Stochastic inverse modeling of transient laboratory-scale three-dimensional two-phase core flooding scenarios

We develop a comprehensive and efficient workflow for a stochastic assessment of key parameters governing two-phase flow conditions associated with core-scale experiments. We rely on original and detailed datasets collected on a Berea sandstone sample. These capture the temporal evolution of pressure drop across the core and three-dimensional maps of phase saturations (determined via X-ray CT) in oil- and brine-displacement flooding scenarios characterized by diverse brine/oil viscosity contrasts. Such experiments are used as a test-bed for the proposed stochastic model calibration strategy. The latter is structured across three main steps: (i) a preliminary calibration, aimed at identifying a behavioral region of the model parameter space; (ii) a Global Sensitivity Analysis (GSA), geared towards identification of the relative importance of model parameters on observed model outputs and assessment of non-influential parameters to reduce dimensionality of the parameter space; and (iii) a stochastic inverse modeling procedure. The latter is based on a differential-evolution genetic algorithm to efficiently explore the reduced parameter space stemming from the GSA. It enables one to obtain a probabilistic description of the relevant model parameters through their frequency distributions conditional on the detailed type of information collected. Coupling GSA with a stochastic parameter estimation approach based on a genetic algorithm of the type we consider enables streamlining the procedure and effectively cope with the considerable computational efforts linked to the two-phase scenario considered. Results show a remarkable agreement with experimental data and imbue us with confidence on the potential of the approach to embed the type of rich datasets considered towards model parameter estimation fully including uncertainty

A Comprehensive Survey of 'Metamaterial Transmission-Line Based Antennas: Design, Challenges, and Applications'

In this review paper, a comprehensive study on the concept, theory, and applications of composite right/left-handed transmission lines (CRLH-TLs) by considering their use in antenna system designs have been provided. It is shown that CRLH-TLs with negative permittivity (epsilon < 0) and negative permeability (mu < 0) have unique properties that do not occur naturally. Therefore, they are referred to as artificial structures called "metamaterials". These artificial structures include series left-handed (LH) capacitances (C-L), shunt LH inductances (L-L), series right-handed (RH) inductances (L-R), and shunt RH capacitances (C-R) that are realized by slots or interdigital capacitors, stubs or via-holes, unwanted current flowing on the surface, and gap distance between the surface and ground-plane, respectively. In the most cases, it is also shown that structures based on CRLH metamaterial-TLs are superior than their conventional alternatives, since they have smaller dimensions, lower-profile, wider bandwidth, better radiation patterns, higher gain and efficiency, which make them easier and more cost-effective to manufacture and mass produce. Hence, a broad range of metamaterial-based design possibilities are introduced to highlight the improvement of the performance parameters that are rare and not often discussed in available literature. Therefore, this survey provides a wide overview of key early-stage concepts of metematerial-based designs as a thorough reference for specialist antennas and microwave circuits designers. To analyze the critical features of metamaterial theory and concept, several examples are used. Comparisons on the basis of physical size, bandwidth, materials, gain, efficiency, and radiation patterns are made for all the examples that are based on CRLH metamaterial-TLs. As revealed in all the metematerial design examples, foot-print area decrement is an important issue of study that have a strong impact for the enlargement of the next generation wireless communication systems

Impedance Bandwidth Improvement of a Planar Antenna Based on Metamaterial-Inspired T-Matching Network

In this paper a metamaterial-inspired T-matching network is directly imbedded inside the feedline of a microstrip antenna to realize optimum power transfer between the front-end of an RF wireless transceiver and the antenna. The proposed T-matching network, which is composed of an arrangement of series capacitor, shunt inductor, series capacitor, exhibits left-handed metamaterial characteristics. The matching network is first theoretically modelled to gain insight of its limitations. It was then implemented directly in the 50-Omega feedline to a standard circular patch antenna, which is an unconventional methodology. The antenna's performance was verified through measurements. With the proposed technique there is 2.7 dBi improvement in the antenna's radiation gain and 12% increase in the efficiency at the center frequency, and this is achieved over a significantly wider frequency range by a factor of approximately twenty. Moreover, there is good correlation between the theoretical model, method of moments simulation, and the measurement results

Performance of BRCA1/2 mutation prediction models in male breast cancer patients

To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), BRCAPRO (BRCA probability) and the Myriad prevalence table ("Myriad"). These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed vs predicted carriers and assessed the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for each model. BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% confidence interval [CI]: [0.60-1.09] and 0.79, 95% CI: [0.57-1.09], vs. BRCAPRO: 1.02, 95% CI: [0.75-1.38] and 0.94, 95% CI: [0.68-1.31], respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671). BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources

The first inherited retinal disease registry in Iran: Research protocol and results of a pilot study

Background: To describe the protocol for developing a national inherited retinal disease (IRD) registry in Iran and present its initial report. Methods: This community-based participatory research was approved by the Ministry of Health and Medical Education of Iran in 2016. To provide the minimum data set (MDS), several focus group meetings were held. The final MDS was handed over to an engineering team to develop a web-based software. In the pilot phase, the software was set up in two referral centers in Iran. Final IRD diagnosis was made based on clinical manifestations and genetic findings. Ultimately, patient registration was done based on all clinical and non-clinical manifestations. Results: Initially, a total of 151 data elements were approved with Delphi technique. The registry software went live at www.IRDReg.org based on DHIS2 open source license agreement since February 2016. So far, a total of 1001 patients have been registered with a mean age of 32.41±15.60 years (range, 3 months to 74 years). The majority of the registered patients had retinitis pigmentosa (42, 95 CI: 38.9 to 45). Genetic testing was done for approximately 20 of the registered individuals. Conclusion: Our study shows successful web-based software design and data collection as a proof of concept for the first IRD registry in Iran. Multicenter integration of the IRD registry in medical centers throughout the country is well underway as planned. These data will assist researchers to rapidly access information about the distribution and genetic patterns of this disease. © 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Correction to: Putting genome-wide sequencing in neonates into perspective

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article

DLG4-related synaptopathy: a new rare brain disorder

PURPOSE: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.METHODS: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing.RESULTS: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies.CONCLUSION: The present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.Genetics of disease, diagnosis and treatmen