The CORE (Consensus on Relevant Elements) Approach to Determining Initial Core Components of an Innovation

Identifying an intervention's core components is indispensable to gauging whether an intervention is implemented with fidelity and/or is modified; it is often a multi-stage process, starting with the first stage of identifying an initial set of core components that are gradually refined. This first stage of identifying initial core components has not been thoroughly examined. Without a clear set of steps to follow, interventions may vary in the rigor and thought applied to identifying their initial core components. We devised the CORE (Consensus on Relevant Elements) approach to synthesize opinions of intervention developers/implementers to identify an intervention's initial core components, particularly applicable to innovative interventions. We applied CORE to a peer-based intervention that aids military veterans with post-incarceration community reintegration. Our CORE application involved four intervention developers/implementers and two moderators to facilitate the seven CORE steps. Our CORE application had two iterations, moving through Steps 1 (individual core component suggestions) through 7 (group discussion for consensus), then repeating Steps 4 (consolidation of component definitions) through 7. This resulted in 18 consensus-reached initial core components of the peer-based intervention, down from the 60 that the developers/implementers individually suggested at Step 1. Removed components were deemed to not threaten the intervention's effectiveness even if absent. CORE contributes to filling a critical gap regarding identifying an intervention's initial core components (so that the identified components can be subsequently refined), by providing concrete steps for synthesizing the knowledge of an intervention's developers/implementers. Future research should examine CORE's utility across various interventions and implementation settings.

Machine learning approaches to identify core and dispensable genes in pangenomes

A gene in a given taxonomic group is either present in every individual (core), or absent in at least a single individual (dispensable). Previous pangenomic studies have identified certain functional differences between core and dispensable genes. However, identifying if a gene belongs to the core or dispensable portion of the genome requires the construction of a pangenome, which involves sequencing the genomes of many individuals. Here we aim to leverage the previously characterized core and dispensable gene content for two grass species (Brachypodium distachyon and Oryza sativa) to construct a machine learning model capable of accurately classifying genes as core or dispensable using only a single annotated reference genome. Such a model may mitigate the need for pangenome construction, an expensive hurdle especially in orphan crops which often lack the adequate genomic resources.

Core Language of Thought

Fodor’s “Language of Thought” (also called Mentalese) hypothesis—that we use a language-like, syntactic system in processing thoughts instead of natural languages—caused controversies in philosophy, psychology, and linguistics. While many researchers proposed their perspectives, both for and against, none of them addressed its evolutionary and sociocultural variabilities as far as I know. Accordingly, I provide a novel perspective on the hypothesis by discussing the interplay among our cognition, natural languages, evolution, and sociocultural factors. First, like one speaks personalized English as his/her idiolect, individuals have their own “Idiolects of Thought” as a derivative of Mentalese. Second, while Mentalese varies from individual to individual, “Core Language of Thought” is cognitively fundamental and largely shared across individuals.

Architectural Mediator subunits are differentially essential for global transcription in Saccharomyces cerevisiae

Mediator is a modular coactivator complex involved in the transcription of the majority of RNA polymerase II-regulated genes. However, the degrees to which individual core subunits of Mediator contribute to its activity have been unclear. Here, we investigate the contribution of two essential architectural subunits of Mediator to transcription in Saccharomyces cerevisiae. We show that acute depletion of the main complex scaffold Med14 or the head module nucleator Med17 is lethal and results in global transcriptional downregulation, though Med17 removal has a markedly greater negative effect. Consistent with this, Med17 depletion impairs preinitiation complex (PIC) assembly to a greater extent than Med14 removal. Co-depletion of Med14 and Med17 reduced transcription and TFIIB promoter occupancy similarly to Med17 ablation alone, indicating that the contributions of Med14 and Med17 to Mediator function are not additive. We propose that, while the structural integrity of complete Mediator and the head module are both important for PIC assembly and transcription, the head module plays a greater role in this process and is thus the key functional module of Mediator in this regard.

Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study†‡

STUDY QUESTION Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their ‘traffic light’ system for infertility treatment ‘add-ons’. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER Core Outcome Measures in Effectiveness Trials Initiative: 1023.