Clinical competence in performing and recognising a mediolateral episiotomy of protective angle and length: a systematic review

Objective: It is assumed that all doctors and midwives understand and apply evidence‐based principles in performing episiotomies in their everyday practice. However, remarkable discrepancies between even the most reputable literature sources in defining and describing the technique of performing mediolateral episiotomy (MLE) suggest that there is much ambiguity and confusion for both researchers and clinicians alike. Design: The systematic review protocol was written prior to starting the review and registered in the international prospective register of systematic reviews (PROSPERO/ID CRD42017070523) last updated on December 15, 2017. The review is reported using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. Methods: A database search was performed using: Medline, CINAHL, Scopus, Informit, the Cochrane Library and PubMed from database inception to 17 September 2017, with a final search on 10 February 2017. Studies were included if they examined clinicians' competency in performing an 'ideal' or 'correct' mediolateral episiotomy, as well as those studies that compared the performance of different professional roles. Studies usually defined an 'ideal' incision as one that met the criteria of an acceptable angle of incision from the midline, starting incision point distance from the midline and in terms of the length of the incision created. Results: While many of the studies included in this review were not of high quality (author self‐assessment) and had their own study criteria for a MLE, the literature suggests clinicians are generally unable to perform or simulate episiotomies within such standards. Overall, most of the literature reported doctors were performing more 'ideal', lateral and longer incisions compared to midwives; however, there were studies that found the opposite, showing statistically significant results in favour of midwives performing more protective episiotomies. There was no association between clinicians' participation in formal training courses and their ability to perform the 'ideal' incision, though one study did find an increased number of episiotomies performed under supervision improved clinicians competency. Conclusion: The obvious lack of understanding around defining and performing MLE for clinicians of various professional roles suggests the need to produce a uniform set of guidelines, and to develop a universal, low‐cost approach for teaching and performing the MLE technique in any clinical environment around the world

Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients.

Belimumab has therapeutic benefit in active systemic lupus erythematosus (SLE), especially in patients with high-titer anti-dsDNA antibodies. We asked whether the profound B cell loss in belimumab-treated SLE patients is accompanied by shifts in the immunoglobulin repertoire. We enrolled 15 patients who had been continuously treated with belimumab for more than 7 years, 17 matched controls, and 5 patients who were studied before and after drug initiation. VH genes of sort-purified mature B cells and plasmablasts were subjected to next-generation sequencing. We found that B cell-activating factor (BAFF) regulates the transitional B cell checkpoint, with conservation of transitional 1 (T1) cells and approximately 90% loss of T3 and naive B cells after chronic belimumab treatment. Class-switched memory B cells, B1 B cells, and plasmablasts were also substantially depleted. Next-generation sequencing revealed no redistribution of VH, DH, or JH family usage and no effect of belimumab on representation of the autoreactive VH4-34 gene or CDR3 composition in unmutated IgM sequences, suggesting a minimal effect on selection of the naive B cell repertoire. Interestingly, a significantly greater loss of VH4-34 was observed among mutated IgM and plasmablast sequences in chronic belimumab-treated subjects than in controls, suggesting that belimumab promotes negative selection of activated autoreactive B cells

A forward genetic screen identifies host factors that influence the lysis-lysogeny decision in phage lambda

The lysis‐lysogeny decision made by bacteriophage lambda is one of the classic problems of molecular biology. Shortly after infecting a cell, the virus can either go down the lytic pathway and make more viruses, or go down the lysogenic pathway and integrate itself into the host genome. While much is known about how this decision takes place, the extent to which host physiology influences this decision and the mechanisms by which this influence takes place has remained mysterious. To answer this question, we performed a forward genetic screen to systematically identify all of the genes in E. coli that influence the lysis‐lysogeny decision. Our results demonstrate previously unknown links between host physiology and viral decision making and shed new light on this classic system

Towards Molecular Simulations that are Transparent, Reproducible, Usable By Others, and Extensible (TRUE)

Systems composed of soft matter (e.g., liquids, polymers, foams, gels, colloids, and most biological materials) are ubiquitous in science and engineering, but molecular simulations of such systems pose particular computational challenges, requiring time and/or ensemble-averaged data to be collected over long simulation trajectories for property evaluation. Performing a molecular simulation of a soft matter system involves multiple steps, which have traditionally been performed by researchers in a "bespoke" fashion, resulting in many published soft matter simulations not being reproducible based on the information provided in the publications. To address the issue of reproducibility and to provide tools for computational screening, we have been developing the open-source Molecular Simulation and Design Framework (MoSDeF) software suite. In this paper, we propose a set of principles to create Transparent, Reproducible, Usable by others, and Extensible (TRUE) molecular simulations. MoSDeF facilitates the publication and dissemination of TRUE simulations by automating many of the critical steps in molecular simulation, thus enhancing their reproducibility. We provide several examples of TRUE molecular simulations: All of the steps involved in creating, running and extracting properties from the simulations are distributed on open-source platforms (within MoSDeF and on GitHub), thus meeting the definition of TRUE simulations

Superabsorption in an organic microcavity : toward a quantum battery

The rate at which matter emits or absorbs light can be modified by its environment, as markedly exemplified by the widely studied phenomenon of superradiance. The reverse process, superabsorption, is harder to demonstrate because of the challenges of probing ultrafast processes and has only been seen for small numbers of atoms. Its central idea—superextensive scaling of absorption, meaning larger systems absorb faster—is also the key idea underpinning quantum batteries. Here, we implement experimentally a paradigmatic model of a quantum battery, constructed of a microcavity enclosing a molecular dye. Ultrafast optical spectroscopy allows us to observe charging dynamics at femtosecond resolution to demonstrate superextensive charging rates and storage capacity, in agreement with our theoretical modeling. We find that decoherence plays an important role in stabilizing energy storage. Our work opens future opportunities for harnessing collective effects in light-matter coupling for nanoscale energy capture, storage, and transport technologies

Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models

In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. What differentiates this approach is the integration of an orthogonal-based local identifiability method into the unscented Kalman filter (UKF), rather than using the more common observability-based method which has inherent limitations. It also introduces a variable step size based on the system uncertainty of the UKF during the sensitivity calculation. This method identified 10 out of 12 parameters as identifiable. These ten parameters were estimated using the UKF, which was run 97 times. Throughout the repetitions the UKF proved to be more consistent than the estimation algorithms used for comparison