Stillbirth and loss: family practices and display

This paper explores how parents respond to their memories of their stillborn child over the years following their loss. When people die after living for several years or more, their family and friends have the residual traces of a life lived as a basis for an identity that may be remembered over a sustained period of time. For the parent of a stillborn child there is no such basis and the claim for a continuing social identity for their son or daughter is precarious. Drawing on interviews with the parents of 22 stillborn children, this paper explores the identity work performed by parents concerned to create a lasting and meaningful identity for their child and to include him or her in their families after death. The paper draws on Finch's (2007) concept of family display and Walter's (1999) thesis that links continue to exist between the living and the dead over a continued period. The paper argues that evidence from the experience of stillbirth suggests that there is scope for development for both theoretical frameworks

Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep

The use of vaccines including aluminum (Al)–based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injection-site granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher (P <.001) in the lymph nodes of the vaccine group (82.65 µg/g) compared with both adjuvant-only (2.53 µg/g) and control groups (0.96 µg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs

Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules

Neisseria meningitis remains a leading cause of sepsis and meningitis, and vaccines are required to prevent infections by this important human pathogen. Factor H binding protein (fHbp) is a key antigen that elicits protective immunity against the meningococcus and recruits the host complement regulator, fH. As the high affinity interaction between fHbp and fH could impair immune responses, we sought to identify non-functional fHbps that could act as effective immunogens. This was achieved by alanine substitution of fHbps from all three variant groups (V1, V2 and V3 fHbp) of the protein; while some residues affected fH binding in each variant group, the distribution of key amino underlying the interaction with fH differed between the V1, V2 and V3 proteins. The atomic structure of V3 fHbp in complex with fH and of the C-terminal barrel of V2 fHbp provide explanations to the differences in the precise nature of their interactions with fH, and the instability of the V2 protein. To develop transgenic models to assess the efficacy of non-functional fHbps, we determined the structural basis of the low level of interaction between fHbp and murine fH; in addition to changes in amino acids in the fHbp binding site, murine fH has a distinct conformation compared with the human protein that would sterically inhibit binding to fHbp. Non-functional V1 fHbps were further characterised by binding and structural studies, and shown in non-transgenic and transgenic mice (expressing chimeric fH that binds fHbp and precisely regulates complement system) to retain their immunogenicity. Our findings provide a catalogue of non-functional fHbps from all variant groups that can be included in new generation meningococcal vaccines, and establish proof-in-principle for clinical studies to compare their efficacy with wild-type fHbps

Cell arrest and cell death in mammalian preimplantation development

The causes, modes, biological role and prospective significance of cell death in preimplantation development in humans and other mammals are still poorly understood. Early bovine embryos represent a very attractive experimental model for the investigation of this fundamental and important issue. To obtain reference data on the temporal and spatial occurrence of cell death in early bovine embryogenesis, three-dimensionally preserved embryos of different ages and stages of development up to hatched blastocysts were examined in toto by confocal laser scanning microscopy. In parallel, transcript abundance profiles for selected apoptosis-related genes were analyzed by real-time reverse transcriptase-polymerase chain reaction. Our study documents that in vitro as well as in vivo, the first four cleavage cycles are prone to a high failure rate including different types of permanent cell cycle arrest and subsequent non-apoptotic blastomere death. In vitro produced and in vivo derived blastocysts showed a significant incidence of cell death in the inner cell mass (ICM), but only in part with morphological features of apoptosis. Importantly, transcripts for CASP3, CASP9, CASP8 and FAS/FASLG were not detectable or found at very low abundances. In vitro and in vivo, errors and failures of the first and the next three cleavage divisions frequently cause immediate embryo death or lead to aberrant subsequent development, and are the main source of developmental heterogeneity. A substantial occurrence of cell death in the ICM even in fast developing blastocysts strongly suggests a regular developmentally controlled elimination of cells, while the nature and mechanisms of ICM cell death are unclear. Morphological findings as well as transcript levels measured for important apoptosis-related genes are in conflict with the view that classical caspase-mediated apoptosis is the major cause of cell death in early bovine development

The invisible plan: how English teachers develop their expertise and the special place of adapting the skills of lesson planning

This paper analyses how English teachers learn to become expert designers of learning and why sharing that expertise is increasingly vital. Its conceptual framework is the widely recognised, empirically tested, five-stage developmental Dreyfus model of skill acquisition, exemplifying the development of teacher expertise, constituted by the “milestone” [m] and “transitory” [t] phases connecting with the five stages of: Novice [m], Advanced Beginner [t], Competent [m], Proficient [t] and Expert [m]. Teacher planning is analysed as one key tacit or non-tangible component of developing expertise. Focusing specifically on English teachers as key participants in this pioneer teacher cognition study, the defining characteristics of milestone stages of expertise development are explored with specific attention to the remarkably under-researched area of planning. We introduce three new categories, defining modes of planning: (i) visible practical planning, (ii) external reflective planning and (iii) internal reflective planning, demonstrating their role in teacher development through the Dreyfus five stages. English is a subject which suffers from frequent disruptive changes to curriculum and assessment: new learning designs are constantly demanded, making planning an ongoing challenge. The implications for practice include the importance of an explicit understanding of how teachers’ planning moves through the three phases from the very “visible” novice phase to the internal relatively “automatic” competent teacher and finally the seemingly “invisible” expert phase. Further research is needed to explore how English teachers can share planning expertise between the three phases to improve teachers’ skills and student learning

Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures.

Formation of superstructures in protein aggregation processes has been indicated as a general pathway for several proteins, possibly playing a role in human pathologies. There is a severe lack of knowledge on the origin of such species in terms of both mechanisms of formation and structural features. We use equine lysozyme as a model protein, and by combining spectroscopic techniques and microscopy with X-ray fiber diffraction and ab initio modeling of Small Angle X-ray Scattering data, we isolate the partially unfolded state from which one of these superstructures (i.e., particulate) originates. We reveal the low-resolution structure of the unfolded state and its mechanism of formation, highlighting the physicochemical features and the possible pathway of formation of the particulate structure. Our findings provide a novel detailed knowledge of such a general and alternative aggregation pathway for proteins, this being crucial for a basic and broader understanding of the aggregation phenomena.This is the author's accepted manuscript and will be under embargo until the 3rd of September 2015. The final version is published by ACS in The Journal of Physical Chemistry Letters here: http://pubs.acs.org/doi/abs/10.1021/jz501614e

Swimming against the tide: A case study of an integrated social studies department

A recent trend in developed countries&rsquo; school curricula has been the transition from disciplinary to generic forms of knowledge, resulting in an emphasis on interdisciplinary organisation and more active forms of learning. Subject specialists are increasingly expected to demonstrate how their subject interconnects and equips pupils with key life skills. Such a change requires a major cultural shift and has been controversial, particularly in Scotland where Curriculum for Excellence, the latest curriculum reform, has seen this debate re-emerge. A detailed empirical case study of one secondary school Social Studies department that has already negotiated these shifts is presented. The case study provides insights into how school and department structures and cultures conducive to a more integrated approach have been developed. Leadership, increased opportunities for teachers to exercise greater autonomy in their work, sources of impetus and support for innovation, and the co-construction of meaning through dialogue are important themes in this process. This case study connects with current policy and provides an insight into strategies that other schools might employ when seeking to embed integrative practices. The department is identified as a significant locus for innovation and one which appears to challenge the norm