BMP signalling: agony and antagony in the family

Bone morphogenetic proteins (BMPs) are secreted extracellular matrix (ECM)-associated proteins that regulate a wide range of developmental processes, including limb and kidney formation. A critical element of BMP regulation is the presence of secreted antagonists that bind and inhibit BMP binding to their cognate Ser/Thr kinase receptors at the plasma membrane. Antagonists such as Noggin, Chordin, Gremlin (Grem1), and twisted gastrulation-1 (Twsg1) have been shown to inhibit BMP action in a range of different cell types and developmental stage-specific contexts. Here we review new developments in the field of BMP and BMP antagonist biology during mammalian development and suggest strategies for targeting these proteins in human disease.

Digital slide viewing for primary reporting in gastrointestinal pathology: a validation study

Despite the increasing availability of digital slide viewing, and numerous advantages associated with its application, a lack of quality validation studies is amongst the reasons for poor uptake in routine practice. This study evaluated primary digital pathology reporting in the setting of routine subspecialist gastrointestinal pathology, commonplace in most tissue pathology laboratories and representing one of the highest volume specialties in most laboratories. Individual digital and glass slide diagnoses were compared amongst three pathologists reporting in a gastrointestinal subspecialty team, in a prospective series of 100 consecutive diagnostic cases from routine practice in a large teaching hospital laboratory. The study included a washout period of at least 6 months. Discordant diagnoses were classified, and the study evaluated against recent College of American Pathologists (CAP) recommendations for evaluating digital pathology systems for diagnostic use. The study design met all 12 of the CAP recommendations. The 100 study cases generated 300 pairs of diagnoses, comprising 100 glass slide diagnoses and 100 digital diagnoses from each of the three study pathologists. 286 of 300 pairs of diagnoses were concordant, representing intraobserver concordance of 95.3 %, broadly comparable to rates previously published in this field. In ten of the 14 discordant pairs, the glass slide diagnosis was favoured; in four cases, the digital diagnosis was favoured, but importantly, the 14 discordant intraobserver diagnoses were considered to be of minor clinical significance. Interobserver, or viewing modality independent, concordance was found in 94 of the total of 100 study cases, providing a comparable baseline discordance rate expected in any second viewing of pathology material. These overall results support the safe use of digital pathology in primary diagnostic reporting in this setting

Looking again at troubled families: parents' perspectives on multiple adversities

The 'Troubled Families' policy and intervention agenda is based on a deficit approach that tends to ignore the role of structural disadvantage in the lives of the families it targets. In an effort to support this rhetoric, both quantitative and qualitative data have been used, and misused, to create a representation of these families, which emphasizes risk and individual blame and minimizes societal factors. This current paper presents findings from an in-depth qualitative study using a biographical narrative approach to explore parents' experiences of multiple adversities at different times over the life-course. Key themes relating to the pattern and nature of adversities experienced by participants provide a more nuanced understanding of the lives of families experiencing multiple and complex problems, highlighting how multiple interpretations are often possible within the context of professional intervention. The findings support the increasing call to move away from procedurally driven, risk averse child protection practice towards more relationally based practice, which addresses not only the needs of all family members but recognizes parents as individuals in their own right.

The prevalence of pica in tuberous sclerosis complex

Background: Pica and Tuberous sclerosis complex (TSC) are rare disorders. We carried out a population survey of pica in our TSC patient population.

Findings: Pica was identified in four percent of cases of TSC. It was associated with adult onset or persistence into adulthood, epilepsy, severe learning difficulties and anaemia.

Conclusions: Pica in TSC is a rare disorder and a coherent history may be difficult to obtain from patients. The prevalence of pica is likely to be underdiagnosed. Pica is a recognised feature in adults with TSC and prompt recognition of this disorder should allow better management of patients with TSC.