Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

PURPOSE: Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer. PATIENTS AND METHODS: Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline). Surrogacy was assessed through the correlation between the end points as well as through the correlation between the treatment effects on the end points. RESULTS: Tumor response (survival odds ratio [OR], 6.2; 95% CI, 5.3 to 7.0) and disease control (survival OR, 5.5; 95% CI, 4.8 to 6.3) were strongly associated with OS. PFS (rank correlation coefficient, 0.688; 95% CI, 0.686 to 0.690) and TTP (rank correlation coefficient, 0.682; 95% CI, 0.680 to 0.684) were moderately associated with OS. Response log ORs were strongly correlated with PFS log hazard ratios (linear coefficient [rho], 0.96; 95% CI, 0.73 to 1.19). Response and disease control log ORs and PFS and TTP log hazard ratios were poorly correlated with log hazard ratios for OS, but the confidence limits of rho were too wide to be informative. CONCLUSION: No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.

Spontaneous secretion of interferon gamma and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes.

BACKGROUND: Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses. AIMS: To quantify interferon gamma (IFN-gamma) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation. PATIENTS: Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa. METHODS: Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-gamma and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT). RESULTS: The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-gamma (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-gamma SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-gamma and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-gamma in the basal state, and 0.1% secreted IL-4. CONCLUSIONS: Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-gamma and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

Getting to the Real Story: What Vietnamese business people wish foreigners understood about doing business in emerging and transition countries like Vietnam – BEFORE they start

Knowledge sharing typically examines organizational transfer of knowledge, often from headquarters to subsidiaries, from developed country sites to emerging country sites, or from host to local employees. Yes, recent research, such as Prahalad’s Bottom of the Pyramid, raises the question of reverse transfer of knowledge, or whether knowledge could and should be transferred from local sites to home country sites within an organization. As several emerging economies build their capabilities in knowledge, research and development, marketing, and the like, it only makes sense to consider what type of knowledge and how to transfer it in reverse or bi-directional manners. This paper takes one step back in the process. Rather than focusing on what knowledge transfer may make sense within an organization, we consider what types of knowledge are important for foreigners to know at the initial stages of engagement abroad as they consider whether to do business in an emerging country.

Infrared spectra of C2H2 under jet-cooled and para-H2 matrix conditions

In spectra of jet-cooled C2H2 recorded with an FTIR spectrometer, the ν5, ν4 + ν5, ν3 and ν2 + ν4 + ν5 bands all exhibit an intensity distribution corresponding to ∼6 K for rotation, with no evidence of nuclear spin conversion. Spectra of C2H2 isolated in solid p-H2 show no evidence of rotation of C2H2. The strong interaction between ν3 and ν2 + ν4 + ν5 in the gas phase is diminished in solid p-H2. Lines associated with dimer, trimer and tetramer of C2H2 are identified. Spectral features characteristic of solid state acetylene are observed under jet-cooled conditions. © 2007 Elsevier B.V. All rights reserved.

Resolved Torsional Splittings in the ν18 and ν19- Bands of Propene

info:eu-repo/semantics/published

Mixed self-assembled monolayers of 2-mercaptobenzimidazole and 2-mercaptobenzimidazole-5-sulfonate: determination and control of the surface composition

The behaviour towards electron transfer of self-assembled monolayers of 2-mercaptobenzimidazole (MBI) and 2-mercaptobenzimidazole-5-sulfonate (MBIS) on Au(1 1 1) was examined by cyclic voltammetry. The influence of the monolayers was drastically dependent on the charge of the redox probe used. When [Ru(NH3)6]3+ is used, a post-adsorption peak characteristic of the adsorption of the redox probe is detected only at the MBIS modified electrode. Taking advantage of this difference, ac voltammetry has been used to determine the surface composition when mixed monolayers are formed by immersion of the gold substrate in mixtures of different molar fractions of MBI and MBIS. Results clearly indicate that the ionic strength of the immersion solution plays a key role in the surface composition when a charged surfactant is mixed with non-charged surfactant. © 2006 Elsevier B.V. All rights reserved.

Electrochemical and FTIR characterization of the self-assembled monolayer of 2-mercaptobenzimidazole on Au(1 1 1)

The behaviour of a self-assembled monolayer of 2-mercaptobenzimidazole (MBI) at the Au(111) electrode has been examined using cyclic voltammetry and in situ FTIR spectroscopy. The charge associated with the reductive desorption is pH independent while the oxidative partial redeposition charge increases when the pH is lowered. This is due to differences between the nature and the solubility of the MBI desorption product. In alkaline and neutral media MBI desorbs as the thiolate. In contrast, in acidic solutions the thiol is the desorbed product. Subtractively normalized interfacial reflection Fourier transform absorption spectroscopy (SNIFTIRS) has been applied to investigate the MBI monolayer in contact with aqueous solutions of different pH. The SNIFTIRS data are in agreement with the electrochemical results. Moreover, quantitative analysis of the IR data provided evidence that adsorbed MBI molecules assume a tilted orientation with an angle of 60±5° between the C2 axis of the molecule and the direction normal to the gold surface. © 2003 Elsevier B.V. All rights reserved.

Impact of various endocrine and paracrine factors on in vitro culture of preantral follicles in rodents

Folliculogenesis is a complex process regulated by various paracrine and autocrine factors. In vitro growth systems of primordial and preantral follicles have been developed for future use of immature oocytes, as sources of fertilizable oocytes and for studying follicular growth and oocyte maturation mechanisms. Rodents were often chosen for in vitro follicular culture research and a lot of factors implicated in folliculogenesis have been identified using this model. To date, the mouse is the only species in which the whole process of follicular growth, oocyte maturation, fertilization and embryo transfer into recipient females was successfully performed. However, the efficiency of in vitro culture systems must still be considerably improved. Within the follicle, numerous events affect cell proliferation and the acquisition of oocyte developmental competency in vitro, including interactions between the follicular cells and the oocyte, and the composition of the culture medium. Effects of the acting factors depend on the stage of follicle development, the culture system used and the species. This paper reviews the action of endocrine, paracrine factors and other components of culture medium on in vitro growth of preantral follicles in rodents.

First- and second-order phase transitions in the adlayer of biadipate on Au(111)

The adsorption of biadipate on Au(111) was studied by cyclic voltammetry and chronocoulometry. The biadipate adlayer undergoes a potential-driven phase transition. It is shown that the phase transition can be either of the first- or second-order depending on the biadipate concentration. At low surfactant concentrations, the first-order transition is characterised by a discontinuity in the charge density-potential curve and by the presence of very sharp peaks in the voltammetric response. At higher concentrations, these peaks are no longer observed but a discontinuity in the capacity curve is still noticeable, in agreement with a second-order transition. © the Owner Societies.

Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action

It has been shown previously that female mice homozygous for an alpha-fetoprotein (AFP) null allele are sterile as a result of anovulation, probably due to a defect in the hypothalamic-pituitary axis. Here we show that these female mice exhibit specific anomalies in the expression of numerous genes in the pituitary, including genes involved in the gonadotropin-releasing hormone pathway, which are underexpressed. In the hypothalamus, the gonadotropin-releasing hormone gene, Gnrh1, was also found to be down-regulated. However, pituitary gene expression could be normalized and fertility could be rescued by blocking prenatal estrogen synthesis using an aromatase inhibitor. These results show that AFP protects the developing female brain from the adverse effects of prenatal estrogen exposure and clarify a long-running debate on the role of this fetal protein in brain sexual differentiation.

Examining Relationships between Culture, Creativity and Business Stage in an Emerging Market: A Categorical Data Analysis of Vietnam’s Data Set

In this article, we offer a new way of exploring relationships between three different dimensions of a business operation, namely the stage of business development, the methods of creativity and the major cultural values. Although separately, each of these has gained enormous attention from the management research community, evidenced by a large volume of research studies, there have been not many studies that attempt to describe the logic that connect these three important aspects of a business; let alone empirical evidences that support any significant relationships among these variables. The paper also provides a data set and an empirical investigation on that data set, using a categorical data analysis, to conclude that examinations of these possible relationships are meaningful and possible for seemingly unquantifiable information. The results also show that the most significant category among all creativity methods employed in Vietnamese enterprises is the “creative disciplines” rule in the “entrepreneurial phase,” while in general creative disciplines have played a critical role in explaining the structure of our data sample, for both stages of development in our consideration.

Development and standardization of solid phase assays for the detection of anti-neutrophil cytoplasmic antibodies (ANCA). A report on the second phase of an international cooperative study on the standardization of ANCA assays

Anti-neutrophil cytoplasmic antibodies (ANCA) are diagnostic markers for systemic vasculitis. They are classically I detected by an indirect immunofluorescence test using normal donor neutrophils as substrate. This assay lacks antigenic specificity and is not quantitative. The 'EC/BCR Project for ANCA Assay Standardization' is an international collaboration study with the aim to develop and standardize solid phase assays for ANCA detection. In this part of the study the isolation and characterization of proteinase-3 and myeloperoxidase, the two main target molecules for ANCA, and the development and standardization of ELISAs with these antigens are described. Six laboratories successfully isolated purified proteinase-3 preparations that could be used. Three of these preparations, together with one myeloperoxidase preparation, were subsequently used for ANCA testing by ELISA. The ELISA technique was standardized in two rounds of testing in the 14 participating laboratories. The coefficient of variation of these new assays decreased from values of approx. 50% in the first round to approx. 20% in the second round. We conclude that purified proteinase-3 and myeloperoxidase can be used in standardized ELISAs for ANCA detection. Whether such procedures offer advantages over the IIF test will be determined in a prospective clinical study.

It Takes Two to Tango: Entrepreneurship and Creativity in Troubled Times – Vietnam 2012

Strikingly, most literature suggests that market competition will push firms to take creativity/innovation seriously as matter of death or survival. Using the data, we examined creativity methods (Napier and Nilsson, 2008; Napier, 2010) in conjunction with three influential cultural values – namely risk tolerance, relationship, and dependence on resources – to assess how they influence decisions of entrepreneurs.The primary objective of this study focuses on perceived values of entrepreneurship and creativity in business conducted within a turbulent environment. Our initial hypothesis is that a typical entrepreneurial process carries with it “creativity-enabling elements.” In a normal situation, when businesses focus more on optimizing their resources for commercial gains, perceptions about values of entrepreneurial creativity are usually vague. However, in difficult times and harsh competition, the difference between survival and failure may be creativity. This paper also examines many previous findings on both entrepreneurship and creativity and suggests a highly possible “organic growth” of creativity in an entrepreneurial environment and reinforcing value of entrepreneurship when creativity power is present. In other words, we see each idea reinforcing the other. We use data from a survey of sample Vietnamese firms during the chaotic economic year 2012 to learn about the ‘entrepreneurshipcreativity nexus.’ A data set of 137 responses qualified for a statistical examination was obtained from an online survey, which started on February 16 and ended May 24, 2012, sent to local entrepreneurs and corporate managers using social networks. The authors employed categorical data analysis (Agresti, 2002; Azen & Walker, 2011). Statistical analyses confirm that for business operation, the creativity and entrepreneurial spirit could hardly be separate; and, this is not only correct with entrepreneurial firm, but also well established companies. The single most important factor before business startup and during early implementation in Vietnam is what we call “connection/relationship.” However, businesspeople are increasingly aware of the need of creativity/innovation. In fact, we suggest that creativity and entrepreneurial spirit cannot be separated in entrepreneurial firms as well as established companies.

Coffee Filters and Creativity: The Value of Multiple Filters in the Creative Process

Creativity is often defined as developing something novel or new, that fits its context, and has value. To achieve this, the creative process itself has gained increasing attention as organizational leaders seek competitive advantages through developing new products, services, process, or business models. In this paper, we explore the notion of the creative process as including a series of “filters” or ways to process information as being a critical component of the creative process. We use the metaphor of coffee making and filters because many of our examples come from Vietnam, which is one of the world’s top coffee exporters and which has created a coffee culture rivaling many other countries. We begin with a brief review of the creative process its connection to information processing, propose a tentative framework for integrating the two ideas, and provide examples of how it might work. We close with implications for further practical and theoretical directions for this idea.

Empirical Evidence on Relationships between Ex Ante Innovation Pursuit and Post-M&A Performance in the Vietnamese M&A Industry, 2005-2012

This research aims to communicate new results of empirical investigations to learn about the relationship between determination of controlling an acquired firm’s capital, assets and brand versus its capability of innovation and ex post performance of the rising Vietnamese M&A industry in the 2005-2012 period. The analysis employs a categorical data sample, consisting of 212 M&A cases reported by various information sources, and performs a number of logistic regressions with significant results as follows. Firstly, the overall relationship between pre-M&A pursuit’s determination on acquiring resources and performance of the post-M&A performance is found significant. There exist profound effects of a ‘size matters’ strategy in M&A ex post performance. When there is an overwhelming ‘resources acquiring’ strategy, the innovation factor’s explanatory power becomes negligible. Secondly, for negative performance of post-M&A operations, the emphasis on both capital base and asset size, and the brand value at the time of the M&A pursuit is the major explanation in the post-M&A period. So does the absence of innovation as a goal in the pre-M&A period. These two insights together are useful in careful M&A planning. Lastly, expensive pre-M&A expenditures tend to adversely affect the post-M&A performance. As a general conclusion, this study shows that innovation can be an important factor to pursue in M&A transitions, together with the need to emphasize and find capable and willing human capital, rather than a capital base (equity or debt) and existing values of the acquired brands.