National ideals or national interest: New Zealand and South Africa, 1981-1994

“National ideals or National Interest?” examines the making and implementation by successive New Zealand governments of policy toward apartheid South Africa from 1981 to 1994. Its main focus is the contradictory relationship between living up to New Zealand’s ideals against doing what was practicable in the context of the time. The dilemma the apartheid state faced, in trying to solve its internal problems while not imperilling its external security was often not appreciated by the New Zealand government. These misconceptions helped shape New Zealand policy. Ironically once the South African regime began to investigate the possibilities of some sort of political transformation, their New Zealand counterparts were less willing to empathise with the risks involved with such an undertaking than they had been in the 1960s and 1970s. “National Ideals’ also examines the role of civil society and what was often a parallel unofficial foreign policy based around these person -to - person contacts, including the problems posed for the government by the need to persuade groups such as the NZRFU to follow government policy without overstepping what were strongly entrenched principles of individual freedom. The conflicts within the two main political parties of New Zealand were also important in shaping policy, as was the adversarial relationship between the major parties. “National Ideals” concluded that more often than not interests came first and indeed that at times policy decisions often to the product of accident and intrigue

Modulation of anabolic and catabolic responses via a porous polymer scaffold manufactured using thermally induced phase separation

We describe two studies encompassing the iterative refinement of a polymer-based rhBMP-2 delivery system for bone tissue engineering. Firstly, we compared the boneforming capacity of porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds produced by thermally induced phase separation (TIPS) with non-porous solvent cast poly(D,L-lactic acid) (PDLLA) used previously. Secondly, we examined the potential synergy between rhBMP-2 and local bisphosphonate in the PLGA scaffold system. In vivo ectopic bone formation studies were performed in C57BL6/J mice. Polymer scaffolds containing 0, 5, 10 or 20 μg rhBMP-2 were inserted into the dorsal musculature. At all rhBMP-2 doses, porous PLGA produced significantly higher bone volume (BV, mm) than the solid PDLLA scaffolds. Next, porous PLGA scaffolds containing 10μg rhBMP-2 ±0.2, or 2μg zoledronic acid (ZA) were inserted into the hind-limb musculature. Co-delivery of local 10μg rhBMP-2/2μg ZA significantly augmented bone formation compared with rhBMP-2 alone (400 % BV increase, p < 0.01). Hydroxyapatite microparticle (HAp) addition (2% w/w) to the 10μg rhBMP-2/0.2μg ZA group increased BV (200 %, p < 0.01). We propose that this was due to controlled ZA release of HAp-bound ZA. Consistent with this, elution analyses showed that HAp addition did not alter the rhBMP-2 elution, but delayed ZA release. Moreover, 2 % w/w HAp addition reduced the scaffold's compressive properties, but did not alter ease of surgical handling. In summary, our data show that refinement of the polymer selection and scaffold fabrication can enhance rhBMP-2 induced bone formation in our bone tissue engineering implant, and this can be further optimised by the local co-delivery of ZA/HAp

A collagen-hydroxyapatite scaffold allows for binding and co-delivery of recombinant bone morphogenetic proteins and bisphosphonates.

An emerging paradigm in orthopedics is that a bone-healing outcome is the product of the anabolic (bone-forming) and catabolic (bone-resorbing) outcomes. Recently, surgical and tissue engineering strategies have emerged that combine recombinant human bone morphogenetic proteins (rhBMPs) and bisphosphonates (BPs) in order to maximize anabolism and minimize catabolism. Collagen-based scaffolds that are the current surgical standard can bind rhBMPs, but not BPs. We hypothesized that a biomimetic collagen-hydroxyapatite (CHA) scaffold would bind both agents and produce superior in vivo outcomes. Consistent with this concept, in vitro elution studies utilizing rhBMP-2 ELISA assays and scintillation counting of (14)C-radiolabeled zoledronic acid (ZA) confirmed delayed release of both agents from the CHA scaffold. Next, scaffolds were tested for their capacity to form ectopic bone after surgical implantation into the rat hind limb. Using CHA, a significant 6-fold increase in bone volume was seen in rhBMP-2/ZA groups compared to rhBMP-2 alone, confirming the ability of ZA to enhance rhBMP-2 bone formation. CHA scaffolds were found to be capable of generating mineralized tissue in the absence of rhBMP-2. This study has implications for future clinical treatments of critical bone defects. It demonstrates the relative advantages of co-delivering anabolic and anti-catabolic agents using a multicomponent scaffold system

Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic RHBMP-2 and anti-resorptive agents

Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs) utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 μg) ± anti-resorptive agents: zoledronic acid (5 μg ZA), ZA pre-adsorbed onto hydroxyapatite microparticles, (5 μg ZA/2 % HA) or IkappaB kinase (IKK) inhibitor (10 μg PS-1145). Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3 % TV, p < 0.01). The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01). Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01). Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation

Myogenic progenitors contribute to open but not closed fracture repair

<p>Abstract</p> <p>Background</p> <p>Bone repair is dependent on the presence of osteocompetent progenitors that are able to differentiate and generate new bone. Muscle is found in close association with orthopaedic injury, however its capacity to make a cellular contribution to bone repair remains ambiguous. We hypothesized that myogenic cells of the MyoD-lineage are able to contribute to bone repair.</p> <p>Methods</p> <p>We employed a <it>MyoD</it>-Cre⁺:Z/AP⁺conditional reporter mouse in which all cells of the MyoD-lineage are permanently labeled with a <it>human alkaline phosphatase (hAP) </it>reporter. We tracked the contribution of MyoD-lineage cells in mouse models of tibial bone healing.</p> <p>Results</p> <p>In the absence of musculoskeletal trauma, MyoD-expressing cells are limited to skeletal muscle and the presence of reporter-positive cells in non-muscle tissues is negligible. In a closed tibial fracture model, there was no significant contribution of hAP⁺cells to the healing callus. In contrast, open tibial fractures featuring periosteal stripping and muscle fenestration had up to 50% of hAP⁺cells detected in the open fracture callus. At early stages of repair, many hAP⁺cells exhibited a chondrocyte morphology, with lesser numbers of osteoblast-like hAP⁺cells present at the later stages. Serial sections stained for hAP and type II and type I collagen showed that MyoD-lineage cells were surrounded by cartilaginous or bony matrix, suggestive of a functional role in the repair process. To exclude the prospect that osteoprogenitors spontaneously express MyoD during bone repair, we created a metaphyseal drill hole defect in the tibia. No hAP⁺staining was observed in this model suggesting that the expression of MyoD is not a normal event for endogenous osteoprogenitors.</p> <p>Conclusions</p> <p>These data document for the first time that muscle cells can play a significant secondary role in bone repair and this knowledge may lead to important translational applications in orthopaedic surgery.</p> <p>Please see related article: <url>http://www.biomedcentral.com/1741-7015/9/136</url></p

Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness.

Nitrate-rich beetroot juice (BRJ) increases plasma nitrite concentrations, lowers the oxygen cost (V̇O2) of steady-state exercise and improves exercise performance in sedentary and moderately-trained, but rarely in well-trained individuals exercising at sea-level. BRJ supplementation may be more effective in a hypoxic environment, where the reduction of nitrite into nitric oxide (NO) is potentiated, such that well-trained and less well-trained individuals may derive a similar ergogenic effect. We conducted a randomised, counterbalanced, double-blind placebo controlled trial to determine the effects of BRJ on treadmill running performance in moderate normobaric hypoxia (equivalent to 2500 m altitude) in participants with a range of aerobic fitness levels. Twelve healthy males (V̇O2max ranging from 47.1 to 76.8 ml kg(-1)·min(-1)) ingested 138 ml concentrated BRJ (∼15.2 mmol nitrate) or a nitrate-deplete placebo (PLA) (∼0.2 mmol nitrate). Three hours later, participants completed steady-state moderate intensity running, and a 1500 m time-trial (TT) in a normobaric hypoxic chamber (FIO2 ∼15%). Plasma nitrite concentrations were significantly greater following BRJ versus PLA 1 h post supplementation, and remained higher in BRJ throughout the testing session (p  0.05). These findings suggests that a high nitrate dose in the form of a BRJ supplement may improve running performance in individuals with a range of aerobic fitness levels conducting moderate and high-intensity exercise in a normobaric hypoxic environment

Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study.

BACKGROUND: This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. METHODS: We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression. RESULTS: Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma. CONCLUSIONS: These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure

Spatial and temporal variability in summertime dissolved carbon dioxide and methane in temperate ponds and shallow lakes

Small waterbodies have potentially high greenhouse gas emissions relative to their small footprint on the landscape, although there is high uncertainty in model estimates. Scaling their carbon dioxide (CO2) and methane (CH4) exchange with the atmosphere remains challenging due to an incomplete understanding and characterization of spatial and temporal variability in CO2 and CH4. Here, we measured partial pressures of CO2 (pCO2) and CH4 (pCH4) across 30 ponds and shallow lakes during summer in temperate regions of Europe and North America. We sampled each waterbody in three locations at three times during the growing season, and tested which physical, chemical, and biological characteristics related to the means and variability of pCO2 and pCH4 in space and time. Summer means of pCO2 and pCH4 were inversely related to waterbody size and positively related to floating vegetative cover; pCO2 was also positively related to dissolved phosphorus. Temporal variability in partial pressure in both gases weas greater than spatial variability. Although sampling on a single date was likely to misestimate mean seasonal pCO2 by up to 26%, mean seasonal pCH4 could be misestimated by up to 64.5%. Shallower systems displayed the most temporal variability in pCH4 and waterbodies with more vegetation cover had lower temporal variability. Inland waters remain one of the most uncertain components of the global carbon budget; understanding spatial and temporal variability will ultimately help us to constrain our estimates and inform research priorities