Editorial - Addressing research priorities in community-acquired pneumonia in children: A case of a missed opportunity

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Representing moisture fluxes and phase changes in glacier debris cover using a reservoir approach

Due to the complexity of treating moisture in supraglacial debris, surface energy balance models to date have neglected moisture infiltration and phase changes in the debris layer. The latent heat flux (QL) is also often excluded due to the uncertainty in determining the surface vapour pressure. To quantify the importance of moisture on the surface energy and climatic mass balance (CMB) of debris-covered glaciers, we developed a simple reservoir parameterization for the debris ice and water content, as well as an estimation of the latent heat flux. The parameterization was incorporated into a CMB model adapted for debris-covered glaciers. We present the results of two point simulations, using both our new “moist” and the conventional “dry” approaches, on the Miage Glacier, Italy, during summer 2008 and fall 2011. The former year coincides with available in situ glaciological and meteorological measurements, including the first eddy-covariance measurements of the turbulent fluxes over supraglacial debris, while the latter contains two refreeze events that permit evaluation of the influence of phase changes. The simulations demonstrate a clear influence of moisture on the glacier energy and mass-balance dynamics. When water and ice are considered, heat transmission to the underlying glacier ice is lower, as the effective thermal diffusivity of the saturated debris layers is reduced by increases in both the density and the specific heat capacity of the layers. In combination with surface heat extraction by QL, subdebris ice melt is reduced by 3.1% in 2008 and by 7.0% in 2011 when moisture effects are included. However, the influence of the parameterization on the total accumulated mass balance varies seasonally. In summer 2008, mass loss due to surface vapour fluxes more than compensates for the reduction in ice melt, such that the total ablation increases by 4.0 %. Conversely, in fall 2011, the modulation of basal debris temperature by debris ice results in a decrease in total ablation of 2.1 %. Although the parameterization is a simplified representation of the moist physics of glacier debris, it is a novel attempt at including moisture in a numerical model of debris-covered glaciers and one that opens up additional avenues for future research

FGF signaling inhibits the proliferation of human myeloma cells and reduces c-myc expression

BACKGROUND: Multiple myeloma is a cancer of antibody producing plasma cells whose etiology is unknown. FGF signaling has been implicated in myeloma pathogenesis but its precise role remains unclear. RESULTS: Here, we investigate the biochemical and phenotypic consequences of FGF stimulation in several different human myeloma cell lines. We find that FGF signaling inhibits cell cycle progression in two lines and surprisingly, reduces the expression of c-myc while turning on c-fos. In several other lines, FGF signaling does not affect proliferation rate, including cells harboring translocated FGF Receptor 3. When cells are presented with a growth arrest signal, FGF addition induces cell death. CONCLUSIONS: By showing that FGF signaling inhibits mitogenesis and induces apoptosis, we demonstrate novel effects of activating this ubiquitous signaling pathway in multiple myeloma

Panel. Current Research on Slavery at the University of Mississippi

The March Toward Militancy: Student Aggression and the Slave Community at the University of Mississippi / Chet Bush, University of MississippiThe first thirteen years of the University of Mississippi offer a window through which to observe the activities that characterized the all-male student culture. While community storytellers have imagined a single meeting where students hatched a plan to form a military company in support of the Confederacy, the archives of the university suggest a much longer gestation of violence and militancy. From the founding of the university in 1848 to the start of the war in 1861 students demonstrated an increasingly obsessive preoccupation with asserting authority. Student concern for displaying power grew particularly hostile toward the slave community in the years leading up to the Civil War. This paper charts the march toward militancy that students expressed, chiefly toward enslaved workers, during the first thirteen years of the University of Mississippi.Proslavery and States’ Rights Incubators: Fraternal Debate Societies at the University of Mississippi, 1848-1861 / Andrew Marion, University of MississippiThis presentation will examine how two fraternal debate societies at the University of Mississippi worked as incubators for proslavery and states\u27 rights ideology for the students from 1848 to 1861. Mandatory participation in these societies put students in academic environments that promoted unwavering loyalty to the state of Mississippi and its most sacred institution, slavery. An examination of proslavery rhetoric delivered at the university and debate society meeting minutes and publications will help explain the incredible commitment that the University of Mississippi\u27s students made to defend slavery and the Confederacy.The World the Slaves Made: Slaveholding, Student Wealth, and the Foundations of the University of Mississippi / Anne TwittyWhen fifteen-year-old John Sanders McRaven of Marshall County matriculated at the University of Mississippi in 1849, his father, planter Robert McRaven, was no doubt the animating force. If Robert was the architect of John’s education, however, the sixty-one men, women, and children Robert claimed in the 1850 census were its underwriters. Although scholars have identified many enslaved people who lived on college campuses and examined the centrality of their work at such facilities, little attention has been paid to the enslaved people laboring tens or hundreds of miles from these institutions who nevertheless helped create, facilitate, and maintain them. To address this omission, this paper traces the slaveholdings of the University of Mississippi’s first students through the 1850 census to explore how enslaved black people far removed from the University of Mississippi made possible the scholarly endeavors of free white men at its campus in Oxford

Unfriendly fire: How the tobacco industry is destroying the future of our children

Tobacco has long been known to be one of the greatest causes of morbidity and mortality in the adults, but the effects on the foetus and young children, which are lifelong, have been less well appreciated. Developing from this are electronic nicotine delivery systems or vapes, promulgated as being less harmful than tobacco. Nicotine itself is toxic to the foetus, with permanent effects on lung structure and function. Most vapes contain nicotine, but they also contain many other compounds which are inhaled and for which there are no toxicity studies. They also contain known toxic substances, whose use is banned by European Union legislation. Accelerating numbers of young people are vaping, and this does not reflect an exchange of vapes for cigarettes. The acute toxicity of e-cigarettes is greater than that of tobacco, and includes acute lung injury, pulmonary haemorrhage and eosinophilic and lipoid pneumonia. Given the worse acute toxicity, it should be impossible to be complacent about medium and long term effects of vaping. Laboratory studies have demonstrated changes in lung proteomics and the innate immune system with vaping, some but not all of which overlap with tobacco. It would be wrong to consider vapes as a weaker form of tobacco, they have their own toxicity. Children and young people are being targeted by the vaping industry (which is largely the same as the tobacco industry), including on-line, and unless an efficient legislative program is put in place, a whole new generation of nicotine addicts will result

Context dependent substitution biases vary within the human genome

Background: Models of sequence evolution typically assume that different nucleotide positions evolve independently. This assumption is widely appreciated to be an over-simplification. The best known violations involve biases due to adjacent nucleotides. There have also been suggestions that biases exist at larger scales, however this possibility has not been systematically explored. Results: To address this we have developed a method which identifies over- and under-represented substitution patterns and assesses their overall impact on the evolution of genome composition. Our method is designed to account for biases at smaller pattern sizes, removing their effects. We used this method to investigate context bias in the human lineage after the divergence from chimpanzee. We examined bias effects in substitution patterns between 2 and 5 bp long and found significant effects at all sizes. This included some individual three and four base pair patterns with relatively large biases. We also found that bias effects vary across the genome, differing between transposons and non-transposons, between different classes of transposons, and also near and far from genes. Conclusions: We found that nucleotides beyond the immediately adjacent one are responsible for substantial context effects, and that these biases vary across the genome

Importance of charge capture in interphase regions during readout of charge-coupled devices

The current understanding of charge transfer dynamics in charge-coupled devices (CCDs) is that charge is moved so quickly from one phase to the next in a clocking sequence and with a density so low that trapping of charge in the interphase regions is negligible. However, simulation capabilities developed at the Centre for Electronic Imaging, which includes direct input of electron density simulations, have made it possible to investigate this assumption further. As part of the radiation testing campaign of the Euclid CCD273 devices, data have been obtained using the trap pumping method, a method that can be used to identify and characterize single defects within CCDs. Combining these data with simulations, we find that trapping during the transfer of charge among phases is indeed necessary to explain the results of the data analysis. This result could influence not only trap pumping theory and how trap pumping should be performed but also how a radiation-damaged CCD is readout in the most optimal way

“Una extensa zona relacionable”: Zambrano y Lezama

Cuando Juan Ramón Jiménez llegó a Cuba al comienzo de la Guerra Civil española en 1936, el joven Lezama Lima, habiéndose comprometido ya con el secreto de Garcilaso o la serpiente de Góngora y siendo, además, lector de Ortega y su Revista de Occidente, estaba preparado para recibirlo . Juan Ramón, por el contrario, no estaba listo para Lezama

Cytokines and Chemokines as Biomarkers of Future Asthma

Antenatal and preschool factors are key in determining the progression to pre-school wheeze and eosinophilic school age asthma. The conventional view of eosinophilic asthma is that airway inflammation is the fundamental underlying abnormality, and airway inflammation and hyper-responsiveness are secondary; in fact, these three are parallel processes. Very early structural changes, independent of inflammation and infection, are associated with early airway hyper-responsiveness and later adverse respiratory outcomes. There is a bidirectional relationship between structural airway wall changes and airway inflammation, with airway contraction per se leading to the release of growth factors, and inflammatory pathways promoting airway remodeling. Early viral infection (and increasingly being appreciated, bacterial infection) is important in wheeze outcomes. There is evidence of abnormal immune function including cytokine release before the onset of viral infections. However, viral infections may also have prolonged effects on the host immune system, and the evidence for beneficial and adverse effects of viral infection is conflicting. In older children and adults, asthmatic epithelial cells show impaired interferon responses to viral infection, but only in the presence of uncontrolled type 2 inflammation, implying these are secondary phenomena. There are also compelling data relating the innate immune system to later asthma and atopy, and animal studies suggest that the effects of a high endotoxin, microbiologically diverse environment may be modulated via the epithelial alarmin IL-33. Whereas, previously only viral infection was thought to be important, early bacterial colonization of the upper airway is coming to the fore, associated with a mixed pattern of TH1/TH2/TH17 cytokine secretion, and adverse long term outcomes. Bacterial colonization is probably a marker of a subtle immune deficiency, rather than directly causal. The airway and gut microbiome critically impacts the development of Type 2 inflammatory responses. However, Type 2 inflammatory cytokines, which are critical both to progression from pre-school wheeze to eosinophilic asthma, and sustaining the eosinophilic asthmatic state, are not implicated in the very early development of the disease. Taken together, the evidence is that the earliest cytokine and chemokine signals will come from the study of bronchial epithelial cell function and their interactions with viruses and the microbiome