To understand patient attitudes and preferences when faced with the uncertainty of pregnancy of unknown location (PUL).
Qualitative, interview-based study.
University Hosptial.
Patients aged >18 ...years sampled from the emergency department and a subspecialty fertility practice of a university hospital system.
Six to 8 weeks after resolution of a PUL, with an ultimate clinical outcome of either an intrauterine pregnancy, spontaneous abortion, or ectopic pregnancy. Participants underwent either surgical, medical, or expectant management.
Thematic analysis of the virtual, semistructured interviews (45–60 minutes in length) conducted with participants to identify commonly expressed priorities was performed.
Interviews were completed from October 2020 to March 2021 until thematic saturation was achieved (n = 15). Resolution diagnoses included intrauterine pregnancy (26.7%, n = 4), ectopic pregnancy (40.0%, (n = 6), and spontaneous abortion (33.3%, n = 5). Moreover, 66.7% (n = 10) of the patients presented to the emergency department, whereas 33.3% (n = 5) presented to a subspecialty fertility clinic. All had desired pregnancies. Thematic analyses revealed 4 related priorities around PUL management: health of pregnancy; health of self; future fertility; and diagnostic prediction and diagnostic certainty. The relative balance of these priorities was dynamic and evolved throughout the course of management with different outcomes. A second set of themes related to logistical preferences included mental healthsupport, clarity of treatment and next steps, and continuity of care. Interrater reliability was validated with a pooled κ of >0.8. Limitations include that all participants had desired pregnancies, and the experiences of those who experienced different pregnancy outcomes may have been affected by recall bias.
These data demonstrate novel themes around related priorities in patients with desired pregnancies diagnosed with a PUL previously underappreciated by clinicians. The balance of these priorities evolved throughout management with increasing information and clarity. Continually reevaluating relevant patient priorities and preferences is essential to the comprehensive management of PUL.
Two types of bifurcation diagrams of cytosolic calcium nonlinear oscillatory systems are presented in rectangular areas determined by two slowly varying parameters. Verification of the periodic ...dynamics in the two-parameter areas requires solving the underlying model a few hundred thousand or a few million times, depending on the assumed resolution of the desired diagrams (color bifurcation figures). One type of diagram shows period-n oscillations, that is, periodic oscillations having n maximum values in one period. The second type of diagram shows frequency distributions in the rectangular areas. Each of those types of diagrams gives different information regarding the analyzed autonomous systems and they complement each other. In some parts of the considered rectangular areas, the analyzed systems may exhibit non-periodic steady-state solutions, i.e., constant (equilibrium points), oscillatory chaotic or unstable solutions. The identification process distinguishes the later types from the former one (periodic). Our bifurcation diagrams complement other possible two-parameter diagrams one may create for the same autonomous systems, for example, the diagrams of Lyapunov exponents, Ls diagrams for mixed-mode oscillations or the 0–1 test for chaos and sample entropy diagrams. Computing our two-parameter bifurcation diagrams in practice and determining the areas of periodicity is based on using an appropriate numerical solver of the underlying mathematical model (system of differential equations) with an adaptive (or constant) step-size of integration, using parallel computations. The case presented in this paper is illustrated by the diagrams for an autonomous dynamical model for cytosolic calcium oscillations, an interesting nonlinear model with three dynamical variables, sixteen parameters and various nonlinear terms of polynomial and rational types. The identified frequency of oscillations may increase or decrease a few hundred times within the assumed range of parameters, which is a rather unusual property. Such a dynamical model of cytosolic calcium oscillations, with mitochondria included, is an important model in which control of the basic functions of cells is achieved through the Ca2+ signal regulation.
Covering: Up to July 2020Ribosomal antimicrobial peptide (AMP) natural products, also known as ribosomally synthesized and post-translationally modified peptides (RiPPs) or host defense peptides, ...demonstrate potent bioactivities and impressive complexity that complicate molecular and biological characterization. Tandem mass spectrometry (MS) has rapidly accelerated bioactive peptide sequencing efforts, yet standard workflows insufficiently address intrinsic AMP diversity. Herein, orthogonal approaches to accelerate comprehensive and accurate molecular characterization without the need for prior isolation are reviewed. Chemical derivatization, proteolysis (enzymatic and chemical cleavage), multistage MS fragmentation, and separation (liquid chromatography and ion mobility) strategies can provide complementary amino acid composition and post-translational modification data to constrain sequence solutions. Examination of two complex case studies, gomesin and styelin D, highlights the practical implementation of the proposed approaches. Finally, we emphasize the importance of heterogeneous AMP peptidoforms that confer varying biological function, an area that warrants significant further development.
This paper presents and compares two-parameter bifurcation diagrams obtained from the 0-1 test for chaos and sample entropy methods for nonlinear oscillating systems. Based on the computed diagrams ...it is often possible to establish a unique correspondence between the two types of diagrams. Comparison of the diagrams are presented for typical chaotic systems, including those of Lorenz, Rössler, electric arc circuits and chemical oscillating systems. The two types of bifurcation diagrams may also be related to the period<inline-formula> <tex-math notation="LaTeX">-n </tex-math></inline-formula> and frequency distribution diagrams. The main goal is to address the issue of obtaining similar results from the 0-1 test for chaos and sample entropy methods and discuss difficulty in properly selecting parameters needed in the two methods. A possible link between the 0-1 test for chaos and surrogate data methods is also mentioned.
The complex reservoir of metabolite-producing bacteria in the gastrointestinal tract contributes tremendously to human health and disease. Bacterial composition, and by extension gut metabolomic ...composition, is undoubtably influenced by the use of modern antibiotics. Herein, we demonstrate that polymyxin B, a last resort antibiotic, influences the production of the genotoxic metabolite colibactin from adherent-invasive
(AIEC) NC101. Colibactin can promote colorectal cancer through DNA double stranded breaks and interstrand cross-links. While the structure and biosynthesis of colibactin have been elucidated, chemical-induced regulation of its biosynthetic gene cluster and subsequent production of the genotoxin by
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are largely unexplored. Using a multiomic approach, we identified that polymyxin B stress enhances the abundance of colibactin biosynthesis proteins (Clb's) in multiple
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strains, including pro-carcinogenic AIEC, NC101; the probiotic strain, Nissle 1917; and the antibiotic testing strain, ATCC 25922. Expression analysis via qPCR revealed that increased transcription of
genes likely contributes to elevated Clb protein levels in NC101. Enhanced production of Clb's by NC101 under polymyxin stress matched an increased production of the colibactin prodrug motif, a proxy for the mature genotoxic metabolite. Furthermore,
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with a heightened tolerance for polymyxin induced greater mammalian DNA damage, assessed by quantification of γH2AX staining in cultured intestinal epithelial cells. This study establishes a key link between the polymyxin B stress response and colibactin production in
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. Ultimately, our findings will inform future studies investigating colibactin regulation and the ability of seemingly innocuous commensal microbes to induce host disease.
The `false-negative' and `false-positive' outcomes of the 0-1 test for chaos in continuous dynamical systems are described and analyzed in this paper. First, typical false outcomes of the 0-1 test ...for chaos are illustrated through several numerical examples of the solutions of chaotic continuous systems. Those examples are based on computation of the K values in the 0-1 test (0 ≤ K ≤ 1) for a selection of two parameters, namely the dt, output step in the numerical solver, and the T value (integer denoting the step of the output sample selection). The central role in the `false-negative' outcome is played by the oversampling phenomenon in the 0-1 test, while the `false-positive' results are possible for a complicated periodic signal having a spectrum with multiple frequencies. Analyzing the spectra of the signals is the key method to avoid the false outcomes and also an important tool in the process of reconstructing of chaotic attractors from the time series signals. The correct computing process for continuous dynamical systems and selection of the parameters dt and T depend on the analyzed system (dynamical model) and should always be preceded (or combined with) the frequency analysis of the examined signals. The computation of special multi-parameter (n-parameter; n ≥ 2) bifurcation diagrams for the 0-1 test should, in most cases, be done by parallel computing, since, obtaining one such multi-parameter bifurcation diagram in practice requires solving of the underlying mathematical model (system of ODEs) millions of times.
Various oscillating (periodic and chaotic) circuits and systems show interesting responses whose nature changes with varying parameters. It often happens that a change of one element (i.e. resistor) ...of a circuit or system may cause a simultaneous change of two (or more) coefficients in the underlying mathematical model (i.e. a system of nonlinear ordinary differential equations, or ODEs). In this paper we present two-parameter bifurcation diagrams of such circuits and systems, obtained when two parameters vary simultaneously. Four different numerical techniques are applied to two selected dynamical systems (an active oscillating circuit with a memristive element and an electric arc circuit). The focus of this paper is on the computationally intensive calculations rather than on analytical analysis of the oscillatory responses. Two-parameter bifurcation diagrams require solving systems of nonlinear ODEs several hundred thousand (or even a few million) times (depending on the assumed resolution), plus additional work to distinguish periodic solutions from chaotic ones. Our computations are done using various combinations of the C++, Fortran/Python and Julia environments with Runge-Kutta order-4 and order-5 numerical solvers and the 0-1 test for chaos. Several two-parameter bifurcation diagrams are presented.
There is growing interest in long-term outcomes following infertility and infertility treatment. However, there are few detailed longitudinal cohorts available for this work. This study aimed to ...assemble a historical cohort of women with primary infertility and age-matched controls to evaluate fertility trends, sequelae, and sociodemographic differences. Described here are cohort group characteristics and associated reproductive trends over time.
A population-based historical cohort was created using the Rochester Epidemiology Project (REP) record-linkage system (Olmsted County, MN). The cohort included women aged 18-50 with a diagnosis of primary infertility between January 1, 1980, and December 31, 1999. As part of a case-control study, we identified 1:1 age-matched female controls from the same community and era.
A total of 1001 women with primary infertility and 1001 age-matched controls were identified. The women with primary infertility were significantly more likely to be married, college educated, use barrier contraception, and non-smokers compared to age-matched controls. The incidence of primary infertility increased from 14 to 20 per 10,000 person years from 1980-1985 to 1995-1999. Ovulatory dysfunction and unexplained infertility were the most common causes of primary infertility and clomiphene was the most widely used fertility medication. Rates of in vitro fertilization (IVF) increased from 1.8% during 1980-1985 to 26.0% during 1995-1999.
Women with primary infertility were found to have unique sociodemographic characteristics compared to age-matched control women, which is consistent with previous research. The incidence of diagnosed primary infertility increased from 1980 to 1999, as did use of IVF.
Two-parameter diagrams obtained through the 0-1 test of chaos for nonlinear oscillatory continuous systems are presented in this paper. The diagrams are the results of a parallel approach to tackle ...enormous memory and computational time requirements due to the known oversampling problem associated with the use of the 0-1 test for chaos in continuous systems. Our rectangular diagrams with black-and-white shades of gray levels correspond to the numbers between 0 and 1 obtained as the result of the 0-1 test for chaos. A comparison between the two-parameter diagrams for the 0-1 test with the color bifurcation diagrams for oscillatory systems obtained from another method (period-n identification) is also considered. Illustrative examples are based on both the well-known Lorenz model and a model describing two equivalent electric arc circuits.
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