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OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.
Patient-reported outcome measures (PROMs) provide a way to measure the impact of a disease and its associated treatments on the quality of life from the patients’ perspective. The aim of this review was to identify PROMs that have been developed and/or validated in patients with carotid artery disease (CAD) undergoing revascularization, and to assess their psychometric properties and examine suitability for research and clinical use.
Eight electronic databases including MEDLINE and CINAHL were searched from inception to May 2015 and updated in the MEDLINE database to February 2017. A two-stage search approach was used to identify studies reporting the development and/or validation of relevant PROMs in patients with CAD undergoing revascularization. Supplementary citation searching and hand-searching reference lists of included studies were also undertaken. The Consensus-based standards for the selection of health measurement instruments (COSMIN) and Oxford criteria were used to assess the methodological quality of the included studies, and the psychometric properties of the PROMs were evaluated using established assessment criteria.
Six PROMs, reported in five studies, were identified: 36-Item Short Form Health Survey (SF-36), Euro-QoL-5-Dimension Scale (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Dizziness Handicap Inventory (DHI), Quality of life for CAD scale by Ivanova 2015 and a disease-specific PROM designed by Stolker 2010. The rigour of the psychometric assessment of the PROMs were variable with most only attempting to assess a single psychometric criterion. No study reported evidence on criterion validity and test-retest reliability. The overall psychometric evaluation of all included PROMs was rated as poor.
This review highlighted a lack of evidence in validated PROMs used for patients undergoing carotid artery revascularization. As a result, the development and validation of a new PROM for this patient population is warranted in order to provide data which can supplement traditional clinical outcomes (stroke >30 days post-procedural, myocardial infarction and death), and capture changes in health status and quality of life in patients to help inform treatment decisions.
Analysis of injuries during military operations has focused on those related to combat. Non-combat complaints have received less attention, despite the need for many troops to be evacuated for non-battle illnesses in Iraq. This study aims to further characterize the disease and non-battle injuries (DNBIs) seen at a tertiary combat hospital and to describe the types of procedures and medications used in the management of these cases.
In this observational study, patients were enrolled from a convenience sample with non-combat-related diseases and injuries who were evaluated in the emergency department (ED) of a US military tertiary hospital in Iraq from 2007-2008. The treating emergency physician (EP) used a data collection form to enroll patients that arrived to the ED whose injury or illness was unrelated to combat.
Data were gathered on 1,745 patients with a median age of 30 years; 84% of patients were male and 85% were US military personnel. The most common diagnoses evaluated in the ED were abdominal disorders, orthopedic injuries, and headache. Many cases involved intravenous access, laboratory testing, and radiographic testing. Procedures performed included electrocardiogram, lumbar puncture, and intubation.
Disease and non-battle traumatic injuries are common in a tertiary combat hospital. Emergency providers working in austere settings should have the diagnostic and procedural skills to evaluate and treat DNBIs.
BebartaVS, MoraAG, NgPC, MasonPE, MuckA, MaddryJK. Disease and Non-Battle Traumatic Injuries Evaluated by Emergency Physicians in a US Tertiary Combat Hospital. Prehosp Disaster Med. 2018;33(1):53–57.
Timing of weed emergence and seed persistence in the soil influence the ability to implement timely and effective control practices. Emergence patterns and seed persistence of kochia populations were monitored in 2010 and 2011 at sites in Kansas, Colorado, Wyoming, Nebraska, and South Dakota. Weekly observations of emergence were initiated in March and continued until no new emergence occurred. Seed was harvested from each site, placed into 100-seed mesh packets, and buried at depths of 0, 2.5, and 10 cm in fall of 2010 and 2011. Packets were exhumed at 6-mo intervals over 2 yr. Viability of exhumed seeds was evaluated. Nonlinear mixed-effects Weibull models were fit to cumulative emergence (%) across growing degree days (GDD) and to viable seed (%) across burial time to describe their fixed and random effects across site-years. Final emergence densities varied among site-years and ranged from as few as 4 to almost 380,000 seedlings m−2. Across 11 site-years in Kansas, cumulative GDD needed for 10% emergence were 168, while across 6 site-years in Wyoming and Nebraska, only 90 GDD were needed; on the calendar, this date shifted from early to late March. The majority (>95%) of kochia seed did not persist for more than 2 yr. Remaining seed viability was generally >80% when seeds were exhumed within 6 mo after burial in March, and declined to <5% by October of the first year after burial. Burial did not appear to increase or decrease seed viability over time but placed seed in a position from which seedling emergence would not be possible. High seedling emergence that occurs very early in the spring emphasizes the need for fall or early spring PRE weed control such as tillage, herbicides, and cover crops, while continued emergence into midsummer emphasizes the need for extended periods of kochia management.
The electrical characteristics of Au/Ni/Ti/ n-SiC contacts have been examined as a function of implant dose (1013-1014 ions/cm2) at 5 KeV and temperature of annealing (750-1000 °C). Measurements of specific contact resistance, ρc, were approximately constant at lower implant doses until increasing at 1 x 1015 ions/cm2 for both C and P ions. Annealing at a temperature of 1000 °C has reduced the value of ρc by an order of magnitude to ∼1 x 10-6 Ω.cm2 at implant doses of 1013-1014 ions/cm2. Auger Electron Spectroscopy (AES) has shown that annealing at 1000 °C resulted in a strong indiffusion of the metallization layers at the interface.
Annual bluegrass is a weed species in turfgrass environments known for exhibiting resistance to multiple herbicide modes of action, including photosystem II (PSII) inhibitors. To evaluate populations of annual bluegrass for susceptibility to PSII inhibitors of varied chemistries, populations were treated with herbicides from triazolinone, triazine, and substituted urea families: amicarbazone, atrazine, and diuron, respectively. Sequencing of the psbA gene confirmed the presence of a Ser264 to Gly amino acid substitution within populations that exhibited resistance to both atrazine and amicarbazone. A single biotype, DR3, which lacked any previously reported psbA gene point mutation, exhibited resistance to diuron, atrazine, and amicarbazone. DR3 had a significantly lower rate of absorption and translocation of atrazine and had enhanced atrazine metabolism when compared with both the Ser264 to Gly resistant mutant and susceptible biotypes. We thus report possible nontarget mechanisms of resistance to PSII-inhibiting herbicides in annual bluegrass.
The aim of this study was to examine whether people differed in change in performance across the first five blocks of an online flanker task and whether those trajectories of change were associated with self-reported aerobic or resistance exercise frequency according to age. A total of 8752 men and women aged 13–89 completed a lifestyle survey and five 45-s games (each game was a block of ~46 trials) of an online flanker task. Accuracy of the congruent and incongruent flanker stimuli was analyzed using latent class and growth curve modeling adjusting for time between blocks, whether the blocks occurred on the same or different days, education, smoking, sleep, caffeinated coffee and tea use, and Lumosity training status (“free play” or part of a “daily brain workout”). Aerobic and resistance exercise were unrelated to first block accuracies. For the more cognitively demanding incongruent flanker stimuli, aerobic activity was positively related to the linear increase in accuracy [B=0.577%, 95% confidence interval (CI), 0.112 to 1.25 per day above the weekly mean of 2.8 days] and inversely related to the quadratic deceleration of accuracy gains (B=−0.619% CI, −1.117 to −0.121 per day). An interaction of aerobic activity with age indicated that active participants younger than age 45 had a larger linear increase and a smaller quadratic deceleration compared to other participants. Age moderates the association between self-reported aerobic, but not self-reported resistance, exercise and changes in cognitive control that occur with practice during incongruent presentations across five blocks of a 45-s online, flanker task. (JINS, 2015, 21, 802–815)
Williams’s (2005) study on “learning without awareness” and three subsequent extensions (Faretta-Stutenberg & Morgan-Short, 2011; Hama & Leow, 2010; Rebuschat, Hamrick, Sachs, Riestenberg, & Ziegler, 2013) have reported conflicting results, perhaps in part due to differences in how awareness has been measured. The present extension of Williams (2005) addresses this possibility directly by triangulating data from three awareness measures: concurrent verbal reports (think-aloud protocols), retrospective verbal reports (postexposure interviews), and subjective measures (confidence ratings and source attributions). Participants were exposed to an artificial determiner system under incidental learning conditions. One experimental group thought aloud during training, another thought aloud during training and testing, and a third remained silent, as did a trained control group. All participants were then tested by means of a forced-choice task to establish whether learning took place. In addition, all participants provided confidence ratings and source attributions on test items and were interviewed following the test. Our results indicate that, although all experimental groups displayed learning effects, only the silent group was able to generalize the acquired knowledge to novel instances. Comparisons of concurrent and retrospective verbal report data shed light on the conflicting findings previously reported in the literature and highlight important methodological issues in implicit and explicit learning research.
The effect of low energy implantation of P or C ions in 3C-SiC on the properties of Ti/Ni/Au contacts has been examined for doses in the range 1013-1015 ions/cm2. Measurements of specific contact resistance, ρc, were performed using the two-contact circular test structure. The magnitude of ρc for the Ti/Ni/Au contacts on unimplanted SiC was 1.29 x 10−6 Ω.cm2. The value of ρc increased significantly at an implant dose of 1 x 1015 ions/cm2. The dependence of ρc on ion dose has been measured using both C and P implant species.
In no other society in the world have urbanisation and industrialization been as comprehensively based on migrant labour as in South Africa. Rather than focusing on the well-documented narrative of displacement and oppression, A Long Way Home captures the humanity, agency and creative modes of self-expression of the millions of workers who helped to build and shape modern South Africa. The book spans a three-hundred-year history beginning with the exportation of slave labour from Mozambique in the eighteenth century and ending with the strikes and tensions on the platinum belt in recent years. It shows not only the age-old mobility of African migrants across the continent but also, with the growing demand for labour in the mining industry, the importation of Chinese indentured migrant workers. Contributions include 18 essays and over 90 artworks and photographs that traverse homesteads, chiefdoms and mining hostels, taking readers into the materiality of migrant life and its customs and traditions, including the rituals practiced by migrants in an effort to preserve connections to “home” and create a sense of “belonging”. The essays and visual materials provide multiple perspectives on the lived experience of migrant labourers and celebrate their extraordinary journeys. A Long Way Home was conceived during the planning of an art exhibition entitled ‘Ngezinyawo: Migrant Journeys’ at Wits Art Museum. The interdisciplinary nature of the contributions and the extraordinary collection of images selected to complement and expand on the text make this a unique collection.