Construction of a nurse shark (Ginglymostoma cirratum) bacterial artificial chromosome (BAC) library and a preliminary genome survey

BACKGROUND: Sharks are members of the taxonomic class Chondrichthyes, the oldest living jawed vertebrates. Genomic studies of this group, in comparison to representative species in other vertebrate taxa, will allow us to theorize about the fundamental genetic, developmental, and functional characteristics in the common ancestor of all jawed vertebrates. AIMS: In order to obtain mapping and sequencing data for comparative genomics, we constructed a bacterial artificial chromosome (BAC) library for the nurse shark, Ginglymostoma cirratum. RESULTS: The BAC library consists of 313,344 clones with an average insert size of 144 kb, covering ~4.5 × 10(10 )bp and thus providing an 11-fold coverage of the haploid genome. BAC end sequence analyses revealed, in addition to LINEs and SINEs commonly found in other animal and plant genomes, two new groups of nurse shark-specific repetitive elements, NSRE1 and NSRE2 that seem to be major components of the nurse shark genome. Screening the library with single-copy or multi-copy gene probes showed 6–28 primary positive clones per probe of which 50–90% were true positives, demonstrating that the BAC library is representative of the different regions of the nurse shark genome. Furthermore, some BAC clones contained multiple genes, making physical mapping feasible. CONCLUSION: We have constructed a deep-coverage, high-quality, large insert, and publicly available BAC library for a cartilaginous fish. It will be very useful to the scientific community interested in shark genomic structure, comparative genomics, and functional studies. We found two new groups of repetitive elements specific to the nurse shark genome, which may contribute to the architecture and evolution of the nurse shark genome

Construction, alignment and analysis of twelve framework physical maps that represent the ten genome types of the genus Oryza

Bacterial artificial chromosome (BAC) fingerprint and end-sequenced physical maps representing the ten genome types of Oryza are presente

TNF-Receptor Inhibitor Therapy for the Treatment of Children with Idiopathic Pneumonia Syndrome. A Joint Pediatric Blood and Marrow Transplant Consortium and Children's Oncology Group Study (ASCT0521)

AbstractIdiopathic pneumonia syndrome (IPS) is an acute, noninfectious lung disorder associated with high morbidity and mortality after hematopoietic cell transplantation. Previous studies have suggested a role for TNFα in the pathogenesis of IPS. We report a multicenter phase II trial investigating a soluble TNF-binding protein, etanercept (Enbrel, Amgen, Thousand Oaks, CA), for the treatment of pediatric patients with IPS. Eligible patients were < 18 years old, within 120 days after transplantation, and with radiographic evidence of a diffuse pneumonitis. All patients underwent a pretherapy broncho-alveolor lavage (BAL) to establish the diagnosis of IPS. Systemic corticosteroids (2.0 mg/kg/day) plus etanercept (.4 mg/kg twice weekly × 8 doses) were administered. Response was defined as survival and discontinuation of supplemental oxygen support by day 28 of study. Thirty-nine patients (median age, 11 years; range, 1 to 17) were enrolled, with 11 of 39 patients nonevaluable because of identification of pathogens from their pretherapy BAL. In the remaining 28 patients, the median fraction of inspired oxygen at study entry was 45%, with 17 of 28 requiring mechanical ventilation. Complete responses were seen in 20 (71%) patients, with a median time to response of 10 days (range, 1 to 24). Response rates were higher for patients not requiring mechanical ventilation at study entry (100% versus 53%, P = .01). Overall survival at 28 days and 1 year after therapy were 89% (95% confidence interval [CI], 70% to 96%) and 63% (95% CI, 42% to 79%), respectively. Plasma levels of proinflammatory cytokines were significantly increased at onset of therapy, subsequently decreasing in responding patients. The addition of etanercept to high-dose corticosteroids was associated with high response rates and survival in children with IPS

Protocol for developing a core outcome set for male infertility research:an international consensus development study

Abstract STUDY QUESTION We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. WHAT IS KNOWN ALREADY Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. STUDY DESIGN, SIZE, DURATION Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health’s consensus development conference. PARTICIPANTS/MATERIALS, SETTING, METHODS An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes. STUDY FUNDING/COMPETING INTEREST(S) This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. TRIAL REGISTRATION NUMBER Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. TRIAL REGISTRATION DATE N/A. DATE OF FIRST PATIENT’S ENROLMENT N/A

Uncertainty at the Limits of Viability: A Qualitative Study of Antenatal Consultations

Background and Objectives: Antenatal consultation between a neonatologist and expectant parent(s) may determine if resuscitation is provided for or withheld from neonates born in the gray zone of viability. In this study, we sought to gain a deeper understanding of uncertainties present and neonatologists' communication strategies regarding such uncertainties in this shared decision-making. Methods: A prospective, qualitative study using transcriptions of audio-recorded antenatal consultations between a neonatologist and expectant parent(s) was conducted. Pregnant women were eligible if anticipating delivery in the gray zone of viability (22 0/7-24 6/7 weeks' gestation). Over 18 months, 25 of 28 pregnant women approached consented to participate. Applied thematic analysis was used to inductively derive and examine conceptual themes. Results: Inductive analysis of consult transcripts revealed uncertainty as a central theme. Several subthemes relating to uncertainty were also derived, including the timing of delivery, NICU course, individual characteristics (of physician, expectant parent(s), and fetus or neonate), and consequences of the decision for the expectant parent(s). Analysis revealed that uncertainty was actively managed by neonatologists through a variety of strategies, including providing more information, acknowledging the limits of medicine, acknowledging and accepting uncertainty, holding hope, and relationship building. Conclusions: Uncertainty is pervasive within the antenatal consultation for periviable neonates and likely plays a significant role in decision-making toward postnatal resuscitative efforts. Uncertainty complicated, or even paralyzed, decision-making efforts while also providing reassurance toward a positive outcome. Directions for future study should consider whether advanced communication training modulates the impact that uncertainty plays in the shared decision-making encounte

The use of projected autonomy in antenatal shared decision-making for periviable neonates: a qualitative study

Abstract Background In this study, we assessed the communication strategies used by neonatologists in antenatal consultations which may influence decision-making when determining whether to provide resuscitation or comfort measures only in the care of periviable neonates. Methods This study employed a qualitative study design using inductive thematic discourse analysis of ‘naturally occurring data’ in the form of antenatal conversations around resuscitation decisions at the grey zone of viability. The study occurred between February 2017 and June 2018 on a labor and delivery unit within a large Midwestern tertiary care hospital. Participants included 25 mothers who were admitted to the study hospital with anticipated delivery in the grey zone of viability and practicing neonatologists or neonatology fellows who partnered in antenatal consultation. We used a two-stage inductive analytic process to focus on how neonatologists’ discourses constructed SDM in antenatal consultations. First, we used a thematic discourse analysis to interpret the recurring patterns of meaning within the transcribed antenatal consultations, and second, we theorized the subsequent effects of these discourses on shaping the context of SDM in antenatal encounters. Results In this qualitative study, that included discourse analysis of real-time audio conversations in 25 antenatal consults, neonatologists used language that creates projected autonomy through (i) descriptions of fetal physiology (ii) development of the fetus’s presence, and (iii) fetal role in decision-making. Conclusion Discourse analysis of real-time audio conversations in antenatal consultations was revelatory of how various discursive patterns brought the fetus into decision-making, thus changing who is considered the key actor in SDM