Tag: pubmed

J Appl Clin Med Phys. 2021 Sep 10. doi: 10.1002/acm2.13421. Online ahead of print.

ABSTRACT

The aim of the present study was to demonstrate cases of cost-benefit analysis within healthcare, of how economic factors can be considered in occupational radiological protection, in agreement with the as low as reasonably achievable principle and present Swedish legislations. In the first part of the present study, a comparison of examples within health economics used by authorities and institutes in Sweden was made. The comparison focused on value of a statistical life, quality-adjusted life year, and monetary cost assigned to a unit of collective dose for radiation protection purposes (α-value). By this comparison, an α-value was determined as an interval between $45 and $450 per man-mSv, for the Swedish society in 2021. The α-value interval can be interpreted as following: Less than $45 per man-mSv is a good investment. From $45 to $450 per man-mSv, other factors than costs and collective dose are important to consider. More than $450 per man-mSv is too expensive. In the second part of the present study, seven cases of cost-benefit analyses in occupational radiological protection were provided. The present study focused specifically on cases where the relevant factors were costs and collective dose. The present case study shows a large variation in costs per collective dose from different types of occupational radiological protection, used at Skaraborg Hospital in Sweden.

PMID:34505345 | DOI:10.1002/acm2.13421

Pharm Stat. 2021 Sep 9. doi: 10.1002/pst.2165. Online ahead of print.

ABSTRACT

In RCTs with an interest in a long-term efficacy endpoint, the follow-up time necessary to observe the endpoint may be substantial. In order to reduce the expected duration of such trials, early-outcome data may be collected to enrich an interim analysis aimed at stopping the trial early for efficacy. We propose to extend such a design with an additional interim analysis using solely early-outcome data in order to expedite the evaluation of treatment’s efficacy. We evaluate the potential gain in operating characteristics (power, expected trial duration, and expected sample size) when introducing such an early interim analysis, in function of the properties of the early outcome as a surrogate for the long-term endpoint. In the context of a longitudinal age-related macular degeneration (ARMD) ophthalmology trial, results show potentially substantial gains in both the expected trial duration and the expected sample size. A prerequisite, though, is that the treatment effect on the early outcome has to be strongly correlated with the treatment effect on the long-term endpoint, that is, that the early outcome is a validated surrogate for the long-term endpoint.

PMID:34505395 | DOI:10.1002/pst.2165

Echocardiography. 2021 Sep 9. doi: 10.1111/echo.15186. Online ahead of print.

ABSTRACT

AIMS: Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be “steep”, and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool.

METHODS AND RESULTS: We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration < 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e’ > 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all < 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p < 0.001).

CONCLUSION: These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep.

PMID:34505312 | DOI:10.1111/echo.15186

Sci Rep. 2021 Sep 9;11(1):17916. doi: 10.1038/s41598-021-96898-0.

ABSTRACT

Exposure of cells or biological tissues to high-power pulses of terahertz (THz) radiation leads to changes in a variety of intracellular processes. However, the role of heating effects due to strong absorption of THz radiation by water molecules still stays unclear. In this study, we performed numerical modelling in order to estimate the thermal impact on water of a single THz pulse as well as a series of THz pulses. A finite-element (FE) model that provides numerical solutions for the heat conduction equation is employed to compute the temperature increase. A simple expression for temperature estimation in the center of the spot of THz radiation is presented for given frequency and fluence of the THz pulse. It has been demonstrated that thermal effect is determined by either the average power of radiation or by the fluence of a single THz pulse depending on pulse repetition rate. Human dermal fibroblasts have been exposed to THz pulses (with an energy of [Formula: see text] and repetition rate of 100 Hz) to estimate the thermal effect. Analysis of heat shock proteins expression has demonstrated no statistically significant difference ([Formula: see text]) between control and experimental groups after 3 h of irradiation.

PMID:34504144 | DOI:10.1038/s41598-021-96898-0

Sci Rep. 2021 Sep 9;11(1):17945. doi: 10.1038/s41598-021-97114-9.

ABSTRACT

Quantile regression offers an invaluable tool to discern effects that would be missed by other conventional regression models, which are solely based on modeling conditional mean. Quantile regression for mixed-effects models has become practical for longitudinal data analysis due to the recent computational advances and the ready availability of efficient linear programming algorithms. Recently, quantile regression has also been extended to additive mixed-effects models, providing an efficient and flexible framework for nonparametric as well as parametric longitudinal forms of data analysis focused on features of the outcome beyond its central tendency. This study applies the additive quantile mixed model to analyze the longitudinal CD4 count of HIV-infected patients enrolled in a follow-up study at the Centre of the AIDS Programme of Research in South Africa. The objective of the study is to justify how the procedure developed can obtain robust nonlinear and linear effects at different conditional distribution locations. With respect to time and baseline BMI effect, the study shows a significant nonlinear effect on CD4 count across all fitted quantiles. Furthermore, across all fitted quantiles, the effect of the parametric covariates of baseline viral load, place of residence, and the number of sexual partners was found to be major significant factors on the progression of patients’ CD4 count who had been initiated on the Highly Active Antiretroviral Therapy study.

PMID:34504147 | DOI:10.1038/s41598-021-97114-9

Sci Data. 2021 Sep 9;8(1):237. doi: 10.1038/s41597-021-01018-2.

ABSTRACT

Regionalization of land use (LU) impact in life cycle assessment (LCA) has gained relevance in recent years. Most regionalized models are statistical, using highly aggregated spatial units and LU classes (e.g. one unique LU class for cropland). Process-based modelling is a powerful characterization tool but so far has never been applied globally for all LU classes. Here, we propose a new set of spatially detailed characterization factors (CFs) for soil organic carbon (SOC) depletion. We used SOC dynamic curves and attainable SOC stocks from a process-based model for more than 17,000 world regions and 81 LU classes. Those classes include 63 agricultural (depending on 4 types of management/production), and 16 forest sub-classes, and 1 grassland and 1 urban class. We matched the CFs to LU elementary flows used by LCA databases at country-level. Results show that CFs are highly dependent on the LU sub-class and management practices. For example, transformation into cropland in general leads to the highest SOC depletion but SOC gains are possible with specific crops.

PMID:34504111 | DOI:10.1038/s41597-021-01018-2

NPJ Parkinsons Dis. 2021 Sep 9;7(1):79. doi: 10.1038/s41531-021-00221-7.

ABSTRACT

Genome-wide association study (GWAS) has seen great strides in revealing initial insights into the genetic architecture of Parkinson’s disease (PD). Since GWAS signals often reside in non-coding regions, relatively few of the associations have implicated specific biological mechanisms. Here, we aimed to integrate the GWAS results with large-scale expression quantitative trait loci (eQTL) in 13 brain tissues to identify candidate causal genes for PD. We conducted a transcriptome-wide association study (TWAS) for PD using the summary statistics of over 480,000 individuals from the most recent PD GWAS. We identified 18 genes significantly associated with PD after Bonferroni corrections. The most significant gene, LRRC37A2, was associated with PD in all 13 brain tissues, such as in the hypothalamus (P = 6.12 × 10^-22) and nucleus accumbens basal ganglia (P = 5.62 × 10^-21). We also identified eight conditionally independent genes, including four new genes at known PD loci: CD38, LRRC37A2, RNF40, and ZSWIM7. Through conditional analyses, we demonstrated that several of the GWAS significant signals on PD could be driven by genetically regulated gene expression. The most significant TWAS gene LRRC37A2 accounts for 0.855 of the GWAS signal at its loci, and ZSWIM7 accounts for all the GWAS signals at its loci. We further identified several phenotypes previously associated with PD by querying the single nucleotide polymorphisms (SNPs) in the final model of the identified genes in phenome databases. In conclusion, we prioritized genes that are likely to affect PD by using a TWAS approach and identified phenotypes associated with PD.

PMID:34504106 | DOI:10.1038/s41531-021-00221-7

Transl Psychiatry. 2021 Sep 9;11(1):471. doi: 10.1038/s41398-021-01580-8.

ABSTRACT

An improved understanding of sterol and lipid abnormalities in individuals with autism spectrum disorder (ASD) could lead to personalized treatment approaches. Toward this end, in blood, we identified reduced synthesis of cholesterol in families with ≥2 children with ASD participating with the Autism Genetic Resource Exchange (AGRE), as well as reduced amounts of high-density lipoprotein cholesterol (HDL), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB), with 19.9% of the subjects presenting with apolipoprotein patterns similar to hypolipidemic clinical syndromes and 30% with either or both ApoA1 and ApoB less than the fifth centile. Subjects with levels less than the fifth centile of HDL or ApoA1 or ApoA1 + ApoB had lower adaptive functioning than other individuals with ASD, and hypocholesterolemic subjects had apolipoprotein deficits significantly divergent from either typically developing individuals participating in National Institutes of Health or the National Health and Nutrition Examination Survey III.

PMID:34504056 | DOI:10.1038/s41398-021-01580-8

Nat Commun. 2021 Sep 9;12(1):5347. doi: 10.1038/s41467-021-25707-z.

ABSTRACT

The experimental discovery of the fractional Hall conductivity in two-dimensional electron gases revealed new types of quantum particles, called anyons, which are beyond bosons and fermions as they possess fractionalized exchange statistics. These anyons are usually studied deep inside an insulating topological phase. It is natural to ask whether such fractionalization can be detected more broadly, say near a phase transition from a conventional to a topological phase. To answer this question, we study a strongly correlated quantum phase transition between a topological state, called a [Formula: see text] quantum spin liquid, and a conventional superfluid using large-scale quantum Monte Carlo simulations. Our results show that the universal conductivity at the quantum critical point becomes a simple fraction of its value at the conventional insulator-to-superfluid transition. Moreover, a dynamically self-dual optical conductivity emerges at low temperatures above the transition point, indicating the presence of the elusive vison particles. Our study opens the door for the experimental detection of anyons in a broader regime, and has ramifications in the study of quantum materials, programmable quantum simulators, and ultra-cold atomic gases. In the latter case, we discuss the feasibility of measurements in optical lattices using current techniques.

PMID:34504099 | DOI:10.1038/s41467-021-25707-z

Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2020562118. doi: 10.1073/pnas.2020562118.

ABSTRACT

Intrinsically disordered proteins (IDPs) interact with globular proteins through a variety of mechanisms, resulting in the structurally heterogeneous ensembles known as fuzzy complexes. While there exists a reasonable comprehension on how IDP sequence determines the unbound IDP ensemble, little is known about what shapes the structural characteristics of IDPs bound to their targets. Using a statistical thermodynamic model, we show that the target-bound ensembles are determined by a simple code that combines the IDP sequence and the distribution of IDP-target interaction hotspots. These two parameters define the conformational space of target-bound IDPs and rationalize the observed structural heterogeneity of fuzzy complexes. The presented model successfully reproduces the dynamical signatures of target-bound IDPs from the NMR relaxation experiments as well as the changes of interaction affinity and the IDP helicity induced by mutations. The model explains how the target-bound IDP ensemble adapts to mutations in order to achieve an optimal balance between conformational freedom and interaction energy. Taken together, the presented sequence-ensemble relationship of fuzzy complexes explains the different manifestations of IDP disorder in folding-upon-binding processes.

PMID:34504009 | DOI:10.1073/pnas.2020562118