MECHANISM OF RECOVERY FROM SYSTEMIC VACCINIA VIRUS INFECTION : I. THE EFFECTS OF CYCLOPHOSPHAMIDE

Administration of Cytoxan in doses capable of inhibiting both humoral and cellular immunity markedly potentiated primary systemic vaccinia virus infection in mice. Immunosuppressed mice did not form neutralizing antibody to vaccinia virus and had a prolonged and more severe viremia than nonimmunosuppressed control mice. Passive transfer of physiologic amounts of neutralizing antibody late in the course of infection, at a time when nonimmunosuppressed mice had similar levels of serum antibody, largely reversed the effect of Cytoxan on vaccinia virus infection. Transfer of 100 million immune spleen cells was much less effective than antibody in reversing the effect of Cytoxan on vaccinia virus infection, and mice receiving these cells did make some antibody. Serum interferon levels were not affected by Cytoxan. The results suggest an essential role for humoral antibody, but not for cellular immunity, in recovery from primary vaccinia virus infection in the mouse

Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery alone may be treatment for early stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. OBJECTIVES: To determine which surgical treatment modalities for oral cavity and oropharyngeal cancers result in increased overall survival, disease free survival, progression free survival and reduced recurrence. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 17 February 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 17 February 2011) and EMBASE via OVID (1980 to 17 February 2011). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared two or more surgical treatment modalities or surgery versus other treatment modalities. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of risk of bias was undertaken independently by two or more review authors. Study authors were contacted for additional information as required. Adverse events data were collected from published trials. MAIN RESULTS: Seven trials (n = 669; 667 with cancers of the oral cavity) satisfied the inclusion criteria, but none were assessed as low risk of bias. Trials were grouped into three main comparisons. Four trials compared elective neck dissection (ND) with therapeutic neck dissection in patients with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate. Three of these trials reported overall and disease free survival. One trial showed a benefit for elective supraomohyoid neck dissection compared to therapeutic ND in overall and disease free survival. Two trials found no difference between elective radical ND and therapeutic ND for the outcomes of overall survival and disease free survival. All four trials found reduced locoregional recurrence following elective ND.A further two trials compared elective radical ND with elective selective ND and found no difference in overall survival, disease free survival or recurrence. The final trial compared surgery plus radiotherapy to radiotherapy alone but data were unreliable because the trial stopped early and there were multiple protocol violations.None of the trials reported quality of life as an outcome. Two trials, evaluating different comparisons reported adverse effects of treatment. AUTHORS' CONCLUSIONS: Seven included trials evaluated neck dissection surgery in patients with oral cavity cancers. The review found weak evidence that elective neck dissection of clinically negative neck nodes at the time of removal of the primary tumour results in reduced locoregional recurrence, but there is insufficient evidence to conclude that elective neck dissection increases overall survival or disease free survival compared to therapeutic neck dissection. There is very weak evidence from one trial that elective supraomohyoid neck dissection may be associated with increased overall and disease free survival. There is no evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery. Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of patients undergoing different surgeries

Large droplet impact on water layers

The impact of large droplets onto an otherwise undisturbed layer of water is considered. The work, which is motivated primarily with regard to aircraft icing, is to try and help understand the role of splashing on the formation of ice on a wing, in particular for large droplets where splash appears, to have a significant effect. Analytical and numerical approaches are used to investigate a single droplet impact onto a water layer. The flow for small times after impact is determined analytically, for both direct and oblique impacts. The impact is also examined numerically using the volume of fluid (VOF) method. At small times there are promising comparisons between the numerical results, the analytical solution and experimental work capturing the ejector sheet. At larger times there is qualitative agreement with experiments and related simulations. Various cases are considered, varying the droplet size to layer depth ratio, including surface roughness, droplet distortion and air effects. The amount of fluid splashed by such an impact is examined and is found to increase with droplet size and to be significantly influenced by surface roughness. The makeup of the splash is also considered, tracking the incoming fluid, and the splash is found to consist mostly of fluid originating in the layer

Dynamics of grain ejection by sphere impact on a granular bed

The dynamics of grain ejection consecutive to a sphere impacting a granular material is investigated experimentally and the variations of the characteristics of grain ejection with the control parameters are quantitatively studied. The time evolution of the corona formed by the ejected grains is reported, mainly in terms of its diameter and height, and favourably compared with a simple ballistic model. A key characteristic of the granular corona is that the angle formed by its edge with the horizontal granular surface remains constant during the ejection process, which again can be reproduced by the ballistic model. The number and the kinetic energy of the ejected grains is evaluated and allows for the calculation of an effective restitution coefficient characterizing the complex collision process between the impacting sphere and the fine granular target. The effective restitution coefficient is found to be constant when varying the control parameters.Comment: 9 page

Pasts and pagan practices: moving beyond Stonehenge

Theorizing the past is not restricted to archaeology and interpretations of 'past' both influence and are themselves constituted within politicized understandings of self, community and in certain instances, spirituality. 'The past in the imagination of the present' is appropriated, variously, to give meaning to the present or to justify actions and interpret experiences. Summer solstice at Stonehenge, with an estimated 21,000 celebrants in 2005, is only the most publicized appropriation (by pagans and other adherents of alternative spirituality and partying) of a 'sacred site'; and conflicts and negotiations occurring throughout Britain are represented in popular and academic presentations of this 'icon of Britishness'. This paper presents work from the Sacred Sites, Contested Rites/Rights Project (http://www.sacredsites.org.uk) project, a collaboration of archaeology and anthropology informed by pagan and alternative approaches and standpoints investigating and theorizing discourse and practice of heritage management and pagan site users. Whether in negotiations around the Stonehenge solstice access or in dealing with numerous other sites, boundaries between groups or discourses are not clearly drawn - discursive communities merge and re-emerge. But clearly 'past' and 'site' are increasingly important within today's Britain, even as television archaeology increases its following, and pagan numbers continue to grow.</p

Association of the CCR5 gene with juvenile idiopathic arthritis

The CC chemokine receptor 5 (CCR5) has been shown to be important in the recruitment of T-helper cells to the synovium, where they accumulate, drive the inflammatory process and the consequent synovitis and joint destruction. A 32 base-pair insertion/deletion variant (CCR5Δ32) within the gene leads to a frame shift and a nonfunctional receptor. CCR5Δ32 has been investigated for its association with juvenile idiopathic arthritis (JIA), with conflicting results. The aim of this study was to investigate whether CCR5Δ32 is associated with JIA in an UK population. CCR5Δ32 was genotyped in JIA cases (n=1054) and healthy controls (n=3129) and genotype and allele frequencies were compared. A meta-analysis of our study combined with previously published studies was performed. CCR5Δ32 was significantly associated with protection from developing JIA, in this UK data set (P(trend)=0.006, odds ratio (OR) 0.79 95% confidence interval (95% CI): 0.66-0.94). The meta-analysis of all published case-control association studies confirmed the protective association with JIA (P=0.001 OR 0.82 95% CI: 0.73-0.93). CCR5Δ32 is a functional variant determining the number of receptors on the surface of T cells, and it is hypothesized that the level of CCR5 expression could influence the migration of proinflammatory T cells into the synovium and thus susceptibility to JIA

Evolutionary Roots of Property Rights; The Natural and Cultural Nature of Human Cooperation

Debates about the role of natural and cultural selection in the development of prosocial, antisocial and socially neutral mechanisms and behavior raise questions that touch property rights, cooperation, and conflict. For example, some researchers suggest that cooperation and prosociality evolved by natural selection (Hamilton 1964, Trivers 1971, Axelrod and Hamilton 1981, De Waal 2013, 2014), while others claim that natural selection is insufficient for the evolution of cooperation, which required in addition cultural selection (Sterelny 2013, Bowles and Gintis 2003, Seabright 2013, Norenzayan 2013). Some scholars focus on the complexity and hierarchical nature of the evolution of cooperation as involving different tools associated with lower and the higher levels of competition (Nowak 2006, Okasha 2006); others suggest that humans genetically inherited heuristics that favor prosocial behavior such as generosity, forgiveness or altruistic punishment (Ridley 1996, Bowles and Gintis 2004, Rolls 2005). We argue these mechanisms are not genetically inherited; rather, they are features inherited through cultural selection. To support this view we invoke inclusive fitness theory, which states that individuals tend to maximize their inclusive fitness, rather than maximizing group fitness. We further reject the older notion of natural group selection - as well as more recent versions (West, Mouden, Gardner 2011) – which hold that natural selection favors cooperators within a group (Wynne-Edwards 1962). For Wynne-Edwards, group selection leads to group adaptations; the survival of individuals therefore depends on the survival of the group and a sharing of resources. Individuals who do not cooperate, who are selfish, face extinction due to rapid and over-exploitation of resources

Mesenchymal stromal cells:inhibiting PDGF receptors or depleting fibronectin induces mesodermal progenitors with endothelial potential

Realizing the full therapeutic potential of mesenchymal stromal/stem cells (MSCs) awaits improved understanding of mechanisms controlling their fate. Using MSCs cultured as spheroids to recapitulate a three-dimensional cellular environment, we show that perturbing the mesenchymal regulators, platelet-derived growth factor (PDGF) receptors or fibronectin, reverts MSCs toward mesodermal progenitors with endothelial potential that can potently induce neovascularization in vivo. MSCs within untreated spheroids retain their mesenchymal spindle shape with abundant smooth muscle α-actin filaments and fibronectin-rich matrix. Inhibiting PDGF receptors or depleting fibronectin induces rounding and depletes smooth muscle α-actin expression; these cells have characteristics of mesenchymoangioblasts, with enhanced expression of mesendoderm and endoderm transcription factors, prominent upregulation of E-cadherin, and Janus kinase signaling-dependent expression of Oct4A and Nanog. PDGF receptor-inhibited spheroids also upregulate endothelial markers platelet endothelial cell adhesion molecule 1 and vascular endothelial-cadherin and secrete many angiogenic factors, and in vivo they potently stimulate neovascularization, and their MSCs integrate within functional blood vessels that are perfused by the circulation. Thus, MSC potency and vascular induction are regulated by perturbing mesenchymal fate

Energy cost associated with vortex crossing in superconductors

Starting from the Ginzburg-Landau free energy of a type II superconductor in a magnetic field we estimate the energy associated with two vortices crossing. The calculations are performed by assuming that we are in a part of the phase diagram where the lowest Landau level approximation is valid. We consider only two vortices but with two markedly different sets of boundary conditions: on a sphere and on a plane with quasi-periodic boundary conditions. We find that the answers are very similar suggesting that the energy is localised to the crossing point. The crossing energy is found to be field and temperature dependent -- with a value at the experimentally measured melting line of $U_\times \simeq 7.5 k T_m \simeq 1.16/c_L^2$, where $c_L$ is the Lindemann melting criterion parameter. The crossing energy is then used with an extension of the Marchetti, Nelson and Cates hydrodynamic theory to suggest an explanation of the recent transport experiments of Safar {{\em et al.}\ }.Comment: 15 pages, RevTex v3.0, followed by 5 postscript figure