Explosive performance parameters: A digital computer solution and error analysis

A program was written for the determination of explosive performance parameters on the Royal-McBee LGP-30 electronic digital computer. The method developed by Dr. M. A. Cook was used, which is based on the thermohydrodynamic theory of detonation. This theory and the specific equations developed by Cook are presented. General statements are made in regard to computer programming, and specific information given concerning the programming concepts used for this particular problem. A detailed explanation of the program operation is given, together with the tabular data required for its use. Equations are presented for an analysis of the effects of roundoff error on the results of this program, and an example of the use of these equations is given. Methods and examples of the use of the computer program in performing error investigations are also presented. The coding sheets, flow charts, and written descriptions are included for each portion of the program, since it was written in such a manner as to be readily modified, and this information is essential if modifications are to be made --Abstract, page ii

Effects of Hydroxyapatite Particulate Debris on the Production of Cytokines and Proteases in Human Fibroblasts

Cytokines and proteases are secreted by fibroblasts in response to particulate wear debris, and these proteins are felt to play an important role in the development of osteolysis and implant loosening. Although metallic and polyethlyene debris have been studied extensively, little is known about the cellular responses to hydroxyapatite, despite the wide clinical use of these materials. Therefore, the effects of hydroxyapatite (HA) and hydroxyapatite/β‐tricalciumphosphate (HA/TCP) on cellular proliferation, cytokine gene expression and protein secretion, protease synthesis, and gelatinolytic activity were investigated in human fibroblasts. HA and HA/TCP particles were synthesized, and their effects were compared to the responses elicited by titanium and cobalt chromium. Sample characterization by scanning electron microscopy and Coulter Counter demonstrated that the materials had a mean particle size of less than 10 μm, and all of the particles were compared using the same concentration ranges. Aliquots of particle suspensions were added to human fibroblasts maintained in tissue culture, and dose‐response and time‐course experiments were performed. Effects of the particles on fibroblast proliferation were assessed, and alterations in cytokine levels were determined by specific enzyme linked immunosorbent assays (ELISA). Cytokines that were evaluated included inter‐leukin‐1 (IL‐β), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α), all of which have been demonstrated to enhance bone resorption and are associated with osteolysis and implant loosening. Gene expression was determined using Northern blot analysis with cytokine‐specific probes, while secretion of the proteases collagenase and stromelysin was determined by Western blot analysis. Functional gelatinolytic assay was assessed using zymogram gels. The particles were evaluated in a concentration range from 0.000021 to 0.021 vol%. All of the particles produced increases in cellular proliferation up to 0.0021 vol%, with the largest increases being seen at 0.021 vol% with HA/TCP and titanium. At the highest concentration, both cobalt chromium and HA samples decreased cellular proliferation relative to lower doses, possibly representing cytotoxicity. Hydroxyapatite particles yielded a 30‐fold increase in interleukin‐6 secretion compared to unstimulated controls, which was also greater than three times the levels produced by cobalt chromium, titanium, or HA/TCP. HA particles also tripled the secretion of IL‐1β at 0.00021 vol%, and doubled TNF‐α secretion at 0.021 vol%. Addition of conditioned media prepared by incubation of the particles in culture medium in the absence of cells did not alter the secretion of any of the cytokines. Northern blot analysis using IL‐6 probes also demonstrated strong increases with HA compared to the other materials, suggesting that the action of the HA particles was at the level of transcription. Secretion of the protease collagenase was increased by all of the samples including HA when compared to unstimulated controls. Stromelysin secretion into the culture medium was decreased by cobalt chromium, but increased by titanium, HA, and HA/TCP. All of the particles including HA increased the gelatinolytic activity of the fibroblasts. These findings demonstrate that HA and HA/TCP particles are capable of stimulating the expression and secretion of cytokines and proteases that enhance bone resorption, and suggest that particulate debris from implants using these coatings may also increase osteolysis and loosening

Renal consequences of preterm birth

BACKGROUND: The developmental origin of health and disease concept identifies the brain, cardiovascular, liver, and kidney systems as targets of fetal adverse programming with adult consequences. As the limits of viability in premature infants have been pushed to lower gestational ages, the long-term impact of prematurity on kidneys still remains a significant burden during hospital stay and beyond. OBJECTIVES: The purpose of this study is to summarize available evidence, mechanisms, and short- and long-term renal consequences of prematurity and identify nephroprotective strategies and areas of uncertainty. RESULTS: Kidney size and nephron number are known to be reduced in surviving premature infants due to disruption of organogenesis at a crucial developmental time point. Inflammation, hyperoxia, and antiangiogenic factors play a role in epigenetic conditioning with potential life-long consequences. Additional kidney injury from hypoperfusion and nephrotoxicity results in structural and functional changes over time which are often unnoticed. Nephropathy of prematurity and acute kidney injury confound glomerular and tubular maturation of preterm kidneys. Kidney protective strategies may ameliorate growth failure and suboptimal neurodevelopmental outcomes in the short term. In later life, subclinical chronic renal disease may progress, even in asymptomatic survivors. CONCLUSION: Awareness of renal implications of therapeutic interventions and renal conservation efforts may lead to a variety of short and long-term benefits. Adequate monitoring and supplementation of microelement losses, gathering improved data on renal handling, and exploration of new avenues such as reliable markers of injury and new therapeutic strategies in contemporary populations, as well as long-term follow-up of renal function, is warranted

Birth weight, malnutrition and kidney-associated outcomes--a global concern

An adverse intrauterine environment is associated with an increased risk of elevated blood pressure and kidney disease in later life. Many studies have focused on low birth weight, prematurity and growth restriction as surrogate markers of an adverse intrauterine environment; however, high birth weight, exposure to maternal diabetes and rapid growth during early childhood are also emerging as developmental risk factors for chronic diseases. Altered programming of nephron number is an important link between exposure to developmental stressors and subsequent risk of hypertension and kidney disease. Maternal, fetal, and childhood nutrition are crucial contributors to these programming effects. Resource-poor countries experience the sequential burdens of fetal and childhood undernutrition and subsequent overnutrition, which synergistically act to augment the effects of developmental programming; this observation might explain in part the disproportionate burden of chronic disease in these regions. Numerous nutritional interventions have been effective in reducing the short-term risk of low birth weight and prematurity. Understanding the potential long-term benefits of such interventions is crucial to inform policy decisions to interrupt the developmental programming cycle and stem the growing epidemics of hypertension and kidney disease worldwide