine learning, providing the Nanotechnology readers with a perspective of challenges and opportunities in this burgeoning field
Numerical study of Bose–Einstein condensation in the Kaniadakis–Quarati model for bosons
Kaniadakis and Quarati (1994) proposed a Fokker–Planck equation with quadratic drift as a PDE model for the dynamics of bosons in the spatially homogeneous setting. It is an open question whether this equation has solutions exhibiting condensates in finite time. The main analytical challenge lies in the continuation of exploding solutions beyond their first blow-up time while having a linear diffusion term. We present a thoroughly validated time-implicit numerical scheme capable of simulating solutions for arbitrarily long time, and thus enabling a numerical study of the condensation process in the Kaniadakis–Quarati model. We show strong numerical evidence that above the critical mass rotationally symmetric solutions of the Kaniadakis–Quarati model in
3D form a condensate in finite time and converge in entropy to the unique minimiser of the natural entropy functional. Our simulations further indicate that the spatial blow-up profile near the origin follows a universal power law and that transient condensates can occur for sufficiently concentrated initial data
Printing R-Evolution and Society 1450-1500: Fifty Years that Changed Europe
The volume contains a reassessment of the economic and social impact of the printing revolution on the development of early modern European society, using 15th-century printed books, which still survive today in their thousands, as historical sources. Papers on production, trade, the cost of books in comparison with the cost of living, literacy, the transmission of texts in print, and the use and circulation of books and illustration are the result of several years of international, collaborative, and multidisciplinary research coordinated by the 15cBOOKTRADE project funded by an ERC Consolidator grant (2014-2019) and supported by the Consortium of European Research Libraries
Development of a rapid test kit for SARS-CoV-2: an example of product design
We present an example of applying ‘need-driven’ product design principle to the development of a rapid test kit to detect SARS-COV-2 (COVID-19). The tests are intended for use in the field and, longer term, for home use. They detect whether a subject is currently infected with the virus and is infectious. The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment, laboratories and skilled technicians to perform the test and interpret results. To meet these needs, an antigen test based on RT-LAMP with colorimetric readout was chosen. Direct use of swab sample with no RNA extraction was explored. After extensive experimental study (reported elsewhere), a rapid test kit has been fabricated to satisfy all design criteria
Whose turn is it anyway? Latency and the organization of turn-taking in video-mediated interaction
Latency in video-mediated interaction can frustrate smooth turn-taking: it may cause participants to perceive silence at points where talk should occur, it may cause them to talk in overlap, and it impedes their ability to return to one-speaker-at-a-time. Whilst potentially frustrating for participants, this makes video-mediated interaction a perspicuous setting for the study of social interaction: it is an environment that nurtures the occurrence of turn-taking problems. For this paper, we conducted secondary analysis of 25 video consultations recorded for heart failure, (antenatal) diabetes, and cancer services in the UK. By comparing video recordings of the patient's and clinician's side of the call, we provide a detailed analysis of how latency interferes with the turn-taking system, how participants understand problems, and how they address them. We conclude that in our data latency unnoticed until it becomes problematic: participants act as if they share the same reality
89Zr-PET imaging of DNA double-strand breaks for the early monitoring of response following α- and β-particle radioimmunotherapy in a mouse model of pancreatic ductal adenocarcinoma
Rationale: The evaluation of early treatment response is critical for patient prognosis and treatment planning. When the current methods rely on invasive protocols that evaluate the expression of DNA damage markers on patient biopsy samples, we aim to evaluate a non-invasive PET imaging approach to monitor the early expression of the phosphorylated histone γH2AX in the context of pancreatic cancer targeted radionuclide therapy. Pancreatic ductal adenocarcinoma has a poor patient prognosis due to the absence of curative treatment for patients with advanced disease. There is therefore a critical need for the fast clinical translation of new therapeutic options. In line with these observations, our group has been focusing on the development of radiotheranostic agents based on a fully human monoclonal antibody (5B1) with exceptional affinity for CA19.9, an antigen overexpressed in PDAC. Two on-going clinical trials resulted from these efforts, one with 89Zr (diagnosis) and one with 177Lu (β-particle therapy). More recently, we successfully developed and evaluated in PDAC mouse models a targeted α-therapy strategy with high clinical translation potential. We aim to expedite the clinical translation of the developed radioimmunotherapy approaches by investigating the early therapeutic response and effect of radiation therapy in a PDAC mouse model via PET imaging.
Methods: Mice bearing BxPC3 tumor xenografts were treated with α- and β-particle pretargeted radioimmunotherapy (PRIT), external beam radiotherapy (EBRT), or sham-treated (vehicle). The phosphorylated histone γH2AX produced as a response to DNA double strand breaks was quantified with the PET radiotracer, [89Zr]Zr-DFO-anti-γH2AX-TAT.
Results: PET imaging studies in BxPC3 PDAC mouse models demonstrated increased uptake of [89Zr]Zr-DFO-anti-γH2AX-TAT (6.29 ± 0.15 %IA/g) following β-PRIT in BxPC3 PDAC xenografts as compared to the saline control group (4.58 ± 0.76 %IA/g) and EBRT control group (5.93 ± 0.76 %IA/g). Similarly, significantly higher uptake of [89Zr]Zr-DFO-anti-γH2AX-TAT was observed in tumors of the 225Ac-PRIT and EBRT (10 Gy) cohorts (7.37 ± 1.23 and 6.80 ± 1.24 %IA/g, respectively) compared to the negative control cohort (5.08 ± 0.95 %IA/g). Ex vivo γH2AX immunohistochemistry and immunofluorescence analysis correlated with in vivo 89Zr-anti-γH2AX PET/CT imaging with increased γH2AX positive cell and γH2AX foci per cell in the treated cohorts. When α-PRIT resulted in prolonged overall survival of treated animals (107.5 days) as compared to β-PRIT (73.0 days), no evidence of difference in [89Zr]Zr-DFO-anti-γH2AX-TAT uptake at the tumor site was observed, highlighting that DNA damage is not the sole radiobiology paradigm and that off-targeted (bystander) effects should be considered.
Conclusions: PET imaging studies with [89Zr]Zr-DFO-anti-γH2AX-TAT following α- and β-particle PRIT in a BxPC3 PDAC subcutaneous xenograft mouse model allowed the monitoring of tumor radiobiological response to treatment