The measurement of applied forces during anterior single rod correction of adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity in paediatrics, prevalent in approximately 2-4% of the general population. While it is a complex three-dimensional deformity, it is clinically characterised by an abnormal lateral curvature of the spine. The treatment for severe deformity is surgical correction with the use of structural implants. Anterior single rod correction employs a solid rod connected to the anterior spine via vertebral body screws. Correction is achieved by applying compression between adjacent vertebral body screws, before locking each screw onto the rod. Biomechanical complication rates have been reported as high as 20.8%, and include rod breakage, screw pull-out and loss of correction. Currently, the corrective forces applied to the spine are unknown. These forces are important variables to consider in understanding the biomechanics of scoliosis correction. The purpose of this study was to measure these forces intra-operatively during anterior single rod AIS correction

An analysis of the role of principals supervising programs for students with disabilities in effective schools as defined by Virginia\u27s Outcome Accountability Project

This case study was concerned with examining the role of principals supervising programs for students with disabilities in effective schools as defined by the Virginia Department of Education\u27s Outcome Accountability Project (OAP). In order to do this, three questions were framed, and after reviewing the literature, a research design was developed allowing data relative to the study questions to be collected. Multiple data sources were used in this investigation.;From the data collected in this study, three major conclusions may be drawn. The first finding is that the role of the principal in a school with an effective special education program, defined by the Outcome Accountability Project (OAP) indicators, differs from the role of a principal in a school with a lower OAP rating. Differences were found in practices that addressed behaviors in the following performance areas: communication, staff development, systematic evaluation of instruction, collaboration, and instructional programming.;The second conclusion is that interaction between the special education administrator and principal of an effective OAP defined school does differ from that of a special education administrator and principal in a school with less effective OAP ratings. Interviews with principals and special education administrators and results from responsibility charts delineated best practices for principals of effective OAP schools.;The third major finding identified the lack of time, lack of knowledge of special programs/curriculum and lack of central office assistance as the three main obstacles that impede the instructional effectiveness of principals. Supporting documentation from the interviews indicated the effects of these obstacles

An Electronic World Grass Flora

The development of an electronic world grass flora database is described in which data for 1090 morphological characters gathered for 11,000 species in 700 genera organized according to accepted names. This descriptive information is linked to a synonym database of 60,000 names. Authors, literature references, and the status of each name are also recorded in the database along with geographical distribution and type information. The list of accepted species is linked to a global herbarium of 350,000 specimens at Kew arranged in a phylogenetic sequence at the generic and species levels and according to broad phytogeographic divisions. From the database, descriptions can be generated for species, genera, and tribes. Character similarities or differences can be identified and character sets generated as an aid to key writing. Taxonomic and geographic subsets can be generated and specimens can be identified using an interactive key

Sixty original plays for primary grades

Thesis (Ed.M.)--Boston Universit

‘Free text is essentially the enemy of what we’re trying to achieve’: the framing of a national vision for delivering digital police contact

Police organisations in England and Wales, as in many other contexts, are increasingly shifting crime reporting and other public-facing contact online. In this paper we explore the beliefs, motivations, and objectives of those tasked with ‘delivering’ the ‘vision’ of digital police contact at the strategic national level. We use Goffman’s concept of frames – the set of expectations an actor brings to a situation or process – to understand how participants enacted this 'channel shift’ (Wells et al., 2023), the ends they were seeking to meet, and how different interests came to be designed-in to the contact architecture. We suggest that the primary frame centred around notions of efficiency and demand management. Running alongside this is a secondary frame of customer service, where it is assumed that the public also wish for the efficient delivery of this technologically mediated service. This, we suggest, is likely to be only a partial reflection of what people want when contacting police; but the framing of 'contact’ as a separate deliverable by those delivering this agenda serves to occlude or evade this point. Technology, we argue, imprints itself on the context by appearing to offer a convenient solution to problems of public wants and police needs

The role of bacterial extracellular vesicles in chronic wound infections: current knowledge and future challenges

Chronic wounds are a significant global problem with an increasing economic and patient welfare impact. How wounds move from an acute to chronic, non-healing, state is not well understood although it is likely that it is driven by a poorly regulated local inflammatory state. Opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa are well known to stimulate a pro-inflammatory response and so their presence may further drive chronicity. Studies have demonstrated that host cell extracellular vesicles (hEVs), in particular exosomes, have multiple roles in both increasing and decreasing chronicity within wounds; however, the role of bacterial extracellular vesicles (bEVs) is still poorly understood. The aim of this review is to evaluate bEV biogenesis and function within chronic wound relevant bacterial species to determine what, if any, role bEVs may have in driving wound chronicity. We determine that bEVs drive chronicity by both increasing persistence of key pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa and stimulating a pro-inflammatory response by the host. Data also suggest that both bEVs and hEVs show therapeutic promise, providing vaccine candidates, decoy targets for bacterial toxins or modulating the bacterial species within chronic wound biofilms. Caution should, however, be used when interpreting findings to date as the bEV field is still in its infancy and as such lacks consistency in bEV isolation and characterization. It is of primary importance that this is addressed, allowing meaningful conclusions to be drawn and increasing reproducibility within the field

‘Channel Shift’:technologically-mediated policing and procedural justice

In recent years, police forces in the United Kingdom have introduced various technologies that alter the methods by which they interact with the public. In a parallel development, many forces have also begun to embrace the concept of procedural justice as a method through which to secure legitimacy and (in turn) public compliance and cooperation. What has not received sufficient attention, within policing or academia, is the extent to which these two trends are compatible, with the procedural justice literature still predicated on an assumption that police–public ‘contacts’ or ‘encounters’ are in-person. The effect of technologically mediating police–public contacts on ‘policing by consent’, is therefore unknown. In this article, we focus specifically on the possible implications of the Single Online Home (SOH) (a portal through which the public can report crime, get updates on cases, give feedback and pay fines, among other things, which is currently being rolled out across forces), considering ‘interactions’ between police and public where there is no physical co-presence. Noting the unique context that is policing, we draw on the limited existing research on procedural justice encounters in technologically mediated contexts to explore whether procedural justice theory is ‘future-proof’ for a policing context increasingly reliant on such encounters. We conclude that, through empirical research, we must update our conceptual understanding of what ‘contact’ can mean, and accept that current developments may in fact be transforming relationships rather than simply facilitating existing ones

Dynamic clonal progression in xenografts of acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21

Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of childhood precursor B-cell acute lymphoblastic leukemia. There are no cell lines with iAMP21 and these abnormalities are too complex to faithfully engineer in animal models. As a resource for future functional and pre-clinical studies, we have created xenografts from intrachromosomal amplification of chromosome 21 leukemia patient blasts and characterised them by in-vivo and ex-vivo luminescent imaging, FLOW immunophenotyping, and histological and ultrastructural analysis of bone marrow and the central nervous system. Investigation of up to three generations of xenografts revealed phenotypic evolution, branching genomic architecture and, compared with other B-cell acute lymphoblastic leukemia genetic subtypes, greater clonal diversity of leukemia initiating cells. In support of intrachromosomal amplification of chromosome 21 as a primary genetic abnormality, it was always retained through generations of xenografts, although we also observed the first example of structural evolution of this rearrangement. Clonal segregation in xenografts revealed convergent evolution of different secondary genomic abnormalities implicating several known tumour suppressor genes and a region, containing the B-cell adaptor, PIK3AP1, and nuclear receptor co-repressor, LCOR, in the progression of B-ALL. Tracking of mutations in patients and derived xenografts provided evidence for co-operation between abnormalities activating the RAS pathway in B-ALL and for their aggressive clonal expansion in the xeno-environment. Bi-allelic loss of the CDKN2A/B locus was recurrently maintained or emergent in xenografts and also strongly selected as RNA sequencing demonstrated a complete absence of reads for genes associated with the deletions

Inhibition of Ral GTPases Using a Stapled Peptide Approach

Aberrant Ras signalling drives numerous cancers and drugs to inhibit this are urgently required. This compelling clinical need, combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly and the focus has moved to the main downstream Ras-signalling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets, which were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development and there have therefore been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This therefore provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

Inhibition of Ral GTPases Using a Stapled Peptide Approach.

Aberrant Ras signaling drives numerous cancers, and drugs to inhibit this are urgently required. This compelling clinical need combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly, and the focus has moved to the main downstream Ras-signaling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets that were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development, and there have, therefore, been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical-stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This, therefore, provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024