66 research outputs found

    Loving-kindness meditation for anxiety and mood disorders: a multiple baseline, single-case experimental evaluation

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    In recent years, kindness-based meditation practices, including loving-kindness meditation (LKM), have gained empirical support for decreasing depression and anxiety symptoms. LKM is defined as the intentional transmission of unselfish kindness toward all beings. It is practiced by contemplating an object of meditation (e.g., self, difficult person) and offering goodwill by silently repeating phrases (e.g., “May you be happy”). Given LKM’s focus on cultivating positive emotional states, researchers have hypothesized that LKM may work by increasing positive affect (PA), promoting cognitive and behavioral flexibility, and reducing negative affect (NA). This study was the first to employ a multiple baseline, single-case design to evaluate the acceptability and clinical efficacy of a brief, individual LKM intervention for individuals (N = 9) with unipolar depressive disorders, social anxiety disorder, or generalized anxiety disorder and low PA. Participants were randomized to a 2-, 4-, or 6-week baseline and completed weekly assessments during baseline, 7 weeks of treatment, and at 1-, 2- and 4-week follow-up. LKM was hypothesized to be acceptable and effective for reducing depression and anxiety symptoms and increasing PA. Secondary hypotheses were that (1) improvements in PA would precede disorder symptom improvement and (2) LKM would lead to improvements in other treatment variables (e.g., NA, anger, mindfulness, affective regulation styles, quality of life, etc.) Results revealed that the study intervention had good feasibility and acceptability. Per visual inspection, LKM led to improvements in principal disorder symptoms for four participants during treatment and five participants at follow-up (three of whom showed clinically reliable change). Contrary to study hypotheses, only one participant demonstrated reliable improvements in PA during treatment. For this participant, increases in PA occurred simultaneously with reductions in depression. Across participants, LKM exerted moderate to large effects on disorder severity, depression and anxiety symptoms, quality of life, mindful nonreactivity, and tolerating affective style. Overall, individuals with principal unipolar depressive disorders showed the strongest response to the study intervention. In summary, this study provided preliminary evidence for the effectiveness of brief, individual LKM for reducing depression and anxiety in a transdiagnostic outpatient sample with low positive affect

    RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

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    Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

    Impact of stratospheric air and surface emissions on tropospheric nitrous oxide during ATom

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    We measured the global distribution of tropospheric N2O mixing ratios during the NASA airborne Atmospheric Tomography (ATom) mission. ATom measured concentrations of ∼ 300 gas species and aerosol properties in 647 vertical profiles spanning the Pacific, Atlantic, Arctic, and much of the Southern Ocean basins, nearly from pole to pole, over four seasons (2016–2018). We measured N2O concentrations at 1 Hz using a quantum cascade laser spectrometer (QCLS). We introduced a new spectral retrieval method to account for the pressure and temperature sensitivity of the instrument when deployed on aircraft. This retrieval strategy improved the precision of our ATom QCLS N2O measurements by a factor of three (based on the standard deviation of calibration measurements). Our measurements show that most of the variance of N2O mixing ratios in the troposphere is driven by the influence of N2O-depleted stratospheric air, especially at mid- and high latitudes. We observe the downward propagation of lower N2O mixing ratios (compared to surface stations) that tracks the influence of stratosphere–troposphere exchange through the tropospheric column down to the surface. The highest N2O mixing ratios occur close to the Equator, extending through the boundary layer and free troposphere. We observed influences from a complex and diverse mixture of N2O sources, with emission source types identified using the rich suite of chemical species measured on ATom and the geographical origin calculated using an atmospheric transport model. Although ATom flights were mostly over the oceans, the most prominent N2O enhancements were associated with anthropogenic emissions, including from industry (e.g., oil and gas), urban sources, and biomass burning, especially in the tropical Atlantic outflow from Africa. Enhanced N2O mixing ratios are mostly associated with pollution-related tracers arriving from the coastal area of Nigeria. Peaks of N2O are often associated with indicators of photochemical processing, suggesting possible unexpected source processes. In most cases, the results show how difficult it is to separate the mixture of different sources in the atmosphere, which may contribute to uncertainties in the N2O global budget. The extensive data set from ATom will help improve the understanding of N2O emission processes and their representation in global models.This research has been supported by the National Aeronautics and Space Administration (grant nos. NNX15AJ23G, NNX17AF54G, NNX15AG58A, NNX15AH33A, and 80NSSC19K0124) and the National Science Foundation (grant nos. 1852977, AGS-1547626, and AGS-1623745)

    Pediatric observation units in the United States: A systematic review

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    BACKGROUND: As more efficient and value-based care models are sought for the US healthcare system, geographically distinct observation units (OUs) may become an integral part of hospital-based care for children. PURPOSE: To systematically review the literature and evaluate the structure and function of pediatric OUs in the United States. DATA SOURCES: Searches were conducted in Medline, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health Care Advisory Board (HCAB), Lexis-Nexis, National Guideline Clearinghouse, and Cochrane Reviews, through February 2009, with review of select bibliographies. STUDY SELECTION: English language peer-reviewed publications on pediatric OU care in the United States. DATA EXTRACTION: Two authors independently determined study eligibility. Studies were graded using a 5-level quality assessment tool. Data were extracted using a standardized form. DATA SYNTHESIS: A total of 21 studies met inclusion criteria: 2 randomized trials, 2 prospective observational, 12 retrospective cohort, 2 before and after, and 3 descriptive studies. Studies present data on more than 22,000 children cared for in OUs, most at large academic centers. This systematic review provides a descriptive overview of the structure and function of pediatric OUs in the United States. Despite seemingly straightforward outcomes for OU care, significant heterogeneity in the reporting of length of stay, admission rates, return visit rates, and costs precluded our ability to conduct meta-analyses. We propose standard outcome measures and future directions for pediatric OU research. CONCLUSIONS: Future research using consistent outcome measures will be critical to determining whether OUs can improve the quality and cost of providing care to children requiring observation-length stays. Journal of Hospital Medicine 2010;5:172–182. © 2010 Society of Hospital Medicine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69173/1/592_ftp.pd

    Temporal Analysis of the Honey Bee Microbiome Reveals Four Novel Viruses and Seasonal Prevalence of Known Viruses, Nosema, and Crithidia

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    Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops. Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD). Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies. To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time. We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing. We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria. Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼1011 viruses per honey bee). Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points. Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January

    Cervical lymph node metastasis in adenoid cystic carcinoma of the larynx: a collective international review

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    Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended

    Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

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    Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

    Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

    Get PDF
    Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

    Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

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    AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

    Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

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    Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement
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