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OBJECTIVES/GOALS: To characterize the oncogenic potential of HNSCC cell lines harboring 17 non-canonical PIK3CA mutations. METHODS/STUDY POPULATION: Non-canonical PIK3CA mutant constructs generated via site-directed mutagenesis are subcloned into doxycycline-inducible vector pLVX-Puro. Serum-dependent HNSCC cell line (PCI-52-SD1) is then stably transfected with vectors and undergo doxycycline-induction. Cell survival is determined by depriving cells of fetal bovine serum for 72 hours and quantifying remaining cells with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Cell proliferation and migration is evaluated with colony formation assays and transwell assays respectively. RESULTS/ANTICIPATED RESULTS: To date, the survival behavior of eight non-canonical mutants was assessed. Three mutants – Q75E, V71I, and E970K – exhibited 18.7-26.7% greater survival rate relative to cells transfected with wild-type. Five mutants – R519G, Y606C, W328S, C905S, and M1040I – demonstrated survival rates that differed only by −4.3% to +6.6% relative to wild-type. We hypothesize the three activating mutants that exhibited increased survival will also demonstrate increased cell proliferation and migratory behavior whereas the three neutral mutants will not differ from control. DISCUSSION/SIGNIFICANCE OF IMPACT: Ongoing HNSCC PI3K inhibitor trials could be more effective if all PIK3CA hyperactivation mutations are known. Identifying non-canonical mutation effects could result in greater efficacy if drugs are restricted only to those with activating mutations. CONFLICT OF INTEREST DESCRIPTION: JRG and DEJ are co-inventors of cyclic STAT3 decoy and have financial interests in STAT3 Therapeutics, Inc. STAT3 Therapeutics, Inc. holds an interest in a cyclic STAT3 decoy oligonucleotide. The remaining authors declare no conflicts.
OBJECTIVES/SPECIFIC AIMS: The aim of this study was to determining how interruptions affect the triage process. METHODS/STUDY POPULATION: Prospective, observational study, where 118 triage interviews were observed. RESULTS/ANTICIPATED RESULTS: In total, 57% of triage interviews were interrupted. The most common interruption was by other nurses; however, 7% of the interruptions were by the triage nurse themselves. When an interruption occurred during the triage process, 67% of the time the triage nurse would stop the triage assessment and attend to the interrupter. In the interrupted interviews, 17% of the entire triage time was dedicated to addressing interruptions. Some interruptions (ie, additionally staff entering to conduct ECG) had a positive impact by expediting care during the triage process; where other interruptions delayed patient care. DISCUSSION/SIGNIFICANCE OF IMPACT: Interruptions increased the total triage time and contributed to patient treatment delays, as well as led to errors in nursing assessment. Understanding the classifications of triage interruptions and the impact on patient outcomes will allow researchers to develop interventions to mitigate the impact of these interruptions.
Operation Canine Lifeline was a tabletop exercise developed by students and faculty of Boston University School of Medicine’s Healthcare Emergency Management master’s program. The tabletop exercise led to discussion on current protocols for canines working in the field, what occurs if a canine encounters a toxin in the field, and what to do in situations of national security that require working with civilian agencies. This discussion led to the creation of a set of recommendations around providing prehospital veterinary care to government working dogs. The recommendations include a government-run veterinary toxicology hotline for the sole use of the government, issuing handlers deployment kits and preprogrammed smartphones that contain information on the care practices for dogs, and an increased effort for civilian integration, through local emergency medical services, in the emergency care of government canines. (Disaster Med Public Health Preparedness. 2017;11:15–20)
Modern Asian Studies was first published in 1967. It was a manifestation of the enthusiasm for ‘area studies’ which swept academia in the mid-twentieth century. This in turn was prompted by a recognition in Western scholarly and other circles of the importance of understanding the history, languages, and cultures of the world beyond North America and Europe. Such knowledge was desirable in its own right, adding to the sum total of human experience and achievement, but, as societies and economies became increasingly interwoven, it was believed to have significant practical value for dealing with problems of business and trade, politics and diplomacy, the migration of peoples on an unprecedented scale, and fears and anxieties as differing cultures and religions came into contact with each other.
The formation of nickel germanide has been examined over a range of low temperatures (200-400 °C) in an attempt to minimize the thermal budget for the process. Cross-sectional Transmission Electron Microscopy (TEM) was used to determine the texture of the germanide layer and the morphology and constituent composition of the Ge/NiGe interface. The onset and completion of reaction between Ni and Ge were identified by means of a heated stage in combination with in-situ x-ray diffraction (XRD) measurements. The stages of reaction were also monitored using measurements of sheet resistance of the germanides by the Van der Pauw technique. The results have shown that the minimum temperature for the initiation of reaction of Ni and Ge to form NiGe was 225 °C. However, an annealing temperature > 275 °C was necessary for the extensive (and practical) formation of NiGe. Between 200 and 300 °C, the duration of annealing required for the formation of NiGe was significantly longer than at higher temperatures. The stoichiometry of the germanide was very close to NiGe (1:1) as determined using energy dispersive spectroscopy (EDS).
The essays published here celebrate the work of Professor John F. Richards, a historian who significantly changed our understanding of Mughal history, and who, long before it became fashionable, argued the case for tackling certain historical problems from a global perspective. A list of his publications appears at the end of this volume and it is, by any measure, an impressive contribution to knowledge and understanding.
He was born on 3 November 1938 in Exeter, New Hampshire, USA and was the first of his family to go into higher education. They were happy to support him in this venture, since, whatever his undoubted intellectual prowess, he demonstrated from an early age an amazing lack of practical ability when it came to tasks like changing light bulbs or mowing grass. (Later in life he would, with a twinkle in the eye, rather trade on these shortcomings, despite the fact that they sat rather uneasily against his mastery of difficult languages and complex financial spread-sheets.) In 1961, he graduated Valedictorian of his class at the University of New Hampshire, marrying his childhood sweetheart, Ann Berry, on the same day. After Ann had completed her own Bachelor's degree, the couple moved to the West coast where John pursued a doctorate at the University of California, Berkeley.
This report outlines the unexpected discovery of a group of Late Neolithic structures at Greenbogs, Monymusk in Aberdeenshire, along with a series of later prehistoric features in the mid-1990s. Recent radiocarbon dating shows that two four-post timber structures found here date to the period 2890–2490 cal bc. These were found in association with a range of other features including an oval structure and diffuse areas of burning. The closest parallels for the four-post structures can be found in a slowly growing body of Late Neolithic timber structures, some being interpreted as roofed dwellings and others as roofed or unroofed monuments. This article places the Greenbogs structures in their wider context, identifies a number of unexcavated parallels in the aerial record and addresses the nature of the four-post structures found across Late Neolithic Britain and Ireland and suggests that four-post structures were a more common element of Late Neolithic architecture than previously identified. A common building type appears to have been shared across large areas of Britain and Ireland in a variety of contexts, from the seemingly mundane to the more ‘charged’, as part of elaborate monument complexes. The later prehistoric features identified at Greenbogs include a concentration of Middle Bronze Age features including graves containing cremated human bones, one with an upright urn, and a number of Iron Age pits and other features.
Interaction of Greenland’s marine-terminating glaciers with the ocean has emerged as a key term in the ice-sheet mass balance and a plausible trigger for their recent acceleration. Our knowledge of the dynamics, however, is limited by scarcity of ocean measurements at the glacier/ocean boundary. Here data collected near six marine-terminating glaciers (79 North, Kangerdlugssuaq, Helheim and Petermann glaciers, Jakobshavn Isbræ, and the combined Sermeq Kujatdleq and Akangnardleq) are compared to investigate the water masses and the circulation at the ice/ocean boundary. Polar Water, of Arctic origin, and Atlantic Water, from the subtropical North Atlantic, are found near all the glaciers. Property analysis indicates melting by Atlantic Water (AW; found at the grounding line depth near all the glaciers) and the influence of subglacial discharge at depth in summer. AW temperatures near the glaciers range from 4.5˚C in the southeast, to 0.16˚C in northwest Greenland, consistent with the distance from the subtropical North Atlantic and cooling across the continental shelf. A review of its offshore variability suggests that AW temperature changes in the fjords will be largest in southern and smallest in northwest Greenland, consistent with the regional distribution of the recent glacier acceleration.
We present a preliminary analysis of known planetary nebulae (PNe) in M31 that were observed in the first year of the Panchromatic Hubble Andromeda Treasury HST Multi-cycle program. We use the properties of this sample to discuss PNe from this new multi-band survey.
The weaning period is associated with an increased prevalence of gastrointestinal infection in many species. Glutamine (Gln) has been shown to improve intestinal barrier function and immune function in both in vivo and in vitro models. The objective of the present study was to determine the effect of dietary Gln supplementation on intestinal barrier function and intestinal cytokines in a model of Escherichia coli infection. We randomised 21-d-old piglets (n 20) to nutritionally complete isonitrogenous diets with or without Gln (4·4 %, w/w) for 2 weeks. Intestinal loops were isolated from anaesthetised pigs and inoculated with either saline or one of the two E. coli (K88AC or K88 wild-type)-containing solutions. Intestinal tissue was studied for permeability, cytokine expression, fluid secretion and tight-junction protein expression. Animals receiving Gln supplementation had decreased potential difference (PD) and short-circuit current (Isc) in E. coli-inoculated intestinal loops (PD 0·628 (sem 0·151) mV; Isc 13·0 (sem 3·07) μA/cm2) compared with control-fed animals (PD 1·36 (sem 0·227) mV; Isc 22·4 (sem 2·24) μA/cm2). Intestinal tissue from control, but not from Gln-supplemented, animals responded to E. coli with a significant increase in mucosal cytokine mRNA (IL-1β, IL-6, transforming growth factor-β and IL-10). Tight-junction protein expression (claudin-1 and occludin) was reduced with exposure to E. coli in control-fed animals and was not influenced in Gln-supplemented piglets. Gln supplementation may be useful in reducing the severity of weaning-related gastrointestinal infections, by reducing the mucosal cytokine response and altering intestinal barrier function.
While it is clear that self-reported racial/ethnic discrimination is related to illness, there are challenges in measuring self-reported discrimination or unfair treatment. In the present study, we evaluate the psychometric properties of a self-reported instrument across racial/ethnic groups in a population-based sample, and we test and interpret findings from applying two different widely-used approaches to asking about discrimination and unfair treatment. Even though we found that the subset of items we tested tap into a single underlying concept, we also found that different groups are more likely to report on different aspects of discrimination. Whether race is mentioned in the survey question affects both frequency and mean scores of reports of racial/ethnic discrimination. Our findings suggest caution to researchers when comparing studies that have used different approaches to measure racial/ethnic discrimination and allow us to suggest practical empirical guidelines for measuring and analyzing racial/ethnic discrimination. No less important, we have developed a self-reported measure of recent racial/ethnic discrimination that functions well in a range of different racial/ethnic groups and makes it possible to compare how racial/ethnic discrimination is associated with health disparities among multiple racial/ethnic groups.
Like a number of other learned societies founded in the
late eighteenth and early nineteenth centuries, the
Royal Asiatic Society was established to support
research and to disseminate knowledge to the public.
It depends for its charitable status and the
privileges attached to its Royal Charter on
upholding these objectives. The Society has a good
record in this respect, extending now over 186
years. To some degree, the work of the learned
societies was first intruded on, and then taken over
by, the universities as they grew in number,
expanded their curricula, and went in for research
as well as teaching. This was particularly true of
the twentieth century where, in our field of
interest, Asian studies in the humanities and social
sciences became firmly lodged in several
universities in the United Kingdom. But there always
remained a place, particularly one where
professional academics and the wider public could
meet, for Society's such as ours to flourish; and,
looking ahead, as university budgets come under
greater pressure, I foresee a growing role for the
Royal Asiatic Society in the future in ensuring that
the interest and importance of understanding Asian
societies and cultures remains in the forefront of
the public mind.
Overweight and obesity have increased to epidemic proportions among adolescents and are associated with chronic non-communicable diseases and excess mortality in adulthood. The association of overweight/obesity with poor dietary habits has not been studied in adolescents in middle-income developing countries. The present study aimed to estimate the prevalence of overweight, obesity and high waist circumference (WC) in 15–19-year-old Jamaican adolescents and to investigate the association with fast-food and sweetened beverage consumption.
The study enrolled 1317 (598 male, 719 female) adolescents aged 15–19 years using multistage, nationally representative sampling. Age-specific prevalence calculation used internal Z-score lines connecting with the WHO adult cut-off points. Logistic regression was used to examine the association of overweight or high WC with fast-food and sweetened beverage consumption, adjusting for potential confounders.
The overall prevalence of overweight, obesity and high WC was approximately 15 %, 6 % and 10 %, respectively. Prevalence estimated using internal Z-scores was similar to that using the International Obesity Taskforce cut-off points. Obesity (8·0 % in females, 3·3 % in males) and high WC (16·2 % in females, 1·7 % in males) were significantly more prevalent in females when using internal Z-score cut-offs. High WC was associated with the absence of fruit consumption (P = 0·043) and overweight with high sweetened beverage consumption (P = 0·018).
Overweight occurs frequently among Jamaican 15–19-year-olds and is associated with increased consumption of sweetened beverages. High WC is more prevalent among females and is related to low consumption of fruits and vegetables. Measures to reduce the consumption of sweetened beverages and increase fruit intake may reduce the prevalence of excess body fat among adolescents.
1. Complex hybrids were produced having twenty-nine chromosomes, consisting of one telocentric and twenty complete chromosomes of T. aestivum (2n = 6x = 42), seven complete chromosomes of Ae. speltoides (2n = 2x = 14) and one telocentric chromosome derived from A. elongatum (2n = 10x = 70). The presence of the Ae. speltoides genome permitted pairing between homoeologous chromosomes at meiosis and the behaviour of the two telocentric chromosomes was observed.
2. The A. elongatum chromosome was seen to pair with chromosomes homoeologous to those of group 6. There was no evidence that it paired with chromosomes of any other group.
3. When the A. elongatum telocentric and those of 6A and 6D occurred in the same configuration it was evident that the telocentrics 6A and 6D were for corresponding chromosome arms, and the A. elongatum telocentric for the opposite arm.
4. The average rate of pairing was much lower for the A. elongatum telocentric than for wheat telocentrics. Previous studies had indicated very good genetic compensation of the A. elongatum chromosome for chromosomes 6A and 6D. It was therefore indicated that genetic equivalence and pairing affinity were not closely related in this case. Some implications of this are discussed.