Eruptive papules during efalizumab (anti-CD11a) therapy of psoriasis vulgaris: a case series

BACKGROUND: Newer biological therapies for moderate-to-severe psoriasis are being used more frequently, but unexpected effects may occur. CASE PRESENTATIONS: We present a group of 15 patients who developed inflammatory papules while on efalizumab therapy (Raptiva, Genentech Inc, anti-CD11a). Immunohistochemistry showed that there were increased CD11b(+), CD11c(+ )and iNOS(+ )cells (myeloid leukocytes) in the papules, with relatively few CD3(+ )T cells. While efalizumab caused a decreased expression of CD11a on T cells, other circulating leukocytes from patients receiving this therapy often showed increased CD11b and CD11c. In the setting of an additional stimulus such as skin trauma, this may predispose to increased trafficking into the skin using these alternative β2 integrins. In addition, there may be impaired immune synapse formation, limiting the development of these lesions to small papules. There is little evidence for these papular lesions being "allergic" in nature as there are few eosinophils on biopsy, and they respond to minimal or no therapy even if efalizumab is continued. CONCLUSION: We hypothesize that these papules may represent a unique type of "mechanistic" inflammatory reaction, seen only in the context of drug-induced CD11a blockade, and not during the natural disease process

‘Not a country at all’: landscape and Wuthering Heights

This article explores the issue of women’s representational genealogies through an analysis of Andrea Arnold’s 2011 Wuthering Heights. Beginning with 1970s feminist arguments for a specifically female literary tradition, it argues that running through both these early attempts to construct an alternative female literary tradition and later work in feminist philosophy, cultural geography and film history is a concern with questions of ‘alternative landscapes’: of how to represent, and how to encounter, space differently. Adopting Mary Jacobus’ notion of intertextual ‘correspondence’ between women’s texts, and taking Arnold’s film as its case study, it seeks to trace some of the intertextual movements – the reframings, deframings and spatial reorderings – that link Andrea Arnold’s film to Emily Brontë’s original novel. Focusing on two elements of her treatment of landscape – her use of ‘unframed’ landscape and her focus on visceral textural detail – it points to correspondences in other women’s writing, photography and film-making. It argues that these intensely tactile close-up sequences which puncture an apparently realist narrative constitute an insistent presence beneath, or within, the ordered framing which is our more usual mode of viewing landscape. As the novel Wuthering Heights is unmade in Arnold’s adaptation and its framings ruptured, it is through this disturbance of hierarchies of time, space and landscape that we can trace the correspondences of an alternative genealogy

Elevated CO2 degassing rates prevented the return of Snowball Earth during the Phanerozoic

The Cryogenian period (~720–635 Ma) is marked by extensive Snowball Earth glaciations. These have previously been linked to CO₂ draw-down, but the severe cold climates of the Cryogenian have never been replicated during the Phanerozoic despite similar, and sometimes more dramatic changes to carbon sinks. Here we quantify the total CO₂ input rate, both by measuring the global length of subduction zones in plate tectonic reconstructions, and by sea-level inversion. Our results indicate that degassing rates were anomalously low during the Late Neoproterozoic, roughly doubled by the Early Phanerozoic, and remained comparatively high until the Cenozoic. Our carbon cycle modelling identifies the Cryogenian as a unique period during which low surface temperature was more easily achieved, and shows that the shift towards greater CO₂ input rates after the Cryogenian helped prevent severe glaciation during the Phanerozoic. Such a shift appears essential for the development of complex animal life

The NAVIGATE Program for First-Episode Psychosis: Rationale, Overview, and Description of Psychosocial Components

Comprehensive coordinated specialty care programs for first episode psychosis have been widely implemented in other countries, but not in the U.S. The National Institute of Mental Health’s (NIMH) Recovery After Initial Schizophrenia Episode (RAISE) initiative focused on the development and evaluation of first episode treatment programs designed for the U.S. healthcare system. This paper describes the background, rationale, and nature of the intervention developed by the Early Treatment Program project, the NAVIGATE program, with a particular focus on its psychosocial components. NAVIGATE is a team-based, multi-component treatment program designed to be implemented in routine mental health treatment settings and aimed at guiding people with a first episode of psychosis (and their families) towards psychological and functional health. The core services provided in the NAVIGATE program include the Family Education Program, Individual Resiliency Training, Supported Employment and Education, and Individualized Medication Treatment. NAVIGATE embraces a shared decision-making approach with a focus on strengths and resiliency, and collaboration with clients and family members in treatment planning and reviews. The NAVIGATE program has the potential to fill an important gap in the U.S. healthcare system by providing a comprehensive intervention specially designed to meet the unique treatment needs of persons recovering from a first episode of psychosis. The program is currently being evaluated in cluster randomized controlled trial comparing NAVIGATE to usual community care