No abstract

BackgroundVideoconferencing has been used to expand medical services to low-access populations and could increase access to genetic services at community sites where in-person visits with genetic providers are not available.ObjectiveTo evaluate the feasibility of, patient feedback of, and cognitive and affective responses to remote two-way videoconferencing (RVC) telegenetic services at multiple sociodemographically diverse community practices without access to genetic providers.MethodsPatients at 3 community sites in 2 US states outside the host center completed RVC pretest (visit 1, V1) and post-test (visit 2, V2) genetic counseling for cancer susceptibility. Surveys evaluated patient experiences, knowledge, satisfaction with telegenetic and cancer genetics services, anxiety, depression, and cancer worry.ResultsA total of 82 out of 100 (82.0%) approached patients consented to RVC services. A total of 61 out of 82 patients (74%) completed pretest counseling and 41 out of 61 (67%) proceeded with testing and post-test counseling. A total of 4 out of 41 (10%) mutation carriers were identified: BRCA2, MSH2, and PMS2. Patients reported many advantages (eg, lower travel burden and convenience) and few disadvantages to RVC telegenetic services. Most patients reported feeling comfortable with the video camera—post-V1: 52/57 (91%); post-V2: 39/41 (95%)—and that their privacy was respected—post-V1: 56/57 (98%); post-V2: 40/41 (98%); however, some reported concerns that RVC might increase the risk of a confidentiality breach of their health information—post-V1: 14/57 (25%); post-V2: 12/41 (29%). While the majority of patients reported having no trouble seeing or hearing the genetic counselor—post-V1: 47/57 (82%); post-V2: 39/41 (95%)—51 out of 98 (52%) patients reported technical difficulties. Nonetheless, all patients reported being satisfied with genetic services. Compared to baseline, knowledge increased significantly after pretest counseling (+1.11 mean score, P=.005); satisfaction with telegenetic (+1.74 mean score, P=.02) and genetic services (+2.22 mean score, P=.001) increased after post-test counseling. General anxiety and depression decreased after pretest (-0.97 mean anxiety score, P=.003; -0.37 mean depression score, P=.046) and post-test counseling (-1.13 mean anxiety score, P=.003; -0.75 mean depression score, P=.01); state anxiety and cancer-specific worry did not significantly increase.ConclusionsRemote videoconferencing telegenetic services are feasible, identify genetic carriers in community practices, and are associated with high patient satisfaction and favorable cognitive and affective outcomes, suggesting an innovative delivery model for further study to improve access to genetic providers and services. Potential barriers to dissemination include technology costs, unclear billing and reimbursement, and state requirements for provider licensure.

Extracelluar signal‐regulated kinase (ERK) pathway activation has been demonstrated following convulsant stimulation; however, little is known about the molecular targets of ERK in seizure models. Recently, it has been shown that ERK phosphorylates Kv4.2 channels leading to down‐regulation of channel function, and substantially alters dendritic excitability. In the kainate model of status epilepticus (SE), we investigated whether ERK phosphorylates Kv4.2 and whether the changes in Kv4.2 were evident at a synaptosomal level during SE. Western blotting was performed on rat hippocampal whole cell, membrane, synaptosomal, and surface biotinylated extracts following systemic kainate using an antibody generated against the Kv4.2 ERK sites and for Kv4.2, ERK, and phospho‐ERK. ERK activation was associated with an increase in Kv4.2 phosphorylation during behavioral SE. During SE, ERK activation and Kv4.2 phosphorylation were evident at the whole cell and synaptosomal levels. In addition, while whole‐cell preparations revealed no alterations in total Kv4.2 levels, a decrease in synaptosomal and surface expression of Kv4.2 was evident after prolonged SE. These results demonstrate ERK pathway coupling to Kv4.2 phosphorylation. The finding of decreased Kv4.2 levels in hippocampal synaptosomes and surface membranes suggest additional mechanisms for decreasing the dendritic A‐current, which could lead to altered intrinsic membrane excitability during SE.

Transcription factors IRF3 and NFκB, are activated by external stimuli, including virus infection, to translocate to the nucleus and bind genomic targets important for immunity and inflammation. To investigate RNA polymerase II (Pol II) recruitment and elongation in the human antiviral gene regulatory network, a comprehensive genome-wide analysis was conducted during the initial phase of virus infection. Results reveal extensive integration of IRF3 and NFκB, with Pol II and associated machinery, and implicate new partners for antiviral transcription. Analysis indicates that both de novo polymerase recruitment and stimulated release of paused polymerase work together to control virus-induced gene activation. In addition to known mRNA-encoding loci, IRF3 and NFκB, stimulate transcription at regions not previously associated with antiviral transcription, including abundant unannotated loci that encode novel virus-inducible RNAs (nviRNAs). These nviRNAs are widely induced by virus infections in diverse cell types and represent a previously overlooked cellular response to virus infection.

Investigating the relationship between immigration, middleman minority status, transnationalism, and U.S. foreign trade, the authors assembled a census‐based data file that contains aggregate‐level variables for 88 foreign‐born groups by national origin between 1980 and 1990. They regressed immigrant characteristics and immigration volume upon time‐lagged import/export statistics from the same 88 nations between 1985 and 1995. Results show the independent influence on exports of immigrant entrepreneurship, transnationalism, and middleman minority status. But these variables, exhaustively derived from the existing literature, had no effect on U.S. imports; they only affected exports. The authors propose that the discrepancy between imports and exports arises because of the dominance of English as a world business language. In this situation, foreigners need no help from immigrants when they export to the United States; but native‐born, monolingual Americans need the help of bicultural immigrants when they export. The empirical results suggest that immigrant entrepreneurs enhance the United States' exports and thus reduce the United States' balance of payments deficit.

No abstract

The immune reaction to pancreatic ductal adenocarcinoma (PDAC) is a strong prognostic determinant of clinical outcomes and may be a promising therapeutic target. We use multiplex immunohistochemistry to illustrate distinct patterns of T-cell and myeloid cell infiltration seen in PDAC that have therapeutic implications and discuss the current state of immunotherapy in this disease. Based on collective findings from clinical and preclinical studies, two conceptual models have emerged for applying immunotherapy in PDAC that involve (1) restoring elements of T-cell immunosurveillance and (2) redirecting myeloid cells to condition tumors with increased sensitivity to cytotoxic therapies. Overall, the success of immunotherapy in PDAC will most likely rely on strategic combinations of therapies that are informed by well-designed correlative analyses that consider the spatial heterogeneity of immune responses detected in malignant tissues.

Published models of the engineering design process are widely available and often illustrated for students with a block diagram showing design as sequential and iterative. Here we examine experts' conceptions of the design process in relation to a model synthesized from several introductory engineering textbooks. How do experts' conceptions compare? What might they see as alternative accounts? We present preliminary results from an investigation of practicing engineers (n=19) who were asked to think aloud while reading a description of this "textbook" model, as well as draw their idea of the engineering design process and choose descriptors of design. Only 3 participants were found to have a view in major disagreement with the model, yet 7 drew alternative types of diagrams, and the experts as a whole emphasized problem scoping and communication. We focus especially on the case of one engineer who commented extensively on communication, articulating a view of engineering design as open, multi-participant, and multidisciplinary, with implications for how to conceptualize expertise in engineering problem solving.