Strategies to Use Nanoparticles to Generate CD4 and CD8 Regulatory T Cells for the Treatment of SLE and Other Autoimmune Diseases

Autoimmune diseases are disorders of immune regulation where the mechanisms responsible for self-tolerance break down and pathologic T cells overcome the protective effects of T regulatory cells (Tregs) that normally control them. The result can be the initiation of chronic inflammatory diseases. Systemic lupus erythematosus (SLE) and other autoimmune diseases are generally treated with pharmacologic or biological agents that have broad suppressive effects. These agents can halt disease progression, yet rarely cure while carrying serious adverse side effects. Recently, nanoparticles have been engineered to correct homeostatic regulatory defects and regenerate therapeutic antigen-specific Tregs. Some approaches have used nanoparticles targeted to antigen presenting cells to switch their support from pathogenic T cells to protective Tregs. Others have used nanoparticles targeted directly to T cells for the induction and expansion of CD4+ and CD8+ Tregs. Some of these T cell targeted nanoparticles have been formulated to act as tolerogenic artificial antigen presenting cells. This article discusses the properties of these various nanoparticle formulations and the strategies to use them in the treatment of autoimmune diseases. The restoration and maintenance of Treg predominance over effector cells should promote long-term autoimmune disease remission and ultimately prevent them in susceptible individuals

Meeting need: realising opportunity: a socio-economic framework for the East Midlands to inform the delivery of EU structural funds (2014-2020)

This document has been produced as part of an EU funded Technical Assistance project led by East Midlands Councils, with support from Nottingham Trent University and Climate East Midlands, to inform the development of the 2014-2020 EU Structural Fund Programme. It tells the economic story of the local economies that make up the East Midlands, sets out a number of key investment opportunities highlighted during six well attended consultation events, and gives some practical advice for LEPs and others about how to make the most of future EU funding, learning from past experience

A video life-world approach to consultation practice: The relevance of a socio-phenomenological approach

This article discusses the [development and] use of a video life-world schema to explore alternative orientations to the shared health consultation. It is anticipated that this schema can be used by practitioners and consumers alike to understand the dynamics of videoed health consultations, the role of the participants within it and the potential to consciously alter the outcome by altering behaviour during the process of interaction. The study examines health consultation participation and develops an interpretative method of analysis that includes image elicitation (via videos), phenomenology (to identify the components of the analytic framework), narrative (to depict the stories of interactions) and a reflexive mode (to develop shared meaning through a conceptual framework for analysis). The analytic framework is derived from a life-world conception of human mutual shared interaction which is presented here as a novel approach to understanding patient-centred care. The video materials used in this study were derived from consultations in a Walk-in Centre (WiC) in East London. The conceptual framework produced through the process of video analysis is comprised of different combinations of movement, knowledge and emotional conversations that are used to classify objective or engaged WiC health care interactions. The videoed interactions organise along an active or passive, facilitative or directive typical situation continuum illustrating different kinds of textual approaches to practice that are in tension or harmony. The schema demonstrates how practitioners and consumers interact to produce these outcomes and indicates the potential for both consumers and practitioners to be educated to develop practice dynamics that support patient-centred care and impact on health outcomes

Or, The Triumph of the Trust

Morganeering is a satire on capitalism in the era of the "Robber Barons" like John Rockefeller, Henry Ford and John Pierpont Morgan. Their success at consolidating industries is taken to extremes by the novel's capitalist villain, Jonathan Wondergilt. Most of the novel depicts how Wondergilt came to own the entire world, how he maintained and supported his powers, and how such greed brought misery to people everywhere

Nanoparticles Engineered as Artificial Antigen-Presenting Cells Induce Human CD4+ and CD8+ Tregs That Are Functional in Humanized Mice

Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring antigen-presenting cells (APCs) that, similar to natural APCs, promote efficient T effector cell responses in vitro. This report describes a method to produce acellular tolerogenic aAPCs made of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 and TGF-β for a paracrine release to T cells. We document that these aAPCs can induce both human CD4(+) and CD8(+) T cells to become FoxP3(+) T regulatory cells (Tregs). The aAPC NP-expanded human Tregs are functional in vitro and can modulate systemic autoimmunity in vivo in humanized NSG mice. These findings establish a proof-of-concept to use PLGA NPs as aAPCs for the induction of human Tregs in vitro and in vivo, highlighting the immunotherapeutic potential of this targeted approach to repair IL-2 and/or TGF-β defects documented in certain autoimmune diseases such as systemic lupus erythematosus

Survey design for Spectral Energy Distribution fitting: a Fisher Matrix approach

The spectral energy distribution (SED) of a galaxy contains information on the galaxy's physical properties, and multi-wavelength observations are needed in order to measure these properties via SED fitting. In planning these surveys, optimization of the resources is essential. The Fisher Matrix formalism can be used to quickly determine the best possible experimental setup to achieve the desired constraints on the SED fitting parameters. However, because it relies on the assumption of a Gaussian likelihood function, it is in general less accurate than other slower techniques that reconstruct the probability distribution function (PDF) from the direct comparison between models and data. We compare the uncertainties on SED fitting parameters predicted by the Fisher Matrix to the ones obtained using the more thorough PDF fitting techniques. We use both simulated spectra and real data, and consider a large variety of target galaxies differing in redshift, mass, age, star formation history, dust content, and wavelength coverage. We find that the uncertainties reported by the two methods agree within a factor of two in the vast majority (~ 90%) of cases. If the age determination is uncertain, the top-hat prior in age used in PDF fitting to prevent each galaxy from being older than the Universe needs to be incorporated in the Fisher Matrix, at least approximately, before the two methods can be properly compared. We conclude that the Fisher Matrix is a useful tool for astronomical survey design.Comment: Accepted by ApJ; online Fisher Matrix tool available at http://galfish.physics.rutgers.ed

Language and iconic gesture use in procedural discourse by speakers with aphasia

Background: Conveying instructions is an everyday use of language, and gestures are likely to be a key feature of this. Although co-speech iconic gestures are tightly integrated with language, and people with aphasia (PWA) produce procedural discourses impaired at a linguistic level, no previous studies have investigated how PWA use co-speech iconic gestures in these contexts.Aims: This study investigated how PWA communicated meaning using gesture and language in procedural discourses, compared with neurologically healthy people (NHP). We aimed to identify the relative relationship of gesture and speech, in the context of impaired language, both overall and in individual events.Methods & Procedures: Twenty-nine PWA and 29 NHP produced two procedural discourses. The structure and semantic content of language of the whole discourses were analysed through predicate argument structure and spatial motor terms, and gestures were analysed for frequency and semantic form. Gesture and language were analysed in two key events, to determine the relative information presented in each modality.Outcomes & Results: PWA and NHP used similar frequencies and forms of gestures, although PWA used syntactically simpler language and fewer spatial words. This meant, overall, relatively more information was present in PWA gesture. This finding was also reflected in the key events, where PWA used gestures conveying rich semantic information alongside semantically impoverished language more often than NHP.Conclusions: PWA gestures, containing semantic information omitted from the concurrent speech, may help listeners with meaning when language is impaired. This finding indicates gesture should be included in clinical assessments of meaning-making

Acute unilateral hearing loss as an unusual presentation of cholesteatoma

BACKGROUND: Cholesteatomas are epithelial cysts that contain desquamated keratin. Patients commonly present with progressive hearing loss and a chronically discharging ear. We report an unusual presentation of the disease with an acute hearing loss suffered immediately after prolonged use of a pneumatic drill. CASE PRESENTATION: A 41 year old man with no previous history of ear problems presented with a sudden loss of hearing in his right ear immediately following the prolonged use of a pneumatic drill on concrete. The cause was found to be a fractured long process of incus which had been eroded by the presence of an attic cholesteatoma. A tympanomastoidectomy and ossiculoplasty was performed with good result. CONCLUSION: Cholesteatomas may be asymptomatic and insidious in their onset. This case illustrates the point that an indolent disease such as this may present in unusual ways and the clinician must always have a high index of suspicion combined with thorough assessment and examination of every patient