105 research outputs found
Mindfulness, Stress Reactivity, and Depressive Symptoms Among “Third Culture Kids” in the United Arab Emirates
So called third culture kids (TCKs), the children and adolescents who accompany their parents on long-term overseas work assignments, often have to face life changes, cultural challenges and threats to social identity. The frequency, intensity and nature of these challenges arguably places some TCKs at heightened risk of stress-related mental health problems. Trait mindfulness, an attribute that can be enhanced through intervention, has been found to buffer against stress reactivity and common mental health problems. This study aims to explore the relationship between stress reactivity, trait mindfulness and depressive symptomatology among expatriate adolescents (TCKs) attending an international school in the United Arab Emirates (UAE). Participants included 230 high school students (57% female) from 45 different nations, with a mean age of 15.5 (±1.3, 12–19). Forty one percent had lived in the UAE for 7+ years. Participants completed measures of trait mindfulness, daily life stress reactivity, and depressive symptoms (CES-D). Mean depression score was high with 68.7% of TCK participants presenting as at risk of clinical depression. Lower stress-reactivity and greater trait mindfulness were associated with lower levels of depression; furthermore, low levels of trait mindfulness partially mediated the relationship between stress reactivity and depression. Efforts that aim to reduce stress reactivity and increase mindfulness might prove especially beneficial among the TCK population
Unusual acylation of chloramphenicol in \u3ci\u3eLysobacter enzymogenes,\u3c/i\u3e a biocontrol agent with intrinsic resistance to multiple antibiotics
Background: The environmental gliding bacteria Lysobacter are emerging as a new group of biocontrol agents due to their prolific production of lytic enzymes and potent antibiotic natural products. These bacteria are intrinsically resistant to many antibiotics, but the mechanisms behind the antibiotic resistance have not been investigated.
Results: Previously, we have used chloramphenicol acetyltransferase gene (cat) as a selection marker in genetic manipulation of natural product biosynthetic genes in Lysobacter, because chloramphenicol is one of the two common antibiotics that Lysobacter are susceptible to. Here, we found L. enzymogenes, the most studied species of this genus, could still grow in the presence of a low concentration of chloramphenicol. Three chloramphenicol derivatives (1–3) with an unusual acylation pattern were identified in a cat-containing mutant of L. enzymogenes and in the wild type. The compounds included chloramphenicol 3\u27-isobutyrate (1), a new compound chloramphenicol 1\u27- isobutyrate (2), and a rare chloramphenicol 3\u27-isovalerate (3). Furthermore, a mutation of a global regulator gene (clp) or a Gcn5-related N-acetyltransferase (GNAT) gene in L. enzymogenes led to nearly no growth in media containing chloramphenicol, whereas a complementation of clp restored the chloramphenicol acylation as well as antibiotic HSAF production in the clp mutant.
Conclusions: The results indicated that L. enzymogenes contains a pool of unusual acyl donors for enzymatic modification of chloramphenicol that confers the resistance, which may involve the Clp-GNAT regulatory system. Because Lysobacter are ubiquitous inhabitants of soil and water, the finding may have important implications in understanding microbial competitions and bioactive natural product regulation
Expert Consensus Recommendations for Robotic Surgery Credentialing
Objective:
To define criteria for robotic credentialing using expert consensus.
Background:
A recent review of institutional robotic credentialing policies identified significant variability and determined current policies are largely inadequate to ensure surgeon proficiency and may threaten patient safety.
Methods:
28 national robotic surgery experts were invited to participate in a consensus conference. After review of available institutional policies and discussion, the group developed a 91 proposed criteria. Using a modified Delphi process the experts were asked to indicate their agreement with the proposed criteria in three electronic survey rounds after the conference. Criteria that achieved 80% or more in agreement (consensus) in all rounds were included in the final list.
Results:
All experts agreed that there is a need for standardized robotic surgery credentialing criteria across institutions that promote surgeon proficiency. 49 items reached consensus in the first round, 19 in the second, and 8 in the third for a total of 76 final items. Experts agreed that privileges should be granted based on video review of surgical performance and attainment of clearly defined objective proficiency benchmarks. Parameters for ongoing outcome monitoring were determined and recommendations for technical skills training, proctoring, and performance assessment were defined.
Conclusions:
Using a systematic approach, detailed credentialing criteria for robotic surgery were defined. Implementation of these criteria uniformly across institutions will promote proficiency of robotic surgeons and has the potential to positively impact patient outcomes
Kinetic analysis of copper transfer from a chaperone to its target protein mediated by complex formation
Chaperone proteins that traffic copper around the cell minimise its toxicity by maintaining it in a tightly bound form. The transfer of copper from chaperones to target proteins is promoted by complex formation, but the kinetic characteristics of transfer have yet to be demonstrated for any chaperone-target protein pair. Here we report studies of copper transfer between the Atx1-type chaperone CopZ from Bacillus subtilis and the soluble domains of its cognate P-type ATPase transporter, CopAab. Transfer of copper from CopZ to CopAab was found to occur rapidly, with a rate constant at 25 °C of ∼267 s−1, many orders of magnitude higher than that for Cu(I) dissociation from CopZ in the absence of CopAab. The data demonstrate that complex formation between CopZ and CopAab, evidence for which is provided by NMR and electrospray ionisation mass spectrometry, dramatically enhances the rate of Cu(I) dissociation from CopZ
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The observed state of the water cycle in the early twenty-first century
Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 28 (2015): 8289–8318, doi:10.1175/JCLI-D-14-00555.1.This study quantifies mean annual and monthly fluxes of Earth’s water cycle over continents and ocean basins during the first decade of the millennium. To the extent possible, the flux estimates are based on satellite measurements first and data-integrating models second. A careful accounting of uncertainty in the estimates is included. It is applied within a routine that enforces multiple water and energy budget constraints simultaneously in a variational framework in order to produce objectively determined optimized flux estimates. In the majority of cases, the observed annual surface and atmospheric water budgets over the continents and oceans close with much less than 10% residual. Observed residuals and optimized uncertainty estimates are considerably larger for monthly surface and atmospheric water budget closure, often nearing or exceeding 20% in North America, Eurasia, Australia and neighboring islands, and the Arctic and South Atlantic Oceans. The residuals in South America and Africa tend to be smaller, possibly because cold land processes are negligible. Fluxes were poorly observed over the Arctic Ocean, certain seas, Antarctica, and the Australasian and Indonesian islands, leading to reliance on atmospheric analysis estimates. Many of the satellite systems that contributed data have been or will soon be lost or replaced. Models that integrate ground-based and remote observations will be critical for ameliorating gaps and discontinuities in the data records caused by these transitions. Continued development of such models is essential for maximizing the value of the observations. Next-generation observing systems are the best hope for significantly improving global water budget accounting.This research was funded by multiple
grants from NASA’s Energy and Water Cycle
Study (NEWS) program.2016-05-0
Climate Science Special Report: Fourth National Climate Assessment (NCA4), Volume I
New observations and new research have increased our understanding of past, current, and future climate change since the Third U.S. National Climate Assessment (NCA3) was published in May 2014. This Climate Science Special Report (CSSR) is designed to capture that new information and build on the existing body of science in order to summarize the current state of knowledge and provide the scientific foundation for the Fourth National Climate Assessment (NCA4)
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The Longleaf Tree-Ring Network: Reviewing and expanding the utility of Pinus palustris Mill. Dendrochronological data
The longleaf pine (Pinus palustris Mill.) and related ecosystem is an icon of the southeastern United States (US). Once covering an estimated 37 million ha from Texas to Florida to Virginia, the near-extirpation of, and subsequent restoration efforts for, the species has been well-documented over the past ca. 100 years. Although longleaf pine is one of the longest-lived tree species in the southeastern US—with documented ages of over 400 years—its use has not been reviewed in the field of dendrochronology. In this paper, we review the utility of longleaf pine tree-ring data within the applications of four primary, topical research areas: climatology and paleoclimate reconstruction, fire history, ecology, and archeology/cultural studies. Further, we highlight knowledge gaps in these topical areas, for which we introduce the Longleaf Tree-Ring Network (LTRN). The overarching purpose of the LTRN is to coalesce partners and data to expand the scientific use of longleaf pine tree-ring data across the southeastern US. As a first example of LTRN analytics, we show that the development of seasonwood chronologies (earlywood width, latewood width, and total width) enhances the utility of longleaf pine tree-ring data, indicating the value of these seasonwood metrics for future studies. We find that at 21 sites distributed across the species’ range, latewood width chronologies outperform both their earlywood and total width counterparts in mean correlation coefficient (RBAR = 0.55, 0.46, 0.52, respectively). Strategic plans for increasing the utility of longleaf pine dendrochronology in the southeastern US include [1] saving remnant material (e.g., stumps, logs, and building construction timbers) from decay, extraction, and fire consumption to help extend tree-ring records, and [2] developing new chronologies in LTRN spatial gaps to facilitate broad-scale analyses of longleaf pine ecosystems within the context of the topical groups presented
Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
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
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