Global clinical response in C ushing's syndrome patients treated with mifepristone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106755/1/cen12332.pd

Modeling the Young Sun's Solar Wind and its Interaction with Earth's Paleomagnetosphere

We present a focused parameter study of solar wind - magnetosphere interaction for the young Sun and Earth, $~3.5$ Ga ago, that relies on magnetohydrodynamic (MHD) simulations for both the solar wind and the magnetosphere. By simulating the quiescent young Sun and its wind we are able to propagate the MHD simulations up to Earth's magnetosphere and obtain a physically realistic solar forcing of it. We assess how sensitive the young solar wind is to changes in the coronal base density, sunspot placement and magnetic field strength, dipole magnetic field strength and the Sun's rotation period. From this analysis we obtain a range of plausible solar wind conditions the paleomagnetosphere may have been subject to. Scaling relationships from the literature suggest that a young Sun would have had a mass flux different from the present Sun. We evaluate how the mass flux changes with the aforementioned factors and determine the importance of this and several other key solar and magnetospheric variables with respect to their impact on the paleomagnetosphere. We vary the solar wind speed, density, interplanetary magnetic field strength and orientation as well as Earth's dipole magnetic field strength and tilt in a number of steady-state scenarios that are representative of young Sun-Earth interaction. This study is done as a first step of a more comprehensive effort towards understanding the implications of Sun-Earth interaction for planetary atmospheric evolution.Comment: 16 pages, 7 figure

Understanding the process that gives rise to household car ownership level changes

© 2016 The Authors Quantitative studies have revealed that changes to the number of cars owned by households are more likely to occur at the time of life events. However, causal explanations of such relationships are either absent or lacking evidence. To address this knowledge gap, this paper presents a qualitative study which enabled the development of a new conceptual framework to explain the process through which the number of cars owned by households changes over time. The framework emerged through an inductive analysis of 15 in-depth biographical interviews and was validated through a mixed methods survey of 184 households located in Bristol (UK). The following mechanisms of the process are identified: Life events alter roles, relationships, spatial contexts and lifestyle preferences. This can lead to a condition of stress which relates to a discrepancy between satisfaction with the current car ownership level and a more desirable alternative. Attempts to adjust to the new situation are made through processes of travel behaviour adaptation and consideration of whether the car ownership level ought to be altered. A propensity to change car ownership level can emerge from this. However, given the effort involved in taking action, households tend to resist making changes to their car ownership level in the short term. Action to change car ownership level is found to often be prompted by another external stimulus such as the receipt of a maintenance bill. A key message from the analysis is that changes in household car ownership level should be considered as the outcome of a continuous process of development over the life course, rather than as discrete decisions

Longitudinal Pathways between Maternal Mental Health in Infancy and Offspring Romantic Relationships in Adulthood: A 30‐year Prospective Study

Longitudinal pathways between maternal mental health in infancy and offspring romantic relationship outcomes in adulthood were examined using a 30‐year prospective longitudinal study of 196 mothers and their children. Structural equation modeling revealed that maternal mental health at 30 months was related to offspring relationship status and relationship attachment insecurity at 30 years. The adolescent variables of offspring mental health and parental relationship status mediated the link between maternal mental health and offspring relationship status. In addition, adolescent mental health and family conflict mediated the pathway between maternal mental health and offspring attachment insecurity. These results highlight the importance of individual and parental mental health to romantic relationship outcomes, and emphasize the value of taking a developmental approach to the study of romantic relationships.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90142/1/j.1467-9507.2011.00610.x.pd

The parenting experience of those with borderline personality disorder traits: practitioner and parent perspectives

Background: Borderline Personality Disorder (BPD) is associated with challenges around emotional intensity and interpersonal difficulties. The children of parents with BPD are at risk of poorer outcomes in terms of their own mental health, educational outcomes and wellbeing. The challenges of being a parent can also exacerbate the symptoms of those with BPD traits. There is a pressing need to understand the experience of these parents and to determine what support would be appropriate and useful. Aim: To explore and compare the experiences and support needs of parents with BPD traits with the experiences and understanding of practitioners who work with them. Methods: Interviews with 12 parents with BPD traits and 21 practitioners with experience of working with individuals with BPD. The two strands of interviews were analyzed independently using a thematic framework approach, after which the superordinate and subordinate themes were subject to comparison. Results: Parents with BPD traits represent themselves as experiencing considerable challenges in their role as a parent. These included the impact of emotional intensity, social isolation and lack of a positive parenting models to draw upon. Practitioners demonstrated a strong degree of shared understanding into these difficulties. Both groups highlighted a lack of appropriate support for these parents. Conclusion: This research highlights the clinical need for parenting-focused support for individuals with BPD traits. Preliminary suggestions for format and content are given

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