Exploring The Media Strategy For International Marketers With Small Budgets: A Cross-Country Consumer Perspective

This paper reports a cross-country comparative study of the media choices for the marketing of Master of Business Administration education in China and the United States from a consumer perspective. To date, limited discussion in the standardization versus adaptation debate has focused specifically on the issue of media strategy from the perspective of a specific category of international marketers, even though media planning is often the most costly and challenging part of international marketing communication. The current study is an effort to bridge this gap

Childhood Obesity: An Old Problem in a New Age

Obesity in America is not a new problem. However, the increasing prevalence of childhood obesity is. This review will examine the literature to explain what childhood obesity is, what causes it, why it is dangerous, and how this trend can be reversed. Childhood obesity has become one of the greatest health challenges of our time and in order to implement and execute real solutions, the causes and effects of this widespread health problem must be examined in detail. Although there are a myriad of actors that contribute to childhood obesity, the main ones that shall be focused on in this review are the quality and quantity of food intake, lack of physical activity, and the influencing effect of media. This paper will explore the effects of childhood obesity on the individual, in terms of physical and psychological health, and on society, in terms of the cost society pays for its obese population. If the goal is to decrease the amount of obese children in America, then the ultimate solution may lie in one of its contributors, the media. If media is truly an important actor in creating this pandemic, then turning it around and utilizing its power to educate the public may be the solution needed to stop this escalating trend.A comprehensive analysis of childhood obesity in the 21st century

Correlating lesion size and location to deficits after ischemic stroke: the influence of accounting for altered peri-necrotic tissue and incidental silent infarcts

<p>Abstract</p> <p>Background</p> <p>Investigators frequently quantify and evaluate the location and size of stroke lesions to help uncover cerebral anatomical correlates of deficits observed after first-ever stroke. However, it is common to discover silent infarcts such as lacunes in patients identified clinically as 'first-ever' stroke, and it is unclear if including these incidental findings may impact lesion-based investigations of brain-behaviour relationships. There is also debate concerning how to best define the boundaries of necrotic stroke lesions that blend in an ill-defined way into surrounding tissue, as it is unclear whether including this altered peri-necrotic tissue region may influence studies of brain-behaviour relationships. Therefore, for patients with clinically overt stroke, we examined whether including altered peri-necrotic tissue and incidental silent strokes influenced either lesion volume correlations with a measure of sensorimotor impairment or the anatomical localization of this impairment established using subtraction lesion analysis.</p> <p>Methods</p> <p>Chronic stroke lesions of 41 patients were manually traced from digital T1-MRI to sequentially include the: necrotic lesion core, altered peri-necrotic tissue, silent lesions in the same hemisphere as the index lesion, and silent lesions in the opposite hemisphere. Lesion volumes for each region were examined for correlation with motor impairment scores, and subtraction analysis was used to highlight anatomical lesion loci associated with this deficit.</p> <p>Results</p> <p>For subtraction lesion analysis, including peri-necrotic tissue resulted in a larger region of more frequent damage being seen in the basal ganglia. For correlational analysis, only the volume of the lesion core was significantly associated with motor impairment scores (r = -0.35, <it>p </it>= 0.025). In a sub-analysis of patients with small subcortical index lesions, adding silent lesions in the opposite hemisphere to the volume of the index stroke strengthened the volume-impairment association.</p> <p>Conclusions</p> <p>Including peri-necrotic tissue strengthened lesion localization analysis, but the influence of peri-necrotic tissue and incidental lesions on lesion volume correlations with motor impairment was negligible barring a small index lesion. Overall, the potential influence of incidental lesions and peri-necrotic tissue on brain-behaviour relationships may depend on the characteristics of the index stroke and on whether one is examining the relationship between lesion volume and impairment or lesion location and impairment.</p

A Programmably Compliant Origami Mechanism for Dynamically Dexterous Robots

We present an approach to overcoming challenges in dynamical dexterity for robots through programmably compliant origami mechanisms. Our work leverages a one-parameter family of flat sheet crease patterns that folds into origami bellows, whose axial compliance can be tuned to select desired stiffness. Concentrically arranged cylinder pairs reliably manifest additive stiffness, extending the programmable range by nearly an order of magnitude and achieving bulk axial stiffness spanning 200–1500 N/m using 8 mil thick polyester-coated paper. Accordingly, we design origami energy-storing springs with a stiffness of 1035 N/m each and incorporate them into a three degree-of-freedom (DOF) tendon-driven spatial pointing mechanism that exhibits trajectory tracking accuracy less than 15% rms error within a (2 cm)^3 volume. The origami springs can sustain high power throughput, enabling the robot to achieve asymptotically stable juggling for both highly elastic (1 kg resilient shotput ball) and highly damped (“medicine ball”) collisions in the vertical direction with apex heights approaching 10 cm. The results demonstrate that “soft” robotic mechanisms are able to perform a controlled, dynamically actuated task

Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies

AbstractBackgroundThe efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy in adults with major depressive disorder (MDD) from two phase 3 studies are reported.MethodsAcross study 1 (placebo, n=201; LDX, n=201) and study 2 (placebo, n=213; LDX, n=211), most participants (placebo and LDX) in the safety analysis set were female (study 1: 66.2% and 64.2%; study 2: 67.1% and 66.8%); mean±SD ages were 41.8±12.04 with placebo and 42.2±12.32 with LDX in study 1 and 42.6±11.41 with placebo and 42.0±11.63 with LDX in study 2. Participants (18–65 y) had DSM-IV-TR–diagnosed MDD and lead-in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores ≥24. Eight-week antidepressant lead-in phases prospectively assessed antidepressant response. Then, 8 weeks of randomized (1:1), double-blind treatment with dose-optimized LDX (20–70mg) or placebo in participants exhibiting inadequate antidepressant monotherapy responses (augmentation baseline MADRS total scores ≥18 and <50% MADRS total score reductions from lead-in baseline to augmentation baseline) was initiated. The primary endpoint was MADRS total score change from augmentation baseline to week 16. Safety and tolerability measures included the occurrence of treatment-emergent adverse events (TEAEs).ResultsLeast squares mean (95% CI) treatment differences (LDX–placebo) for MADRS total score changes from augmentation baseline to week 16 were not statistically significant in study 1 (0.1 [–1.7, 2.0], P=0.883) or study 2 (–0.5 [–2.3, 1.3], P=0.583). The only TEAE reported by >5% of LDX participants at twice the placebo rate in both studies was dry mouth.LimitationsLimitations include the exclusion of participants with psychiatric comorbidities/active medical disorders, the inability to assess specific MDD symptom domains (eg, anhedonia, cognition) or subtypes, the use of telephone-based depression assessments, and the potential influence of placebo response.ConclusionContrary to expectations, LDX augmentation was not superior to placebo in reducing depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy

IL-1 receptor like 1 protects against alcoholic liver injury by limiting NF-κB activation in hepatic macrophages

Background & Aim Alcohol consumption increases intestinal permeability and causes damage to hepatocytes, leading to the release of pathogen- and damage-associated molecular pattern molecules (PAMPs and DAMPs), stimulating hepatic macrophages and activating NF-κB. The resultant inflammation exacerbates alcoholic liver disease (ALD). However, much less is known about the mechanisms attenuating inflammation and preventing disease progression in most heavy drinkers. Interleukin (IL)-33 is a DAMP (alarmin) released from dead cells that acts through its receptor, IL-1 receptor like 1 (ST2). ST2 signaling has been reported to either stimulate or inhibit NF-κB activation. The role of IL-33/ST2 in ALD has not been studied. Methods Serum levels of IL-33 and its decoy receptor, soluble ST2 (sST2) were measured in ALD patients. Alcohol-induced liver injury, inflammation and hepatic macrophage activation were compared between wild-type, IL-33−/− and ST2−/− mice in several models. Results Elevation of serum IL-33 and sST2 were only observed in patients with severe decompensated ALD. Consistently, in mice with mild ALD without significant cell death and IL-33 release, IL-33 deletion did not affect alcohol-induced liver damage. However, ST2-deletion exacerbated ALD, through enhancing NF-κB activation in liver macrophages. In contrast, when extracellular IL-33 was markedly elevated, liver injury and inflammation were attenuated in both IL-33−/− and ST2−/− mice compared to wild-type mice. Conclusion Our data revealed a dichotomous role of IL-33/ST2 signaling during ALD development. At early and mild stages, ST2 restrains the inflammatory activation of hepatic macrophages, through inhibiting NF-κB, and plays a protective function in an IL-33-independent fashion. During severe liver injury, significant cell death and marked IL-33 release occur, which triggers IL-33/ST2 signaling and exacerbates tissue damage. Lay summary In mild ALD, ST2 negatively regulates the inflammatory activation of hepatic macrophages, thereby protecting against alcohol-induced liver damage, whereas in the case of severe liver injury, the release of extracellular IL-33 may exacerbate tissue inflammation by triggering the canonical IL-33/ST2L signaling in hepatic macrophages

Proteomic resistance biomarkers for PI3K inhibitor in triple negative breast cancer patient-derived xenograft models

PI3K pathway activation is frequently observed in triple negative breast cancer (TNBC). However, single agent PI3K inhibitors have shown limited anti-tumor activity. To investigate biomarkers of response and resistance mechanisms, we tested 17 TNBC patient-derived xenograft (PDX) models representing diverse genomic backgrounds and varying degrees of PI3K pathway signaling activities for their tumor growth response to the pan-PI3K inhibitor, BKM120. Baseline and post-treatment PDX tumors were subjected to reverse phase protein array (RPPA) to identify protein markers associated with tumor growth response. While BKM120 consistently reduced PI3K pathway activity, as demonstrated by reduced levels of phosphorylated AKT, percentage tumor growth inhibition (%TGI) ranged from 35% in the least sensitive to 84% in the most sensitive model. Several biomarkers showed significant association with resistance, including elevated baseline levels of growth factor receptors (EGFR, pHER3 Y1197), PI3Kp85 regulatory subunit, anti-apoptotic protein BclXL, EMT (Vimentin, MMP9, IntegrinaV), NFKB pathway (IkappaB, RANKL), and intracellular signaling molecules including Caveolin, CBP, and KLF4, as well as treatment-induced increases in the levels of phosphorylated forms of Aurora kinases. Interestingly, increased AKT phosphorylation or PTEN loss at baseline were not significantly correlated to %TGI. These results provide important insights into biomarker development for PI3K inhibitors in TNBC

The Vaginal Microbiome: Disease, Genetics and the Environment

The vagina is an interactive interface between the host and the environment. Its surface is covered by a protective epithelium colonized by bacteria and other microorganisms. The ectocervix is nonsterile, whereas the endocervix and the upper genital tract are assumed to be sterile in healthy women. Therefore, the cervix serves a pivotal role as a gatekeeper to protect the upper genital tract from microbial invasion and subsequent reproductive pathology. Microorganisms that cross this barrier can cause preterm labor, pelvic inflammatory disease, and other gynecologic and reproductive disorders. Homeostasis of the microbiome in the vagina and ectocervix plays a paramount role in reproductive health. Depending on its composition, the microbiome may protect the vagina from infectious or non-infectious diseases, or it may enhance its susceptibility to them. Because of the nature of this organ, and the fact that it is continuously colonized by bacteria from birth to death, it is virtually certain that this rich environment evolved in concert with its microbial flora. Specific interactions dictated by the genetics of both the host and microbes are likely responsible for maintaining both the environment and the microbiome. However, the genetic basis of these interactions in both the host and the bacterial colonizers is currently unknown. _Lactobacillus_ species are associated with vaginal health, but the role of these species in the maintenance of health is not yet well defined. Similarly, other species, including those representing minor components of the overall flora, undoubtedly influence the ability of potential pathogens to thrive and cause disease. Gross alterations in the vaginal microbiome are frequently observed in women with bacterial vaginosis, but the exact etiology of this disorder is still unknown. There are also implications for vaginal flora in non-infectious conditions such as pregnancy, pre-term labor and birth, and possibly fertility and other aspects of women&#x2019;s health. Conversely, the role of environmental factors in the maintenance of a healthy vaginal microbiome is largely unknown. To explore these issues, we have proposed to address the following questions:&#xd;&#xa;&#xd;&#xa;*1.&#x9;Do the genes of the host contribute to the composition of the vaginal microbiome?* We hypothesize that genes of both host and bacteria have important impacts on the vaginal microbiome. We are addressing this question by examining the vaginal microbiomes of mono- and dizygotic twin pairs selected from the over 170,000 twin pairs in the Mid-Atlantic Twin Registry (MATR). Subsequent studies, beyond the scope of the current project, may investigate which host genes impact the microbial flora and how they do so.&#xd;&#xa;*2.&#x9;What changes in the microbiome are associated with common non-infectious pathological states of the host?* We hypothesize that altered physiological (e.g., pregnancy) and pathologic (e.g., immune suppression) conditions, or environmental exposures (e.g., antibiotics) predictably alter the vaginal microbiome. Conversely, certain vaginal microbiome characteristics are thought to contribute to a woman&#x2019;s risk for outcomes such as preterm delivery. We are addressing this question by recruiting study participants from the ~40,000 annual clinical visits to women&#x2019;s clinics of the VCU Health System.&#xd;&#xa;*3.&#x9;What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions?* We hypothesize that susceptibility to infectious disease (e.g. HPV, _Chlamydia_ infection, vaginitis, vaginosis, etc.) is impacted by the vaginal microbiome. In turn, these infectious conditions clearly can affect the ability of other bacteria to colonize and cause pathology. Again, we are exploring these issues by recruiting participants from visitors to women&#x2019;s clinics in the VCU Health System.&#xd;&#xa;&#xd;&#xa;Three kinds of sequence data are generated in this project: i) rDNA sequences from vaginal microbes; ii) whole metagenome shotgun sequences from vaginal samples; and iii) whole genome shotgun sequences of bacterial clones selected from vaginal samples. The study includes samples from three vaginal sites: mid-vaginal, cervical, and introital. The data sets also include buccal and perianal samples from all twin participants. Samples from these additional sites are used to test the hypothesis of a per continuum spread of bacteria in relation to vaginal health. An extended set of clinical metadata associated with these sequences are deposited with dbGAP. We have currently collected over 4,400 samples from ~100 twins and over 450 clinical participants. We have analyzed and deposited data for 480 rDNA samples, eight whole metagenome shotgun samples, and over 50 complete bacterial genomes. These data are available to accredited investigators according to NIH and Human Microbiome Project (HMP) guidelines. The bacterial clones are deposited in the Biodefense and Emerging Infections Research Resources Repository (&#x22;http://www.beiresources.org/&#x22;:http://www.beiresources.org/). &#xd;&#xa;&#xd;&#xa;In addition to the extensive sequence data obtained in this study, we are collecting metadata associated with each of the study participants. Thus, participants are asked to complete an extensive health history questionnaire at the time samples are collected. Selected clinical data associated with the visit are also obtained, and relevant information is collected from the medical records when available. This data is maintained securely in a HIPAA-compliant data system as required by VCU&#x2019;s Institutional Review Board (IRB). The preponderance of these data (i.e., that judged appropriate by NIH staff and VCU&#x2019;s IRB are deposited at dbGAP (&#x22;http://www.ncbi.nlm.nih.gov/gap&#x22;:http://www.ncbi.nlm.nih.gov/gap). Selected fields of this data have been identified by NIH staff as &#x2018;too sensitive&#x2019; and are not available in dbGAP. Individuals requiring access to these data fields are asked to contact the PI of this project or NIH Program Staff. &#xd;&#xa