Early Stages of Homopolymer Collapse

Interest in the protein folding problem has motivated a wide range of theoretical and experimental studies of the kinetics of the collapse of flexible homopolymers. In this Paper a phenomenological model is proposed for the kinetics of the early stages of homopolymer collapse following a quench from temperatures above to below the theta temperature. In the first stage, nascent droplets of the dense phase are formed, with little effect on the configurations of the bridges that join them. The droplets then grow by accreting monomers from the bridges, thus causing the bridges to stretch. During these two stages the overall dimensions of the chain decrease only weakly. Further growth of the droplets is accomplished by the shortening of the bridges, which causes the shrinking of the overall dimensions of the chain. The characteristic times of the three stages respectively scale as the zeroth, 1/5 and 6/5 power of the the degree of polymerization of the chain.Comment: 11 pages, 3 figure

Performance of the 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) in the diagnostic management of pulmonary embolism:An external validation study

Background: The recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE). Aim: To externally validate the performance of 4PEPS in an independent cohort. Methods: In this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer &lt;1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold. Results: Of the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80–0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57–60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86–1.9). Conclusion: In this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study.</p

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients

Background The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. Methods A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract-transform-load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. Results Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive. Conclusions In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Content and performance of the MiniMUGA genotyping array: A new tool to improve rigor and reproducibility in mouse research

The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research

Severity of urinary incontinence is associated with prevalence of sexual dysfunction

Introduction and hypothesis: Urinary incontinence (UI) affects overall health-related and sexual quality of life (QoL) in women. There is no consensus on the impact of severity and type of UI on the prevalence of sexual dysfunction (DS). The aim of this study was to evaluate the association between types and severity of UI and DS. Methods: A cross-sectional study of women with UI. Inclusion criteria: women complaining of UI and > 18 years old. Women with a history of previous treatment for UI, recurrent urinary tract infections, renal lithiasis, previous radiation therapy or pelvic organ prolapse above stage 2 in the Pelvic Organ Prolapse Quantification (POP-Q) system were excluded. Clinical and epidemiological data were collected, and the following questionnaires were applied: ICIQ-SF, ICIQ-OAB, King’s Health Questionnaire (KHQ) and Female Sexual Function Index (FSFI). Results: Concerning the type of UI, the majority of women had MUI (69.1%) and 56.8% reported having coital UI. The mean score was 20.81 ± 8.45 in the FSFI questionnaire. There was a prevalence of SD in 71.6% of women, with no difference in types of UI (p = 0.753) and loss during sexual intercourse (p = 0.217). There was a correlation between severity of UI (ICIQ-SF) and arousal (r = −0.26; p = 0.008), lubrication (r = −0.25; p = 0.009), orgasm (r = −0.25; p = 0.009), pain (r = −0.26; p = 0.007) and total (r = −0.28; p = 0.004) domain scores. Conclusions: There is a high prevalence of SD in women with urinary incontinence, irrespective of the type of UI and urine leakage during sexual intercourse. However, the greater the severity of UI is, the worse the sexuality questionnaire scores

Atmospheric CO sub 2 concentrations derived from flask samples collected at USSR-operated sampling sites

This document presents daily atmospheric CO{sub 2} concentrations from four USSR-operated sampling sites (Teriberka Station, Ocean Station Charlie, Bering Island, and Kotelny Island). The period of record varies by station with the earliest measurements dating back to 1983 and recent estimates from early 1991. These CO{sub 2} concentrations are derived from air samples collected in 1.5-L stainless steel electropolished flasks and later analyzed at the Main Geophysical Observatory (St. Petersburg, USSR) using a nondispersive infrared gas analyzer. Measurements not meeting wind direction, wind speed, inter-flask agreement, and climate condition criteria were either discarded or flagged. All measurements have been corrected for drift biases introduced during flask storage. These atmospheric CO{sub 2} concentrations are considered indicative of regional background air conditions and are directly traceable to the World Meteorological Organization's primary CO{sub 2} standards. These measurements support the rising trend in atmospheric CO{sub 2} concentrations measured at other monitoring sites around the world and may be compared with similar measurements made by various monitoring programs at other northern latitude sites. The document presents the atmospheric CO{sub 2} concentrations in graphical and tabular form, describes the sampling methods, defines limitations and restrictions of the data, and describes the information on the magnetic media