Promising results with exemestane in the first-line treatment of metastatic breast cancer: a randomized phase II EORTC trial with a tamoxifen control.

Because tamoxifen (TAM), a nonsteroidal antiestrogen, is routinely used in the adjuvant setting, other hormone therapies are needed as alternatives for first-line treatment of metastatic breast cancer (MBC). Currently, exemestane (EXE) and other antiaromatase agents are indicated for use in patients who experience failure of TAM. In this multicenter, randomized, open-label, TAM-controlled (20 mg/day), phase II trial, we examined the activity and tolerability of EXE 25 mg/day for the first-line treatment of MBC in postmenopausal women. Exemestane was well tolerated and demonstrated substantial first-line antitumor activity based on intent-to-treat analysis of peer-reviewed responses. In the EXE arm, values for complete, partial, and objective response, clinical benefit, and time to tumor progression (TTP) exceeded those reported for TAM although no statistical comparison was made. Based on these encouraging results, a phase III trial will compare EXE and TAM.

Probabilistic choice: A simple invariance.

When subjects must choose repeatedly between two or more alternatives, each of which dispenses reward on a probabilistic basis (two-armed bandit ), their behavior is guided by the two possible outcomes, reward and nonreward. The simplest stochastic choice rule is that the probability of choosing an alternative increases following a reward and decreases following a nonreward (reward following ). We show experimentally and theoretically that animal subjects behave as if the absolute magnitudes of the changes in choice probability caused by reward and nonreward do not depend on the response which produced the reward or nonreward (source independence ), and that the effects of reward and nonreward are in constant ratio under fixed conditions (effect-ratio invariance )--properties that fit the definition of satisficing . Our experimental results are either not predicted by, or are inconsistent with, other theories of free-operant choice such as Bush-Mosteller, molar maximization, momentary maximizing, and melioration (matching).

Screening the human exome: a comparison of whole genome and whole transcriptome sequencing.

BACKGROUND: There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important. RESULTS: Here we provide a systematic exploration of how well RNA-Seq can identify human coding variants by comparing variants identified through high coverage whole-genome sequencing to those identified by high coverage RNA-Seq in the same individual. This comparison allowed us to directly evaluate the sensitivity and specificity of RNA-Seq in identifying coding variants, and to evaluate how key parameters such as the degree of coverage and the expression levels of genes interact to influence performance. We find that although only 40% of exonic variants identified by whole genome sequencing were captured using RNA-Seq; this number rose to 81% when concentrating on genes known to be well-expressed in the source tissue. We also find that a high false positive rate can be problematic when working with RNA-Seq data, especially at higher levels of coverage. CONCLUSIONS: We conclude that as long as a tissue relevant to the trait under study is available and suitable quality control screens are implemented, RNA-Seq is a fast and inexpensive alternative approach for finding coding variants in genes with sufficiently high expression levels.

Accessibility, availability and affordability of anti-malarials in a rural district in Kenya after implementation of a national subsidy scheme.

BACKGROUND: Poor access to prompt and effective treatment for malaria contributes to high mortality and severe morbidity. In Kenya, it is estimated that only 12% of children receive anti-malarials for their fever within 24 hours. The first point of care for many fevers is a local medicine retailer, such as a pharmacy or chemist. The role of the medicine retailer as an important distribution point for malaria medicines has been recognized and several different strategies have been used to improve the services that these retailers provide. Despite these efforts, many mothers still purchase ineffective drugs because they are less expensive than effective artemisinin combination therapy (ACT). One strategy that is being piloted in several countries is an international subsidy targeted at anti-malarials supplied through the retail sector. The goal of this strategy is to make ACT as affordable as ineffective alternatives. The programme, called the Affordable Medicines Facility - malaria was rolled out in Kenya in August 2010. METHODS: In December 2010, the affordability and accessibility of malaria medicines in a rural district in Kenya were evaluated using a complete census of all public and private facilities, chemists, pharmacists, and other malaria medicine retailers within the Webuye Demographic Surveillance Area. Availability, types, and prices of anti-malarials were assessed. There are 13 public or mission facilities and 97 medicine retailers (registered and unregistered). RESULTS: The average distance from a home to the nearest public health facility is 2 km, but the average distance to the nearest medicine retailer is half that. Quinine is the most frequently stocked anti-malarial (61% of retailers). More medicine retailers stocked sulphadoxine-pyramethamine (SP; 57%) than ACT (44%). Eleven percent of retailers stocked AMFm subsidized artemether-lumefantrine (AL). No retailers had chloroquine in stock and only five were selling artemisinin monotherapy. The mean price of any brand of AL, the recommended first-line drug in Kenya, was $2.7 USD. Brands purchased under the AMFm programme cost 40% less than non-AMFm brands. Artemisinin monotherapies cost on average more than twice as much as AMFm-brand AL. SP cost only $0.5, a fraction of the price of ACT. CONCLUSIONS: AMFm-subsidized anti-malarials are considerably less expensive than unsubsidized AL, but the price difference between effective and ineffective therapies is still large.

Chimpanzees and bonobos distinguish between risk and ambiguity.

Although recent research has investigated animal decision-making under risk, little is known about how animals choose under conditions of ambiguity when they lack information about the available alternatives. Many models of choice behaviour assume that ambiguity does not impact decision-makers, but studies of humans suggest that people tend to be more averse to choosing ambiguous options than risky options with known probabilities. To illuminate the evolutionary roots of human economic behaviour, we examined whether our closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus), share this bias against ambiguity. Apes chose between a certain option that reliably provided an intermediately preferred food type, and a variable option that could vary in the probability that it provided a highly preferred food type. To examine the impact of ambiguity on ape decision-making, we interspersed trials in which chimpanzees and bonobos had no knowledge about the probabilities. Both species avoided the ambiguous option compared with their choices for a risky option, indicating that ambiguity aversion is shared by humans, bonobos and chimpanzees.

AMERICAN WOMEN COMPOSERS: SELECTED PUBLISHED WORKS FOR FLUTE AND PIANO AND FOR UNACCOMPANIED FLUTE COMPOSED BETWEEN 1930 AND 2008

The music of women composers often comprises only a small percentage of flutists‘ repertoire, yet there are actually many active women composers, many of whom have written for the flute. The aim of this dissertation is to chronicle a selection of works by several American women composers that have contributed to accessible flute repertoire. For the purpose of this dissertation, accessibility is described by the following parameters: works that limit the use of extended techniques, works that are suitable for performers from high school through a reasonably advanced level, works that are likely to elicit emotionally musical communication from the performer to the listener, and works that are reasonably available through music stores or outlets on the Internet that have a fairly comprehensive reach to the general public. My subjective judgment also played a role in the final selection of the 25 works included as part of this dissertation, and performed on three musically well-balanced recitals. A variety of resources were consulted for the repertoire, including Boenke‘s Flute Music by Women Composers: An Annotated Catalog, and the catalogs of publishers such as Arsis Press and Hildegard Publishing, both of which specialize in the music of women composers. The works performed and discussed are the following: Adrienne Albert – Sunswept; Marion Bauer – Prelude and Fugue, Op. 43.; Marilyn Bliss – Lament; Ann Callaway – Updraft; Ruth Crawford – Diaphonic Suite; Emma Lou Diemer – Sonata; Vivian Fine – Emily’s Images; Cynthia Folio – Arca Sacra; Nancy Galbraith – Atacama; Lita Grier – Sonata; Jennifer Higdon – The Jeffrey Mode; Edie Hill – This Floating World; Katherine Hoover – Masks; Mary Howe – Interlude between Two Pieces; Laura Kaminsky – Duo; Libby Larsen – Aubade; Alex Shapiro – Shiny Kiss; Judith Shatin – Coursing Through the Still Green; Faye-Ellen Silverman – Taming the Furies; Augusta Read Thomas – Euterpe’s Caprice; Joan Tower – Valentine Trills; Ludmila Ulehla – Capriccio; Elizabeth Vercoe – Kleemation; Gwyneth Walker – Sonata; and Judith Lang Zaimont – ‘Bubble-Up’ Rag. All of these works are worthy alternatives to the more frequently played flute repertoire, and they serve as a good starting point for anyone interested i n exploring the works of women composers.

Evaluating Alternative Nutrient Sources in Subsistence-Level Aquaponic Systems

Many food production methods are both economically and environmentally unsustainable. Our project investigated aquaponics, an alternative method of agriculture that could address these issues. Aquaponics combines fish and plant crop production in a symbiotic, closed-loop system. We aimed to reduce the initial and operating costs of current aquaponic systems by utilizing alternative feeds. These improvements may allow for sustainable implementation of the system in rural or developing regions. We conducted a multi-phase process to determine the most affordable and effective feed alternatives for use in an aquaponic system. At the end of two preliminary phases, soybean meal was identified as the most effective potential feed supplement. In our final phase, we constructed and tested six full-scale aquaponic systems of our own design. Data showed that soybean meal can be used to reduce operating costs and reliance on fishmeal. However, a more targeted investigation is needed to identify the optimal formulation of alternative feed blends.

Intracellular Cytokine Staining and Flow Cytometry: Considerations for Application in Clinical Trials of Novel Tuberculosis Vaccines.

Intracellular cytokine staining combined with flow cytometry is one of a number of assays designed to assess T-cell immune responses. It has the specific advantage of enabling the simultaneous assessment of multiple phenotypic, differentiation and functional parameters pertaining to responding T-cells, most notably, the expression of multiple effector cytokines. These attributes make the technique particularly suitable for the assessment of T-cell immune responses induced by novel tuberculosis vaccines in clinical trials. However, depending upon the particular nature of a given vaccine and trial setting, there are approaches that may be taken at different stages of the assay that are more suitable than other alternatives. In this paper, the Tuberculosis Vaccine Initiative (TBVI) TB Biomarker Working group reports on efforts to assess the conditions that will determine when particular assay approaches should be employed. We have found that choices relating to the use of fresh whole blood or peripheral blood mononuclear cells (PBMC) and frozen PBMC; use of serum-containing or serum-free medium; length of stimulation period and use of co-stimulatory antibodies can all affect the sensitivity of intracellular cytokine assays. In the case of sample material, frozen PBMC, despite some loss of sensitivity, may be more advantageous for batch analysis. We also recommend that for multi-site studies, common antibody panels, gating strategies and analysis approaches should be employed for better comparability.

Alternativas técnicas para el almacenamiento de calabacitas Butternut o coreanas (Cucurbita moschata Duch.)

p.61-68

Pastizales naturales y pasturas cultivadas : dos sistemas complementarios y no opuestos

p.1-11

Aplicación del método electre para la evaluación de alternativas en la realización de un estudio de impacto ambiental

p.69-77

A forest model archive?

The recent history and current trends in the collection and archiving of forest information and models is reviewed. The question is posed as to whether the community of forest modellers ought to take some action in setting up a Forest Model Archive (FMA) as a means of conserving and sharing the heritage of forest models that have been developed over several decades. The paper discusses the various alternatives of what an FMA could be, and should be. It then goes on to formulate a conceptual model as the basis for the construction of a FMA. Finally the question of software architecture is considered. Again there are a number of possible solutions. We discuss the alternatives, some in considerable detail, but leave the final decisions on these issues to the forest modelling community. This paper has spawned the “Greenwich Initiative” on the FMA. An internet discussion group on the topic will be started and launched by the “Trafalar Group”, which will span both IUFRO 4.1 and 4.11, and further discussion is planned to take place at the Forest Modelling Conference in Portugal, June 2002.

Decision support systems for eco-friendly electronic products

This paper discusses an optimisation based decision support system and methodology for electronic packaging and product design and development which is capable of addressing in efficient manner specified environmental, reliability and cost requirements. A study which focuses on the design of a flip-chip package is presented. Different alternatives for the design of the flip-chip package are considered based on existing options for the applied underfill and volume of solder material used to form the interconnects. Variations in these design input parameters have simultaneous effect on package aspects such as cost, environmental impact and reliability. A decision system for the design of the flip-chip that uses numerical optimisation approach is used to identify the package optimal specification which satisfies the imposed requirements. The reliability aspect of interest is the fatigue of solder joints under thermal cycling. Transient nonlinear finite element analysis (FEA) is used to simulate the thermal fatigue damage in solder joints subject to thermal cycling. Simulation results are manipulated within design of experiments and response surface modelling framework to provide numerical model for reliability which can be used to quantify the package reliability. Assessment of the environmental impact of the package materials is performed by using so called Toxic Index (TI). In this paper we demonstrate the evaluation of the environmental impact only for underfill and lead-free solder materials. This evaluation is based on the amount of material per flip-chip package. Cost is the dominant factor in contemporary flip-chip packaging industry. In the optimisation based decision support system for the design of the flip-chip package, cost of materials which varies as a result of variations in the design parameters is considered.

Public Private Partnerships (PPPs) summary paper

The summary of three reports on PPPs in Europe, including a critical overview, a study of alternatives, and a study on the protection of working conditions, in the context of EU law on procurement and other subjects.

Fluoridation for dental public health

This article reviews the means by which fluoride is supplied to populations. Many public health authorities provide fluoridated drinking water, with typical concentrations of fluoride of between 0.5 and 1.0 ppm. This has been found to be safe and effective, though differences in caries incidence between fluoridated and non-fluoridated regions are less than they were 50 years ago, because of the wider availability of fluoridated products to the whole population. Concerns about the effect of fluoride on bone density and associated conditions are reviewed and the general conclusion from considering the literature on fluoride is that there is almost no cause for concern. Alternatives to water as a means of delivering fluoride to the general public that are being used in a number of countries are salt and milk. These alternatives are also reviewed and have been shown to give satisfactory levels of protection against caries, though milk is shown to be less satisfactory than water as a vehicle for fluoride delivery. Milk is also less effective in providing fluoride to individuals in the population, and is less likely to be consumed by people in lower socio-economic groups, precisely those who suffer most from dental caries. This study concludes that mass water fluoridation remains an important contribution to good oral health throughout the community.