Methodological Report on Kaul and Wolf's Working Papers on the Effect of Plain Packaging on Smoking Prevalence in Australia and the Criticism Raised by OxyRomandie

This report contains a methodological assessment of two working papers by Ashok Kaul and Michael Wolf on the effect of plain packaging on smoking prevalence in Australia and the criticism raised against these working papers by OxyRomandie. First, the potential of the data used by Kaul and Wolf for identifying causal effects is discussed. Second, a reanalysis of the data is provided. Third, the criticism raised by OxyRomandie is commented.

Effects of congressional modernization laws on public access to innovative medical device technologies

The Federal Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid (CMS) play key roles in making Class III, medical devices available to the public, and they are required by law to meet statutory deadlines for applications under review. Historically, both agencies have failed to meet their respective statutory requirements. Since these failures affect patient access and may adversely impact public health, Congress has enacted several “modernization” laws. However, the effectiveness of these modernization laws has not been adequately studied or established for Class III medical devices. ^ The aim of this research study was, therefore, to analyze how these modernization laws may have affected public access to medical devices. Two questions were addressed: (1) How have the FDA modernization laws affected the time to approval for medical device premarket approval applications (PMAs)? (2) How has the CMS modernization law affected the time to approval for national coverage decisions (NCDs)? The data for this research study were collected from publicly available databases for the period January 1, 1995, through December 31, 2008. These dates were selected to ensure that a sufficient period of time was captured to measure pre- and post-modernization effects on time to approval. All records containing original PMAs were obtained from the FDA database, and all records containing NCDs were obtained from the CMS database. Source documents, including FDA premarket approval letters and CMS national coverage decision memoranda, were reviewed to obtain additional data not found in the search results. Analyses were conducted to determine the effects of the pre- and post-modernization laws on time to approval. Secondary analyses of FDA subcategories were conducted to uncover any causal factors that might explain differences in time to approval and to compare with the primary trends. The primary analysis showed that the FDA modernization laws of 1997 and 2002 initially reduced PMA time to approval; after the 2002 modernization law, the time to approval began increasing and continued to increase through December 2008. The non-combined, subcategory approval trends were similar to the primary analysis trends. The combined, subcategory analysis showed no clear trends with the exception of non-implantable devices, for which time to approval trended down after 1997. The CMS modernization law of 2003 reduced NCD time to approval, a trend that continued through December 2008. This study also showed that approximately 86% of PMA devices do not receive NCDs. ^ As a result of this research study, recommendations are offered to help resolve statutory non-compliance and access issues, as follows: (1) Authorities should examine underlying causal factors for the observed trends; (2) Process improvements should be made to better coordinate FDA and CMS activities to include sharing data, reducing duplication, and establishing clear criteria for “safe and effective” and “reasonable and necessary”; (3) A common identifier should be established to allow tracking and trending of applications between FDA and CMS databases; (4) Statutory requirements may need to be revised; and (5) An investigation should be undertaken to determine why NCDs are not issued for the majority of PMAs. Any process improvements should be made without creating additional safety risks and adversely impacting public health. Finally, additional studies are needed to fully characterize and better understand the trends identified in this research study.^

Perchlorate remediation technologies: A systematic review of solely biodegradation versus a combination of ion-exchange and biodegradation technologies

A systematic review was performed in order to evaluate perchlorate remediation technologies. The two included technologies were ion-exchange concerted with biodegradation and solely biodegradation. A meta-analysis was completed and subsequently, a regression model was formed to conduct a degradation rate analysis and to depict the association between rate and various dependent variables (salinity/sali, nitrate concentration/nitc and carbon source concentration/csou). The outcome of the model analysis suggested that salt concentration did have an effect on the degradation rate in the ion-exchange process and that with a salt concentration greater than or equal to 18.6 g/L, the biodegradation process will produce a greater reduction of perchlorate than ion-exchange concerted with biodegradation. However, when a t-test examined the difference in perchlorate degradation rate between the two cleanup methods, there was no significant difference seen (p=0.7351, α = 0.05).^

NOVEL THERAPEUTIC TARGETS IDENTIFIED BY HIGH-THROUGHPUT TECHNOLOGIES FOR TRIPLE-NEGATIVE BREAST CANCER

Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to identify and validate novel therapeutic targets for triple-negative breast cancers. 681 genes showed consistent and highly significant overexpression in TNBC compared to receptor-positive cancers in 2 data sets. For two genes, 3 of the 4 siRNAs showed preferential growth inhibition in TNBC cells. These two genes were the low density lipoprotein receptor-related protein 8 (LRP8) and very low-density lipoprotein receptor (VLDLR). Exposure to their cognate ligands, reelin and apolipoprotein E isoform 4 (ApoE4), stimulated the growth of TNBC cells in vitro. Suppression of the expression of either LRP8 or VLDLR or exposure to RAP (an inhibitor of ligand binding to LRP8 and VLDLR) abolished this ligand-induced proliferation. High-throughput protein and metabolic arrays revealed that ApoE4 stimulation rescued TNBC cells from serum-starvation induced up-regulation of genes involved in lipid biosynthesis, increased protein expression of oncogenes involved in the MAPK/ERK and DNA repair pathways, and reduced the serum-starvation induction of biochemicals involved in oxidative stress response and glycolytic metabolism. shLRP8 MDA-MB-231 xenografts had reduced tumor volume, in comparison to parental and shCON xenografts. These results indicate that LRP8-APOE signaling confers survival advantages to TNBC tumors under reduced nutrient conditions and during cellular environmental stress. We revealed that the LRP8-APOE receptor-ligand system is overexpressed in human TNBC. We also demonstrated that this receptor system mediates a strong growth promoting and survival function in TNBC cells in vitro and helps to sustain the growth of MDA-MD-231 xenografts. We propose that inhibitors of LRP8-APOE signaling may be clinically useful therapeutic agents for triple-negative breast cancer.

Cross -packing among retroviruses and characterization of the feline immunodeficiency virus (FIV) packaging signal: Implications for the development of FIV-based gene transfer systems

Feline immunodeficiency virus (FIV)-based gene transfer systems are being seriously considered for human gene therapy as an alternative to vectors based on primate lentiviruses, a genetically complex group of retroviruses capable of infecting non-dividing cells. The greater phylogenetic distance between the feline and primate lentiviruses is thought to reduce chances of the generation of recombinant viruses. However, safety of FIV-based vector systems has not been tested experimentally. Since primate lentiviruses such as human and simian immunodeficiency viruses (HIV/SIV) can cross-package each other's genomes, we tested this trait with respect to FIV. Unexpectedly, both feline and primate lentiviruses were reciprocally able to both cross-package and propagate each other's RNA genomes. This was largely due to the recognition of viral packaging signals by the heterologous proteins. However, a simple retrovirus such as Mason-Pfizer monkey virus (MPMV) was unable to package FIV RNA. Interestingly, FIV could package MPMV RNA, but not propagate it for further steps of replication. These findings suggest that upon co-infection of the same host, cross-packaging may allow distinct retroviruses to generate chimeric variants with unknown pathogenic potential. ^ In order to understand the packaging determinants in FIV, we conducted a detailed mutational analysis of the region thought to contain FIV packaging signal. We show that the first 90–120 nt of the 5′ untranslated region (UTR) and the first 90 nt of gag were simultaneously required for efficient FIV RNA packaging. These results suggest that the primary FIV packaging signal is multipartite and discontinuous, composed of two core elements separated by 150 nt of the 5 ′UTR. ^ The above studies are being used towards the development of safer FIV-based self-inactivating (SIN) vectors. These vectors are being designed to eliminate the ability of FIV transfer vector RNAs to be mobilized by primate lentiviral proteins that may be present in the target cells. Preliminary test of the first generation of these vectors has revealed that they are incapable of being propagated by feline proteins. The inability of FIV transfer vectors to express packageable vector RNA after integration should greatly increase the safety of FIV vectors for human gene therapy. ^

Sistema de identidad, packaging y promoción para la Bodega Orgánica Pulmary

El siguiente trabajo busca construir un sistema integrado de comunicación visual, aplicado al packaging y promoción de las diferentes líneas de vino de la Bodega Orgánica Pulmary.

Sistema de identidad corporativa, packaging y promoción para productos de la empresa Sabores

El proyecto busca a través del diseño de comunicación gráfica, lograr un identidad visual novedosa dentro del rubro de productos naturales envasados de la empresa Sabores. De esta manera lograr incrementar las ventas y aumentar la presencia en el mercado mendocino, apostando a una expansión de la misma y a posicionarse como empresa líder dentro del rubro, transmitiendo siempre la calidad y naturalidad de sus productos.

Diseño de sistemas de identidad corporativa, packaging y promoción para productos alimenticios Ballesta.

El proyecto busca crear un sistema de comunicación visual, del que carece la empresa. El mismo le permitirá diferenciarse de la competencia e insertarse en el mercado nacional y posicionarse dentro del mismo. Se plantea un sistema gráfico de etiquetas para sus nuevas líneas de productos. La aplicación desarrollada abarca piezas editoriales como multimedial.

Rediseño y promoción de sistema de identidad y packaging de cervecería y restaurant Jerome

El siguiente proyecto plantea el rediseño de la identidad corporativa de "Jerome" empresa familiar productora de cerveza artesanal, ubicada en Potrerillos, Mendoza, Argentina. S busca construir una personalidad que le permita promocionar y posicionar el producto en el mercado interno y externo. La aplicación del sistema abarca el packaging y el desarrollo de piezas editoriales como multimediales.

Rediseño de identidad y packaging de la línea de vinos Fuzion de Bodega Familia Zuccardi

El proyecto se basa en el desarrollo del rediseño de la identidad visual y la construcción de un sistema para el packaging de la línea de vinos "Fuzion" de Bodega Familia Zuccardi, ya que el diseño que presenta actualmente dicho producto no tuvo la llegada esperada al consumidor.

Identidad y packaging Bodega Doña Elvira

El proyecto surge como respuesta a la identidad actual de la Bodega boutique "Doña Elvira" ubicada en Vista Flores, Tunuyán, Mendoza, la cual no coincide con lo que la bodega pretende comunicar. Con el diseño de su identidad y con la implementación de un sistema gráfico que unifique gráficamente sus vinos, pretende alcanzar un mayor posicionamiento con respecto a la competencia y de esta manera promocionar la bodega y sus productos para incrementar las ventas.

Sistema de identidad y packaging de la bodega Benvenuto de la Serna

El presente proyecto, por medio del Diseño Gráfico busca lograr una mejor identificación de la bodega y un posicionamiento de la misma en el mercado nacional e internacional. El objetivo es lograr un sistema en el que todas sus piezas mantengan coherencia y variedad formal, generando de este modo, piezas gráficas que respondan y refuercen la imagen que la bodega pretende mostrar.

Rediseño, promoción de sistema de identidad y packaging de MQA Productos Gourmet

El siguiente proyecto desarrolla la identidad de MQA, empresa de conservas gourmet, del departamento de Las Heras. Se buscó construir un sistema integral de comunicación entre sus productos y las piezas gráficas para la promoción, comercialización y difusión de los mismos.

Consumer preferences towards beef cattle in Chile : Importance of country of origin, cut, packaging, brand and price

A study was carried out to evaluate preferences for two cuts, four countries of origin, two forms of presentation, brand and different prices of beef cattle among supermarket buyers in southern Chile, and to distinguish the existence of different market segments, through a survey of 800 people. Using a fractional factorial design for conjoint analysis, it was determined overall that the origin was more important (44.5%) than price (20.8%), form of presentation (12.2%), cut (12.0%) and brand (10.5%), with preference for Chilean and Argentinean striploin, packaged on trays, with no brand at medium price. Using a cluster analysis, three market segments were distinguished. The largest (52.3%) placed great importance on origin and preferred the highest price. The second (27.5%) also valued origin with the greatest preference for Argentinean beef, and it was the only group that preferred the ribeye as the cut. The third (20.5%) placed the greatest importance on price, and was the only group that preferred Paraguayan meat. The segments differed in the importance of eating meat for their personal well-being. The low importance of packaging and brand indicates poorly developed marketing of this product. In order to properly insert brand beef in the Chilean market, communication strategies must be implemented that identify the product with superior quality and that position the brand in the consumer's mind.