Efficacy and Cost Effectiveness of Adjuvant Chemotherapy in Women with Node-Negative Breast Cancer — A Decision-Analysis Model

Abstract BACKGROUND. In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated. METHODS. Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment. RESULTS. For the 45-year-old woman, the base-line analysis found an average lifetime benefit from chemotherapy of 5.1 quality-months at a cost of $15,400 per quality-year. The 60-year-old women gained 4.0 quality-months at a cost of$18,800 per quality-year. Under the more and less optimistic scenarios, the benefit of chemotherapy varied from 1.4 to 14.0 quality-months for both groups. CONCLUSIONS. Chemotherapy substantially increases the quality-adjusted life expectancy of an average woman at a cost comparable to that of other widely accepted therapies. This benefit decreases markedly if the changes in long-term survival are less than in disease-free survival. Given its uncertain duration, the benefit may be too small for many women to choose chemotherapy. Selective use of chemotherapy to maximize the benefit to individual patients may be possible with refinements in risk stratification and explicit assessment of the patients\u27 risk preferences. (N Engl J Med 1991; 324:160–8.

Pair Formation within Multi-Agent Populations

We present a simple model for the formation of pairs in multi-agent populations of type A and B which move freely on a spatial network. Each agent of population A (and B) is labeled as Ai (and Bj) with i=1,.. NA (and j=1,..NB) and carries its own individual list of characteristics or 'phenotype'. When agents from opposite populations encounter one another on the network, they can form a relationship if not already engaged in one. The length of time for which any given pair stays together depends on the compatibility of the two constituent agents. Possible applications include the human dating scenario, and the commercial domain where two types of businesses A and B have members of each type looking for a business partner, i.e. Ai+Bj-->Rij. The pair Rij then survives for some finite time before dissociating Rij-->Ai+Bj. There are many possible generalizations of this basic setup. Here we content ourselves with some initial numerical results for the simplest of network topologies, together with some accompanying analytic analysis.Comment: Special Issue on Complex Networks, edited by Dirk Helbin

Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

© Jeffrey Green, Matthew D Rolfe, and Laura J Smith. Molecular oxygen (O2) and nitric oxide (NO) are diatomic gases that play major roles in infection. The host innate immune system generates reactive oxygen species and NO as bacteriocidal agents and both require O2 for their production. Furthermore, the ability to adapt to changes in O2 availability is crucial for many bacterial pathogens, as many niches within a host are hypoxic. Pathogenic bacteria have evolved transcriptional regulatory systems that perceive these gases and respond by reprogramming gene expression. Direct sensors possess iron-containing co-factors (iron-sulfur clusters, mononuclear iron, heme) or reactive cysteine thiols that react with O2 and/or NO. Indirect sensors perceive the physiological effects of O2 starvation. Thus, O2 and NO act as environmental cues that trigger the coordinated expression of virulence genes and metabolic adaptations necessary for survival within a host. Here, the mechanisms of signal perception by key O2and NO-responsive bacterial transcription factors and the effects on virulence gene expression are reviewed, followed by consideration of these aspects of gene regulation in two major pathogens, Staphylococcus aureus and Mycobacterium tuberculosis

Modelling Social Structures and Hierarchies in Language Evolution

Language evolution might have preferred certain prior social configurations over others. Experiments conducted with models of different social structures (varying subgroup interactions and the role of a dominant interlocutor) suggest that having isolated agent groups rather than an interconnected agent is more advantageous for the emergence of a social communication system. Distinctive groups that are closely connected by communication yield systems less like natural language than fully isolated groups inhabiting the same world. Furthermore, the addition of a dominant male who is asymmetrically favoured as a hearer, and equally likely to be a speaker has no positive influence on the disjoint groups.Comment: 14 pages, 3 figures, 1 table. In proceedings of AI-2010, The Thirtieth SGAI International Conference on Innovative Techniques and Applications of Artificial Intelligence, Cambridge, England, UK, 14-16 December 201

Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

BACKGROUND Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. RESULTS A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P CONCLUSIONS In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone

Automatic annotation of bioinformatics workflows with biomedical ontologies

Legacy scientific workflows, and the services within them, often present scarce and unstructured (i.e. textual) descriptions. This makes it difficult to find, share and reuse them, thus dramatically reducing their value to the community. This paper presents an approach to annotating workflows and their subcomponents with ontology terms, in an attempt to describe these artifacts in a structured way. Despite a dearth of even textual descriptions, we automatically annotated 530 myExperiment bioinformatics-related workflows, including more than 2600 workflow-associated services, with relevant ontological terms. Quantitative evaluation of the Information Content of these terms suggests that, in cases where annotation was possible at all, the annotation quality was comparable to manually curated bioinformatics resources.Comment: 6th International Symposium on Leveraging Applications (ISoLA 2014 conference), 15 pages, 4 figure

Intergenerational social mobility and mid-life status attainment: influences of childhood intelligence, childhood social factors, and education

We examined the influences of childhood social background, childhood cognitive ability, and education on intergenerational social mobility and social status attainment at midlife. The subjects were men born in 1921 and who participated in the Scottish Mental Survey of 1932 and thereafter in the Midspan Collaborative study in Scotland between 1970 and 1973. In logistic regression analyses, childhood cognitive ability and height were associated with upward and downward change from father's social class to participant's social class at mid-life. Education significantly influenced upward social mobility. Number of siblings had no significant effect on social mobility. These effects were also examined after adjusting for the other variables. In structural equation modelling analyses, father's social class and childhood cognitive ability influenced social status attainment at midlife, with education and occupational status in young adulthood as partially mediating factors. It was noteworthy that childhood cognitive ability related more strongly to occupation in midlife than to first occupation. These data add to the relatively few studies that track the process of status attainment in adulthood, they provide information from a new geographical setting, and they contain information from a greater proportion of the lifecourse than do most existing studies

An analysis of the FIR/RADIO Continuum Correlation in the Small Magellanic Cloud

The local correlation between far-infrared (FIR) emission and radio-continuum (RC) emission for the Small Magellanic Cloud (SMC) is investigated over scales from 3 kpc to 0.01 kpc. Here, we report good FIR/RC correlation down to ~15 pc. The reciprocal slope of the FIR/RC emission correlation (RC/FIR) in the SMC is shown to be greatest in the most active star forming regions with a power law slope of ~1.14 indicating that the RC emission increases faster than the FIR emission. The slope of the other regions and the SMC are much flatter and in the range of 0.63-0.85. The slopes tend to follow the thermal fractions of the regions which range from 0.5 to 0.95. The thermal fraction of the RC emission alone can provide the expected FIR/RC correlation. The results are consistent with a common source for ultraviolet (UV) photons heating dust and Cosmic Ray electrons (CRe-s) diffusing away from the star forming regions. Since the CRe-s appear to escape the SMC so readily, the results here may not provide support for coupling between the local gas density and the magnetic field intensity.Comment: 19 pages, 7 Figure

Childhood IQ and social factors on smoking behaviour, lung function and smoking-related outcomes in adulthood: linking the Scottish Mental Survey 1932 and the Midspan studies

OBJECTIVE: To investigate the associations of childhood IQ and adult social factors, and smoking behaviour, lung function (forced expiratory volume in one second; FEV(1)), and smoking-related outcomes in adulthood. DESIGN: Retrospective cohort study. METHOD: Participants were from the Midspan prospective studies conducted on Scottish adults in the 1970s. The sample consisted of 938 Midspan participants born in 1921 who were successfully matched with their cognitive ability test results on the Scottish Mental Survey 1932. RESULTS: Structural equation modelling showed that age 11 IQ was not directly associated with smoking consumption, but that IQ and adult social class had indirect effects on smoking consumption via deprivation category. The influence of IQ on FEV(1) was partly indirect via social class. Gender influenced smoking consumption and also IQ and social class. There was a 21% higher risk of having a smoking-related hospital admission, cancer, or death during 25 years of follow-up for each standard deviation disadvantage in IQ. Adjustment for adult social class, deprivation category, and smoking reduced the association to 10%. CONCLUSION: Childhood IQ was associated with social factors which influenced lung function in adulthood, but was not associated directly with smoking consumption. In future studies, it is important to consider other pathways which may account for variance in the link between childhood IQ and health in later life

Resolving the ‘Nitrogen Paradox’ of arbuscular mycorrhizas : fertilization with organic matter brings considerable benefits for plant nutrition and growth

Arbuscular mycorrhizal fungi (AMF) can transfer nitrogen (N) to host plants but the ecological relevance is debated, as total plant N and biomass do not generally increase. The extent to which the symbiosis is mutually beneficial is thought to rely on the stoichiometry of N, phosphorus (P) and carbon (C) availability. While inorganic N fertilisation has been shown to elicit strong mutualism, characterised by improved plant and fungal growth and mineral nutrition, similar responses following organic N addition are lacking. Using a compartmented microcosm experiment, we determined the significance to a mycorrhizal plant of placing a 15N‐labelled, nitrogen‐rich patch of organic matter in a compartment to which only AMF hyphae had access. Control microcosms denied AMF hyphal access to the patch compartment. When permitted access to the patch compartment, the fungus proliferated extensively in the patch and transferred substantial quantities of N to the plant. Moreover, our data demonstrate that allowing hyphal access to an organic matter patch enhanced total plant N and P contents, with a simultaneous and substantial increase in plant biomass. Moreover, we demonstrate that organic matter fertilization of arbuscular mycorrhizal plants can foster a mutually beneficial symbiosis based on nitrogen transfer, a phenomenon previously thought irrelevant