108 research outputs found

    Quick Response Freight Manual II

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    DTFH61-06-D-00004This manual is an update to the Quick Response Freight Manual developed for FHWA in 1996. Like its predecessor, it is designed to provide background information on the freight transportation system and factors affecting freight demand to planners who may be relatively new to this area; to help planners locate available data and freight-related forecasts compiled by others, and to apply this information in developing forecasts for specific facilities; to provide simple techniques and transferable parameters that can be used to develop freight vehicle trip tables

    Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair

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    Double strand breaks (DSBs) and interstrand crosslinks (ICLs) are toxic DNA lesions that can be repaired through multiple pathways, some of which involve shared proteins. One of these proteins, DNA Polymerase theta (Pol theta), coordinates a mutagenic DSB repair pathway named microhomology-mediated end joining (MMEJ) and is also a critical component for bypass or repair of ICLs in several organisms. Pol theta contains both polymerase and helicase-like domains that are tethered by an unstructured central region. While the role of the polymerase domain in promoting MMEJ has been studied extensively both in vitro and in vivo, a function for the helicase-like domain, which possesses DNA-dependent ATPase activity, remains unclear. Here, we utilize genetic and biochemical analyses to examine the roles of the helicase-like and polymerase domains of Drosophila Pol theta. We demonstrate an absolute requirement for both polymerase and ATPase activities during ICL repair in vivo. However, similar to mammalian systems, polymerase activity, but not ATPase activity, is required for ionizing radiation-induced DSB repair. Using a site-specific break repair assay, we show that overall end-joining efficiency is not affected in ATPase-dead mutants, but there is a significant decrease in templated insertion events. In vitro, Pol theta can efficiently bypass a model unhooked nitrogen mustard crosslink and promote DNA synthesis following microhomology annealing, although ATPase activity is not required for these functions. Together, our data illustrate the functional importance of the helicase-like domain of Pol theta and suggest that its tethering to the polymerase domain is important for its multiple functions in DNA repair and damage tolerance

    Attitudes toward and experiences of gender issues among physician teachers: A survey study conducted at a university teaching hospital in Sweden

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    <p>Abstract</p> <p>Background</p> <p>Gender issues are important to address during medical education, however research about the implementation of gender in medical curricula reports that there are obstacles. The aim of this study was to explore physician teachers' attitudes to gender issues.</p> <p>Methods</p> <p>As part of a questionnaire, physician teachers at Umeå University in Sweden were given open-ended questions about explanations for and asked to write examples why they found gender important or not. The 1 469 comments from the 243 respondents (78 women, 165 men) were analyzed by way of content analysis. The proportion of comments made by men and women in each category was compared.</p> <p>Results</p> <p>We found three themes in our analysis: Understandings of gender, problems connected with gender and approaches to gender. Gender was associated with differences between women and men regarding behaviour and disease, as well as with inequality of life conditions. Problems connected with gender included: delicate situations involving investigations of intimate body parts or sexual attraction, different expectations on male and female physicians and students, and difficulty fully understanding the experience of people of the opposite sex. The three approaches to gender that appeared in the comments were: 1) avoidance, implying that the importance of gender in professional relationships was recognized but minimized by comparing gender with aspects, such as personality and neutrality; 2) simplification, implying that gender related problems were easy to address, or already solved; and 3) awareness, implying that the respondent was interested in gender issues or had some insights in research about gender. Only a few individuals described gender as an area of competence and knowledge. There were comments from men and women in all categories, but there were differences in the relative weight for some categories. For example, recognizing gender inequities was more pronounced in the comments from women and avoidance more common in comments from men.</p> <p>Conclusion</p> <p>The surveyed physician teachers gave many examples of gender-related problems in medical work and education, but comments describing gender as an area of competence and knowledge were few. Approaches to gender characterized by avoidance and simplification suggest that faculty development programs on gender need to address and reflect on attitudes as well as knowledge.</p

    Effects of a refugee elective on medical student perceptions

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    <p>Abstract</p> <p>Background</p> <p>There are growing numbers of refugees throughout the world. Refugee health is a relatively unstudied and rarely taught component of medical education. In response to this need, a Refugee Health Elective was begun. Medical student perceptions toward cultural aspects of medicine and refugee health before and after participation in the elective were measured.</p> <p>Methods</p> <p>Preliminary questionnaires were given to all preclinical students at the academic year commencement with follow-up questionnaires at the refugee elective's conclusion. Both questionnaires examined students' comfort in interacting with patients and familiarity with refugee medical issues, alternative medical practices, and social hindrances to medical care. The preliminary answers served as a control and follow-up questionnaire data were separated into participant/non-participant categories. All preclinical medical students at two Midwestern medical schools were provided the opportunity to participate in the Refugee Health Elective and surveys. The 3 data groups were compared using unadjusted and adjusted analysis techniques with the Kruskall-Wallis, Bonferroni and ANCOVA adjustment. P-values < 0.05 were considered significant.</p> <p>Results</p> <p>408 and 403 students filled out the preliminary and follow-up questionnaires, respectfully, 42 of whom participated in the elective. Students considering themselves minorities or multilingual were more likely to participate. Elective participants were more likely to be able to recognize the medical/mental health issues common to refugees, to feel comfortable interacting with foreign-born patients, and to identify cultural differences in understanding medical/mental health conditions, after adjusting for minority or multilingual status.</p> <p>Conclusion</p> <p>As medical schools integrate a more multicultural curriculum, a Refugee Health Elective for preclinical students can enhance awareness and promote change in attitude toward medical/mental health issues common to refugees. This elective format offers tangible and effective avenues for these topics to be addressed.</p

    Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

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    BACKGROUND: For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. METHODS: The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. RESULTS: Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. CONCLUSIONS: For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review

    Cohesin-dependence of neuronal gene expression relates to chromatin loop length

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    Cohesin and CTCF are major drivers of 3D genome organization, but their role in neurons is still emerging. Here, we show a prominent role for cohesin in the expression of genes that facilitate neuronal maturation and homeostasis. Unexpectedly, we observed two major classes of activity-regulated genes with distinct reliance on cohesin in mouse primary cortical neurons. Immediate early genes (IEGs) remained fully inducible by KCl and BDNF, and short-range enhancer-promoter contacts at the IEGs Fos formed robustly in the absence of cohesin. In contrast, cohesin was required for full expression of a subset of secondary response genes characterized by long-range chromatin contacts. Cohesin-dependence of constitutive neuronal genes with key functions in synaptic transmission and neurotransmitter signaling also scaled with chromatin loop length. Our data demonstrate that key genes required for the maturation and activation of primary cortical neurons depend on cohesin for their full expression, and that the degree to which these genes rely on cohesin scales with the genomic distance traversed by their chromatin contacts. Editor'

    Stereotyping of medical disability claimants' communication behaviour by physicians: towards more focused education for social insurance physicians

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    Background: Physicians who hold medical disability assessment interviews (social insurance physicians) are probably influenced by stereotypes of claimants, especially because they have limited time available and they have to make complicated decisions. Because little is known about the influences of stereotyping on assessment interviews, the objectives of this paper were to qualitatively investigate: (1) the content of stereotypes used to classify claimants with regard to the way in which they communicate; (2) the origins of such stereotypes; (3) the advantages and disadvantages of stereotyping in assessment interviews; and (4) how social insurance physicians minimise the undesirable influences of negative stereotyping. Methods: Data were collected during three focus group meetings with social insurance physicians who hold medical disability assessment interviews with sick-listed employees (i.e. claimants). The participants also completed a questionnaire about demographic characteristics. The data were qualitatively analysed in Atlas.ti in four steps, according to the grounded theory and the principle of constant comparison. Results: A total of 22 social insurance physicians participated. Based on their responses, a claimant's communication was classified with regard to the degree of respect and acceptance in the physician-claimant relationship, and the degree of dominance. Most of the social insurance physicians reported that they classify claimants in general groups, and use these classifications to adapt their own communication behaviour. Moreover, the social insurance physicians revealed that their stereotypes originate from information in the claimants' files and first impressions. The main advantages of stereotyping were that this provides a framework for the assessment interview, it can save time, and it is interesting to check whether the stereotype is correct. Disadvantages of stereotyping were that the stereotypes often prove incorrect, they do not give the complete picture, and the claimant's behaviour changes constantly. Social insurance physicians try to minimise the undesirable influences of stereotypes by being aware of counter transference, making formal assessments, staying neutral to the best of their ability, and being compassionate. Conclusions: We concluded that social insurance physicians adapt their communication style to the degree of respect and dominance of claimants in the physician-claimant relationship, but they try to minimise the undesirable influences of stereotypes in assessment interviews. It is recommended that this issue should be addressed in communication skills trainin

    Image perception and interpretation of abnormalities; can we believe our eyes? Can we do something about it?

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    The radiologist’s visual impression of images is transmitted, via non-visual means (the report), to the clinician. There are several complex steps from the perception of the images by the radiologist to the understanding of the impression by the clinician. With a process as complex as this, it is no wonder that errors in perception, cognition, interpretation, transmission and understanding are very common. This paper reviews the processes of perception and error generation and possible strategies for minimising them

    Ortholog of the polymerase theta helicase domain modulates DNA replication in Trypanosoma cruzi

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    DNA polymerase theta (Polθ), a member of the DNA polymerase family A, exhibits a polymerase C-terminal domain, a central domain, and an N-terminal helicase domain. Polθ plays important roles in DNA repair via its polymerase domain, regulating genome integrity. In addition, in mammals, Polθ modulates origin firing timing and MCM helicase recruitment to chromatin. In contrast, as a model eukaryote, Trypanosoma cruzi exhibits two individual putative orthologs of Polθ in different genomic loci; one ortholog is homologous to the Polθ C-terminal polymerase domain, and the other is homologous to the Polθ helicase domain, called Polθ-polymerase and Polθ-helicase, respectively. A pull-down assay using the T. cruzi component of the prereplication complex Orc1/Cdc6 as bait captured Polθ-helicase from the nuclear extract. Orc1/Cdc6 and Polθ-helicase directly interacted, and Polθ-helicase presented DNA unwinding and ATPase activities. A T. cruzi strain overexpressing the Polθ-helicase domain exhibited a significantly decreased amount of DNA-bound MCM7 and impaired replication origin firing. Taken together, these data suggest that Polθ-helicase modulates DNA replication by directly interacting with Orc1/Cdc6, which reduces the binding of MCM7 to DNA and thereby impairs the firing of replication origins
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