"Lose 30lbs in 30 days" : assigning responsibility for deceptive advertising of weight-loss products

Purpose &ndash; The aim of this paper is to outline key social marketing issues apparent in deceptive weight-loss advertising, from the perspective of government policy-makers, manufacturers, the media, and consumers. The purpose is to examine the complexity of one aspect of the obesity battle and provide a framework for coordinated and integrated social marketing initiatives from a multiple stakeholder perspective.Design/methodology/approach &ndash; The results of deceptive weight-loss advertising are framed using the harm chain model, and the paper offers recommended solutions based on a framework of marketing, education and policy changes across the network of stakeholders.Findings &ndash; This paper concludes that a resolution to the harm created by deceptive weight-loss advertising can be achieved by the creation of a more holistic, system-wide solution to this important health and policy issue. This networked approach must involve all aspects of harm in a multi-stakeholder solution, including both upstream and downstream integration. Specific recommendations are made for policy-makers, manufacturers, the media, and consumers to achieve this goal.Social implications &ndash; From a marketing perspective, analyzing the issue of deceptive weight-loss advertising using the harm chain allows for the creation of a more holistic, system-wide solution involving stakeholders in all aspects of harm for this important health and policy issue.Originality/value &ndash; This research examines the problem of obesity and weight-loss advertising from the unique perspective of the harm chain framework. The authors make unified recommendations for various stakeholders including industry, media, government and consumers, in order to direct integrated social marketing and consumer-oriented strategies within this industry.<br /

Extending the tactical horizon networking aircraft to enable persistent surveillance and target development for SOF

The NPS Tactical Horizon Extension Project objective is to define and demonstrate a concept by which task force-level commanders and below can obtain a persistent, over-the-horizon surveillance capability for the purpose of target development and other missions without tasking national or theater-level assets. Our goal is to increase the ISR capacity of units who normally would not rate the priority to task a Predator, Global Hawk, or U-2. There are two guiding tenets in developing this concept. First, the equipment and its control should be organic to the SOF unit or task force. Second, utilizing this capability should not require the soldier to carry any additional equipment into the field. Initial research led us to the idea of using networked unmanned aerial systems (UAS's) to generate an over-the-horizon surveillance capability for SOF. We demonstrated the concept by forming a network comprised of a forward ground team, an inexpensive, test-bed UAS equipped with an off-the-shelf video camera, a manned aircraft, and a tactical operations center (TOC). We attained connectivity through an ITT Mesh structure at 2.4 GHz, amplified to 1W. Researchers were from the Defense Analysis, Mechanical and Astronautical Engineering, and Information Sciences Departments. We conducted successful experiments through the USSOCOM-NPS Cooperative Field Experimentation Program.http://archive.org/details/extendingtactica109452582Outstanding ThesisApproved for public release; distribution is unlimited

Cholesterol-Metabolizing Enzyme Cytochrome P450 46A1 as a Pharmacologic Target for Alzheimer’s Disease

Cytochrome P450 46A1 (CYP46A1 or cholesterol 24-hydroxylase) controls cholesterol elimination from the brain and plays a role in higher order brain functions. Genetically enhanced CYP46A1 expression in mouse models of Alzheimer's disease mitigates the manifestations of this disease. We enhanced CYP46A1 activity pharmacologically by treating 5XFAD mice, a model of rapid amyloidogenesis, with a low dose of the anti-HIV medication efavirenz. Efavirenz was administered from 1 to 9 months of age, and mice were evaluated at specific time points. At one month of age, cholesterol homeostasis was already disturbed in the brain of 5XFAD mice. Nevertheless, efavirenz activated CYP46A1 and mouse cerebral cholesterol turnover during the first four months of administration. This treatment time also reduced amyloid burden and microglia activation in the cortex and subiculum of 5XFAD mice as well as protein levels of amyloid precursor protein and the expression of several genes involved in inflammatory response. However, mouse short-term memory and long-term spatial memory were impaired, whereas learning in the context-dependent fear test was improved. Additional four months of drug administration (a total of eight months of treatment) improved long-term spatial memory in the treated as compared to the untreated mice, further decreased amyloid-β content in 5XFAD brain, and also decreased the mortality rate among male mice. We propose a mechanistic model unifying the observed efavirenz effects. We suggest that CYP46A1 activation by efavirenz could be a new anti-Alzheimer's disease treatment and a tool to study and identify normal and pathological brain processes affected by cholesterol maintenance

ERK2 alone drives inflammatory pain but cooperates with ERK1 in sensory neuron survival

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are highly homologous yet distinct components of signal transduction pathways known to regulate cell survival and function. Recent evidence indicates an isoform-specific role for ERK2 in pain processing and peripheral sensitization. However, the function of ERK2 in primary sensory neurons has not been directly tested. To dissect the isoform-specific function of ERK2 in sensory neurons, we used mice with Cre-loxP-mediated deletion of ERK2 in Na(v)1.8(+) sensory neurons that are predominantly nociceptors. We find that ERK2, unlike ERK1, is required for peripheral sensitization and cold sensation. We also demonstrate that ERK2, but not ERK1, is required to preserve epidermal innervation in a subset of peptidergic neurons. Additionally, deletion of both ERK isoforms in Na(v)1.8(+) sensory neurons leads to neuron loss not observed with deletion of either isoform alone, demonstrating functional redundancy in the maintenance of sensory neuron survival. Thus, ERK1 and ERK2 exhibit both functionally distinct and redundant roles in sensory neurons. SIGNIFICANCE STATEMENT ERK1/2 signaling affects sensory neuron function and survival. However, it was not clear whether ERK isoform-specific roles exist in these processes postnatally. Previous work from our laboratory suggested either functional redundancy of ERK isoforms or a predominant role for ERK2 in pain; however, the tools to discriminate between these possibilities were not available at the time. In the present study, we use new genetic knock-out lines to demonstrate that ERK2 in sensory neurons is necessary for development of inflammatory pain and for postnatal maintenance of peptidergic epidermal innervation. Interestingly, postnatal loss of both ERK isoforms leads to a profound loss of sensory neurons. Therefore, ERK1 and ERK2 display both functionally distinct and redundant roles in sensory neurons

“Why Should I Go Vote Without Understanding What I Am Going to Vote For?” The Impact of First Generation Voting Barriers on Alaska Natives

This article explores the many forms of discrimination that have persisted in Alaska, the resulting first generation voting barriers faced by Alaska Native voters, and the two contested lawsuits it took to attain a measure of equality for those voters in four regions of Alaska: Nick v. Bethel and Toyukak v. Treadwell. In the end, the court’s decision in Toyukak came down to a comparison of just two pieces of evidence: (1) the Official Election Pamphlet that English-speaking voters received that was often more than 100 pages long; and (2) the single sheet of paper that Alaska Native language speakers received, containing only the date, time, and location of the election, along with a notice that they could request language assistance. Those two pieces of evidence, when set side by side, showed the fundamental unequal access to the ballot. The lessons learned from Nick and Toyukak detailed below are similarly simple: (1) first generation voting barriers still exist in the United States; and (2) Section 203 of the VRA does not permit American Indian and Alaska Native language speaking voters to receive less information than their English-speaking counterparts. The voters in these cases had been entitled to equality for 40 years, but they had to fight for nearly a decade in two federal court cases to get it

Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections

Application of single-molecule switching nanoscopy (SMSN) beyond the coverslip surface poses substantial challenges due to sample-induced aberrations that distort and blur single-molecule emission patterns. We combined active shaping of point spread functions and efficient adaptive optics to enable robust 3D-SMSN imaging within tissues. This development allowed us to image through 30-μm-thick brain sections to visualize and reconstruct the morphology and the nanoscale details of amyloid-β filaments in a mouse model of Alzheimer's disease

The Feasibility, Appropriateness, Meaningfulness, and Effectiveness of Parenting and Family Support Programs Delivered in the Criminal Justice System: A Systematic Review

Children whose parents are involved in the criminal justice system (CJS) are at increased risk of developing social, emotional, and behavioural difficulties and are more likely than their peers to become involved in the CJS themselves. Parenting behaviour and parent-child relationships have the potential to affect children’s outcomes with positive parenting practices having the potential to moderate some of the negative outcomes associated with parental involvement in the CJS. However, many parents in the CJS may lack appropriate role models to support the development of positive parenting beliefs and practices. Parenting programs offer an opportunity for parents to enhance their parenting knowledge and behaviours and improve relationships with children. Quantitative and qualitative evidence pertaining to the implementation and effectiveness of parenting programs delivered in the CJS was included. Five databases were searched and a total of 1145 articles were identified of which 29 met the review inclusion criteria. Overall, programs were found to significantly improve parenting attitudes; however, evidence of wider effects is limited. Additionally, the findings indicate that parenting programs can be meaningful for parents. Despite this, a number of challenges for implementation were found including the transient nature of the prison population and a lack of parent-child contact. Based on these findings, recommendations for the future development and delivery of programs are discussed

The Pathway Coexpression Network: Revealing pathway relationships.

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer's Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/

Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment

HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage

Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component.Peer reviewe