Evidence for methane and ammonia in the coma of comet P/Halley

Methane and ammonia abundances in the coma of Halley are derived from Giotto IMS data using an Eulerian model of chemical and physical processes inside the contact surface to simulate Giotto HIS ion mass spectral data for mass-to-charge ratios (m/q) from 15 to 19. The ratio m/q = 19/18 as a function of distance from the nucleus is not reproduced by a model for a pure water coma. It is necessary to include the presence of NH_3 , and uniquely NH_3 , in coma gases in order to explain the data. A ratio of production rates Q(NH_3)/Q(H20) = 0.01-Q.02 results in model values approximating the Giotto data. Methane is identified as the most probable source of the distinct peak at m/q = 15. The observations are fit best with Q(CH_4)/Q(H_20) = 0.02. The chemical composition of the comet nucleus implied by these production rate ratios is unlike that of the outer planets. On the other hand, there are also significant differences from observations of gas phase interstellar material

Design of a randomized controlled trial for multiple cancer risk behaviors among Spanish-speaking Mexican-origin smokers

Background: Smoking, poor diet, and physical inactivity account for as much as 60% of cancer risk. Latinos experience profound disparities in health behaviors, as well as the cancers associated with them. Currently, there is a dearth of controlled trials addressing these health behaviors among Latinos. Further, to the best of our knowledge, no studies address all three behaviors simultaneously, are culturally sensitive, and are guided by formative work with the target population. Latinos represent 14% of the U. S. population and are the fastest growing minority group in the country. Efforts to intervene on these important lifestyle factors among Latinos may accelerate the elimination of cancer-related health disparities

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

Immune mechanisms in malaria: new insights in vaccine development.

Early data emerging from the first phase 3 trial of a malaria vaccine are raising hopes that a licensed vaccine will soon be available for use in endemic countries, but given the relatively low efficacy of the vaccine, this needs to be seen as a major step forward on the road to a malaria vaccine rather than as arrival at the final destination. The focus for vaccine developers now moves to the next generation of malaria vaccines, but it is not yet clear what characteristics these new vaccines should have or how they can be evaluated. Here we briefly review the epidemiological and immunological requirements for malaria vaccines and the recent history of malaria vaccine development and then put forward a manifesto for future research in this area. We argue that rational design of more effective malaria vaccines will be accelerated by a better understanding of the immune effector mechanisms involved in parasite regulation, control and elimination

Current measures of metabolic heterogeneity within cervical cancer do not predict disease outcome

<p>Abstract</p> <p>Background</p> <p>A previous study evaluated the intra-tumoral heterogeneity observed in the uptake of F-18 fluorodeoxyglucose (FDG) in pre-treatment positron emission tomography (PET) scans of cancers of the uterine cervix as an indicator of disease outcome. This was done via a novel statistic which ostensibly measured the spatial variations in intra-tumoral metabolic activity. In this work, we argue that statistic is intrinsically <it>non</it>-spatial, and that the apparent delineation between unsuccessfully- and successfully-treated patient groups via that statistic is spurious.</p> <p>Methods</p> <p>We first offer a straightforward mathematical demonstration of our argument. Next, we recapitulate an assiduous re-analysis of the originally published data which was derived from FDG-PET imagery. Finally, we present the results of a principal component analysis of FDG-PET images similar to those previously analyzed.</p> <p>Results</p> <p>We find that the previously published measure of intra-tumoral heterogeneity is intrinsically non-spatial, and actually is only a surrogate for tumor volume. We also find that an optimized linear combination of more canonical heterogeneity quantifiers does not predict disease outcome.</p> <p>Conclusions</p> <p>Current measures of intra-tumoral metabolic activity are not predictive of disease outcome as has been claimed previously. The implications of this finding are: clinical categorization of patients based upon these statistics is invalid; more sophisticated, and perhaps innately-geometric, quantifications of metabolic activity are required for predicting disease outcome.</p

Protective Immunity Induced with the RTS,S/AS Vaccine Is Associated with IL-2 and TNF-α Producing Effector and Central Memory CD4+ T Cells

A phase 2a RTS,S/AS malaria vaccine trial, conducted previously at the Walter Reed Army Institute of Research, conferred sterile immunity against a primary challenge with infectious sporozoites in 40% of the 80 subjects enrolled in the study. The frequency of Plasmodium falciparum circumsporozoite protein (CSP)-specific CD4+ T cells was significantly higher in protected subjects as compared to non-protected subjects. Intrigued by these unique vaccine-related correlates of protection, in the present study we asked whether RTS,S also induced effector/effector memory (TE/EM) and/or central memory (TCM) CD4+ T cells and whether one or both of these sub-populations is the primary source of cytokine production. We showed for the first time that PBMC from malaria-non-exposed RTS,S-immunized subjects contain both TE/EM and TCM cells that generate strong IL-2 responses following re-stimulation in vitro with CSP peptides. Moreover, both the frequencies and the total numbers of IL-2-producing CD4+ TE/EM cells and of CD4+ TCM cells from protected subjects were significantly higher than those from non-protected subjects. We also demonstrated for the first time that there is a strong association between the frequency of CSP peptide-reactive CD4+ T cells producing IL-2 and the titers of CSP-specific antibodies in the same individual, suggesting that IL-2 may be acting as a growth factor for follicular Th cells and/or B cells. The frequencies of CSP peptide-reactive, TNF-α-producing CD4+ TE/EM cells and of CD4+ TE/EM cells secreting both IL-2 and TNF-α were also shown to be higher in protected vs. non-protected individuals. We have, therefore, demonstrated that in addition to TNF-α, IL-2 is also a significant contributing factor to RTS,S/AS vaccine induced immunity and that both TE/EM and TCM cells are major producers of IL-2

Evolutionary Dynamics of Intratumor Heterogeneity

Intraneoplastic diversity in human tumors is a widespread phenomenon of critical importance for tumor progression and the response to therapeutic intervention. Insights into the evolutionary events that control tumor heterogeneity would be a major breakthrough in our comprehension of cancer development and could lead to more effective prevention methods and therapies. In this paper, we design an evolutionary mathematical framework to study the dynamics of heterogeneity over time. We consider specific situations arising during tumorigenesis, such as the emergence of positively selected mutations (“drivers”) and the accumulation of neutral variation (“passengers”). We perform exact computer simulations of the emergence of diverse tumor cell clones over time, and derive analytical estimates for the extent of heterogeneity within a population of cancer cells. Our methods contribute to a quantitative understanding of tumor heterogeneity and the impact of heritable alterations on this tumor trait

Coping and sickness absence

Objectives: The aim of this study is to examine the role of coping styles in sickness absence. In line with findings that contrast the reactive-passive focused strategies, problem-solving strategies are generally associated with positive results in terms of well-being and overall health outcomes; our hypothesis is that such strategies are positively related to a low frequency of sickness absence and with short lengths (total number of days absent) and durations (mean duration per spell). Methods: Using a prospective design, employees' (N = 3,628) responses on a self-report coping inventory are used to predict future registered sickness absence (i.e. frequency, length, duration, and median time before the onset of a new sick leave period). Results and conclusions: In accordance with our hypothesis, and after adjustment for potential confounders, employees with an active problem-solving coping strategy are less likely to drop out because of sickness absence in terms of frequency, length (longer than 14 days), and duration (more than 7 days) of sickness absence. This positive effect is observed in the case of seeking social support only for the duration of sickness absence and in the case of palliative reaction only for the length and frequency of absence. In contrast, an avoidant coping style, representing a reactive-passive strategy, increases the likelihood of frequent absences significantly, as well as the length and duration of sickness absence. Expression of emotions, representing another reactive-passive strategy, has no effect on future sickness absenteeism. The median time before the onset of a new episode of absenteeism is significantly extended for active problem-solving and reduced for avoidance and for a palliative response. The results of the present study support the notion that problem-solving coping and reactive-passive strategies are inextricably connected to frequency, duration, length and onset of sickness absence. Especially, active problem-solving decreases the chance of future sickness absence. © Springer-Verlag 2007

A Model of Mindful Parenting: Implications for Parent–Child Relationships and Prevention Research

This paper introduces a model of “mindful parenting” as a framework whereby parents intentionally bring moment-to-moment awareness to the parent–child relationship. This is done by developing the qualities of listening with full attention when interacting with their children, cultivating emotional awareness and self-regulation in parenting, and bringing compassion and nonjudgmental acceptance to their parenting interactions. First, we briefly outline the theoretical and empirical literature on mindfulness and mindfulness-based interventions. Next, we present an operational definition of mindful parenting as an extension of mindfulness to the social context of parent–child relationships. We discuss the implications of mindful parenting for the quality of parent–child relationships, particularly across the transition to adolescence, and we review the literature on the application of mindfulness in parenting interventions. We close with a synopsis of our own efforts to integrate mindfulness-based intervention techniques and mindful parenting into a well-established, evidence-based family prevention program and our recommendations for future research on mindful parenting interventions

Examination of Apoptosis Signaling in Pancreatic Cancer by Computational Signal Transduction Analysis

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pathway in pancreatic cancer computationally by evaluation of experimental data from high-throughput technologies and public data bases. Therefore, gene expression analysis of microdissected pancreatic tumor tissue was implemented in a model of the apoptosis pathway obtained by computational protein interaction prediction. METHODOLOGY/PRINCIPAL FINDINGS: Apoptosis pathway related genes were assembled from electronic databases. To assess expression of these genes we constructed a virtual subarray from a whole genome analysis from microdissected native tumor tissue. To obtain a model of the apoptosis pathway, interactions of members of the apoptosis pathway were analysed using public databases and computational prediction of protein interactions. Gene expression data were implemented in the apoptosis pathway model. 19 genes were found differentially expressed and 12 genes had an already known pathophysiological role in PDAC, such as Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry. Implementation of the gene expression data in the apoptosis pathway map suggested two higher level defects of the pathway at the level of cell death receptors and within the intrinsic signaling cascade consistent with references on apoptosis in PDAC. Protein interaction prediction further showed possible new interactions between the single pathway members, which demonstrate the complexity of the apoptosis pathway. CONCLUSIONS/SIGNIFICANCE: Our data shows that by computational evaluation of public accessible data an acceptable virtual image of the apoptosis pathway might be given. By this approach we could identify two higher level defects of the apoptosis pathway in PDAC. We could further for the first time identify IL1R2 as possible candidate gene in PDAC