2,179 research outputs found
Partner or supplier: an examination of client/agency relationships in an IMC context
There is growing evidence from practitioners that the advertising industry is in a state of crisis. As campaigns become more integrated and multi-disciplinary, the relationship between advertising agencies and clients is being tested to its limits and is presently considered to be at an all-time low. Agencies feel less valued and are being excluded from C-suite discussion. Clients feel that agencies do not appreciate the changing landscape and how the customer experience is now key. Both sides recognise the need for more trust and collaboration. This study applies the agency theory and the social power theory to understand the pressures that the relationship is under. It looks for evidence that IMC is creating a movement away from a business alliance relationship by comparing qualitative data collected from both agencies and clients, using NVivo to identify themes. The findings identify four themes which illustrate this shift towards a supplier relationship: the client ownership of the customer journey, the lack of a strategic role of agencies, the challenges of agency collaboration and difficulties of agency specialisation
Statistical physics of the Schelling model of segregation
We investigate the static and dynamic properties of a celebrated model of
social segregation, providing a complete explanation of the mechanisms leading
to segregation both in one- and two-dimensional systems. Standard statistical
physics methods shed light on the rich phenomenology of this simple model,
exhibiting static phase transitions typical of kinetic constrained models,
nontrivial coarsening like in driven-particle systems and percolation-related
phenomena.Comment: 4 pages, 3 figure
Perforated Small Intestine: A Case of a Delayed Presentation of an Intra-Abdominal Injury in a Pediatric Patient With a Seatbelt Sign
With the use of seatbelts comes a unique injury profile that has been called "the seatbelt syndrome." The classically described "seatbelt sign" has become a pattern of injury, describing potential underlying damage. As a clinician, clues to the underlying damage follow a thorough physical examination including the removal of all clothing to locate abrasions and bruises to the skin that potentially follow a seatbelt pattern. Delayed presentation of an intra-abdominal injury in the setting of a seatbelt sign has been well documented; however, the question is how long to observe these patients. We present the case of a 17-year-old woman involved in a motor vehicle collision who presented to the emergency department (ED) hemodynamically stable with a lower abdominal wall seatbelt sign. Her initial imaging revealed only an abdominal wall contusion. She was admitted for observation. Approximately 12 h later she started developing abdominal pain, and by 14 h abdominal distention, with repeat imaging showing free fluid and free air. She was taken to the operating room for an exploratory laparotomy and was ultimately discharged back home on day 7
Removal of a frameshift between the hsdM and hsdS genes of the EcoKI Type IA DNA restriction and modification system produces a new type of system and links the different families of Type I systems
The EcoKI DNA methyltransferase is a trimeric protein comprised of two modification subunits (M) and one sequence specificity subunit (S). This enzyme forms the core of the EcoKI restriction/modification (RM) enzyme. The 3ā² end of the gene encoding the M subunit overlaps by 1 nt the start of the gene for the S subunit. Translation from the two different open reading frames is translationally coupled. Mutagenesis to remove the frameshift and fuse the two subunits together produces a functional RM enzyme in vivo with the same properties as the natural EcoKI system. The fusion protein can be purified and forms an active restriction enzyme upon addition of restriction subunits and of additional M subunit. The Type I RM systems are grouped into families, IA to IE, defined by complementation, hybridization and sequence similarity. The fusion protein forms an evolutionary intermediate form lying between the Type IA family of RM enzymes and the Type IB family of RM enzymes which have the frameshift located at a different part of the gene sequence
Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection
In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist
Chronotropic incompetence predicts mortality in severe obstructive pulmonary disease
We evaluated the prevalence of chronotropic incompetence (CI), a marker of autonomic dysfunction, and its prognostic value in patients with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of 449 patients with severe COPD who underwent a cardiopulmonary exercise test, after excluding patients with lung volume reduction surgery, left ventricular dysfunction and those not in sinus rhythm. CI was defined as percent predicted heart rate reserve (%HRR). Events were defined as death or lung transplant during a median follow-up of 68 months. Median age was 61 years; median percent predicted forced expiratory volume in one second (%FEV1) of 25% and median %HRR of 33%. The hazard ratio for an event in the lowest quartile of %HRR, taking the highest quartile as reference, was of 3.2 (95% confidence interval: 2.1-4.8; p < 0.001). In a multivariate regression model, %HRR was an independent predictor of events. In conclusion, Cl was an independent and powerful outcome predictor in patients with severe COPD. (C) 2013 Elsevier B.V. All rights reserved
Atomic force microscopy of the EcoKI Type I DNA restriction enzyme bound to DNA shows enzyme dimerization and DNA looping
Atomic force microscopy (AFM) allows the study of single proteināDNA interactions such as those observed with the Type I RestrictionāModification systems. The mechanisms employed by these systems are complicated and understanding them has proved problematic. It has been known for years that these enzymes translocate DNA during the restriction reaction, but more recent AFM work suggested that the archetypal EcoKI protein went through an additional dimerization stage before the onset of translocation. The results presented here extend earlier findings confirming the dimerization. Dimerization is particularly common if the DNA molecule contains two EcoKI recognition sites. DNA loops with dimers at their apex form if the DNA is sufficiently long, and also form in the presence of ATPĪ³S, a non-hydrolysable analogue of the ATP required for translocation, indicating that the looping is on the reaction pathway of the enzyme. Visualization of specific DNA loops in the proteināDNA constructs was achieved by improved sample preparation and analysis techniques. The reported dimerization and looping mechanism is unlikely to be exclusive to EcoKI, and offers greater insight into the detailed functioning of this and other higher order assemblies of proteins operating by bringing distant sites on DNA into close proximity via DNA looping
Identification of C-C Chemokine Receptor 1 (CCR1) as the Monocyte Hemofiltrate C-C Chemokine (HCC)-1 Receptor
Hemofiltrate C-C chemokine (HCC)-1 is a recently cloned C-C chemokine that is structurally similar to macrophage inflammatory protein (MIP)-1Ī±. Unlike most chemokines, it is constitutively secreted by tissues and is present at high concentrations in normal human plasma. Also atypical for chemokines, HCC-1 is reported not to be chemotactic for leukocytes. In this paper, we have investigated the chemokine receptor usage and downstream signaling pathways of HCC-1. Cross-desensitization experiments using THP-1 cells suggested that HCC-1 and MIP-1Ī± activated the same receptor. Experiments using a panel of cloned chemokine receptors revealed that HCC-1 specifically activated C-C chemokine receptor (CCR)1, but not closely related receptors, including CCR5. HCC-1 competed with MIP-1Ī± for binding to CCR1-transfected cells, but with a markedly reduced affinity (IC50 = 93 nM versus 1.3 nM for MIP-1Ī±). Similarly, HCC-1 was less potent than MIP-1Ī± in inducing inhibition of adenylyl cyclase in CCR1-transfected cells. HCC-1 induced chemotaxis of freshly isolated human monocytes, THP-1 cells, and CCR1-transfected cells, and the optimal concentration for cell migration (100 nM) was ā¼100-fold lower than that of MIP-1Ī± (1 nM). These data demonstrate that HCC-1 is a chemoattractant and identify CCR1 as a functional HCC-1 receptor on human monocytes
The structure of M.EcoKI Type I DNA methyltransferase with a DNA mimic antirestriction protein
Type-I DNA restrictionāmodification (R/M) systems are important agents in limiting the transmission of mobile genetic elements responsible for spreading bacterial resistance to antibiotics. EcoKI, a Type I R/M enzyme from Escherichia coli, acts by methylation- and sequence-specific recognition, leading to either methylation of DNA or translocation and cutting at a random site, often hundreds of base pairs away. Consisting of one specificity subunit, two modification subunits, and two DNA translocase/endonuclease subunits, EcoKI is inhibited by the T7 phage antirestriction protein ocr, a DNA mimic. We present a 3D density map generated by negative-stain electron microscopy and single particle analysis of the central core of the restriction complex, the M.EcoKI M2S1 methyltransferase, bound to ocr. We also present complete atomic models of M.EcoKI in complex with ocr and its cognate DNA giving a clear picture of the overall clamp-like operation of the enzyme. The model is consistent with a large body of experimental data on EcoKI published over 40 years
Sources to Seafood: Mercury Pollution in the Marine Environment
In 2010, the Toxic Metals Superfund Research Program at Dartmouth College brought together a group of 50 scientists and policy stakeholders to form C-MERC, the Coastal and Marine Mercury Ecosystem Research Collaborative. The goal was to review current knowledgeāand knowledge gapsārelating to a global environmental health problem, mercury contamination of the worldās marine fish. C-MERC participants attended two workshops over a two-year period, and in 2012 C-MERC authors published a series of peer-reviewed papers in the journals Environmental Health Perspectives and Environmental Research that elucidated key processes related to the inputs, cycling, and uptake of mercury in marine ecosystems, effects on human health, and policy implications. This report synthesizes the knowledge from these papers in an effort to summarize the science relevant to policies being considered at regional, national, and global levels.
The Dartmouth Toxic Metals Superfund Research Program uses an interdisciplinary approach to investigate the ways that arsenic and mercury in the environment affect ecosystems and human health. Arsenic and mercury are commonly found in Superfund sites around the U.S. as well as other areas that result in exposures to certain communities. The Research Translation Core of the program communicates program science to government partners, non-governmental organizations, health care providers and associations, universities and the lay community, and facilitates the use of its research for the protection of public health. The Research Translation Core organized the C-MERC effort.
The Superfund Research Program of the National Institute of Environmental Health Sciences supports a network of university programs that investigate the complex health and environmental issues associated with contaminants found at the nationās hazardous waste sites. The Program coordinates with the Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry of the Centers for Disease Control and Prevention, federal entities charged with management of environmental and human health hazards associated with toxic substances
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