191 research outputs found
Multi-state Models for Natural History of Disease
Longitudinal studies are a useful tool for investigating the course of chronic diseases. Many chronic diseases can be characterized by a set of health states. We can improve our understanding of the natural history of the disease by modeling the sequence of visited health states and the duration in each state. However, in most applications, subjects are observed only intermittently. This observation scheme creates a major modeling challenge: the transition times are not known exactly, and in some cases the path through the health states is not known.
In this manuscript we review existing approaches for modeling multi-state longitudinal data. We introduce Bayesian estimation methods and illustrate their use in two longitudinal studies of chronic disease
Skin disease and non-syndromic hearing loss-linked Cx30 mutations exhibit several distinct cellular pathologies
Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated the underlying mechanisms of four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus and exhibited loss of gap junction channel and hemichannel function, but did not cause cell death. Lastly, the A88V mutant related to Clouston syndrome also significantly induced apoptosis, although through an endoplasmic reticulum-independent mechanism. Collectively, we discovered that four unique Cx30 mutants may cause disease through different mechanisms that also likely include their selective transdominant effects on co-expressed connexins, highlighting the overall complexity of connexin-linked diseases and the importance of GJIC in disease prevention
Developing the host for targeted integration cell line development
Unlike the conventional random integration (RI) cell line development (CLD), the targeted integration (TI) CLD introduces the transgene at a predetermined “hot-spot” in the CHO genome with a defined copy number (1-2 copies). Given the low copy number and the pretested integration site, TI cell lines likely exhibit better stability compared to RI cell lines. In this study, we performed a genome wide screening using transposon based cassette integration and established a TI host (255-3) that has a single landing cassette inserted in its genome. Host 255-3 was able to support the CLD for three test molecules with product titers similar to those of the corresponding RI cell lines. For two regular antibody test cases, the top four TI cell lines achieved ~4-5g/L. For a proven difficult to express antibody, the top four TI lines achieved ~1-1.2g/L. The product titer for this hard to express molecule was increased 3-fold with additional vector improvement. Moreover, the timeline for CLD was shortened by ~2 weeks and resources required per cell line were substantially reduced using the TI method. Together these data indicate that the TI host we developed can be a suitable host to support our clinical / commercial CLD
Enhancing Vitality in Academic Medicine: Faculty Development and Productivity
The prevalence of low satisfaction and increased stress among faculty in academic medicine makes understanding facuity vitality in this field more important than ever before. To explore the contributors to and outcomes of faculty vitality, we conducted a multi-institutional study of faculty in academic medicine (N = 1,980, 42 percent response rate). Faculty were surveyed about climate and leadership, career and life management, satisfaction, engagement, productivity, and involvement in faculty development. Analysis reveals that controlling for other factors, academic medicine faculty who participate regularly in facuity development activ ities are significantly more satisfied, engaged, and productive
Genomic screening in family-based association testing
Due to the recent gains in the availability of single-nucleotide polymorphism data, genome-wide association testing has become feasible. It is hoped that this additional data may confirm the presence of disease susceptibility loci, and identify new genetic determinants of disease. However, the problem of multiple comparisons threatens to diminish any potential gains from this newly available data. To circumvent the multiple comparisons issue, we utilize a recently developed screening technique using family-based association testing. This screening methodology allows for the identification of the most promising single-nucleotide polymorphisms for testing without biasing the nominal significance level of our test statistic. We compare the results of our screening technique across univariate and multivariate family-based association tests. From our analyses, we observe that the screening technique, applied to different settings, is fairly consistent in identifying optimal markers for testing. One of the identified markers, TSC0047225, was significantly associated with both the ttth1 (p = 0.004) and ttth1-ttth4 (p = 0.004) phenotype(s). We find that both univariate- and multivariate-based screening techniques are powerful tools for detecting an association
Comparison of linkage and association strategies for quantitative traits using the COGA dataset
Genome scans using dense single-nucleotide polymorphism (SNP) data have recently become a reality. It is thought that the increase in information content for linkage analysis as a result of the denser scans will help refine previously identified linkage regions and possibly identify new regions not identifiable using the sparser, microsatellite scans. In the context of the dense SNP scans, it is also possible to consider association strategies to provide even more information about potential regions of interest. To circumvent the multiple-testing issues inherent in association analysis, we use a recently developed strategy, implemented in PBAT, which screens the data to identify the optimal SNPs for testing, without biasing the nominal significance level. We compare the results from the PBAT analysis to that of quantitative linkage analysis on chromosome 4 using the Collaborative Study on the Genetics of Alcoholism data, as released through Genetic Analysis Workshop 14
Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 1 Maintaining Inequality: An Analysis of College Pathways among Women at Large Public Institutions
Abstract Armstrong and Hamilton (2013) proposed a framework of three college pathways -party, professional, and mobility -that lead to economically unequal post-graduation outcomes, and vastly different college experiences for female students. Using data from the National Survey of Student Engagement, we examined the responses from 42,504 women seniors at 183 four-year large public institutions to identify how the potential income of their college major choice relate to the pathways. We found that the economic advantage of major choice is not equally distributed among students: party pathway students selected the least lucrative college majors, professional pathway students selected the most lucrative majors, and first-generation students on all pathways tended to select majors with less potential income than their peers with collegeeducated parents. Students on the three pathways also engaged differently in three measures of Maintains Inequality by Other researchers have also attempted to classify students according to their college experience, and/or how they spend their time while in college. The purpose of our study is to build on the work of Armstrong and Hamilton Conceptual Framework Lucas Armstrong and Hamilton (2013) provide many clues as to why college experiences should be different for students on the three pathways (see The college pathways, and the choices students make (or, in the case of students who have to support themselves by working for pay, are pressured to make) about how they spend their time in college may be a representation of so-called "temporal capital -the amount of time the student is able to dedicate to scholarly pursuits" (Gardner & Holley, 2011, p. 79). We argue that in this light, a student's pathway itself is already, potentially, a (loose) manifestation of student's cultural and/or socio-economic capital. Support for this argument can be found in another equally insightful book on how student's SES shapes college experience -Inside College Gates: How Class and Culture Matter in Higher Education by Stuber (2011), who posits that it is through the process of experiencing college life and qualitative differences of college experiences that social inequality manifests itself, as opposed to quantitative studies of students' SES. It is the rich descriptions of the differences in academic experiences of the women of Paying for the Party that informed our decision to focus on qualitative outcomes (reflective and integrative learning, learning strategies and student-faculty interaction) for women on the three pathways, in addition to examining their college major choice. Relevant Literature In this section we present some relevant literature about our main variables of interestpotential college earnings, Reflective and Integrative Learning, Learning Strategies, StudentRunning head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 7 Faculty Interaction, and first-generation students. We conclude this section with an argument and evidence from research literature for why gender and institution type are important for our study. Potential college earnings One of the reasons students attend college is the expectation of making more money and securing a good job after graduation Another key factor that leads to different levels of income among college graduates is an individual's college major/field of study, with the difference ranging between 25 to 35 percent depending on an individual's major The highest-paid fields of study tend to have a well-defined body of content knowledge, often with an emphasis on quantitative skills, and a direct link to functional/applied occupations One significant drawback of many of the studies of the relationship between major and income is that they tend to group individual majors into larger categories, which does not allow for a more refined analysis of the effects of a particular major on earnings and career outcomes. For example, in a study by Reflective and Integrative Learning The NSSE "Reflective and Integrative Learning" scale was originally part of the "Deep Approaches to Learning" scale in the NSSE survey Rogers (2001) examined several theoretical approaches to the reflective process, and found four common elements: reflection as a cognitive activity " Integrative learning is defined broadly as "an umbrella term for structures, strategies, and activities, that bridge numerous divides, such as high school and college, general education and the major, introductory and advanced levels, experiences inside and outside the classroom, theory and practices, and disciplines and fields" (Klein, 2005, p. 8). Integrative learning is widely recognized as a valuable learning outcome in and of itself Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 10 Learning Strategies In general, being strategic about studying involves effective time-management, finding conditions and materials conducive to effective studying, and understanding course requirements and assessment criteria Learning strategies have been defined as "any thoughts, behaviors, beliefs or emotions that facilitate the acquisition, understanding or later transfer of new knowledge and skills" Learning strategies, such as identifying key points in a text, notetaking, review of notes, and summarizing, significantly improve recall, factual learning, retention of information, and academic performance Student-Faculty Interaction The higher education literature overwhelmingly supports the positive impact studentfaculty interaction (SFI) can have on student development. Decades of research have documented a vast variety of benefits of SFI on student academic achievement, persistence, intellectual and personal development, satisfaction with college, and career and educational aspirations First-generation students Armstrong and Hamilton (2013) demonstrate that SES, class background, and cultural capital of the students in the sample of Paying in the Party play a critical role in shaping students' experiences while at MU and beyond. Having highly educated parents provided a significant competitive advantage to students on the professional pathway; students on the party Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 12 pathway were expected to be financially supported by their parents in order to maintain the party lifestyle; while students on the mobility pathway had to compensate for lack of family resources by working for pay, which took their time and attention away from academics and forming relationships with peers. In our study, we use first-generation student status as a proxy for student SES and cultural capital, as first-generation status and SES are closely related (Terenzini, Spinger, Yaeger, Pascarella, & Nora, 1996). In their review of the literature on first-generation students, Pascarella, Pierson, Wolniak, and Terenzini Students of low SES background display similar patterns of outcomes with regards to persistence, educational degree aspirations, and achievement Findings of Pascarella et al. 's (2004) own research study indicated that first-generation students tend to work more hours per week compare to students with parents with a high level of education, which may explain the fact that they had lower grades, on average, than their peers Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 13 with highly educated parents, despite having lighter academic workloads. It appears that firstgeneration students particularly benefit from contact with peers, which impacts their educational degree plans, among other outcomes However, some disadvantages first-generation students experience in college may not necessarily be due to the lack of cultural resources. For example, Gender Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 14 Armstrong and Hamilton (2013) focused on women students. They noted that many affluent students on the party pathway were not expected to reproduce their parents' success but were rather oriented towards a successful marriage. According to 249), echoing earlier findings of a similar peer culture at Duke University Sons from comparable families may be oriented to college and professional success differently, thus possibly changing the entire three-pathway framework of Paying for the Party. In fact, indirect evidence of this thesis can be found in a study by Institutional setting Armstrong and Hamilton (2013) made a convincing case for why an institutional setting was a significant factor for the emergence of these three college pathways. At a large institution the professional pathway is highly competitive and, effectively, zero-sum in nature, where only the most capable and best-prepared students with appropriate aspirations can take advantage of the rewards this pathway offers (e.g., high-paying jobs, or admission to graduate and professional school), while all others on this pathway are left behind. Public institutions also rely on the tuition and fees brought by the affluent students, and are thus compelled to service students, both socially and academically: partying, socializing, and college athletics events make the party pathway highly visible on campus, and the availability of undemanding academic majors helps students maintain the party pathway. Further, women on the mobility pathway often felt alienated by the campus culture, and with inadequate academic advising services were left on their own to figure out how to navigate academic life. Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 16 Other institutional settings may present a different framework of student pathways altogether. As Armstrong and Hamilton (2013) demonstrate, regional campuses of MU turned out to be a better fit for some students, because of the absence of a robust party scene. Mullen (2014) explored how female and male students select majors at a private liberal arts college and found that because all students developed strong personal identification with bodies of knowledge (as opposed to pre-professional fields), it became important for male students not to select a major considered too "feminine". A student body composition at institutions of other types may present some different social and academic life patterns. For example, Martin Combined together students from these groups represented more than 40 percent of the entire student body at both Duke and a sample of similar institutions Thus, the type of institution may be a significant feature of the three-pathway framework proposed by Purpose Our study aims to test these findings on a broader scale by examining the college experiences of women at over 180 four-year large public institutions. In particular, we focus on the college pathways of women in the senior year and the impact of their chosen pathway on a quantitative educational outcome, future potential earnings of an earned bachelor's degree, and qualitative education outcomes, three forms of effective educational practices -learning Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 17 strategies, student-faculty interaction, and reflective and integrative learning. We also examine the college pathways of first-generation students and students with college-educated parents to determine to what extent, if at all, students may experience a quantitative and/or qualitative advantage. Guided by the rich descriptions of women's academic experiences in Paying for the Party, this study applies students' estimated time spent on three activities-socializing with friends, studying and preparing for class, and working for pay-as proxies for three distinct college pathways. For example, it is possible that students who spend a significant amount of time socializing and relaxing with friends (party pathway) are less engaged in effective educational practices but tend to seek advantage by majoring in fields with higher potential income. Students who spend a significant amount of time working (mobility pathway) may have less time to engage in effective educational practices and tend to choose majors in fields with lower potential earnings. Students who do not have heavy working responsibilities and spend a significant amount of time studying (professional pathway) may engage in effective educational practices more and choose a major leading to lucrative career. Using how students structure their time as a measure of college pathway, we may gain additional insights as to if these college pathways are advantageous for students from lower-SES backgrounds, such as first-generation students. Alternatively, we may also better understand the mechanisms in which non-firstgeneration students maintain their social status; by choosing majors leading to lucrative incomes while also gaining qualitatively better educational experience through their engagement with effective educational practices such as learning strategies, interacting with faculty, and reflective and integrative learning. The specific research questions guiding this study are: Methods Data and Sample Using data from the 2014 administration of the National Survey of Student Engagement (NSSE), we examined the responses from 42,504 women seniors enrolled full-time at 183 fouryear large public institutions. Slightly less than half (47%) of the sample were first-generation students, and nearly three-quarters (71%) expected to earn a graduate degree. About two in five (18%) were majoring in STEM (science, technology, engineering, and mathematics) fields. Around half (51%) earned mostly A grades at their current institution with slightly less than half (44%) earning mostly B grades. Three-quarters of the sample (75%) were of traditional age (23 years old or younger). Over two-thirds of the sample identified as White (65%) with smaller proportions identifying as Asian (7%), Black or African American (8%), Hispanic or Latino (9%), multiracial (6%), another race (2%), or preferred not to respond to race (3%). For more details about the sample, see Measures College pathways. The survey asks students a series of questions about how they chose to spend their time during a typical 7-day week. Response options ranged from 'zero' to 'more Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 19 than 30 hours per week'. Students who spent over 20 hours per week relaxing and socializing and less than 11 hours per week working for pay or preparing for class were coded as being on the party pathway. Students who spent over 20 hours per week working for pay and less than 11 hours per week on socializing activities and preparing for class were coded as being on the mobility pathway. Students who spent over 20 hours per week on class preparation and less than 11 hours per week working or socializing were identified as being on the professional pathway. Students who balanced their time among all three activities were coded as being on the balanced pathway, a pathway we created to capture those students who did not meet the criteria for the other pathways. The majority of the sample (80%) were on a balanced pathway with smaller proportions in the professional pathway (13%), mobility pathway (5%), and the party pathway (2%). To check if the trends found by Armstrong and Hamilton (2013) are represented by our proposed coding scheme, a frequency crosstab was calculated by select demographics and academic variables. Running head: MAINTAINTING INEQUALITY AND COLLEGE PATHWAYS 21 Reflective and Integrative Learning. Reflective and Integrative Learning is a subscale measuring students' uses of Deep Approaches to Learning (Nelson Laird et al., 2005). This scale consists of seven survey items asking students how often they connect ideas to societal problems or issues and from prior knowledge; combine ideas from different courses; examine strengths and weaknesses of their own viewpoints as well as try to better understand someone else's point of view; and include diverse perspectives in their course discussions or assignments (for details, see Appendix). Students provide responses to these items from a four-point scale ranging from 'very often' to 'never.' The internal consistency of this measure is deemed acceptable for research (Cronbach's alpha=.89). Learning Strategies. Learning Strategies scale on NSSE consists of three items related to how students approach studying (Appendix A). Students were asked how often they engaged in identifying key information from reading assignments, reviewing notes after class, and summarizing what they learned in class or from course material. Four-point response options ranging from 'very often' to 'never' were presented to students. The internal consistency of thi
Absence of CALR Mutations in Idiopathic Erythrocytosis Patients with Low Serum Erythropoietin Levels
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Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study
Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits
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