Pandora's box? An exploration of s 81 of the Land Transfer Act 1952 and its effect on the indefeasibility of title

Section 81 of the Land Transfer Act 1952 has a tumultuous past. It has faced various criticisms surrounding its potential for undermining indefeasibility of title, a key concept under our Torrens system of transfer. This paper addresses some of these criticisms, positing first that s 81 does in fact grant the District Land Registrar a wide discretion to correct or cancel titles which have been gained fraudulently or wrongfully, and secondly that this discretion should be exercised if an appropriate case surfaces. Such an exercise is supported by the approach taken in other Torrens jurisdictions and can be regulated through the adoption of a number of simple guidelines, to be considered during any exercise of discretion under s 81. This will reduce the risk of any uncertainty arising from a wide interpretation of s 81 and ensure that the overall justice of the case is the central consideration of any exercise of discretion

The μ-calpain-ezrin axis: a potential target for therapy in inflammatory disease

Neutrophils are the most abundant class of white blood cell in humans. They are among the first inflammatory cells to respond during infection or tissue damage, and their excessive recruitment to synovial joints in rheumatoid arthritis has been implicated in the progression of the disease. The process of neutrophil extravasation from blood vessels involves a rapid expansion of the available cell surface area. This ~200% increase is facilitated by the release of cell membrane microridges. As ezrin forms crucial cross-links between the plasma membrane and cortical F-actin, in neutrophils and other myeloid cells, it is thought to maintain the structure of these microridges, which act as a reservoir of plasma membrane for spreading. It has been suggested that elevating the cytosolic Ca2+ concentration, thereby activating the Ca2+-activated cysteine protease μ-calpain, would break the ezrin link and permit cell spreading. This thesis has investigated the relationship between, μ-calpain, ezrin and Ca2+ concentration. Through immunocytochemistry, confocal microscopy of live phagocytosis and chemotaxis experiments, observations in neutrophils have been complemented by investigations in a RAW 264.7 model cell line, amenable to transfection. By generating the novel genetically encoded Ca2+ indicator EPIC (Ezrin Peripheral Indicator of Ca2+), it has been possible to experimentally measure the cytosolic Ca2+ concentration in ezrin-rich microdomains beneath plasma membrane microridges, in transfected myeloid cells, during Ca2+ influx. It has thus been found that sub-membranous cytosolic Ca2+ in these microridges reaches highmicromolar concentrations, well within the range required to activate μ-calpain and result in ezrin cleavage. The work in this thesis contributes to the understanding of the molecular mechanisms which govern neutrophil morphological changes during events such as phagocytosis and extravasation. It is hoped that these findings will help contribute towards the body of research aimed at influencing the design of novel therapeutics to treat autoimmune conditions

Concurrent associations between mothers' references to internal states and children's social understanding in middle childhood

Although it is well established that features of maternal speech are associated with children’s social understanding in the preschool years, few studies explore this relationship in middle childhood. Within the context of a prospective longitudinal study of a representative community sample of families (subsample n = 207, mean age = 82.88 months), we investigated concurrent associations between mothers’ internal state language and aspects of 7‐year‐olds’ social understanding, including children’s understanding of belief and spontaneous references to internal states during free play. When sociodemographic, maternal, and child characteristics were controlled, mothers’ references to their own cognitions were associated with dimensions of children’s social understanding. Our findings suggest that exposure to others’ perspectives contributes to children’s advanced understanding of minds, which has implications for interventions that foster social understanding

Understanding the educational experiences and opinions, attainment, achievement and aspirations of looked after children in Wales

This report presents the findings of research that explored the educational experiences attainment and aspirations of looked after children and young people (LACYP) in Wales. The findings of the report are drawn from interviews with LACYP and an analysis of available statistics and literature on the looked after children population

Preferences of older patients regarding hip fracture rehabilitation service configuration:A feasibility discrete choice experiment

Objective: As part of a wider feasibility study, the feasibility of gaining older patients’ views for hip fracture rehabilitation services was tested using a discrete choice experiment in a UK context. Design: Discrete choice experiment is a method used for eliciting individuals’ preferences about goods and services. Subjects/patients: The discrete choice experiment was administered to 41 participants who had experienced hip fracture (mean age 79.3 years; standard deviation (SD) 7.5 years), recruited from a larger feasibility study exploring a new multidisciplinary rehabilitation for hip fracture. Methods: Attributes and levels for this discrete choice experiment were identified from a systematic review and focus groups. The questionnaire was administered at the 3-month follow-up. Results: Participants indicated a significant preference for a fully-qualified physiotherapist or occupational therapist to deliver the rehabilitation sessions (β = 0·605, 95% confidence interval (95% CI) 0.462–0.879), and for their rehabilitation session to last less than 90 min (β = –0.192, 95% CI –0.381 to –0.051). Conclusion: The design of the discrete choice experiment using attributes associated with service configuration could have the potential to inform service implementation, and assist rehabilitation service design that incorporates the preferences of patients

Lessons learnt from prenatal exome sequencing

BACKGROUND: Prenatal exome sequencing (ES) for monogenic disorders in fetuses with structural anomalies increases diagnostic yield. In England there is a national trio ES service delivered from two laboratories. To minimise incidental findings and reduce the number of variants investigated, analysis uses a panel of 1205 genes where pathogenic variants may cause abnormalities presenting prenatally. Here we review our laboratory's early experience developing and delivering ES to identify challenges in interpretation and reporting and inform service development. METHODS: A retrospective laboratory records review from 01.04.2020 to 31.05.2021. RESULTS: Twenty-four of 116 completed cases were identified as challenging including 13 resulting in difficulties in analysis and reporting, nine where trio inheritance filtering would have missed the diagnosis, and two with no prenatal diagnosis; one due to inadequate pipeline sensitivity, the other because the gene was not on the panel. Two cases with copy number variants identified were not detectable by microarray. CONCLUSIONS: Variant interpretation requires close communication between referring clinicians, with occasional additional examination of the fetus or parents and communication of evolving phenotypes. Inheritance filtering misses ∼5% of diagnoses. Panel analysis reduces but does not exclude incidental findings. Regular review of published literature is required to identify new reports that may aid classification

Reconciling competing priorities in commissioning: the future of bone densitometry service for North Wales

BACKGROUND: Osteoporosis creates brittle bones susceptible to fracture, with resulting high levels of morbidity and mortality. Poor access to bone densitometry services for the residents of North Wales led to the Welsh Assembly Government offering capital to purchase a dual-energy X-ray absorptiometry (DXA) scanner, used to diagnose osteoporosis, for the region. The commissioning question for the six Local Health Boards across North Wales was where to site the new scanner. This decision needed to reflect current inequalities in access to services and concerns over inappropriate prescribing relative to Welsh norms. METHODS: Epidemiological, corporate and comparative healthcare needs assessments were performed. In addition, two cross-sectional surveys were conducted to determine the views of general practices and users of bone densitometry services resident in North Wales. An option appraisal and sensitivity analysis of 13 costed options for DXA scanning was conducted. RESULTS: We estimated that only 31% of the people in North Wales who met national guidelines were receiving DXA scans. There was definite inequity of access to the current service provided by area of residence. There was also evidence of inequity of access by age and sex. The most suitable option identified in the option appraisal was a bone densitometry service based in the central location of Llandudno. CONCLUSION: The assessment identified significant unmet need for DXA scanning. A recommendation was made to improve access through the introduction of a new bone densitometry service based at Llandudno. This would double scanning provision provided and reduce travel costs and time for many North Wales residents. This recommendation was adopted by a joint commissioning group established by the six Local Health Boards in North Wales at the end of 2004 – evidence based commissioning in practice