Pharmacovigilance in pregnancy: adverse drug reactions associated with fetal disorders.

Abstract Objective: To provide the first update on drug safety profiles and adverse drug reactions (ADRs) associated with fetal disorders from the Swiss national ADR database. Methods: We conducted a retrospective study using data from 202 pharmacovigilance reports on drug-associated fetal disorders from the Swiss national ADR database from 1990 to 2009. Evaluated aspects included administrative information on the report, drug exposure, and disorders. Results: The ADR reporting frequency on the topic of fetal disorders has increased during the last 20 years, from only 1 report in 1991 to a maximum of 31 reports in 2008. Nervous system drugs were the most frequently reported drug group (40.2%) above all antidepressants and antiepileptics. The highest level of overall drug intake could be observed for the 1st trimester (85.4%), especially for the first 6 weeks of pregnancy. The most frequently reported types of fetal disorders were malformations (68.8%), especially those of the musculoskeletal and circulatory systems. A positive association was discovered between antiepileptics and malformations in general and in particular of the circulatory system and the eye, ear, face, and neck. Conclusions: The results suggest that the nervous system drug group bears an especially high risk for malformations. The most commonly identified drug exposures can help focus pharmacoepidemiologic efforts in drug-induced birth defects

Genetic and transcriptomic analysis of transcription factor genes in the model halophilic Archaeon: coordinate action of TbpD and TfbA

<p>Abstract</p> <p>Background</p> <p>Archaea are prokaryotic organisms with simplified versions of eukaryotic transcription systems. Genes coding for the general transcription factors TBP and TFB are present in multiple copies in several Archaea, including <it>Halobacterium </it>sp. NRC-1. Multiple TBP and TFBs have been proposed to participate in transcription of genes via recognition and recruitment of RNA polymerase to different classes of promoters.</p> <p>Results</p> <p>We attempted to knock out all six TBP and seven TFB genes in <it>Halobacterium </it>sp. NRC-1 using the <it>ura</it>3-based gene deletion system. Knockouts were obtained for six out of thirteen genes, <it>tbp</it>CDF and <it>tfb</it>ACG, indicating that they are not essential for cell viability under standard conditions. Screening of a population of 1,000 candidate mutants showed that genes which did not yield mutants contained less that 0.1% knockouts, strongly suggesting that they are essential. The transcriptomes of two mutants, Δ<it>tbp</it>D and Δ<it>tfb</it>A, were compared to the parental strain and showed coordinate down regulation of many genes. Over 500 out of 2,677 total genes were regulated in the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutants with 363 regulated in both, indicating that over 10% of genes in both strains require the action of both TbpD and TfbA for normal transcription. Culturing studies on the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains showed them to grow more slowly than the wild-type at an elevated temperature, 49°C, and they showed reduced viability at 56°C, suggesting TbpD and TfbA are involved in the heat shock response. Alignment of TBP and TFB protein sequences suggested the expansion of the TBP gene family, especially in <it>Halobacterium </it>sp. NRC-1, and TFB gene family in representatives of five different genera of haloarchaea in which genome sequences are available.</p> <p>Conclusion</p> <p>Six of thirteen TBP and TFB genes of <it>Halobacterium </it>sp. NRC-1 are non-essential under standard growth conditions. TbpD and TfbA coordinate the expression of over 10% of the genes in the NRC-1 genome. The Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains are temperature sensitive, possibly as a result of down regulation of heat shock genes. Sequence alignments suggest the existence of several families of TBP and TFB transcription factors in <it>Halobacterium </it>which may function in transcription of different classes of genes.</p

Improving Trip Generation Methods for Livable Communities

Recent efforts to improve trip generation data available for transportation impact analysis of new development include the collection of multimodal trip generation data, development of models that account for the built environment, and new recommendations for practice. Building on a long line of research on transportation and built environment, many studies have identified important features of the surrounding built environment that most impact trip rates and mode shares, building on a long line of research on transportation and the built environment. Despite these improvements in data and methods, less attention is placed on identifying the conditions of the site itself and the immediate surrounding environment that influence trip generation and mode choice. To fill this gap, this study builds upon previous work (Contextual Influences on Trip Generation (Project Number: OTREC 2011-407), 2012), re-examines the information collected in that study, and includes new site-level observations. The objective of this study is to examine establishment multimodal trip generation more closely from a finer-grained scale and identify site-level attributes of the built environment that help explain multimodal trip generation. From this, we have the additional objective of developing a framework for trip generation analysis that takes findings from this study into consideration. We placed emphasis on those sites in our previous study with a discord between the expected travel patterns, based upon the larger urban context and built environment of the site, and the observed. The research approach will make use of mixed methods. In addition to using archived data from the previous study, site visits provided direct observation of the overall performance of the site, including travel patterns on and around the site as well as specific site configuration, urban design details and traffic operations. The analysis of this combination of data provided a more complete picture of site-level trip generation and our findings highlight the influence of: people living nearby and using the site; the nature of the land use on the site; the development along arterial roadways; site permeability and access; and the local culture around walking and cycling. Finally, this report ends by reflecting on the numerous concerns identified from practice, the research findings from various recent studies, and the need for a sustainable process for evaluating the transportation impacts of new land development. We present a potential framework to advance the methods for how site plans fit into neighborhood and regional planning, using locally defined standards and goals. Here, we de-emphasize the site and its immediate environs as the primary (and only) scale of analysis and lessen the reliance on the problematic methodologies for estimating site-level travel demand. Rather, we argue that transportation impact analysis would benefit by first taking a district, neighborhood or area-wide approach with attention to the urban context—the built and social environment—where a site is located. At this larger scale, there is a better ability to understand the various elements that work together to shape travel demand and allows for a better assessment of how a specific site proposal will integrate into this larger context. This effort involves several faculty from across the country, including Kelly Clifton (PSU Engineering) and Nico Larco (UO Architecture) from our consortium and Susan Handy (UC Davis Environmental Studies) and Robert Schneider (UW Milwaukee Planning) as consultants/advisors

United-pulse : feeling your partner's pulse

This paper introduces a device that creates remote intimacy by the use of two rings named “united-pulse”. Each ring can measure the wearer’s heartbeat and send it to the partner’s ring. Hereby, artificial corporeality is created between the couple. By means of a working prototype, united-pulse has been successfully tested. Among the 28 participants the prototype has attracted large interest. Through the heartbeat – the essential vital sign – a feeling of being very close to the partner is provided. Touching the ring allows a small moment of intimacy in situations where emotional support is needed

Exploring vibrotactile feedback on the body and foot for the purpose of pedestrian navigation

In this paper, we present an evaluation of vibrotactile onbody feedback for the purpose of pedestrian navigation. For this specific task, many researchers already provide different approaches such as vibrating belts, wristbands or shoes. Still, there are issues left that have to be considered, such as which body position is most suitable, what kind of vibration patterns are easy to interpret, and how applicable are vibrotactile feedback systems in real scenarios. To find answers, we reconstructed prototypes commonly found in literature and continued to further evaluate different foot-related designs. On the one hand, we learned that vibrotactile feedback at the foot reduces visual attention and thus also potentially reduces stress. However, on the other hand, we found that urban space can be very diverse, and ambiguous and therefore a vibrotactile system cannot completely replace common path finding systems for pedestrians. Rather, we envision such a system to be applied complementary as an assistive technology