17 research outputs found

    Three facets of employee wellness: the potential moderating influences of exercise, mindfulness-based practices, and vacation on select worker characteristics

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    Current research notes a disconnect between well-being programs offered by organizations and those most valued by employees (Agarwal, Bersin, Lahiri, Schwartz, & Violini, 2018). Thus, the current study attempts to better understand the potential influence of health-driven, leisure activities on three worker characteristics, namely, workaholism, work stress, and work engagement. With a greater understanding, we hope to emphasize the importance of comprehensive well-being programs for both employers and employees who may experience any of the aforementioned characteristics. To best assess potential components of a well-being program, three leisure activities of interest (i.e., exercise, mindfulness-based practices, and vacation) were selected. These specific activities were chosen for their alignment with the recognized domains of individual health: physical, mental, and social (“Constitution of the World Health Organization, 2006), respectively. The potential relationships between these factors will be assessed through three questions. The first two questions explore the corollary relationships that may exist between workaholism, work stress, work engagement, and overall participation in leisure activities. This research posits workaholism will be positively related to work stress (Q1:H1), while work engagement will be negatively related to workaholism (Q1:H2) and work stress (Q1:H3). Considering the relationship between worker characteristics and leisure activities, it is hypothesized that participation in leisure activities will be negatively correlated with workaholism (Q2:H1) and work stress (Q2:H2), but positively correlated with work engagement (Q2:H3). The third question considers the potential moderating influence of each identified leisure activity on the relationship between workaholism and work stress. It is anticipated that participation in exercise (Q3:H1), mindfulness-based practices (Q3:H2), and vacation (Q3:H3) will have moderating influences on the relationship between workaholism and work stress, such that as participation in each of these activities increases, the relationship between workaholism and work stress will weaken. Surveys will be dispersed through Amazon’s Mechanical Turk (MTurk) platform and will include demographic questions and study measures. To assess participation in vacation activities, select questions from de Bloom et al.’s (2011) research will be used. Correlations will be obtained to test the first six hypotheses. To test the final three hypotheses regarding the potential moderating influence of leisure activities, a multiple regression analysis and Hayes’ PROCESS (2013) will be used

    Social Influence When Males Gamble: Perceptions and Behavior

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    Experiment 1 tested whether the gambling behavior of 12 non-pathological male participants would be altered by the presence and/or gender of a confederate who also gambled and whether participants’ self reports would match their actual behavior. Results showed that although actual gambling behavior did not vary as a function of the presence or gender of a confederate, participants reported that it did. Experiment 2 tested whether the gambling behavior of nine non-pathological males would be altered by the presence of a confederate and/or whether the confederate won or lost. Results showed that the presence of the confederate increased gambling, but whether the confederate won or lost did not influence participants’ gambling behavior. As in Experiment 1, participants’ self reports did not match their actual behavior; participants reported no influence of the confederate. The present study sheds light on the situations in which the presence of other gamblers may influence gambling behavior. They also suggest that conclusions based on self reports of gambling should be made with caution as they may not accurately represent actual behavior

    Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

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    SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    Three facets of employee wellness: the potential moderating influences of physical activities, mindfulness, and vacation

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    Current research notes a disconnect between well-being programs offered by organizations and those most valued by employees (Agarwal, Bersin, Lahiri, Schwartz, & Violini, 2018). Thus, the current study attempts to better understand the potential influence of health-driven, leisure activities on three worker characteristics, namely, workaholism, work stress, and work engagement. With a greater understanding, we hope to emphasize the importance of comprehensive well-being programs for both employers and employees who may experience any of the aforementioned characteristics. To best assess potential components of a well-being program, three leisure activities of interest (i.e., physical activities, mindfulness, and vacation) were selected. These specific activities were chosen for their alignment with the recognized domains of individual health: physical, mental, and social (“Constitution of the World Health Organization, 2006), respectively. The potential relationships between these factors will be assessed through three questions. The first two questions explore the corollary relationships that may exist between workaholism, work stress, work engagement, and overall participation in leisure activities. This research posits workaholism will be positively related to work stress (Q1:H1), while work engagement will be negatively related to workaholism (Q1:H2) and work stress (Q1:H3). Considering the relationship between worker characteristics and leisure activities, it is hypothesized that participation in leisure activities will be negatively correlated with workaholism (Q2:H1) and work stress (Q2:H2), but positively correlated with work engagement (Q2:H3). The third question considers the potential moderating influence of each identified leisure activity on the relationship between workaholism and work stress. It is anticipated that participation in physical activities (Q3:H1), mindfulness (Q3:H2), and vacation (Q3:H3) will have moderating influences on the relationship between workaholism and work stress, such that as participation in each of these activities increases, the relationship between workaholism and work stress will weaken. The potential moderating influence of a composite measure of leisure participation on the relationship between workaholism and work stress (Q3:H4) will also be assessed. Surveys will be dispersed through Amazon’s Mechanical Turk (MTurk) platform and will include demographic questions and study measures. Correlations will be obtained to test the first six hypotheses. To test the final four hypotheses regarding the potential moderating influence of leisure activities, a multiple regression analysis will be conducted

    Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers

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    DNA replication-associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutation consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (>250/Mb), which was greater than all childhood and most cancers (>7,000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerase ɛ or δ. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germ-line bMMRD (P < 10(-13)). Sequential tumor biopsy analysis revealed that bMMRD/polymerase-mutant cancers rapidly amass an excess of simultaneous mutations (∼600 mutations/cell division), reaching but not exceeding ∼20,000 exonic mutations in <6 months. This implies a threshold compatible with cancer-cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair.status: publishe

    Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

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    To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

    \u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

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    The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu
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