The effects of isometric exercise on resting blood pressure: a home-based approach

The main focus of this thesis was to develop an accessible home-based isometric exercise training (IET) protocol for the reduction of resting blood pressure (BP). Hypertension is estimated to affect nearly 30% of the world’s population (WHO, 2012) and represents an inordinate health and economic burden worldwide. A growing body of research suggests that IET can lower resting BP. However, the majority of studies have utilised expensive and/or laboratory-based equipment, which may not be accessible to the general population. To this end, the studies within this thesis explored whether the novel isometric wall squat exercise could be prescribed for home-based training using relatively simple, inexpensive equipment. The first study determined a method for adjusting the wall squat intensity. It was found that knee joint angle reliably produced inverse relationships with heart rate (HR) and BP when individual bouts of wall squat exercise were completed (r at least -0.80; P < 0.05). Study 2 then established that these inverse relationships could be replicated from completing an incremental test (r at least -0.88; P < 0.05), from which wall squat training intensity could then be prescribed at an individualised knee joint angle (104 ± 7°) to elicit a target training HR (95% peak HR: 121 ± 14 beats∙min-1). Finally, using these methods, study 3 implemented a 4 week home-based isometric wall squat training protocol and found statistically significant and clinically relevant resting BP reductions (systolic BP: -4 mmHg; diastolic BP -3 mmHg; mean arterial pressure: -3 mmHg). These results support the majority of previous research that has found reductions in resting BP following IET. Furthermore, the primary BP control mechanisms were also explored and the results suggested that a reduction in resting BP was potentially mediated by a decrease in resting cardiac output (-0.54 ± 0.66 L∙min-1), which may have been governed by a reduction in resting HR (-5 ± 7 beats∙min-1). The novel home-based IET protocol developed within this thesis may be more time and cost effective, which may ultimately increase the adherence to and efficacy of IET for the reduction of resting BP

Assessing Learning-Centered Leadership: Connections to Research, Professional Standards, and Current Practices

Describes an assessment model designed to evaluate school leaders' performance. Unlike existing tools, this new system will assess both individuals and teams, and focuses specifically on instructional leadership and behaviors that improve learning

Chondrocyte responses to neurovascular peptides, cytokines, and a 3D environment: focus on ADAMs

Chondrocyte exposure to inflammatory stimuli in several arthritic conditions, including osteoarthritis, results in the well-characterised induction of extracellular matrix (ECM) degrading proteinases, notably members of a disintegrin and metalloproteinase with thrombospondin domains (ADAMTS) and matrix metalloproteinase (MMP) families. Here we briefly review the less-studied a disintegrin and metalloproteinase (ADAM) family of proteinases in chondrocyte and cartilage biology. Following damage, cartilage is exposed to neurovascular peptides, and in this study we hypothesised that substance P and bradykinin, alongside inflammatory cytokines, may modulate chondrocyte steady state messenger RNA levels for the proteolytic ADAM family members as well as for key cytokines and neuropeptides. We compared chondrocytes cultured in both 2-dimensional (2D) and 3D environments and found that 3D culture generally resulted in repression of expression of the genes under investigation, with the exception of anti-inflammatory interleukin 10 (IL10) which was markedly up-regulated in a 3D environment. Substance P and bradykinin had little effect on ADAM family expression but further investigation revealed that a combination of bradykinin and cytokines led to enhanced expression of ADAM28 and a synergistic up-regulation of IL6, also observed under hypoxic conditions. Overall this data reveals wider chondrocyte responses to neurovascular peptides which may have an impact in an osteoarthritis context

Confirmation of Parity Violation in the Gamma Decay of 180Hfm^{180}Hf^{m}

This paper reports measurements using the technique of On Line Nuclear Orientation (OLNO) which reexamine the gamma decay of isomeric $^{\rm 180}$Hf$^{\rm m}$ and specifically the 501 keV 8$^{\rm -}$ -- 6$^{\rm +}$ transition. The irregular admixture of E2 to M2/E3 multipolarity in this transition, deduced from the forward-backward asymmetry of its angular distribution, has for decades stood as the prime evidence for parity mixing in nuclear states. The experiment, based on ion implantation of the newly developed mass-separated $^{\rm 180}$Hf$^{\rm m}$ beam at ISOLDE, CERN into an iron foil maintained at millikelvin temperatures, produces higher degrees of polarization than were achieved in previous studies of this system. The value found for the E2/M2 mixing ratio, $\epsilon$ = -0.0324(16)(17), is in close agreement with the previous published average value $\epsilon$ = - 0.030(2), in full confirmation of the presence of the irregular E2 admixture in the 501 keV transition. The temperature dependence of the forward-backward asymmetry has been measured over a more extended range of nuclear polarization than previously possible, giving further evidence for parity mixing of the 8$^{\rm -}$ and 8$^{\rm +}$ levels and the deduced E2/M2 mixing ratio.Comment: 28 pages, 9 figures, accepted for publication in Physical Review

Further search for a neutral boson with a mass around 9 MeV/c2

Two dedicated experiments on internal pair conversion (IPC) of isoscalar M1 transitions were carried out in order to test a 9 MeV/c2 X-boson scenario. In the 7Li(p,e+e-)8Be reaction at 1.1 MeV proton energy to the predominantly T=0 level at 18.15 MeV, a significant deviation from IPC was observed at large pair correlation angles. In the 11B(d,n e+e-)12C reaction at 1.6 MeV, leading to the 12.71 MeV 1+ level with pure T=0 character, an anomaly was observed at 9 MeV/c2. The compatibility of the results with the scenario is discussed.Comment: 12 pages, 5 figures, 2 table

Dessins, their delta-matroids and partial duals

Given a map $\mathcal M$ on a connected and closed orientable surface, the delta-matroid of $\mathcal M$ is a combinatorial object associated to $\mathcal M$ which captures some topological information of the embedding. We explore how delta-matroids associated to dessins d'enfants behave under the action of the absolute Galois group. Twists of delta-matroids are considered as well; they correspond to the recently introduced operation of partial duality of maps. Furthermore, we prove that every map has a partial dual defined over its field of moduli. A relationship between dessins, partial duals and tropical curves arising from the cartography groups of dessins is observed as well.Comment: 34 pages, 20 figures. Accepted for publication in the SIGMAP14 Conference Proceeding

Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA

Objective: To use deep sequencing to identify novel microRNAs in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate microRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3’-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. Results: We identified 990 known microRNAs and 1621 potential novel microRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate microRNAs were analysed further, of which 6 remained after northern blot analysis. Three novel microRNAs were regulated across models of chondrogenesis, chondrocyte differentiation or cartilage injury. One sequence (novel #11), annotated in rodents as microRNA-3085-3p, was preferentially expressed in cartilage, dependent on chondrocyte differentiation and, in man, is located in an intron of the cartilage-expressed gene CRTAC-1. This microRNA was shown to target the ITGA5 gene directly (which encodes integrin alpha5) and inhibited adhesion to fibronectin (dependent on alpha5beta1 integrin). Conclusion: Deep sequencing has uncovered many potential microRNA candidates expressed in human cartilage. At least three of these show potential functional interest in cartilage homeostasis and osteoarthritis. Particularly, novel #11 (microRNA-3085-3p) which has been identified for the first time in man

Shell structure underlying the evolution of quadrupole collectivity in S-38 and S-40 probed by transient-field g-factor measurements on fast radioactive beams

The shell structure underlying shape changes in neutron-rich nuclei between N=20 and N=28 has been investigated by a novel application of the transient field technique to measure the first-excited state g factors in S-38 and S-40 produced as fast radioactive beams. Details of the new methodology are presented. In both S-38 and S-40 there is a fine balance between the proton and neutron contributions to the magnetic moments. Shell model calculations which describe the level schemes and quadrupole properties of these nuclei also give a satisfactory explanation of the g factors. In S-38 the g factor is extremely sensitive to the occupation of the neutron p3/2 orbit above the N=28 shell gap as occupation of this orbit strongly affects the proton configuration. The g factor of deformed S-40 does not resemble that of a conventional collective nucleus because spin contributions are more important than usual.Comment: 10 pages, 36 figures, accepted for publication in Physical Review

The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery for aseptic loosening after total joint replacement. Cells were examined for the expression of several markers associated with the osteoclast phenotype using immunohistochemistry, histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by multiple macrophage lineage cell types, was detected in mononucleated and multinucleated cells associated with polyethylene particles and the bone surface. Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both mononucleated and multinucleated cells associated with the bone surface. Levels of expression were much lower in cells associated with polyethylene particles. High levels of β(3 )integrin protein were detected in cells in contact with bone. Multinucleated cells associated with polyethylene particles exhibited faint positive staining. Calcitonin receptor mRNA expression was detected solely in multinucleated cells present in resorption lacunae on the bone surface and was absent in cells associated with polyethylene particles. Our findings provide further evidence that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. They also demonstrate that foreign body giant cells, although believed to be phenotypically and functionally distinct from osteoclasts, express many osteoclast-associated genes and gene products. However, the levels and patterns of expression of these genes in the two cell types differ. We speculate that, in addition to the role of cytokines and growth factors, the substrate with which these cells interact plays a critical role in their differential phenotypic and functional properties