Registered reports: an early example and analysis

© 2019 Wiseman et al.The recent ‘replication crisis’ in psychology has focused attention on ways of increasing methodological rigor within the behavioral sciences. Part of this work has involved promoting ‘Registered Reports’, wherein journals peer review papers prior to data collection and publication. Although this approach is usually seen as a relatively recent development, we note that a prototype of this publishing model was initiated in the mid-1970s by parapsychologist Martin Johnson in the European Journal of Parapsychology (EJP). A retrospective and observational comparison of Registered and non-Registered Reports published in the EJP during a seventeen-year period provides circumstantial evidence to suggest that the approach helped to reduce questionable research practices. This paper aims both to bring Johnson’s pioneering work to a wider audience, and to investigate the positive role that Registered Reports may play in helping to promote higher methodological and statistical standards.Peer reviewe

Early respiratory viral infections in infants with cystic fibrosis

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. Methods Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. Results Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0–10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. Conclusions Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF

Integrating a newly developed BAC-based physical mapping resource for Lolium perenne with a genome-wide association study across a L. Perenne European ecotype collection identifies genomic contexts associated with agriculturally important traits

Background and Aims Lolium perenne (perennial ryegrass) is the most widely cultivated forage and amenity grass species in temperate areas worldwide and there is a need to understand the genetic architectures of key agricultural traits and crop characteristics that deliver wider environmental services. Our aim was to identify genomic regions associated with agriculturally important traits by integrating a bacterial artificial chromosome (BAC)-based physical map with a genome-wide association study (GWAS). Methods BAC-based physical maps for L. perenne were constructed from similar to 212 000 high-information-content fingerprints using Fingerprint Contig and Linear Topology Contig software. BAC clones were associated with both BAC-end sequences and a partial minimum tiling path sequence. A panel of 716 L. perenne diploid genotypes from 90 European accessions was assessed in the field over 2 years, and genotyped using a Lolium Infinium SNP array. The GWAS was carried out using a linear mixed model implemented in TASSEL, and extended genomic regions associated with significant markers were identified through integration with the physical map. Key Results Between similar to 3600 and 7500 physical map contigs were derived, depending on the software and probability thresholds used, and integrated with similar to 35 k sequenced BAC clones to develop a resource predicted to span the majority of the L. perenne genome. From the GWAS, eight different loci were significantly associated with heading date, plant width, plant biomass and water-soluble carbohydrate accumulation, seven of which could be associated with physical map contigs. This allowed the identification of a number of candidate genes. Conclusions Combining the physical mapping resource with the GWAS has allowed us to extend the search for candidate genes across larger regions of the L. perenne genome and identified a number of interesting gene model annotations. These physical maps will aid in validating future sequence-based assemblies of the L. perenne genome.UK Biotechnology and Biological Sciences Research Council [BB/J004405/1, BB/CSP1730/1, BB/G012342/1]; Germinal Holdings (UK); Syngenta (UK); Vialactia Biosciences (NZ)Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Autonomous GN and C for Spacecraft Exploration of Comets and Asteroids

A spacecraft guidance, navigation, and control (GN&C) system is needed to enable a spacecraft to descend to a surface, take a sample using a touch-and-go (TAG) sampling approach, and then safely ascend. At the time of this reporting, a flyable GN&C system that can accomplish these goals is beyond state of the art. This article describes AutoGNC, which is a GN&C system capable of addressing these goals, which has recently been developed and demonstrated to a maturity TRL-5-plus. The AutoGNC solution matures and integrates two previously existing JPL capabilities into a single unified GN&C system. The two capabilities are AutoNAV and GREX. AutoNAV is JPL s current flight navigation system, and is fairly mature with respect to flybys and rendezvous with small bodies, but is lacking capability for close surface proximity operations, sampling, and contact. G-REX is a suite of low-TRL algorithms and capabilities that enables spacecraft operations in close surface proximity and for performing sampling/contact. The development and integration of AutoNAV and G-REX components into AutoGNC provides a single, unified GN&C capability for addressing the autonomy, close-proximity, and sampling/contact aspects of small-body sample return missions. AutoGNC is an integrated capability comprising elements that were developed separately. The main algorithms and component capabilities that have been matured and integrated are autonomy for near-surface operations, terrain-relative navigation (TRN), real-time image-based feedback guidance and control, and six degrees of freedom (6DOF) control of the TAG sampling event. Autonomy is achieved based on an AutoGNC Executive written in Virtual Machine Language (VML) incorporating high-level control, data management, and fault protection. In descending to the surface, the AutoGNC system uses camera images to determine its position and velocity relative to the terrain. This capability for TRN leverages native capabilities of the original AutoNAV system, but required advancements that integrate the separate capabilities for shape modeling, state estimation, image rendering, defining a database of onboard maps, and performing real-time landmark recognition against the stored maps. The ability to use images to guide the spacecraft requires the capability for image-based feedback control. In Auto- GNC, navigation estimates are fed into an onboard guidance and control system that keeps the spacecraft guided along a desired path, as it descends towards its targeted landing or sampling site. Once near the site, AutoGNC achieves a prescribed guidance condition for TAG sampling (position/orientation, velocity), and a prescribed force profile on the sampling end-effector. A dedicated 6DOF TAG control then implements the ascent burn while recovering from sampling disturbances and induced attitude rates. The control also minimizes structural interactions with flexible solar panels and disallows any part of the spacecraft from making contact with the ground (other than the intended end-effector)

Peripheral Nervous System Genes Expressed in Central Neurons Induce Growth on Inhibitory Substrates

Trauma to the spinal cord and brain can result in irreparable loss of function. This failure of recovery is in part due to inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans (CSPGs). Peripheral nervous system (PNS) neurons exhibit increased regenerative ability compared to central nervous system neurons, even in the presence of inhibitory environments. Previously, we identified over a thousand genes differentially expressed in PNS neurons relative to CNS neurons. These genes represent intrinsic differences that may account for the PNS’s enhanced regenerative ability. Cerebellar neurons were transfected with cDNAs for each of these PNS genes to assess their ability to enhance neurite growth on inhibitory (CSPG) or permissive (laminin) substrates. Using high content analysis, we evaluated the phenotypic profile of each neuron to extract meaningful data for over 1100 genes. Several known growth associated proteins potentiated neurite growth on laminin. Most interestingly, novel genes were identified that promoted neurite growth on CSPGs (GPX3, EIF2B5, RBMX). Bioinformatic approaches also uncovered a number of novel gene families that altered neurite growth of CNS neurons

Vitamin D and breast cancer: interpreting current evidence

Preclinical investigations and selected clinical observational studies support an association between higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk. However, the recently updated report from the Institute of Medicine concluded that, for cancer and vitamin D, the evidence was 'inconsistent and insufficient to inform nutritional requirements'. Against this background, reports examining vitamin D intake, 25-hydroxyvitamin D levels and breast cancer incidence and outcome were reviewed. Current evidence supports the pursuit of several research questions but not routine 25-hydroxyvitamin D monitoring and vitamin D supplementation to reduce breast cancer incidence or improve breast cancer outcome

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo