43 research outputs found

    The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

    Get PDF
    X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

    automobile and United States trade policy : where do we go from here?

    No full text
    Series from publisher's list"Research paper, International Policy Forum, Eagle Lodge, Pennsylvania, U.S.A., 28 June-1 July 1981.""#2353."--Handwritten on cover"US-A-81-4-1."Includes bibliographical reference

    Providers\u27 Experiences with a Melanoma Web-Based Course: a Discussion on Barriers and Intentions

    No full text
    Primary care visits provide an opportunity for skin examinations with the potential to reduce melanoma mortality. The INFORMED (INternet curriculum FOR Melanoma Early Detection) Group developed a Web-based curriculum to improve primary care providers\u27 (PCPs\u27) skin cancer detection skills. This study details feedback obtained from participant focus groups, including the feasibility of implementing in other PCP practices. Practicing PCPs at Henry Ford Health System and Kaiser Permanente Northern California completed the curriculum. Feedback sessions were conducted with standardized questions focusing on four domains: (1) overall impressions of the curriculum, (2) recommendations for improvement, (3) current skin examination practices, and (4) suggestions for increasing skin screening by PCPs. Discussions at each site were audio recorded, transcribed verbatim, and de-identified. Providers (N = 54) had a positive impression of the Web-based curriculum, with suggestions to provide offline teaching aids and request assistance. Despite having improved confidence in diagnosing malignant lesions, many providers felt a lack of confidence in performing the screening and time constraints affected their current practices, as did institutional constraints. Providers intended to increase discussion with patients about skin cancer. The accessibility, effectiveness, and popularity of the curriculum indicate potential for implementation in the primary care setting. Participating providers noted that institutional barriers remain which must be addressed for successful dissemination and implementation

    Cardiology clinical trial participation in community-based healthcare systems: obstacles and opportunities

    No full text
    BACKGROUND: The objective of our study was to examine cardiologists\u27 and organizational leaders\u27 interest in clinical trial participation and perceived barriers and facilitators to participation within ten diverse non-profit healthcare delivery systems. Trials play a pivotal role in advancing knowledge about the safety and efficacy of cardiovascular interventions and tests. Although cardiovascular trials successfully enroll patients, recruitment challenges persist. Community-based health systems could be an important source of participants and investigators, but little is known about community cardiologists\u27 experiences with trials. METHODS: We interviewed 25 cardiology and administrative leaders and mailed questionnaires to all 280 cardiologists at 10 U.S. healthcare organizations. RESULTS: The survey received a 73% response rate. While 60% of respondents had not participated in any trials in the past year, nearly 75% wanted greater participation. Cardiologists reported positive attitudes toward trial participation; more than half agreed that trials were their first choice of therapy for patients, if available. Almost all leaders described their organizations as valuing research but not necessarily trials. Major barriers to participation were lack of physician time and insufficient skilled research nurses. CONCLUSIONS: Cardiologists have considerable interest in trial participation. Major obstacles to increased participation are lack of time and effective infrastructure to support trials. These results suggest that community-based health systems are a rich source for cardiovascular research but additional funding and infrastructure are needed to leverage this resource

    Being Present: A single-arm feasibility study of audio-based mindfulness meditation for colorectal cancer patients and caregivers

    No full text
    <div><p>A metastatic cancer diagnosis is associated with high levels of distress in patients and caregivers. Mindfulness interventions can reduce distress and improve quality of life in cancer patients. However, standard mindfulness training relies on in-person instruction, which is often not practical for either patients receiving chemotherapy or their caregivers. In the <i>Being Present</i> single arm pilot study, we designed and tested an 8-week audio-based mindfulness meditation program for patients with metastatic colorectal cancer receiving chemotherapy with or without a participating caregiver. The study accrued 33 of 74 (45%) eligible patients consenting together with 20 family caregivers (53 participants total) within nine months. Forty-one participants were evaluable (77%); 10 of 12 cases of attrition were attributable to hospitalization or death. Median participant age was 51 (range 21–78 years); 38% were men. Baseline levels of distress were similar in patients and caregivers. The top reasons for participation cited in pre-intervention interviews were to increase relaxation/calm, improve mood/emotions, and reduce stress/anxiety. In measures of adherence, 59% of responses to weekly texts asking: “Have you practiced today?” were “Yes” and 59% of interviewees reported practicing >50% of the time. Compared to baseline, post-intervention surveys demonstrated significantly reduced distress (p = 0.01) and anxiety (p = 0.03); as well as increased non-reactivity (p<0.01), and feeling at peace (p<0.01). Post-intervention qualitative interviews, where 71% of participants reported benefit, were consistent with quantitative findings. In the interviews, participants spontaneously described reduced stress/anxiety and increased relaxation/calm. Benefits appeared to be accentuated in patient-caregiver pairs as compared to unpaired patients. Seventy-nine percent of participants reported plans for continued practice after study completion. We conclude that the <i>Being Present</i> audio-based mindfulness meditation program is of interest to, feasible, and acceptable for patients with metastatic colorectal cancer and caregivers, with initial evidence of efficacy. These results will guide plans for a follow-up study.</p><p><b>Trial registration</b>: ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02423720" target="_blank">NCT02423720</a></p></div

    Graphic representations of survey scores at baseline and week 8.

    No full text
    <p>N = 24. A) Box plots of National Comprehensive Cancer Network (NCCN) Distress Thermometer ratings: 0 = no distress; 10 = extreme distress. B) Box plots of National Institutes of Health Patient Reported Outcomes Measurement Information System (NIH PROMIS) Anxiety Short Form 4A scores. C) Box plots of Five Facet Mindfulness Questionnaire Short Form (FFMQ-SF) “Non-React” scores. D) Histograms of “Are You at Peace?" one-item spiritual probe ratings: 1 = not at all; 2 = a little bit; 3 = a moderate amount; 4 = quite a bit; 5 = completely. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199423#pone.0199423.t006" target="_blank">Table 6</a> for <i>P</i>-values from paired t-tests.</p
    corecore