Background -Lokivetmab is an injectable anti-canine-IL-31 monoclonal antibody to treat clinical manifestations of atopic dermatitis (AD) in dogs.Hypothesis/Objectives -To characterize the efficacy and safety of lokivetmab, and to demonstrate its noninferiority to ciclosporin under field conditions. Animals -Dogs with chronic AD (n = 274) were enrolled from 40 practices in Belgium, The Netherlands, France and Germany.Methods -Animals were randomized (1:1) to oral ciclosporin (5 mg/kg/once daily) or monthly injectable lokivetmab (1-3.3 mg/kg) for three months. Eighty one animals that successfully completed the comparative phase were enrolled in a continuation phase receiving lokivetmab for an additional six months. Owners assessed pruritus on a Visual Analog Scale, skin lesions were assessed by veterinary investigators with a Canine AD Extent and Severity Index (CADESI-03) scale. Results -Lokivetmab was noninferior to ciclosporin for pruritus reduction on Day 28 (51.90% versus 43.72%).For Day 28 CADESI-03 percentage reduction, noninferiority of lokivetmab (54.17) versus ciclosporin (56.86%) was not achieved. At none of the time points were mean CADESI-03 scores significantly different between groups. Continued efficacy towards pruritus and lesions was demonstrated in the continuation phase where 76.3% of animals (n = 45) were assessed as 'normal' for pruritus at study end. No abnormal health events associated with lokivetmab were observed during the initial three month phase (142 dogs) or during the subsequent six month phase (81 dogs).Conclusions and clinical importance -Lokivetmab at a minimum monthly dose of 1 mg/kg provided quick onset (within one day) of a lasting effect in reducing pruritus and skin lesions with a good safety profile.

The goal of this study was to assess cortical reorganization in the visual system of adult mice in detail. A combination of deprivation of one eye and stimulation of the remaining eye previously led to the identification of input-specific subdivisions in mouse visual cortex. Using this information as a reference map, we established to what extent each of these functional subdivisions take part in cortical reactivation and reorganization upon unilateral enucleation. A recovery experiment revealed a differential laminar and temporal reactivation profile. Initiation of infragranular recovery of molecular activity near the border with nonvisual cortex and simultaneous hyperactivation of this adjacent cortex implied a partial nonvisual contribution to this plasticity. The strong effect of somatosensory deprivation as well as stimulation on infragranular visual cortex activation in long-term enucleated animals support this view. Furthermore, targeted tracer injections in visual cortex of control and enucleated animals revealed preexisting connections between the visual and somatosensory cortices of adult mice as possible mediators. In conclusion, this study supports an important cross-modal component in reorganization of adult mouse visual cortex upon monocular enucleation.

This study was designed to assess the chemoarchitectural organization and extent of the mouse visual cortex. We used nonphosphorylated neurofilament protein, a neuronal marker that exhibits region-specific cellular and laminar patterns, to delineate cortical subdivisions. A comprehensive analysis demonstrated that pyramidal and nonpyramidal neurons expressing neurofilament proteins display striking laminar and regional patterns in the mouse visual cortex permitting the delineation of the primary visual cortex (V1) and its monocular and binocular zones, 2 lateral, and 5 medial extrastriate cortical areas with clear anatomical boundaries and providing evidence that the mouse medial extrastriate cortex is not homogeneous. We also investigated the expression profiles of 2 neuronal activity markers, the immediate early genes c-fos and zif-268, following deprivation paradigms to ascertain the visual nature of all subdivisions caudal, medial, and lateral to V1. The present data indicate that neurochemically identifiable subdivisions of the mouse visual cortex exist laterally and medially to V1 and reveal specific anatomical and functional characteristics at the cellular and regional levels.

We investigated the anatomical characteristics of the mouse visual system through in situ hybridization for the neuronal activity marker zif268. Our main goal was to delineate the full extent of the cortical region processing visual information and additionally to identify the monocularly and binocularly driven subregions therein. We therefore analyzed the neocortex of monocularly and binocularly enucleated mice versus visually stimulated control mice. These visual manipulations revealed eye-specific parcellations at the neocortical level. In binocularly enucleated mice we detected an unambiguous lateral border between visually driven and nonvisual cortex based on the clear deprivation-induced reduction in zif268 expression in the first. However, medially a transition zone of intermediate intensity was found between primarily visual, that is V1 and multimodal retrosplenial cortex. Also in monocularly enucleated mice, the visual cortex contralateral to the deprived eye clearly displayed distinct regions of lower signal than the ipsilateral cortex. Yet interspersed between these regions of basal activity we could clearly identify a zone of high activity spanning the V1-V2L border. A second zone of higher activity was noticeable near the medial border of visual cortex. Comparison with binocularly enucleated mice indicates the presence of both binocular input as well as nonvisual input in this medial cortical region and thus confirms the transitional nature of the recently described rostromedial areas.

The concept of a good death is central to contemporary discourses on death and dying; it is also frequently used in contexts of end-of-life decision-making. We argue that in and through the medical-revivalist discourse, which challenges the idea that curative treatment is necessary beneficial and constructs death as something familiar, a good death is discursively organised around two nodal clusters: control, autonomy and dignity, and awareness and heroism. Moreover, we also argue that -within this framework of the medical-revivalist discourse -political contestation exists over the articulation of these nodal points. Especially two social movements, the right to die movement and the palliative care movement, have been at the forefront of the political struggle over the good death. In this article, we use a discourse-theoretical approach to develop an analytical model of the construction of the good death and the present-day political struggles over these constructions. This model then allows us to identify and analyse the constructions of the good death in the North Belgian newspaper coverage on three 2008 euthanasia cases. Using discourse-theoretical analysis (DTA) (Carpentier & De Cleen, 2007), our analysis shows that the articulations of the right to die variation are privileged in the newspaper coverage. There is a celebration of the extraordinariness and heroism of the dying subject who autonomously chooses on how and when to die and who preferably dies in a state of full awareness so that he can die with dignity. This privileging is often accompanied by the symbolic annihilation of many other ways of dying. Consequentially, the richness of ways of dying that characterize contemporary social realities becomes curtailed in the analysed newspaper representations.

No abstract

No abstract

No abstract