Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study

BACKGROUND Up to 8% of the general population have a rare disease, however, for lack of ICD-10 codes for many rare diseases, this population cannot be generically identified in large medical datasets. We aimed to explore frequency-based rare diagnoses (FB-RDx) as a novel method exploring rare diseases by comparing characteristics and outcomes of inpatient populations with FB-RDx to those with rare diseases based on a previously published reference list. METHODS Retrospective, cross-sectional, nationwide, multicenter study including 830,114 adult inpatients. We used the national inpatient cohort dataset of the year 2018 provided by the Swiss Federal Statistical Office, which routinely collects data from all inpatients treated in any Swiss hospital. Exposure: FB-RDx, according to 10% of inpatients with the least frequent diagnoses (i.e.1.decile) vs. those with more frequent diagnoses (deciles 2-10). Results were compared to patients having 1 of 628 ICD-10 coded rare diseases. PRIMARY OUTCOME In-hospital death. SECONDARY OUTCOMES 30-day readmission, admission to intensive care unit (ICU), length of stay, and ICU length of stay. Multivariable regression analyzed associations of FB-RDx and rare diseases with these outcomes. RESULTS 464,968 (56%) of patients were female, median age was 59 years (IQR: 40-74). Compared with patients in deciles 2-10, patients in the 1. were at increased risk of in-hospital death (OR 1.44; 95% CI: 1.38, 1.50), 30-day readmission (OR 1.29; 95% CI 1.25, 1.34), ICU admission (OR 1.50; 95% CI 1.46, 1.54), increased length of stay (Exp(B) 1.03; 95% CI 1.03, 1.04) and ICU length of stay (1.15; 95% CI 1.12, 1.18). ICD-10 based rare diseases groups showed similar results: in-hospital death (OR 1.82; 95% CI 1.75, 1.89), 30-day readmission (OR 1.37; 95% CI 1.32, 1.42), ICU admission (OR 1.40; 95% CI 1.36, 1.44) and increased length of stay (OR 1.07; 95% CI 1.07, 1.08) and ICU length of stay (OR 1.19; 95% CI 1.16, 1.22). CONCLUSION(S) This study suggests that FB-RDx may not only act as a surrogate for rare diseases but may also help to identify patients with rare disease more comprehensively. FB-RDx associate with in-hospital death, 30-day readmission, intensive care unit admission, and increased length of stay and intensive care unit length of stay, as has been reported for rare diseases

Strong detection of the CMB lensingxgalaxy weak lensingcross-correlation from ACT-DR4,PlanckLegacy and KiDS-1000

We measure the cross-correlation between galaxy weak lensing data from the Kilo Degree Survey (KiDS-1000, DR4) and cosmic microwave background (CMB) lensing data from the Atacama Cosmology Telescope (ACT, DR4) and the Planck Legacy survey. We use two samples of source galaxies, selected with photometric redshifts, $(0.1<z_{\rm B}<1.2)$ and $(1.2<z_{\rm B}<2)$, which produce a combined detection significance of the CMB lensing/weak galaxy lensing cross-spectrum of $7.7\sigma$. With the lower redshift galaxy sample, for which the cross-correlation is detected at a significance of $5.3\sigma$, we present joint cosmological constraints on the matter density parameter, $\Omega_{\rm m}$, and the matter fluctuation amplitude parameter, $\sigma_8$, marginalising over three nuisance parameters that model our uncertainty in the redshift and shear calibration, and the intrinsic alignment of galaxies. We find our measurement to be consistent with the best-fitting flat $\Lambda$CDM cosmological models from both Planck and KiDS-1000. We demonstrate the capacity of CMB-weak lensing cross-correlations to set constraints on either the redshift or shear calibration, by analysing a previously unused high-redshift KiDS galaxy sample $(1.2<z_{\rm B}<2)$, with the cross-correlation detected at a significance of $7\sigma$. This analysis provides an independent assessment for the accuracy of redshift measurements in a regime that is challenging to calibrate directly owing to known incompleteness in spectroscopic surveys.Comment: 13 pages, 9 figures, 1 tables, submitted to A&

Consistent lensing and clustering in a low-S8 Universe with BOSS, DES Year 3, HSC Year 1, and KiDS-1000

We evaluate the consistency between lensing and clustering based on measurements from Baryon Oscillation Spectroscopic Survey combined with galaxy-galaxy lensing from Dark Energy Survey (DES) Year 3, Hyper Suprime-Cam Subaru Strategic Program (HSC) Year 1, and Kilo-Degree Survey (KiDS)-1000. We find good agreement between these lensing data sets. We model the observations using the DARK EMULATOR and fit the data at two fixed cosmologies: Planck (S8 = 0.83), and a Lensing cosmology (S8 = 0.76). For a joint analysis limited to large scales, we find that both cosmologies provide an acceptable fit to the data. Full utilization of the higher signal-to-noise small-scale measurements is hindered by uncertainty in the impact of baryon feedback and assembly bias, which we account for with a reasoned theoretical error budget. We incorporate a systematic inconsistency parameter for each redshift bin, A, that decouples the lensing and clustering. With a wide range of scales, we find different results for the consistency between the two cosmologies. Limiting the analysis to the bins for which the impact of the lens sample selection is expected to be minimal, for the Lensing cosmology, the measurements are consistent with A = 1; A = 0.91 ± 0.04 (A = 0.97 ± 0.06) using DES+KiDS (HSC). For the Planck case, we find a discrepancy: A = 0.79 ± 0.03 (A = 0.84 ± 0.05) using DES+KiDS (HSC). We demonstrate that a kinematic Sunyaev-Zeldovich-based estimate for baryonic effects alleviates some of the discrepancy in the Planck cosmology. This analysis demonstrates the statistical power of small-scale measurements; however, caution is still warranted given modelling uncertainties and foreground sample selection effects

DES Y3 + KiDS-1000: Consistent cosmology combining cosmic shear surveys

We present a joint cosmic shear analysis of the Dark Energy Survey (DES Y3) and the Kilo-Degree Survey (KiDS-1000) in a collaborative effort between the two survey teams. We find consistent cosmological parameter constraints between DES Y3 and KiDS-1000 which, when combined in a joint-survey analysis, constrain the parameter $S_8 = \sigma_8 \sqrt{\Omega_{\rm m}/0.3}$ with a mean value of $0.790^{+0.018}_{-0.014}$. The mean marginal is lower than the maximum a posteriori estimate, $S_8=0.801$, owing to skewness in the marginal distribution and projection effects in the multi-dimensional parameter space. Our results are consistent with $S_8$ constraints from observations of the cosmic microwave background by Planck, with agreement at the $1.7\sigma$ level. We use a Hybrid analysis pipeline, defined from a mock survey study quantifying the impact of the different analysis choices originally adopted by each survey team. We review intrinsic alignment models, baryon feedback mitigation strategies, priors, samplers and models of the non-linear matter power spectrum.Comment: 38 pages, 21 figures, 15 tables, submitted to the Open Journal of Astrophysics. Watch the core team discuss this analysis at https://cosmologytalks.com/2023/05/26/des-kid

Locally reinforced polymer-based composites for elastic electronics

A promising approach to fabricating elastic electronic systems involves processing thin film circuits directly on the elastic substrate by standard photolithography. Thin film devices are generally placed onto stiffer islands on the substrate surface to protect devices from excessive strain while still achieving a globally highly deformable system. Here we report a new method to achieve island architectures by locally reinforcing polymeric substrates at the macro- and microscale using magnetically responsive anisotropic microparticles. We demonstrate that the resulting particle-reinforced elastic substrates can be made smooth enough for the patterning and successful operation of thin film transistors with transfer characteristics comparable to state-of-the-art device

19F NMR-based fragment screening for 14 different biologically active RNAs and 10 DNA and protein counter-screens

We report here the nuclear magnetic resonance 19F screening of 14 RNA targets with different secondary and tertiary structure to systematically assess the druggability of RNAs. Our RNA targets include representative bacterial riboswitches that naturally bind with nanomolar affinity and high specificity to cellular metabolites of low molecular weight. Based on counter-screens against five DNAs and five proteins, we can show that RNA can be specifically targeted. To demonstrate the quality of the initial fragment library that has been designed for easy follow-up chemistry, we further show how to increase binding affinity from an initial fragment hit by chemistry that links the identified fragment to the intercalator acridine. Thus, we achieve low-micromolar binding affinity without losing binding specificity between two different terminator structures