Virus-Like Particle-Mediated Vaccination against Interleukin-13 May Harbour General Anti-Allergic Potential beyond Atopic Dermatitis

Virus-like particle (VLP)-based anti-infective prophylactic vaccination has been established in clinical use. Although validated in proof-of-concept clinical trials in humans, no VLP-based therapeutic vaccination against self-proteins to modulate chronic disease has yet been licensed. The present review summarises recent scientific advances, identifying interleukin-13 as an excellent candidate to validate the concept of anti-cytokine vaccination. Based on numerous clinical studies, long-term elimination of IL-13 is not expected to trigger target-related serious adverse effects and is likely to be safer than combined targeting of IL-4/IL-13. Furthermore, recently published results from large-scale trials confirm that elimination of IL-13 is highly effective in atopic dermatitis, an exceedingly common condition, as well as eosinophilic esophagitis. The distinctly different mode of action of a polyclonal vaccine response is discussed in detail, suggesting that anti-IL-13 vaccination has the potential of outperforming monoclonal antibody-based approaches. Finally, recent data have identified a subset of follicular T helper cells dependent on IL-13 which selectively trigger massive IgE accumulation in response to anaphylactoid allergens. Thus, prophylactic IL-13 vaccination may have broad application in a number of allergic conditions

Isospin-violating dark-matter-nucleon scattering via two-Higgs-doublet-model portals

We show that in a multi-Higgs model in which one Higgs fits the LHC 125 GeV state, one or more of the other Higgs bosons can mediate DM-nucleon interactions with maximal DM isospin violation being possible for appropriate Higgs-quark couplings, independent of the nature of DM. We then consider the explicit example of a Type II two-Higgs-doublet model, identifying the h or H as the 125 GeV state while the H or h, respectively, mediates DM-nucleon interactions. Finally, we show that if a stable scalar, S, is added then it can be a viable light DM candidate with correct relic density while obeying all direct and indirect detection limits.Comment: Two subsections are added to address the collider bounds from direct search for heavy Higgs bosons and from jet plus missing energy final states. The LUX (2013) bound considered in the previous version is replaced by the latest LUX (2016) bound and the SuperCDMS limit is taken into account. The conclusions remain unchanged. A very minor change made in the title and new references include

Two-Higgs-Doublet Models and Enhanced Rates for a 125 GeV Higgs

We examine the level of enhancement that can be achieved in the ZZ and \gamma\gamma channels for a two-Higgs-doublet model Higgs boson (either the light h or the heavy H) with mass near 125 GeV after imposing all constraints from LEP data, B physics, precision electroweak data, vacuum stability, unitarity and perturbativity. The latter constraints restrict substantially the possibilities for enhancing the gg -> h -> \gamma\gamma or gg -> H -> \gamma\gamma signal relative to that for the SM Higgs, hSM. Further, we find that a significant enhancement of the gg -> h -> \gamma\gamma or gg -> H -> \gamma\gamma signal in Type II models is possible only if the gg -> h -> ZZ or gg -> H -> ZZ mode is even more enhanced, a situation disfavored by current data. In contrast, in the Type I model one can achieve enhanced rates in the \gamma\gamma final state for the h while having the ZZ mode at or below the SM rate - the largest [gg -> h -> \gamma\gamma]/[gg -> hSM -> \gamma\gamma] ratio found is of order ~1.3 when the two Higgs doublet vacuum expectation ratio is tan\beta = 4 or 20 and the charged Higgs boson has its minimal LEP-allowed value of m_{H^\pm} = 90 GeV.Comment: 15 pages, 9 figure

Assessment of the relationships between myocardial contractility and infarct tissue revealed by serial magnetic resonance imaging in patients with acute myocardial infarction

Imaging changes in left ventricular (LV) volumes during the cardiac cycle and LV ejection fraction do not provide information on regional contractility. Displacement ENcoding with Stimulated Echoes (DENSE) is a strain-encoded cardiac magnetic resonance (CMR) technique that measures strain directly. We investigated the relationships between strain revealed by DENSE and the presence and extent of infarction in patients with recent myocardial infarction (MI). 50 male subjects were invited to undergo serial CMR within 7 days of MI (baseline) and after 6 months (follow-up; n = 47). DENSE and late gadolinium enhancement (LGE) images were acquired to enable localised regional quantification of peak circumferential strain (Ecc) and the extent of infarction, respectively. We assessed: (1) receiver operating characteristic (ROC) analysis for the classification of LGE, (2) strain differences according to LGE status (remote, adjacent, infarcted) and (3) changes in strain revealed between baseline and follow-up. 300 and 258 myocardial segments were available for analysis at baseline and follow-up respectively. LGE was present in 130/300 (43 %) and 97/258 (38 %) segments, respectively. ROC analysis revealed moderately high values for peak Ecc at baseline [threshold 12.8 %; area-under-curve (AUC) 0.88, sensitivity 84 %, specificity 78 %] and at follow-up (threshold 15.8 %; AUC 0.76, sensitivity 85 %, specificity 64 %). Differences were observed between remote, adjacent and infarcted segments. Between baseline and follow-up, increases in peak Ecc were observed in infarcted segments (median difference of 5.6 %) and in adjacent segments (1.5 %). Peak Ecc at baseline was indicative of the change in LGE status between baseline and follow-up. Strain-encoded CMR with DENSE has the potential to provide clinically useful information on contractility and its recovery over time in patients with MI

Crisis Events as a Catalyst for Change in the US Air Transportation

Historically, aircraft accidents have preceded the implementation of many changes in the US Air Transportation System. These accidents act as catalytic events which generate awareness of a problem and pressure for change to occur. Specifically, aircraft accidents indicate the presence of safety problems. As past safety problems were addressed the frequency of accidents decreased causing new drivers for system change to emerge. Current drivers for change in the US Air Transportation System include increases in demand in the face of limited capacity, emerging requirements such as the need to address growing environmental concerns, and the need to replace and update aging system components. This paper explores the role of catalytic events in bringing change to the US Air Transportation System with a focus on the implications for capacity driven change. In order to address capacity constraints, infrastructure improvements, such as construction of new runways, or efficiency improvements, which would allow aircraft to be spaced closer together, can be made. However, changing the system in response to capacity can be difficult due to barriers posed by stakeholder conflicts and complex decision making and approval processes. The capacity problem, the need to address it, as well as the barriers to addressing it are presented in this paper. Finally, the paper explores the role of delays as catalytic capacity events and the likely actions following such an event.This work was supported by the FAA under the Joint University Program (JUP) [FAA95-G-017] and the National Center of Excellence for Aviation Operations Research (NEXTOR) [DTFA01-C-00030]

Having your Privacy Cake and Eating it Too: Platform-supported Auditing of Social Media Algorithms for Public Interest

Social media platforms curate access to information and opportunities, and so play a critical role in shaping public discourse today. The opaque nature of the algorithms these platforms use to curate content raises societal questions. Prior studies have used black-box methods to show that these algorithms can lead to biased or discriminatory outcomes. However, existing auditing methods face fundamental limitations because they function independent of the platforms. Concerns of potential harm have prompted proposal of legislation in both the U.S. and the E.U. to mandate a new form of auditing where vetted external researchers get privileged access to social media platforms. Unfortunately, to date there have been no concrete technical proposals to provide such auditing, because auditing at scale risks disclosure of users' private data and platforms' proprietary algorithms. We propose a new method for platform-supported auditing that can meet the goals of the proposed legislation. Our first contribution is to enumerate the challenges of existing auditing methods to implement these policies at scale. Second, we suggest that limited, privileged access to relevance estimators is the key to enabling generalizable platform-supported auditing by external researchers. Third, we show platform-supported auditing need not risk user privacy nor disclosure of platforms' business interests by proposing an auditing framework that protects against these risks. For a particular fairness metric, we show that ensuring privacy imposes only a small constant factor increase (6.34x as an upper bound, and 4x for typical parameters) in the number of samples required for accurate auditing. Our technical contributions, combined with ongoing legal and policy efforts, can enable public oversight into how social media platforms affect individuals and society by moving past the privacy-vs-transparency hurdle

The Dynamics of Air Transportation System Transition

Both U.S. and European Air Transportation Systems face substantial challenges in transforming to meet future demand. This paper uses a feedback model to identify and describe key issues in the dynamics of system transition, with particular emphasis on stakeholder cost-benefit dynamics and processes for reviewing and implementing new system capabilities. Understanding of these dynamics is further reinforced through discussion of ADS-B and new runway construction examples. To implement the significant changes currently envisioned for ATM systems, it will be critical to structure system changes to anticipate and overcome stakeholder disagreements and improve the efficiency of the approval and implementation processes