The Vacuum in Light-Cone Field Theory

This is an overview of the problem of the vacuum in light-cone field theory, stressing its close connection to other puzzles regarding light-cone quantization. I explain the sense in which the light-cone vacuum is ``trivial,'' and describe a way of setting up a quantum field theory on null planes so that it is equivalent to the usual equal-time formulation. This construction is quite helpful in resolving the puzzling aspects of the light-cone formalism. It furthermore allows the extraction of effective Hamiltonians that incorporate vacuum physics, but that act in a Hilbert space in which the vacuum state is simple. The discussion is fairly informal, and focuses mainly on the conceptual issues. [Talk presented at {\sc Orbis Scientiae 1996}, Miami Beach, FL, January 25--28, 1996. To appear in the proceedings.]Comment: 20 pages, RevTeX, 4 Postscript figures. Minor typos correcte

Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases.

The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts

Perspectives on the Social, Physical and Emotional Impact of Living with Perthes’ Disease in Children and their Family: a Mixed Methods Study.

Aim: To determine the social, physical and emotional impact of living with Perthes’ disease on affected children and their family (caregivers). Patients and Methods: Through a mixed methods approach, we interviewed 18 parents and explored the perspectives of 12 children affected by Perthes’ disease (mean 7.1 years, SD±4.1 years) using a survey tool. Thematic analysis of parents’ interviews provided an insight into disease-specific factors influencing patients and family’s daily life activities. Using the childhood survey tool, good and bad day scores were analyzed using MANOVA. Results: Thematic analysis of the parent interviews (main themes n=4) identified a marked effect of the disease on many facets of the child’s life, particularly pain and the impact on sleep, play and school attendance. In addition, the interviews identified a negative effect on the family life of the parents and siblings. Children indicated that activities of daily living were affected even during ‘good days’ (p<0.05) but pain was the key limiting factor. Conclusion: Perthes’ disease negatively affects the social, physical and emotional well-being of children and their family. These findings provide outcome domains that are important to measure in day-to-day care and add in-depth insight into the challenges caused by this disease for health care professionals involved in clinical management

Black Stork Down: Military Discourses in Bird Conservation in Malta

Tensions between Maltese hunters and bird conservation NGOs have intensified over the past decade. Conservation NGOs have become frustrated with the Maltese State for conceding to the hunter lobby and negotiating derogations from the European Union’s Bird Directive. Some NGOs have recently started to organize complex field-operations where volunteers are trained to patrol the landscape, operate drones and other surveillance technologies, detect illegalities, and lead police teams to arrest poachers. We describe the sophisticated military metaphors which conservation NGOs have developed to describe, guide and legitimize their efforts to the Maltese public and their fee-paying members. We also discuss why such groups might be inclined to adopt these metaphors. Finally, we suggest that anthropological studies of discourse could help understand delicate contexts such as this where conservation NGOs, hunting associations and the State have ended in political deadlock

Rich Situated Attitudes

We outline a novel theory of natural language meaning, Rich Situated Semantics [RSS], on which the content of sentential utterances is semantically rich and informationally situated. In virtue of its situatedness, an utterance’s rich situated content varies with the informational situation of the cognitive agent interpreting the utterance. In virtue of its richness, this content contains information beyond the utterance’s lexically encoded information. The agent-dependence of rich situated content solves a number of problems in semantics and the philosophy of language (cf. [14, 20, 25]). In particular, since RSS varies the granularity of utterance contents with the interpreting agent’s informational situation, it solves the problem of finding suitably fine- or coarse-grained objects for the content of propositional attitudes. In virtue of this variation, a layman will reason with more propositions than an expert

The utility of c-Met as a diagnostic tissue biomarker in primary colorectal cancer

The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial. Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c-Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi-quantifiable score, and differences in median scores analysed using the Wilcoxon signed-rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c-Met as a biomarker in CRC. Epithelial cell membrane expression of c-Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6-15) versus median 6.00 (IQR 2.70-12.00) respectively (P = <.0001). ROC-AUC analysis of c-Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%-89.45%) but sensitivity of only 30.92% (CI 25.37%-36.90%). Thus c-Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c-Met expression may have a role in diagnosis and prognostication if combined with other biomarkers

Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer

Background: Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids. Methods: Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm²) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated. Results: Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01). Conclusions: Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition

Perceived Academic Control and Academic Emotions Predict Undergraduate University Student Success: Examining Effects on Dropout Intention and Achievement

It is difficult to demonstrate that safety-critical software is completely free of dangerous faults. Prior testing can be used to demonstrate that the unsafe failure rate is below some bound, but in practice, the bound is not low enough to demonstrate the level of safety performance required for critical software-based systems like avionics. This paper argues higher levels of safety performance can be claimed by taking account of: 1)external mitigation to prevent an accident: 2) the fact that software is corrected once failures are detected in operation. A model based on these concepts is developed to derive an upper bound on the number of expected failures and accidents under different assumptions about fault fixing, diagnosis, repair and accident mitigation. A numerical example is used to illustrate the approach. The implications and potential applications of the theory are discussed

Strain control of a bandwidth-driven spin reorientation in Ca₃Ru₂O₇

The layered-ruthenate family of materials possess an intricate interplay of structural, electronic and magnetic degrees of freedom that yields a plethora of delicately balanced ground states. This is exemplified by Ca3Ru2O7, which hosts a coupled transition in which the lattice parameters jump, the Fermi surface partially gaps and the spins undergo a 90∘ in-plane reorientation. Here, we show how the transition is driven by a lattice strain that tunes the electronic bandwidth. We apply uniaxial stress to single crystals of Ca3Ru2O7, using neutron and resonant x-ray scattering to simultaneously probe the structural and magnetic responses. These measurements demonstrate that the transition can be driven by externally induced strain, stimulating the development of a theoretical model in which an internal strain is generated self-consistently to lower the electronic energy. We understand the strain to act by modifying tilts and rotations of the RuO6 octahedra, which directly influences the nearest-neighbour hopping. Our results offer a blueprint for uncovering the driving force behind coupled phase transitions, as well as a route to controlling them