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"Tran, Christopher"
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The South China Sea : a crucible of regional cooperation or conflict-making sovereignty claims?
\"As a primary trade route for more than half of the world's shipping, the location of potentially huge oil and gas reserves, and the main source of protein in maritime South- East Asia, the South China Sea is a governing determinant of security, prosperity and development in East Asia and the wider Indo-Pacific region. The disputes in the South China Sea have long been seen as a source of tension and instability in the region. Although peace has been maintained until now, the South China Sea is the epicentre of changes in the international balance of power which have the potential to trigger military conflict. The South China Sea sovereignty disputes are among the most complicated in the world and engage claims from Brunei, China, Malaysia, Philippines, Taiwan, and Vietnam. Given the complex convergence of national interests in the region, the prospect of settling the decades-old disputes completely is very slim\"-- Provided by publisher.
Book
Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells
Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis. Nuclear reprogramming to pluripotency can revert both the age and the identity of any cell to that of an embryonic cell. Recent evidence shows that transient reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice. However, it is unknown how this form of rejuvenation would apply to naturally aged human cells. Here we show that transient expression of nuclear reprogramming factors, mediated by expression of mRNAs, promotes a rapid and broad amelioration of cellular aging, including resetting of epigenetic clock, reduction of the inflammatory profile in chondrocytes, and restoration of youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity.
Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.
Journal Article
Complications of button battery ingestion or insertion in children: a systematic review and pooled analysis of individual patient-level data
Background
Button battery (BB) exposures are common in children and can have devastating consequences. We reviewed current evidence on the complications associated with BB exposure and identified predictors of outcomes using individual patient-level data.
Data sources
We carried out a systematic review and pooled analysis by searching MEDLINE, Embase, and Scopus up to May 19, 2023. Included studies describe complications following BB exposures in children (aged < 18 years). Odds ratios (ORs) were calculated using binary logistic regression to measure associations between predictive factors and different outcomes.
Results
Two-hundred seventeen studies (439 children) were included. The median age at presentation was 1.75 [interquartile range (IQR) 1.00–3.00] years and 399 (90.9%) exposures were ingestions. Of the 380 cases reporting sex, 162 (42.6%) were female. Feeding (192, 48.1%) and respiratory difficulties (138, 34.6%) were common presenting features for ingestions, while symptomatology was site-specific for insertions. Common complications included oesophageal mucosal damage alone (105, 26.3%) and tracheooesophageal fistula (93, 23.3%) for ingestions, and nasal septal perforation (22, 55.0%) and mucosal damage alone (13, 32.5%) for insertions. Intestinal perforation occurred in 2.5% of ingestion cases, including perforation of Meckel's diverticulum, peritonitis, and jejunocolic fistula. Vascular complications were common among children who died. Age (≤ 2 years), battery exposure duration (> 6 hours), and battery diameter (≥ 20 mm) were associated with common and severe complications of ingestions.
Conclusion
BB injuries are time-critical, with severe sequelae predominantly affecting young children. Diagnosis is challenging. Preventative work through regulation and safer battery design are required to eliminate this problem.
Graphical abstract
Journal Article
Protocol for an extended scoping review on the use of virtual nominal group technique in research
Consensus group methods such as the Nominal Group Technique (NGT) and Delphi method are commonly used in research to elicit and synthesize expert opinions when evidence is lacking. Traditionally, the NGT involves a face-to-face interaction. However, due to the COVID-19 pandemic, many in-person meetings have moved to online settings. It is unclear to what extent the NGT has been undertaken in virtual settings. The overarching aim of this scoping review is to explore the use of the virtual NGT in research. Our specific objectives are to answer the following questions: To what extent has the NGT been used virtually? What modifications were made to accommodate this online format? What advantages and disadvantages were noted by authors in comparison with the face-to-face mode of the technique?
This scoping review will follow the steps outlined by Arksey and O'Malley and the PRISMA-ScR guidelines. Several pilot searches were completed to refine inclusion and exclusion criteria. Media Synchronicity Theory will provide a conceptual framework to inform the research, including data extraction and summarizing results. As an additional extension to the literature review, online interviews with corresponding authors will be conducted to gather further information.
Journal Article
Drosophila glucome screening identifies Ck1alpha as a regulator of mammalian glucose metabolism
Circulating carbohydrates are an essential energy source, perturbations in which are pathognomonic of various diseases, diabetes being the most prevalent. Yet many of the genes underlying diabetes and its characteristic hyperglycaemia remain elusive. Here we use physiological and genetic interrogations in
D. melanogaster
to uncover the ‘glucome’, the complete set of genes involved in glucose regulation in flies. Partial genomic screens of ∼1,000 genes yield ∼160 hyperglycaemia ‘flyabetes’ candidates that we classify using fat body- and muscle-specific knockdown and biochemical assays. The results highlight the minor glucose fraction as a physiological indicator of metabolism in
Drosophila
. The hits uncovered in our screen may have conserved functions in mammalian glucose homeostasis, as heterozygous and homozygous mutants of
Ck1alpha
in the murine adipose lineage, develop diabetes. Our findings demonstrate that glucose has a role in fly biology and that genetic screenings carried out in flies may increase our understanding of mammalian pathophysiology.
Diabetes is associated with aberrations in glucose metabolism. Here the authors perform a genomic screen in fruit flies to identify new regulators of fly glucose metabolism, and show that mice lacking the murine homologue of one of their hits, the protein kinase CK1alpha, in the adipose lineage develop diabetes.
Journal Article
Overexpression of Fatty Acid Amide Hydrolase Induces Early Flowering in Arabidopsis thaliana
N-acylethanolamines (NAEs) are bioactive lipids derived from the hydrolysis of the membrane phospholipid N-acylphosphatidylethanolamine (NAPE). In animal systems this reaction is part of the \"endocannabinoid\" signaling pathway, which regulates a variety of physiological processes. The signaling function of NAE is terminated by fatty acid amide hydrolase (FAAH), which hydrolyzes NAE to ethanolamine and free fatty acid. Our previous work in Arabidopsis thaliana showed that overexpression of AtFAAH (At5g64440) lowered endogenous levels of NAEs in seeds, consistent with its role in NAE signal termination. Reduced NAE levels were accompanied by an accelerated growth phenotype, increased sensitivity to abscisic acid (ABA), enhanced susceptibility to bacterial pathogens, and early flowering. Here we investigated the nature of the early flowering phenotype of AtFAAH overexpression. AtFAAH overexpressors flowered several days earlier than wild type and AtFAAH knockouts under both non-inductive short day (SD) and inductive long day (LD) conditions. Microarray analysis revealed that the FLOWERING LOCUS T (FT) gene, which plays a major role in regulating flowering time, and one target MADS box transcription factor, SEPATALLA3 (SEP3), were elevated in AtFAAH overexpressors. Furthermore, AtFAAH overexpressors, with the early flowering phenotype had lower endogenous NAE levels in leaves compared to wild type prior to flowering. Exogenous application of NAE 12:0, which was reduced by up to 30% in AtFAAH overexpressors, delayed the onset of flowering in wild type plants. We conclude that the early flowering phenotype of AtFAAH overexpressors is, in part, explained by elevated FT gene expression resulting from the enhanced NAE hydrolase activity of AtFAAH, suggesting that NAE metabolism may participate in floral signaling pathways.
Journal Article
Oncogenic RAS pathway activation promotes resistance to anti-VEGF therapy through G-CSF–induced neutrophil recruitment
Granulocyte-colony stimulating factor (G-CSF) promotes mobilization of CD11b ⁺Gr1 ⁺ myeloid cells and has been implicated in resistance to anti-VEGF therapy in mouse models. High G-CSF production has been associated with a poor prognosis in cancer patients. Here we show that activation of the RAS/MEK/ERK pathway regulates G-CSF expression through the Ets transcription factor. Several growth factors induced G-CSF expression by a MEK-dependent mechanism. Inhibition of G-CSF release with a MEK inhibitor markedly reduced G-CSF production in vitro and synergized with anti-VEGF antibodies to reduce CD11b ⁺Ly6G ⁺ neutrophil mobilization and tumor growth and led to increased survival in animal models of cancer, including a genetically engineered mouse model of pancreatic adenocarcinoma. Analysis of biopsies from pancreatic cancer patients revealed increased phospho-MEK, G-CSF, and Ets expression and enhanced neutrophil recruitment compared with normal pancreata. These results provide insights into G-CSF regulation and on the mechanism of action of MEK inhibitors and point to unique anticancer strategies.
Journal Article
eCONSULTS TO ENDOCRINOLOGISTS IMPROVE ACCESS AND CHANGE PRIMARY CARE PROVIDER BEHAVIOR
To describe the impact of an eConsult service on access to endocrinologists along with its influence on changing primary care provider (PCP) course of action and referral behaviors.
Established in 2011, the Champlain BASE (Building Access to Specialist Care via eConsult) service allows PCPs to access specialist care in lieu of traditional face-to-face referrals. We conducted a cross-sectional study of eConsult cases submitted to endocrinologists by PCPs between April 15, 2011 and January 31, 2015. Usage data and PCP responses to a mandatory closeout survey were analyzed to determine eConsult response times, PCP practice behavior, referral outcomes, and provider satisfaction. Each eConsult was coded according to clinical topic and question type based on established taxonomies.
A total of 180 PCPs submitted 464 eConsults to endocrinology during the study period. Specialist median response time was 7 hours, with 90% of responses occurring within 3 days. PCPs received a new or additional course of action in 62% of submitted cases. An unnecessary face-to-face referral was avoided in 44% of all eConsults and in 67% of cases where the PCP initially contemplated requesting a referral. Over 95% of cases were rated at least 4 out of 5 in value for PCPs and their patients.
The use of eConsult improves access to endocrinologists by providing timely, highly rated practice-changing clinical advice while reducing the need for patients to attend face-to-face office visits.
BASE = Building Access to Specialist Advice through eConsult PCP = primary care physician UCSF = University of California San Francisco.
Journal Article
Using pathology data to evaluate surgical backlogs: considerations for resource planning
Kadour et al examine surgical pathology and Cancer Care Ontario summary data from the London Health Sciences Centre and St. Joseph's Health Care in London, Ontario. In Apr 2020, the total number of specimens received decreased by 67.5%, and resection specimens decreased by 51.4%. Cancer Care Ontario report submissions, largely reflecting newly staged cancer cases, decreased by 30.5%. The relatively modest drop in resections and Cancer Care Ontario submissions relative to total specimens likely reflects efforts to prioritize cancer surgeries.
Journal Article
Anti-Cartel Enforcement in a Contemporary Age
Leniency policies are seen as a revolution in contemporary anti-cartel law enforcement. Unique to competition law, these policies are regarded as essential to detecting, punishing and deterring business collusion – conduct that subverts competition at national and global levels. Featuring contributions from leading scholars, practitioners and enforcers from around the world, this book probes the almost universal adoption and zealous defence of leniency policies by many competition authorities and others. It charts the origins of and impetuses for the leniency movement, captures key insights from academic research and practical experience relating to the operation and effectiveness of leniency policies and examines leniency from the perspectives of corporate and individual applicants, advisers and authorities. The book also explores debates surrounding the intersections between leniency and other crucial elements of the enforcement system such as compensation, compliance and criminalisation. The rich critical analysis in the book draws on the disciplines of law, regulation, economics and criminology. It makes a substantial and distinctive contribution to the literature on a topic that is highly significant to a wide range of actors in the field of competition law and business regulation generally. From the Foreword by Professor Frederic Jenny ‘ … fundamental questions are raised and thoroughly discussed in this book which is undoubtedly the most comprehensive scholarly work on leniency policies produced so far … [the] book should be required reading for all seeking to acquire a deeper insight into the issues related to leniency policy. It is a priceless contribution ... ’
eBook