Assembly of objects with not fully predefined shapes

An assembly problem in a non-deterministic environment, i.e., where parts to be assembled have unknown shape, size and location, is described. The only knowledge used by the robot to perform the assembly operation is given by a connectivity rule and geometrical constraints concerning parts. Once a set of geometrical features of parts has been extracted by a vision system, applying such a rule allows the dtermination of the composition sequence. A suitable sensory apparatus allows the control the whole operation

The Impact of Rural Nebraska Industrial Development on the Migration of Rural Youth

For more than a century Americans have migrated from the rural communities in which they were raised, but by 1970 this process had begun to change. Nebraska, however, has not reflected this change, and Nebraskans have continued to leave non-metropolitan areas in large numbers. By 1976 the State stood alone among seven central and southern plains states in having non-metropolitan population losses (Miller, 1978)

Combining Flexible Queries and Knowledge Anchors to facilitate the exploration of Knowledge Graphs

Semantic web and information extraction technologies are enabling the creation of vast information and knowledge repositories, particularly in the form of knowledge graphs comprising entities and the relationships between them. Users are often unfamiliar with the complex structure and vast content of such graphs. Hence, users need to be assisted by tools that support interactive exploration and flexible querying. In this paper we draw on recent work in flexible querying for graph-structured data and identifying good anchors for knowledge graph exploration in order to demonstrate how users can be supported in incrementally querying, exploring and learning from large complex knowledge graphs. We demonstrate our techniques through a case study in the domain of lifelong learning and career guidance

Combining flexible queries and knowledge anchors to facilitate the exploration of knowledge graphs

Semantic web and information extraction technologies are enabling the creation of vast information and knowledge repositories, particularly in the form of knowledge graphs comprising entities and the relationships between them. Users are often unfamiliar with the complex structure and vast content of such graphs. Hence, users need to be assisted by tools that support interactive exploration and flexible querying. In this paper we draw on recent work in flexible querying for graph-structured data and identifying good anchors for knowledge graph exploration in order to demonstrate how users can be supported in incrementally querying, exploring and learning from large complex knowledge graphs. We demonstrate our techniques through a case study in the domain of lifelong learning and career guidance

A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies.

Purpose Avadomide is a novel, small-molecule therapeutic agent that modulates cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory activities. This first-in-human phase I study (NCT01421524) evaluated the safety and clinical activity of avadomide in patients with advanced solid tumors, non-Hodgkin lymphoma (NHL), and multiple myeloma.Patients and methods Thirty-four patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3 design (0.5-3.5 mg, 28-day continuous dosing cycles). The primary objectives were to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of avadomide. The secondary objective was to determine preliminary avadomide efficacy. Exploratory objectives included evaluation of pharmacodynamic effects of avadomide.Results DLTs were reported in 2 patients, and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common TEAEs (≥15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5 and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response, and 2 had partial responses. Although no objective responses were observed in patients with solid tumors, 5 of 6 patients with brain cancer experienced nonprogression of ≥6 months. A dose-dependent relationship between Aiolos degradation in peripheral B and T cells occurred within 5 hours of the first dose of avadomide administered, starting at 0.5 mg.Conclusions Avadomide monotherapy demonstrated acceptable safety and favorable pharmacokinetics in patients with solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were observed in NHL

SMaRT lncRNA controls translation of a G-quadruplex-containing mRNA antagonizing the DHX36 helicase

Guanine-quadruplexes (G4) included in RNA molecules exert several functions in controlling gene expression at post-transcriptional level; however, the molecular mechanisms of G4-mediated regulation are still poorly understood. Here, we describe a regulatory circuitry operating in the early phases of murine muscle differentiation in which a long non-coding RNA (SMaRT) base pairs with a G4-containing mRNA (Mlx-γ) and represses its translation by counteracting the activity of the DHX36 RNA helicase. The time-restricted, specific effect of lnc-SMaRT on the translation of Mlx-γ isoform modulates the general subcellular localization of total MLX proteins, impacting on their transcriptional output and promoting proper myogenesis and mature myotube formation. Therefore, the circuitry made of lnc-SMaRT, Mlx-γ, and DHX36 not only plays an important role in the control of myogenesis but also unravels a molecular mechanism where G4 structures and G4 unwinding activities are regulated in living cells

Expanding phenotype of schimke immuno-osseous dysplasia: Congenital anomalies of the kidneys and of the urinary tract and alteration of nk cells

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype\u2013genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD\u2014both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7R\u3b1 expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies

Elaborating on theory with middle managers’ experience implementing healthcare innovations in practice

Abstract Background The theory of middle managers’ role in implementing healthcare innovations hypothesized that middle managers influence implementation effectiveness by fulfilling the following four roles: diffusing information, synthesizing information, mediating between strategy and day-to-day activities, and selling innovation implementation. The theory also suggested several activities in which middle managers might engage to fulfill the four roles. The extent to which the theory aligns with middle managers’ experience in practice is unclear. We surveyed middle managers (n = 63) who attended a nursing innovation summit to (1) assess alignment between the theory and middle managers’ experience in practice and (2) elaborate on the theory with examples from middle managers’ experience overseeing innovation implementation in practice. Findings Middle managers rated all of the theory’s hypothesized four roles as “extremely important” but ranked diffusing and synthesizing information as the most important and selling innovation implementation as the least important. They reported engaging in several activities that were consistent with the theory’s hypothesized roles and activities such as diffusing information via meetings and training. They also reported engaging in activities not described in the theory such as appraising employee performance. Conclusions Middle managers’ experience aligned well with the theory and expanded definitions of the roles and activities that it hypothesized. Future studies should assess the relationship between hypothesized roles and the effectiveness with which innovations are implemented in practice. If evidence supports the theory, the theory should be leveraged to promote the fulfillment of hypothesized roles among middle managers, doing so may promote innovation implementation

Impact of the COVID-19 pandemic on the implementation of mobile health to improve the uptake of hydroxyurea in patients with sickle cell disease: Mixed methods study

BACKGROUND: Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. METHODS: The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients\u27 daily app use. Adherence to hydroxyurea was calculated as the proportion of days covered (PDC) from prescription records over the first 12 and 24 weeks after implementation. A linear model examined the relationship between app usage and PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured interviews with patients, health care providers, administrators, and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed methods approach to investigate the convergence of qualitative and quantitative findings. RESULTS: The percentage of patients accessing the app decreased after March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: -8.2%; P=.14; 24 weeks: -10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B\u27s closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. CONCLUSIONS: We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may insulate the implementation of interventions to increase medication adherence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080167; https://clinicaltrials.gov/ct2/show/NCT04080167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/16319