Graphical programming and the use of simulation for space-based manipulators

Robotic manipulators are difficult to program even without the special requirements of a zero-gravity environment. While attention should be paid to investigating the usefulness of industrial application programming methods to space manipulators, new methods with potential application to both environments need to be invented. These methods should allow various levels of autonomy and human-in-the-loop interaction and simple, rapid switching among them. For all methods simulation must be integrated to provide reliability and safety. Graphical programming of manipulators is a candidate for an effective robot programming method despite current limitations in input devices and displays. A research project in task-level robot programming has built an innovative interface to a state-of-the-art commercial simulation and robot programming platform. The prototype demonstrates simple augmented methods for graphical programming and simulation which may be of particular interest to those concerned with Space Station applications; its development has also raised important issues for the development of more sophisticated robot programming tools. Both aspects of the project are discussed

Prehabilitation for Shoulder Dysfunction in Breast Cancer

Objective: To evaluate prehabilitation exercises to improve shoulder pain and abduction range of motion (ROM) after breast cancer surgery; to evaluate methods of exercise teaching; to assess postsurgical seroma formation. Design: Pilot study Setting: Academic medical center Participants: 60 breast cancer patients were randomly assigned to either personal exercise instruction, group 1, n=36, or video only instruction, group 2, n=24. Interventions: Shoulder exercises were assigned to both groups 1 month prior to surgery at an outpatient visit. Group 1 received personal instruction on exercises, plus written exercise instruction, and a link to access an online video. Group 2 received only written exercise instruction and a link to access the online video. Main Outcome Measures: Exercise compliance, pain (via visual analog scale), shoulder abduction ROM (via goniometer), and presence or absence of seroma. Results or Clinical Course: 76% of study patients chose to exercise. There was no difference in exercise compliance between personal instruction versus video teaching. (75%, 24/32 in-person vs. 77%, 10/13 video only, OR=1.03). 66% of patients (20/30) lost greater than 10 degrees shoulder abduction ROM at 1 month post surgery. 29% of patients (9/31) had worse shoulder pain at one month post surgery than at baseline (24%, 6/25 exercisers, and 50%, 3/6 non-exercisers). 15% of patients (4/27) had worse shoulder pain at 3 months post surgery than at baseline (8%, 2/25 exercisers, and 100%, 2/2 non-exercisers). Prehabilitation exercise program inferred no additional risk of seroma formation (21%, 7/33 exercisers vs. 22%, 2/9 non-exercisers OR=.94). Conclusion: In-person teaching does not appear superior to video teaching for prehabilitation exercises in breast cancer. A high quality randomized controlled trial is necessary to assess efficacy of prehabilitation for improving post surgical outcomes. Prehabilitation exercises do not appear to increase risk of seroma formation in breast cancer surgery

MyD88 in lung resident cells governs airway inflammatory and pulmonary function responses to organic dust treatment.

Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in MyD88 KO tracheal epithelial cells as compared to wild type (WT) control. Similarly, the normative ODE-induced slowing of cell migration in response to wound repair was aberrant in MyD88 KO cells. Next, we created MyD88 bone marrow chimera mice to investigate the relative contribution of MyD88-dependent signaling in lung resident (predominately epithelial cells) versus hematopoietic cells. Importantly, we demonstrate that ODE-induced airway hyperresponsiveness is MyD88-dependent in lung resident cells, whereas MyD88 action in hematopoietic cells is mainly responsible for ODE-induced TNF-α release. MyD88 signaling in lung resident and hematopoietic cells are necessary for ODE-induced IL-6 and neutrophil chemoattractant (CXCL1 and CXCL2) release and neutrophil influx. Collectively, these findings underscore an important role for MyD88 in lung resident cells for regulating ciliary motility, wound repair and inflammatory responses to ODE, and moreover, show that airway hyperresponsiveness appears uncoupled from airway inflammatory consequences to organic dust challenge in terms of MyD88 involvement

The National Childrens Study: Recruitment Outcomes Using the Provider-Based Recruitment Approach

In 2009, the National Children’s Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment using a birth-rate probability sample. In 2010, the NCS Program Office launched 3 additional recruitment approaches. We tested whether provider-based recruitment could improve recruitment outcomes compared with household-based recruitment

αβ T cells and a mixed Th1/Th17 response are important in organic dust-induced airway disease

Abstract Background Organic dust exposure in agricultural environments induces an inflammatory response that attenuates over time, yet repetitive dust exposures result in chronic lung diseases. Animal models resembling this chronic lung inflammatory response have been developed, yet the underlying cellular mechanisms are not well defined. Objective Because mice repetitively exposed to organic dust extracts (DE) display increased CD3+ T cell lung infiltrates, we sought to determine the phenotype and importance of these cells. Methods Mice received swine confinement DE repetitively for 3 weeks by established intranasal inhalation protocol. Studies were conducted with peptidoglycan (PGN) because it is a major DE component in large animal farming environments and has shared similar biologic effects with DE. Enumeration of T cells and intracellular cytokine profiles were conducted by flow cytometry techniques. Whole lung homogenate cytokines were analyzed by multiplex immunoassay. T cell receptor (TCR) αβ knockouts were used to determine the functional importance of αβ-expressing T cells. Results DE increased lung-associated CD3+CD4+ T cells and interleukin (IL)-17 (but not IL-4, interferon [IFN]-γ, IL-10) producing CD4+ T cells. PGN treatment resulted in increased IL-17 and IFN-γ producing CD4+ T cells and IFN-γ producing CD8+ T cells. Both DE and PGN augmented expression of cytokines associated with Th1 and Th17 polarization in lung homogenates. DE-induced lung mononuclear aggregates and bronchiolar compartment inflammation were significantly reduced in TCR knockout animals; however, neutrophil influx and alveolar compartment inflammation were not affected. Conclusion Studies demonstrated that DE and PGN exposure promote a Th1/Th17 lung microenvironment and that αβ-expressing T cells are important in mediating DE-induced lung pathologic conditions

CD11c + /CD11b + Cells Are Critical for Organic Dust–Elicited Murine Lung Inflammation

Organic dust exposure in the agricultural industry results in significant lung disease. Macrophage infiltrates are increased in the lungs after organic dust exposures, yet the phenotype and functional importance of these cells remain unclear. Using an established intranasal inhalation murine model of dust-induced lung inflammation, animals were treated once or daily for 3 weeks with swine confinement organic dust extract (DE). Repetitive DE treatment for 3 weeks resulted in significant increases in CD11c+/CD11b+ macrophages in whole lung–associated tissue. These cells displayed increased costimulatory molecule (CD80 and CD86) expression, enhanced phagocytic ability, and an increased production of IL-6, CXCL1, and CXCL2. Similar findings were observed with the CD11c+/CD11b+ macrophage infiltrate after repetitive exposure to peptidoglycan, a major DE component. To determine the functional importance of macrophages in mediating DE-induced airway inflammation, lung macrophages were selectively depleted using a well-established intranasal clodronate liposome depletion/suicide strategy. First, macrophage depletion by clodronate liposomes resulted in significant reductions in airway neutrophil influx and TNF-α and IL-6 production after a single exposure to DE. In contrast, after repetitive 3-week exposure to DE, airway lavage fluid and lung tissue neutrophils were significantly increased in clodronate liposome–treated mice compared with control mice. A histological examination of lung tissue demonstrated striking increases in alveolar and bronchiolar inflammation, as well as in the size and distribution of cellular aggregates in clodronate–liposome versus saline–liposome groups repetitively exposed to DE. These studies demonstrate that DE elicits activated CD11c+/CD11b+ macrophages in the lung, which play a critical role in regulating the outcome of DE-induced airway inflammation

Association of DASH Diet With Cardiovascular Risk Factors in Youth With Diabetes Mellitus: The SEARCH for Diabetes in Youth Study

We have shown that adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is related to blood pressure in youth with type 1 and type 2 diabetes mellitus. We explored the impact of the DASH diet on other cardiovascular disease risk factors

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin