Optimal low-thrust trajectories to asteroids through an algorithm based on differential dynamic programming

In this paper an optimisation algorithm based on Differential Dynamic Programming is applied to the design of rendezvous and fly-by trajectories to near Earth objects. Differential dynamic programming is a successive approximation technique that computes a feedback control law in correspondence of a fixed number of decision times. In this way the high dimensional problem characteristic of low-thrust optimisation is reduced into a series of small dimensional problems. The proposed method exploits the stage-wise approach to incorporate an adaptive refinement of the discretisation mesh within the optimisation process. A particular interpolation technique was used to preserve the feedback nature of the control law, thus improving robustness against some approximation errors introduced during the adaptation process. The algorithm implements global variations of the control law, which ensure a further increase in robustness. The results presented show how the proposed approach is capable of fully exploiting the multi-body dynamics of the problem; in fact, in one of the study cases, a fly-by of the Earth is scheduled, which was not included in the first guess solution

Familial Bainbridge-Ropers syndrome: report of familial ASXL3 inheritance and a milder phenotype

De novo truncating and splicing pathogenic variants in the Additional Sex Combs-Like 3 (ASXL3) gene are known to cause neurodevelopmental delay, intellectual disability, behavioral difficulties, hypotonia, feeding problems and characteristic facial features. We previously reported 45 patients with ASXL3-related disorder including three individuals with a familial variant. Here we report the detailed clinical and molecular characteristics of these three families with inherited ASXL3-related disorder. First, a father and son with c.2791_2792del p.Gln931fs pathogenic variant. The second, a mother, daughter and son with c.4534C > T, p.Gln1512Ter pathogenic variant. The third, a mother and her daughter with c.4441dup, p.Leu1481fs maternally inherited pathogenic variant. This report demonstrates intrafamilial phenotypic heterogeneity and confirms heritability of ASXL3-related disorder

Implementation of a pharmacogenomics consult service to support the INGENIOUS trial

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding

Practice level factors associated with enhanced engagement with practice facilitators; findings from the heart health now study

Background: Practice facilitation is a promising strategy to enhance care processes and outcomes in primary care settings. It requires that practices and their facilitators engage as teams to drive improvement. In this analysis, we explored the practice and facilitator factors associated with greater team engagement at the mid-point of a 12-month practice facilitation intervention focused on implementing cardiovascular prevention activities in practice. Understanding factors associated with greater engagement with facilitators in practice-based quality improvement can assist practice facilitation programs with planning and resource allocation. Methods: One hundred thirty-six ambulatory care small to medium sized primary care practices that participated in the EvidenceNow initiative's NC Cooperative, named Heart Health Now (HHN), fit the eligibility criteria for this analysis. We explored the practice and facilitator factors associated with greater team engagement at the mid-point of a 12-month intervention using a retrospective cohort design that included baseline survey data, monthly practice activity implementation data and information about facilitator's experience. Generalized linear mixed-effects models (GLMMs) identified variables associated with greater odds of team engagement using an ordinal scale for level of team engagement. Results: Among our practice cohort, over half were clinician-owned and 27% were Federally Qualified Health Centers. The mean number of clinicians was 4.9 (SD 4.2) and approximately 40% of practices were in Medically Underserved Areas (MUA). GLMMs identified a best fit model. The Model presented as odd ratios and 95% confidence intervals suggests greater odds ratios of higher team engagement with greater practice QI leadership 17.31 (5.24-57.19), [0.00], and practice location in a MUA 7.25 (1.8-29.20), [0.005]. No facilitator characteristics were independently associated with greater engagement. Conclusions: Our analysis provides information for practice facilitation stakeholders to consider when considering which practices may be more amendable to embracing facilitation services

Comparative genomics of plant-asssociated Pseudomonas spp.: Insights into diversity and inheritance of traits involved in multitrophic interactions

We provide here a comparative genome analysis of ten strains within the Pseudomonas fluorescens group including seven new genomic sequences. These strains exhibit a diverse spectrum of traits involved in biological control and other multitrophic interactions with plants, microbes, and insects. Multilocus sequence analysis placed the strains in three sub-clades, which was reinforced by high levels of synteny, size of core genomes, and relatedness of orthologous genes between strains within a sub-clade. The heterogeneity of the P. fluorescens group was reflected in the large size of its pan-genome, which makes up approximately 54% of the pan-genome of the genus as a whole, and a core genome representing only 45–52% of the genome of any individual strain. We discovered genes for traits that were not known previously in the strains, including genes for the biosynthesis of the siderophores achromobactin and pseudomonine and the antibiotic 2-hexyl-5-propyl-alkylresorcinol; novel bacteriocins; type II, III, and VI secretion systems; and insect toxins. Certain gene clusters, such as those for two type III secretion systems, are present only in specific sub-clades, suggesting vertical inheritance. Almost all of the genes associated with multitrophic interactions map to genomic regions present in only a subset of the strains or unique to a specific strain. To explore the evolutionary origin of these genes, we mapped their distributions relative to the locations of mobile genetic elements and repetitive extragenic palindromic (REP) elements in each genome. The mobile genetic elements and many strain-specific genes fall into regions devoid of REP elements (i.e., REP deserts) and regions displaying atypical tri-nucleotide composition, possibly indicating relatively recent acquisition of these loci. Collectively, the results of this study highlight the enormous heterogeneity of the P. fluorescens group and the importance of the variable genome in tailoring individual strains to their specific lifestyles and functional repertoir

Why is management research irrelevant?

At least since 1980, there has been a practically continuous, but somewhat fragmented discussion on the relevance of management research. This discussion has addressed practically all fields of management; here, besides general management, operations management, project management and construction management are examined in more detail. Although many different proposals have been made to rectify the situation, no definitive resolution has been found. In this paper, it is argued that prior analyses have not reached the root causes of the irrelevance problem. By an analysis of the recent history of management research, the following novel findings are reached. First, the root cause of the irrelevance is argued to lie in the 1959 reports on American business education, written by Pierson and Gordon & Howell. Second, while the proposed direction in the 1959 reports was deficient in several ways, the rejection of production as an integral part of organizations and management has been perhaps the most damaging feature of those reports. Third, current research on management suffers from a variety of immediate causes for irrelevance, insufficiently recognized by the scholarly community. It is suggested that reaching the root causes for irrelevance will facilitate finding suitable cures

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy