Comparison of extramedullary versus intramedullary referencing for tibial component alignment in total ankle arthroplasty.

BACKGROUND: The majority of total ankle arthroplasty (TAA) systems use extramedullary alignment guides for tibial component placement. However, at least 1 system offers intramedullary referencing. In total knee arthroplasty, studies suggest that tibial component placement is more accurate with intramedullary referencing. The purpose of this study was to compare the accuracy of extramedullary referencing with intramedullary referencing for tibial component placement in total ankle arthroplasty. METHODS: The coronal and sagittal tibial component alignment was evaluated on the postoperative weight-bearing anteroposterior (AP) and lateral radiographs of 236 consecutive fixed-bearing TAAs. Radiographs were measured blindly by 2 investigators. The postoperative alignment of the prosthesis was compared with the surgeon's intended alignment in both planes. The accuracy of tibial component alignment was compared between the extramedullary and intramedullary referencing techniques using unpaired t tests. Interrater and intrarater reliabilities were assessed with intraclass correlation coefficients (ICCs). RESULTS: Eighty-three tibial components placed with an extramedullary referencing technique were compared with 153 implants placed with an intramedullary referencing technique. The accuracy of the extramedullary referencing was within a mean of 1.5 ± 1.4 degrees and 4.1 ± 2.9 degrees in the coronal and sagittal planes, respectively. The accuracy of intramedullary referencing was within a mean of 1.4 ± 1.1 degrees and 2.5 ± 1.8 degrees in the coronal and sagittal planes, respectively. There was a significant difference (P < .001) between the 2 techniques with respect to the sagittal plane alignment. Interrater ICCs for coronal and sagittal alignment were high (0.81 and 0.94, respectively). Intrarater ICCs for coronal and sagittal alignment were high for both investigators. CONCLUSIONS: Initial sagittal plane tibial component alignment was notably more accurate when intramedullary referencing was used. Further studies are needed to determine the effect of this difference on clinical outcomes and long-term survivability of the implants. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Evaluating the effectiveness of Z: The claims made about CICS and where we go from here

There have been few genuine success stories about industrial use of formal methods. Perhaps the best known and most celebrated is the use of Z by IBM (in collaboration with Oxford University's Programming Research Group) during the development of CICS/ESA (version 3.1). This work was rewarded with the prestigious Queen's Award for Technological Achievement in 1992 and is especially notable for two reasons: 1) because it is a commercial, rather than safety- or security-critical, system and 2) because the claims made about the effectiveness of Z are quantitative as well as qualitative. The most widely publicized claims are: less than half the normal number of customer-reported errors and a 9% savings in the total development costs of the release. This paper provides an independent assessment of the effectiveness of using Z on CICS based on the set of public domain documents. Using this evidence, we believe that the case study was important and valuable, but that the quantitative claims have not been substantiated. The intellectual arguments and rationale for formal methods are attractive, but their widespread commercial use is ultimately dependent upon more convincing quantitative demonstrations of effectiveness. Despite the pioneering efforts of IBM and PRG, there is still a need for rigorous, measurement-based case studies to assess when and how the methods are most effective. We describe how future similar case studies could be improved so that the results are more rigorous and conclusive.

Predicting the behaviour of micro-electronic displays using computational mechanics

Micro-electronic displays are indispensible devices used in high performance applications such as aerospace, medical, marine and industrial sectors.These devices provide an interface to real time mission critical devices and therefore require good optical visual performance and high reliability, all this within varied and challenging environments.

English Channel towed sledge seabed images. Phase 2: Analysis of selected tow images

During the 1970s and 1980s, the late Dr Norman Holme undertook extensive towed sledge surveys in the English Channel and some in the Irish Sea. Only a minority of the resulting images were analysed and reported before his death in 1989 but logbooks, video and film material has been archived in the National Marine Biological Library (NMBL) in Plymouth. A study was therefore commissioned by the Joint Nature Conservation Committee and as a part of the Mapping European Seabed Habitats (MESH) project to identify the value of the material archived and the procedure and cost to undertake further work (Phase 1 of the study reported here: Oakley & Hiscock, 2005). Some image analysis was undertaken as a part of Phase 1. Phase 2 (this report) was to further analyse selected images. Having determined in Phase 1 that only the 35 mm photographic transparencies provided sufficient clarity to identify species and biotopes, the tows selected for analysis were ones where 35mm images had been taken. The tows selected for analysis of images were mainly in the vicinity of Plymouth and especially along the area between Rame Head and the region of the Eddystone. The 35 mm films were viewed under a binocular microscope and the taxa that could be recognised recorded in note form. Twenty-five images were selected for inclusion in the report. Almost all of the images were of level sediment seabed. Where rocks were included, it was usually unplanned and the sled was hauled before being caught or damaged. The main biotopes or biotope complexes identified were: SS.SMU.CSaMu. Circalittoral sandy mud. Extensively present between the shore and the Eddystone Reef complex and at depths of about 48 to 52 m. At one site offshore of Plymouth Sound, the turret shell Turritella communis was abundant. In some areas, this biotope had dense anemones, Mesacmaea mitchelli and (more rarely) Cerianthus lloydii. Queen scallops, Aequipecten opercularis and king scallops, Pecten maximus, were sometimes present in small numbers. Hard substratum species such as hydroids, dead mens fingers Alcyonium digitatum and the cup coral Caryophyllia smithii occurred in a few places, probably attached to shells or stones beneath the surface. South of the spoil ground off Hilsea Point at 57m depth, the sediment was muddier but is still assigned to this biotope complex. It is notable that three small sea pens, most likely Virgularia mirabilis, were seen here. SS.SMx.CMx. Circalittoral mixed sediment. Further offshore but at about the same depth as SS.SMU.CSaMu occurred, coarse gravel with some silt was present. The sediment was characterised must conspicuously by small queen scallops, Aequipecten opercularis. Peculiarly, there were ‘bundles’ of the branching bryozoan Cellaria sp. – a species normally found attached to rock. It could not be seen whether these bundles of Cellaria had been brought-together by terebellid worms but it is notable that Cellaria is recorded in historical surveys. As with many other sediments, there were occasional brittle stars, Ophiocomina nigra and Ophiura ophiura. Where sediments were muddy, the burrowing anemone Mesacmaea mitchelli was common. Where pebbles or cobbles occurred, there were attached species such as Alcyonium digitatum, Caryophyllia smithii and the fleshy bryozoan Alcyonidium diaphanum. Undescribed biotope. Although most likely a part of SS.SMx.CMx, the biotope visually dominated by a terebellid worm believed to be Thelepus cincinnatua, is worth special attention as it may be an undescribed biotope. The biotope occurred about 22 nautical miles south of the latitude of the Eddystone and in depths in excess of 70 m. SS.SCS.CCS.Blan. Branchiostoma lanceolatum in circalittoral coarse sand with shell gravel at about 48m depth and less. This habitat was the ‘classic’ ‘Eddystone Shell Gravel’ which is sampled for Branchiostoma lanceolatum. However, no Branchiostoma lanceolatum could be seen. The gravel was almost entirely bare of epibiota. There were occasional rock outcrops or cobbles which had epibiota including encrusting calcareous algae, the sea fan Eunicella verrucosa, cup corals, Caryophyllia smithii, hydroids and a sea urchin Echinus esculentus. The variety of species visible on the surface is small and therefore identification to biotope not usually possible. Historical records from sampling surveys that used grabs and dredges at the end of the 19th century and early 20th century suggest similar species present then. Illustrations of some of the infaunal communities from work in the 1920’s is included in this report to provide a context to the epifaunal photographs.

Using WebCT to Support a Community of Practice

Reflecting a view of “teaching as both an intellectual and practical activity” the Queen’s University Bachelor of Education program has multi-week in-school practicum sessions separated by periods of on-campus course work. The expectation is that teacher candidates will bring together theory and practice as they reflect upon their daily classroom experiences. The reality often is that, while isolated from the university environment and caught up in the pressures of teaching, little deep reflection takes place. For reflection and critical examination of experience to occur, teacher candidates need to share and discuss on a daily basis their practice teaching experience. For the past few years, students in my secondary school mathematics curriculum course, through a WebCT based conference, have been provided, while away from campus, with a place for on-going sharing of teaching stories and dilemmas. In the Fall of 2004 eight-five percent of the class took part in the discussions, posting a total of 667 messages over a 9 week period. In an effort to increase the value of this practicum conference we have analysed the topic threads arising in the conversation, surveyed the participants concerning their impressions of the sharing experience, and conducted in-depth interviews with a sampling of the class. This session will present the results of this study and provide an opportunity to discuss ways in which an online discussion can support the building of community and the exchange of experience while students in professional programs are disbursed in practice/clinical settings.

Single Canadian mothers of Jamaican heritage share experiences about their children's education

This thesis examines the experiences of four single Canadian mothers of Jamaican heritage with respect to their children’s education. Four themes suggested in the literature—beliefs, practices, barriers, and supports—guided the research. The interviews with the mothers largely confirmed previous research in the field. As such, all the mothers believed that it was a shared responsibility between parents and teachers in supporting children’s education. The mothers’ practices included primarily at-home support and to a lesser extent at-school support but did not include strict discipline. The barriers most salient for these mothers were lack of time and resources. To help overcome these barriers, the mothers relied on domestic kin networks. From these findings, the thesis provides implications for both research and practice.

The Influence of Copper Binding on the Stability of the SCO Protein from Bacillus subtilis

Every aerobic organism expresses cytochrome c oxidase to catalyze reduction of molecular oxygen to water, and takes advantage of this energy releasing reaction to produce an electrochemical gradient used in cellular energy production. The protein SCO (Synthesis of cytochrome c oxidase) is a required assembly factor for the oxidase, conserved across many species. SCO is implicated in the assembly of one of two copper centres (ie., CuA) of cytochrome oxidase. The exact mechanism of SCO’s participation in CuA assembly is not known. SCO has been proposed to bind and deliver copper, or alternatively to act in reductive preparation of the CuA site within the oxidase. In this body of work, the strength and stability of Cu(II) binding to Bacillus subtilis SCO is explored via electronic absorption and fluorescence spectroscopies and by calorimetric methods. An equilibrium dissociation constant (Kd) of 3.5x10-12 M was determined as an upper limit for the BsSCO-Cu(II) interaction, via differential scanning calorimetry. In the first reported case for a SCO homolog, dissociation kinetics of Cu(II) from BsSCO were characterized, and found to be dependent on both ionic strength and the presence of free Cu(II) in solution. Further differential scanning calorimetry experiments performed at high ionic strength support a two-step model of BsSCO and Cu(II) binding. The implications of this model for the BsSCO-Cu(II) interaction are presented in relation to the mechanism of interaction between SCO and the CuA site of cytochrome c oxidase.

CONTRIBUTION OF A SPERM PROTEIN, PAWP, TO THE SIGNAL TRANSDUCT PATHWAY DURING VERTEBRATE FERTILIZATION

PAWP, postacrosomal sheath WW domain binding protein, is a novel sperm protein identified as a candidate sperm borne, oocyte-activating factor (SOAF). PAWP induces both early and later egg activation events including meiotic resumption, pronuclear formation and egg cleavage. Based on the fact that calcium increase is universally accepted as the sole requirement for egg activation, we hypothesized that PAWP is an upstream regulator of the calcium signaling pathway during fertilization. Intracellular calcium increase was detected by two-photon laser scanning fluorescence microscopy following microinjection of recombinant PAWP into Xenopus oocytes, bolstering our hypothesis and suggesting the involvement of a novel PAWP-mediated signaling pathway during fertilization. The N-terminal of PAWP shares a high homology to WW domain binding protein while the C-terminal half contains a functional PPXY motif, which allows it to interact with group I WW domain proteins. These structural considerations together with published data indicating that PPXY synthetic peptide derived from PAWP inhibits ICSI-induced fertilization led to the hypothesis that PAWP triggers egg activation by binding to a group I WW domain protein in the oocyte. By far-Western analysis of oocyte cytoplasmic fraction, PAWP was found to bind to a 52 kDa protein. The competitive inhibition studies with PPXY synthetic peptide, WW domain constructs, and their point mutants demonstrated that the interaction between PAWP and its binding partner is specifically via the PPXY-WW domain module. The 52 kDa protein band crossreacted with antibodies against group I WW domain protein YAP in Western blot assay, indicating that this 52 kDa PAWP binding partner is either YAP or a YAP-related protein. In addition, the far-Western competitive inhibition studies with recombinant GST fusion protein YAP and another WW domain-containing protein, TAZ, demonstrated that the binding of PAWP to its binding partner was significantly reduced by TAZ, providing evidence that TAZ could be the 52 kDa protein candidate. Mass spectrometry was employed to identify this PAWP binding partner candidate. However, due to the low abundance of the candidate protein and the complexity of the sample, several strategies are still needed to enrich this protein. This study correlates PAWP induced meiotic resumption and calcium efflux at fertilization and uncovers a 52 kDa candidate WW domain protein in the oocyte cytoplasm that most likely interacts with PAWP to trigger egg activation.

A Quantitative Investigation of Selected Reactions in the Fibrinolytic Cascade

Previous work has shown that thrombin activatable fibrinolysis inhibitor (TAFI) was unable to prolong lysis of purified clots in the presence of Lys-plasminogen (Lys-Pg), indicating a possible mechanism for fibrinolysis to circumvent prolongation mediated by activated TAFI (TAFIa). Therefore, the effects of TAFIa on Lys-Pg activation and Lys-plasmin (Lys-Pn) inhibition by antiplasmin (AP) were quantitatively investigated using a fluorescently labeled recombinant Pg mutant which does not produce active Pn. High molecular weight fibrin degradation products (HMW-FDPs), a soluble fibrin surrogate that models Pn modified fibrin, treated with TAFIa decreased the catalytic efficiency (kcat/Km) of 5IAF-Glu-Pg cleavage by 417-fold and of 5IAF-Lys-Pg cleavage by 55-fold. A previously devised intact clot system was used to measure the apparent second order rate constant (k2) for Pn inhibition by AP over time. While TAFIa was able to abolish the protection associated with Pn modified fibrin in clots formed with Glu-Pg, it was not able to abolish the protection in clots formed with Lys-Pg. However, TAFIa was still able to prolong the lysis of clots formed with Lys-Pg. TAFIa prolongs clot lysis by removing the positive feedback loop for Pn generation. The effect of TAFIa modification of the HMW-FDPs on the rate of tissue type plasminogen activator (tPA) inhibition by plasminogen activator inhibitor type 1 (PAI-1) was investigated using a previously devised end point assay. HMW-FDPs decreased the k2 for tPA inhibition rate by 3-fold. Thus, HMW-FDPs protect tPA from PAI-1. TAFIa treatment of the HMW-FDPs resulted in no change in protection. Vitronectin also did not appreciably affect tPA inhibition by PAI-1. Pg, in conjunction with HMW-FDPs, decreased the k2 for tPA inhibition by 30-fold. Hence, Pg, when bound to HMW-FDPs, protects tPA by an additional 10-fold. TAFIa treatment of the HMW-FDPs completely removed this additional protection provided by Pg. In conclusion, an additional mechanism was identified whereby TAFIa can prolong clot lysis by increasing the rate of tPA inhibition by PAI-1 by eliminating the protective effects of Pn-modified fibrin and Pg. Because TAFIa can suppress Lys-Pg activation but cannot attenuate Lys-Pn inhibition by AP, the Glu- to Lys-Pg/Pn conversion is able to act as a fibrinolytic switch to ultimately lyse the clot.

IN SITU AND IN VITRO IMMUNOLOCALIZATION OF OVIDUCTIN BINDING SITES ON HAMSTER UTERINE EPITHELIAL CELLS AND DETECTION OF A HAMSTER OVIDUCTIN HOMOLOGUE IN THE FEMALE RAT REPRODUCTIVE TRACT

Oviductin is an oviduct-specific and high-molecular-weight glycoprotein that has been suggested to play important roles in the early events of reproduction. The present study was undertaken to localize the oviductin binding sites in the uterine epithelial cells of the golden hamster (Mesocricetus auratus) both in situ and in vitro, and to detect a hamster oviductin homologue in the female rat reproductive tract. Immunohistochemical localization of oviductin in the hamster uterus revealed certain uterine epithelial cells reactive to the monoclonal anti-hamster oviductin antibody. In order to study the interaction between hamster oviductin and the endometrium in vitro, a method for culturing primary hamster uterine epithelial cells has been established and optimized. Study with confocal microscopy of the cell culture system showed a labeling pattern similar to what was observed using immunohistochemistry. Pre-embedding immunolabeling of cultured uterine epithelial cells also showed gold particles associated with the plasma membrane and microvilli. These results demonstrated that hamster oviductin can bind to the plasma membrane of certain hamster uterine epithelial cells, suggesting the presence of a putative oviductin receptor on the uterine epithelial cell surface. In the second part of the present study, using the monoclonal anti-hamster oviductin antibody that cross-reacts with the rat tissue, we have been able to detect an oviduct-specific glycoprotein, with a molecular weight of 180~300kDa, in the female rat reproductive tract. Immunohistochemical labeling of the female rat reproductive tract revealed a strong immunolabeling in the non-ciliated oviductal epithelial cells and a faint immunoreaction on the cell surface of some uterine epithelial cells. Ultrastructurally, immunogold labeling was restricted to the secretory granules, Golgi apparatus, and microvilli of the non-ciliated secretory cells of the oviduct. In the uterus, immunogold labeling was observed on the cell surface of some uterine epithelial cells. Furthermore, electron micrographs of ovulated oocytes showed an intense immunolabeling for rat oviductin within the perivitelline space surrounding the ovulated oocytes. The findings of the present study demonstrated that oviductin is present in the rat oviduct and uterus, and it appears that, in the rat, oviductin is secreted by the non-ciliated secretory cells of the oviduct.

Investigation of the effect of intrauterine inflammation and infection on fetal brain injury using human and animal models

In recent years, increased focus has been placed on the role of intrauterine infection and inflammation in the pathogenesis of fetal brain injury leading to neurodevelopmental disorders such as cerebral palsy. At present, the mechanisms by which inflammatory processes during pregnancy cause this effect on the fetus are poorly understood. Our previous work has indicated an association between experimentally-induced intrauterine infection, increased proinflammatory cytokines, and increased white matter injury in the guinea pig fetus. In order to further elucidate the pathways by which inflammation in the maternal system or the fetal membranes leads to fetal impairment, a number of studies investigating aspects of the disease process have been performed. These studies represent a body of work encompassing novel research and results in a number of human and animal studies. Using a guinea pig model of inflammation, increased amniotic fluid proinflammatory cytokines and fetal brain injury were found after a maternal inflammatory response was initiated using endotoxin. In order to more closely monitor the fetal response to chorioamnionitis, a model using the chronically catheterized fetal ovine was carried out. This study demonstrated the adverse effects on fetal white matter after intrauterine exposure to bacterial inoculation, though the physiological parameters of the fetus were relatively stable throughout the experimental protocol, even when challenged with intermittent hypoxic episodes. The placenta is an important mediator between mother and fetus during gestation, though its role in the inflammatory process is largely undefined. Studies on the placental role in the inflammatory process were undertaken, and the limited ability of proinflammatory cytokines and endotoxin to cross the placenta are detailed herein. Neurodevelopmental disorders can be monitored in animal models in order to determine effective disease models for characterization of injury and use in therapeutic strategies. Our characterizations of postnatal behaviour in the guinea pig model using motility monitoring and spatial memory testing have shown small but significant differences in pups exposed to inflammatory processes in utero. The data presented herein contributes a breadth of knowledge to the ongoing elucidation of the pathways by which fetal brain injury occurs. Determining the pathway of damage will lead to discovery of diagnostic criteria, while determining the vulnerabilities of the developing fetus is essential in formulating therapeutic options.

Small Proline Rich Protein-2 Expression and Regulation in the Caco-2 model of Intestinal Epithelial Differentiation along the Crypt-Villus Axis

Small proline-rich protein-2 (SPRR2) functions as a determinant of flexibility and permeability in the mature cornified envelope of the skin. SPRR2 is strongly upregulated by the commensal flora and may mediate signaling to differentiated epithelia of the small intestine and colon. Yet, SPRR2 function in the GI tract is largely unexplored. Using the Caco-2 model of intestinal epithelial differentiation along the crypt-villus axis, we hypothesized that SPRR2 would be preferentially expressed in post-confluent differentiated Caco-2 cells and examined SPRR2 regulation by the protein kinase A pathway (PKA) and short chain fatty acids (SCFAs). Differentiation-dependent SPRR2 expression was examined in cytoskeletal-, membrane-, and nuclear-enriched fractions by immunoblotting and confocal immunofluorescence. We studied the effect of SCFAs, known inducers of differentiation, on SPRR2 expression in pre-confluent undifferentiated Caco-2 cells and explored potential mechanisms involved in this induction using MAP kinase inhibitors. SPRR2 expression was also compared between HIEC crypt cells and 16 to 20 week primary fetal villus cells as well as in different segments in mouse small intestine and colon. We determined if SPRR2 is increased by gram negative bacteria such as S. typhimurium. SPRR2 expression increased in a differentiation-dependent manner in Caco-2 cells and was present in human fetal epithelial villus cells but absent in HIEC crypt cells. Differentiation-induced SPRR2 was down-regulated by 8-Br-cAMP as well as by forskolin/IBMX co-treatment. SPRR2 was predominantly cytoplasmic and did not accumulate in Triton X-100-insoluble cytoskeletal fractions. SPRR2 was present in the membrane- and nuclear-enriched fractions and demonstrated co-localization with F-actin at the apical actin ring. No induction was seen with the specific HDAC inhibitor trichostatin A, while SCFAs and the HDAC inhibitor SBHA all induced SPRR2. SCFA responses were inhibited by MAP kinase inhibitors SB203580 and U0126, thus suggesting that the SCFA effect may be mediated by orphan G-protein receptors GPR41 and GPR43. S. typhimurium induced SPRR2 in undifferentiated cells. We conclude that SPRR2 protein expression is associated with differentiated epithelia and is regulated by PKA signaling and by by-products of the bowel flora. This is the first report to establish an in vitro model to study the physiology and regulation of SPRR2.

LibQUAL+ Survey 2007 at Queen’s University Library: Analysis of Results

Analysis of 2007 LibQUAL+ results from the survey conducted by Queen's University in February 2007.

2007 LibQUAL+™ Survey @ Queen's: Findings and Actions

Summary of the finding from the 2007 Queen's LibQUAL+ survey and action items developed by the Library.