Supporting evidence-based rotavirus vaccine introduction decision-making and implementation: Lessons from 8 Gavi-eligible countries.

Despite the 2009 World Health Organization recommendation that all countries introduce rotavirus vaccines (RVV) into their national immunization programs, just 81 countries had introduced RVV by the end of 2015, leaving millions of children at risk for rotavirus morbidity and mortality. In response, the Rotavirus Accelerated Vaccine Introduction Network (RAVIN) was established in 2016 to provide support to eight Gavi-eligible countries that had yet to make an RVV introduction decision and/or had requested technical assistance with RVV preparations: Afghanistan, Bangladesh, Benin, Cambodia, Democratic Republic of Congo, Lao People's Democratic Republic, Myanmar, and Nepal. During 2016-2020, RAVIN worked with country governments and partners to support evidence-based immunization decision-making, RVV introduction preparation and implementation, and multilateral coordination. By the September 2020 program close-out, five of the eight RAVIN focus countries successfully introduced RVV into their routine childhood immunization programs. We report on the RAVIN approach, describe how the project responded collectively to an evolving RVV product landscape, synthesize common characteristics of the RAVIN country experiences, highlight key lessons learned, and outline the unfinished agenda to inform future new vaccine introduction efforts by countries and global partners.

A Systematic Review of Structural Health Monitoring Systems to Strengthen Post-Earthquake Assessment Procedures.

Structural health monitoring (SHM) is vital to ensuring the integrity of people and structures during earthquakes, especially considering the catastrophic consequences that could be registered in countries within the Pacific ring of fire, such as Ecuador. This work reviews the technologies, architectures, data processing techniques, damage identification techniques, and challenges in state-of-the-art results with SHM system applications. These studies use several data processing techniques such as the wavelet transform, the fast Fourier transform, the Kalman filter, and different technologies such as the Internet of Things (IoT) and machine learning. The results of this review highlight the effectiveness of systems aiming to be cost-effective and wireless, where sensors based on microelectromechanical systems (MEMS) are standard. However, despite the advancement of technology, these face challenges such as optimization of energy resources, computational resources, and complying with the characteristic of real-time processing.

Genetics professionals' attitudes toward prenatal exome sequencing.

Prenatal exome sequencing (ES) currently has limited use in the clinical setting, but research suggests that it has added diagnostic utility over karyotyping and array techniques for prenatal diagnosis of fetuses presenting with ultrasound abnormalities. The purpose of this study was to assess the attitudes of genetics professionals toward the clinical implementation of prenatal ES in order to guide development of professional guidelines. A survey was developed using themes identified in previous qualitative studies and was distributed to members of the American College of Medical Genetics and Genomics (ACMG), the American Society of Human Genetics (ASHG), and the National Society of Genetic Counselors (NSGC). A total of 498 participants completed some portion of the survey. There was consensus among participants that there would be clinical utility of prenatal ES when used for diagnosis, pregnancy management, and termination decisions. The majority also agreed that prenatal ES was distinct from its current use in the pediatric and adult settings. There were many areas of contention regarding which types of results should be returned to families and whether or not the current ACMG guidelines for return of incidental findings should also apply to the prenatal setting. Overall, professional guidance is needed to address the continuing concerns surrounding prenatal ES as its utilization in this setting is expected to grow.

Ancestral and conserved cis-regulatory architectures in developmental control genes.

Among developmental control genes, transcription factor-target gene "linkages"--the direct connections between target genes and the factors that control their patterns of expression--can show remarkable evolutionary stability. However, the specific binding sites that mediate and define these regulatory connections are themselves often subject to rapid turnover. Here we describe several instances in which particular transcription factor binding motif combinations have evidently been conserved upstream of orthologous target genes for extraordinarily long evolutionary periods. This occurs against a backdrop in which other binding sites for the same factors are coming and going rapidly. Our examples include a particular Dpp Silencer Element upstream of insect brinker genes, in combination with a novel motif we refer to as the Downstream Element; combinations of a Suppressor of Hairless Paired Site (SPS) and a specific proneural protein binding site associated with arthropod Notch pathway target genes; and a three-motif combination, also including an SPS, upstream of deuterostome Hes repressor genes, which are also Notch targets. We propose that these stable motif architectures have been conserved intact from a deep ancestor, in part because they mediate a special mode of regulation that cannot be supplied by the other, unstable motif instances.

Lateral inhibition in proneural clusters: cis-regulatory logic and default repression by Suppressor of Hairless.

Lateral inhibition, wherein a single cell signals to its neighbors to prevent them from adopting its own fate, is the best-known setting for cell-cell communication via the Notch (N) pathway. During peripheral neurogenesis in Drosophila, sensory organ precursor (SOP) cells arise within proneural clusters (PNCs), small groups of cells endowed with SOP fate potential by their expression of proneural transcriptional activators. SOPs use N signaling to activate in neighboring PNC cells the expression of multiple genes that inhibit the SOP fate. These genes respond transcriptionally to direct regulation by both the proneural proteins and the N pathway transcription factor Suppressor of Hairless [Su(H)], and their activation is generally highly asymmetric; i.e. only in the inhibited (non-SOP) cells of the PNC, and not in SOPs. We show that the substantially higher proneural protein levels in the SOP put this cell at risk of inappropriately activating the SOP-inhibitory genes, even without input from N-activated Su(H). We demonstrate that this is prevented by direct ;default' repression of these genes by Su(H), acting through the same binding sites it uses for activation in non-SOPs. We show that de-repression of even a single N pathway target gene in the SOP can extinguish the SOP cell fate. Finally, we define crucial roles for the adaptor protein Hairless and the co-repressors Groucho and CtBP in conferring repressive activity on Su(H) in the SOP. Our work elucidates the regulatory logic by which N signaling and the proneural proteins cooperate to create the neural precursor/epidermal cell fate distinction during lateral inhibition.

New Drosophila transgenic reporters: insulated P-element vectors expressing fast-maturing RFP.

In vivo green fluorescent protein (GFP)/red fluorescent protein (RFP) double-labeling studies have been hampered by several inconvenient properties of DsRed, the first described RFP. These disadvantages include a very slow (> 24 h) maturation time, emission of contaminating green light, and low solubility. A recently developed variant of DsRed, called DsRed.T4, has a much shorter maturation time, no significant green emission, and improved solubility. We have constructed Drosophila P-element transformation vectors encoding DsRed.T4 for promoter/enhancer analysis, labeling of living cells, or RFP tagging of proteins. These new vectors have all of the features of the widely used Pelican/Stinger GFP vectors, including insulator sequences to reduce position effects, an extensive polylinker, and both cytoplasmic and nuclear-localized forms of the reporter. We have also constructed an upstream activating sequence (UAS)-DsRed.T4 vector, for GAL4 activation of the reporter. We find that DsRed.T4 is very easily detected in transgenic flies without contamination of the GFP signal and that it matures to its fluorescent form nearly simultaneously with GFP. This advance in Drosophila reporter technology makes timed double-labeling experiments in developing transgenic animals possible for the first time.