Verification of Composite Beam Theory with Finite Element Model for Pretensioned Concrete Members with Prestressing FRP Tendons.

Composite beam theory was previously developed to establish an analytical solution for determining the transfer length of prestressed fiber-reinforced polymers (FRP) tendons in pretensioned concrete members. In the present study, a novel finite element (FE) modeling approach is proposed to provide further verification of the developed analytical method. The present FE model takes into account the friction coefficients obtained from pull-out tests on the FRP tendons and prestressed concrete members. Convergence analysis of two numerical simulations with different mesh densities is carried out as well. The results demonstrated that the transfer length predicted by the fine FE model with a friction coefficient of α = 0.3 for high pretension is in good agreement with the measured values and the analytical solutions. The consistency between the analytical solution and FE simulation not only further proves the reliability of composite beam theory but also demonstrates the importance of the bond-slip relationship in predicting the transfer length of pretensioned concrete members prestressed with FRP tendons.

Biomechanical response of the pubic symphysis in lateral pelvic impacts: a finite element study.

Automotive side impacts are a leading cause of injuries to the pubic symphysis, yet the mechanisms of those injuries have not been clearly established. Previous mechanical testing of isolated symphyses revealed increased joint laxity following drop tower lateral impacts to isolated pelvic bone structures, which suggested that the joints were damaged by excessive stresses and/or deformations during the impact tests. In the present study, a finite element (FE) model of a female pelvis including a previously validated symphysis sub-model was developed from computed tomography data. The full pelvis model was validated against measured force-time impact responses from drop tower experiments and then used to study the biomechanical response of the symphysis during the experimental impacts. The FE models predicted that the joint underwent a combination of lateral compression, posterior bending, anterior/posterior and superior/inferior shear that exceeded normal physiological levels prior to the onset of bony fractures. Large strains occurred concurrently within the pubic ligaments. Removal of the contralateral constraints to better approximate the boundary conditions of a seated motor vehicle occupant reduced cortical stresses and deformations of the pubic symphysis; however, ligament strains, compressive and shear stresses in the interpubic disc, as well as posterior bending of the joint structure remained as potential sources of joint damage during automotive side impacts.

Clinical validation of urine 3-methoxytyramine as a biomarker of neuroblastoma and comparison with other catecholamine-related biomarkers.

Background Urinary dopamine, homovanillic acid and 4-hydroxy-3-methoxymandelic acid are established tests for diagnosis and monitoring of neuroblastic disease. We compared the diagnostic performance of total urinary 3-methoxytyramine, the O-methylated product of dopamine, to these three established tumour markers. Methods Urinary 3-methoxytyramine, dopamine, homovanillic acid and 4-hydroxy-3-methoxymandelic acid were measured by high-performance liquid chromatography with electrochemical detection on consecutive urine samples from histologically proven neuroblastic patients and controls. Patients with neuroblastic disease were further classified as untreated, advancing, residual or absent disease based on clinical and radiological criteria. Receiver operating characteristic curve analysis was used to compare the diagnostic performance of the four tumour markers. Results Urinary 3-methoxytyramine was well correlated with established tumour markers and its concentration correlated with disease activity. It was the most commonly elevated tumour marker in neuroblastic disease and showed similar sensitivity to dopamine and homovanillic acid. The diagnostic utility of urinary 3-methoxytyramine as measured by area under the receiver operating characteristic curve was similar to dopamine and homovanillic acid. Conclusion Our results support the use of urinary 3-methoxytyramine as a tumour marker in the diagnosis and the monitoring of neuroblastoma disease.

A case of low cortisol-binding globulin: use of plasma free cortisol in interpretation of hypothalamic-pituitary-adrenal axis tests.

We investigated a patient with suspected hypopituitarism who showed subnormal cortisol responses to stimulation tests with adrenocorticotrophic hormone (ACTH) and hypoglycaemia, but normal ACTH and 11-deoxycortisol responses in the metyrapone test. Cortisol-binding globulin (CBG) was measured by enzyme-linked immunosorbent assay (ELISA), and was used to calculate plasma free cortisol and free cortisol index. The patient had a low plasma CBG concentration. Reinterpreted in terms of free cortisol and free cortisol index, his responses to ACTH were normal. We conclude that despite subnormal total cortisol responses to ACTH and hypoglycaemia, the patient had a normal hypothalamic-pituitary-adrenal (HPA) axis. Measurement of CBG concentration and calculation of free cortisol or free cortisol index can help avoid false interpretations of dynamic tests of the HPA axis based on plasma total cortisol.

Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency.

Vitamin D insufficiency is common in patients with primary hyperparathyroidism (PHPT) and may be associated with more severe and progressive disease. Uncertainty exists, however, as to whether repletion of vitamin D should be undertaken in patients with PHPT. Here we report the effects of vitamin D repletion on biochemical outcomes over 1 yr in a group of 21 patients with mild PHPT [serum calcium <12 mg/dl (3 mmol/liter)] and coexistent vitamin D insufficiency [serum 25 hydroxyvitamin D [25(OH)D] <20 microg/liter (50 nmol/liter)]. In response to vitamin D repletion to a serum 25(OH)D level greater than 20 microg/liter (50 nmol/liter), mean levels of serum calcium and phosphate did not change, and serum calcium did not exceed 12 mg/dl (3 mmol/liter) in any patient. Levels of intact PTH fell by 24% at 6 months (P < 0.01) and 26% at 12 months (P < 0.01). There was an inverse relationship between the change in serum 25(OH)D and that in intact PTH (r = -0.43, P = 0.056). At 12 months, total serum alkaline phosphatase was significantly lower, and urine N-telopeptides tended to be lower than baseline values (P = 0.02 and 0.13, respectively). In two patients, 24-h urinary calcium excretion rose to exceed 400 mg/d, but the group mean 24-h urinary calcium excretion did not change. These preliminary data suggest that vitamin D repletion in patients with PHPT does not exacerbate hypercalcemia and may decrease levels of PTH and bone turnover. Some patients with PHPT may experience an increase in urinary calcium excretion after vitamin D repletion.

Effects of a beta-blocker on bone turnover in normal postmenopausal women: a randomized controlled trial.

INTRODUCTION: The central nervous system has been demonstrated to regulate bone mass in mice, possibly via the beta2-adrenoreceptors on osteoblasts. beta-blockers increase bone mass in mice, and some observational studies have suggested a beneficial effect of these drugs on bone in humans EXPERIMENTAL SUBJECTS: We studied 41 normal postmenopausal women. MATERIALS AND METHODS: We conducted a randomized, placebo- controlled trial, comparing the effects on bone markers of propranolol 160 mg/d and placebo over 3 months. RESULTS: Serum osteocalcin declined by almost 20% in the first 2 wk of propranolol treatment, and this effect increased over time (P < 0.0001). Other osteoblast markers, procollagen type-I N-terminal propeptide and total alkaline phosphatase activity, were not significantly changed by propranolol. Urine free deoxypyridinoline declined by approximately 10% between 0 and 6 wk (P = 0.019) in the beta-blocker group and was stable thereafter. Serum C-terminal telopeptide of type I collagen also showed a small decrease, but this was not significantly different between groups. Serum albumin concentrations decreased by more than 2 g/liter in the first 2 wk of propranolol treatment, remaining stable subsequently (P = 0.007). Serum creatinine tended to increase in the propranolol group (P = 0.06), as did weight. Bone densities in the lumbar spine and total proximal femur did not change significantly in either group. CONCLUSIONS: The present study provides no evidence that beta-blocker drugs stimulate bone formation; if anything, propranolol reduces osteoblast activity. It also influences renal function and fluid balance, effects that might indirectly affect bone metabolism. Current evidence does not justify the use of beta-blockers for treatment of osteoporosis.

Multiple determinants for rapid agonist-induced internalization of a nonmammalian gonadotropin-releasing hormone receptor: a putative palmitoylation site and threonine doublet within the carboxyl-terminal tail Are critical.

The chicken GnRH receptor (cGnRH-R) differs from all mammalian GnRH-Rs in possessing a cytoplasmic carboxyl-terminal tail. We have previously demonstrated that the cGnRH-R undergoes more rapid agonist-induced internalization than the mammalian GnRH-Rs and requires the carboxyl-terminal tail for this process. To investigate the structural determinants mediating this rapid internalization, a series of mutant receptors was generated, including progressive truncations of the tail and substitution of serine and threonine residues with alanine. Truncation of the carboxyl-terminal tail to position 366 and then to position 356 resulted in a progressive attenuation of the rate and total extent of receptor internalization. However, truncation between positions 356 and 346 did not alter the kinetics of internalization further, whereas a further truncation to position 337 resulted in an additional marked reduction of internalization. We show that the membrane-proximal Cys(328) and the Thr(369)Thr(370) doublet located in the distal carboxyl terminus play a critical role in mediating rapid internalization. We demonstrate that the cGnRH-R, when expressed in both COS-7 and HEK 293 cells, preferentially undergoes rapid agonist-induced internalization in a caveolae-like, dynamin-dependent manner. These conclusions are based on our observation that pretreatments with filipin and methyl-beta-cyclodextrin, agents that disrupt lipid rafts such as caveolae, and coexpression of dominant-negative dynamin-1 (K44A) and caveolin-1 (Delta 1-81) mutants, effectively inhibited rapid agonist-induced internalization. Furthermore, cGnRH-Rs appeared to be mobilized to the beta-arrestin- and clathrin-coated, vesicle-mediated endocytic pathway upon beta-arrestin overexpression.

Comparative responses of bone turnover markers to bisphosphonate therapy in Paget's disease of bone.

The measurement of biochemical markers of bone turnover is integral to the diagnosis and management of Paget's disease. Recently, there has been a proliferation of new markers and a move to carry out existing assays on automated platforms. We have assessed the performance of seven currently available markers in 20 patients with Paget's disease undergoing ibandronate therapy (6 or 12 mg) and in nine placebo-treated controls. Samples were collected at baseline and 6 months following intervention. The mean reductions in serum markers following treatment with either dose of ibandronate were: total alkaline phosphatase (AP; Roche Modular) 70%, bone AP (Beckman Access, Ostase) 80%, osteocalcin (Roche Elecsys 2010) 33%, beta-C-terminal telopeptide of type I collagen (betaCTX; Roche Elecsys 2010) 50%, and procollagen-N-terminal peptide (P1NP; Roche Elecsys 2010) 80%. For urine markers the reductions were: free deoxypyridinoline/creatinine (fDPD/creat) (DPC Immulite 2000) 36%, and N-telopeptide/creatinine (NTX/creat) (Osteomark) 81%. Total AP, bone AP, P1NP, and NTX all showed >95% of subjects to have abnormal values at baseline, reducing to 15-30% following treatment, and these treatment effects were highly significant (P < or = 0.0005), except for NTX (P = 0.02). The poorer precision of NTX reduced its utility. Baseline sensitivity was lower for the other markers (osteocalcin 68% of subjects abnormal, fDPD 22%, betaCTX 50%). Total AP, bone AP, and P1NP are suitable osteoblast markers for monitoring bisphosphonate therapy in Paget's disease, with performance approaching that of bone scintigraphy. NTX is less sensitive in detecting the effects of therapy, but is the best performing bone resorption marker. There is no clear evidence from this study that any of these newer markers are superior to total AP in assessing patients with this severity of Paget's disease.

A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension.

OBJECTIVE: To determine the relationship between R563Q, a mutation of the renal epithelial sodium channel, and hypertension. METHODS: Hypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced. RESULTS: A previously undescribed mutation, R563Q, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia. CONCLUSIONS: R563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddle's syndrome phenotype.

Direct urine ammonium measurement: time to discard urine anion and osmolar gaps.

BACKGROUND: A failure of urine ammonium to increase during acidosis indicates impaired renal acidification, and the urinary ammonium concentration is therefore a useful investigation in determining the cause of a metabolic acidosis. However, urine ammonium measurements are not widely available in routine diagnostic laboratories. This has led to the use of urine anion or osmolar gaps, which are unsatisfactory as surrogates for urine ammonium measurement. METHODS: We evaluated the adaptation of two widely available automated plasma ammonium assays for measurement of urinary ammonium. RESULTS: Both assays showed good recovery and linearity in urine samples spiked with ammonium chloride, and acceptable precision. Urine ammonium concentrations estimated from urinary anion and osmolar gaps showed poor agreement with measured urine ammonium concentrations. CONCLUSIONS: Direct urine ammonium measurements are easily performed with modern autoanalysers by simple adaptation of routine plasma ammonium assays. The use of urine anion and osmolar gaps should be abandoned where direct measurement is available.

Should measurement of vitamin D and treatment of vitamin D insufficiency be routine in New Zealand?

Epidemiological studies have reported associations between lower vitamin D levels and a great variety of diseases, prompting calls for widespread treatment of individuals with low vitamin D levels. Most of New Zealand's population have vitamin D levels for at least part of the year that are considered insufficient (25-hydroxyvitamin D <50-80 nmol/L). However, evidence for benefits of vitamin D supplementation in such populations is controversial and there is some evidence of harmful effects. Until adequately powered, randomised, controlled trials of vitamin D supplementation demonstrate safe improvements in health, clinicians should not focus on detecting/treating individuals with vitamin D insufficiency, instead treating those at high risk of vitamin D deficiency (25-hydroxyvitamin D <25 nmol/L), such as the frail elderly, and those with specific clinical indications. Treatment for such individuals does not require vitamin D measurements. Requests for vitamin D measurements in Auckland have nearly quadrupled in the past decade, from 8500 in the year 2000 to 32,800 in 2010, with substantial increases in cost. Vitamin D measurement is often inaccurate and imprecise, and the vast majority of tests performed currently do not reveal vitamin D deficiency. Therefore, a move away from routine vitamin D measurements seems sensible, though they are still indicated when investigating suspected metabolic bone disease or hypocalcaemia.

Inappropriate trace element testing in the Auckland region.

AIM: To understand recent changes in trace element test usage in the Auckland region of New Zealand. METHODS: Laboratory records of trace element tests between 2004 and 2008 were analysed. A questionnaire was sent to a frequent requestor group to elicit reasons for requesting trace element tests. RESULTS: The annual number of trace element test requests increased by 3.5-fold over the study period. The increase was largely due to a 2.8-fold increase in serum copper, a 3.8-fold increase in serum zinc, and a 3.4-fold increase in serum selenium tests. Most of the increase was accounted for by a small number of requestors, mainly general practitioners. An outlier group of 24 requestors was identified who were responsible for ordering 55% of serum copper, 61% of serum zinc, 63% of serum selenium and 66% of blood mercury tests in the last year of the study. Responses to the questionnaire suggest that among the outlier group the reasons for requesting serum zinc, copper and selenium tests are not evidence-based. CONCLUSION: The majority of trace element tests performed in the Auckland region appear to be non-evidence-based, and represent a significant wastage of public laboratory resources. This suggests that laboratories could achieve significant savings in expenditure by clearly defining appropriate indications for performing trace element tests.

The effects of seasonal variation of 25-hydroxyvitamin D on diagnosis of vitamin D insufficiency.

AIMS: To explore the effects of seasonal variation on the diagnosis of vitamin D sufficiency and to determine whether age, gender, and ethnicity modify these effects. METHODS: 21,987 adults had a measurement of serum 25-hydroxyvitamin D (25OHD) at Labplus, Auckland City Hospital, between January 2002 and September 2003, and sine curves were fitted for 25OHD versus day of year to predict the 25OHD nadir for each individual. RESULTS: 48% (range: 30-63%) of individuals had 25OHD <50 nmol/L in the month of measurement, but 63% were predicted to have 25OHD <50 nmol/L in late winter or early spring based on expected seasonal variation. The 25OHD levels required to ensure 25OHD levels >50 nmol/L throughout the year varied substantially by season (in summer at least 60-75 nmol/L), and tended to be higher in men than women, decrease with age, and vary with ethnicity. Mean 25OHD levels were very low (<40 nmol/L) in people of Indian, Middle Eastern, and African descent. CONCLUSION: Seasonal variation in 25OHD affects the diagnosis of vitamin D sufficiency. Clinicians should consider the month of sampling when interpreting the results of 25OHD measurements. In New Zealand, a summertime 25OHD <60-75 nmol/L is generally required to ensure year-round 25OHD levels <50 nmol/L.

Three-dimensional finite element models of the human pubic symphysis with viscohyperelastic soft tissues.

Three-dimensional finite element (FE) models of human pubic symphyses were constructed from computed tomography image data of one male and one female cadaver pelvis. The pubic bones, interpubic fibrocartilaginous disc and four pubic ligaments were segmented semi-automatically and meshed with hexahedral elements using automatic mesh generation schemes. A two-term viscoelastic Prony series, determined by curve fitting results of compressive creep experiments, was used to model the rate-dependent effects of the interpubic disc and the pubic ligaments. Three-parameter Mooney-Rivlin material coefficients were calculated for the discs using a heuristic FE approach based on average experimental joint compression data. Similarly, a transversely isotropic hyperelastic material model was applied to the ligaments to capture average tensile responses. Linear elastic isotropic properties were assigned to bone. The applicability of the resulting models was tested in bending simulations in four directions and in tensile tests of varying load rates. The model-predicted results correlated reasonably with the joint bending stiffnesses and rate-dependent tensile responses measured in experiments, supporting the validity of the estimated material coefficients and overall modeling approach. This study represents an important and necessary step in the eventual development of biofidelic pelvis models to investigate symphysis response under high-energy impact conditions, such as motor vehicle collisions.

Mental retardation and ataxia due to normotriglyceridemic hypobetalipoproteinemia.

A 12-year-old boy with mental retardation, obesity, ataxia, and visual impairment was shown to have normal fasting plasma triglyceride but low cholesterol and vitamin E levels. Investigations indicated that he was compound heterozygous for two mutations in the apolipoprotein B gene (APOB), resulting in a failure to express apolipoprotein B-100, yet retain apolipoprotein B-48 production. The proband therefore was able to form chylomicrons, but not a low-density lipoprotein capable of receptor-mediated endocytosis. This resulted in chronic vitamin E deficiency. We suggest the term normotriglyceridemic hypobetalipoproteinemia for this easily recognizable condition.

The applicability of a computer model for predicting head injury incurred during actual motor vehicle collisions.

BACKGROUND: Head injury is a significant cause of both morbidity and mortality. Motor vehicle collisions (MVCs) are the most common source of head injury in the United States. No studies have conclusively determined the applicability of computer models for accurate prediction of head injuries sustained in actual MVCs. This study sought to determine the applicability of such models for predicting head injuries sustained by MVC occupants. METHODS: The Crash Injury Research and Engineering Network (CIREN) database was queried for restrained drivers who sustained a head injury. These collisions were modeled using occupant dynamic modeling (MADYMO) software, and head injury scores were generated. The computer-generated head injury scores then were evaluated with respect to the actual head injuries sustained by the occupants to determine the applicability of MADYMO computer modeling for predicting head injury. RESULTS: Five occupants meeting the selection criteria for the study were selected from the CIREN database. The head injury scores generated by MADYMO were lower than expected given the actual injuries sustained. In only one case did the computer analysis predict a head injury of a severity similar to that actually sustained by the occupant. CONCLUSION: Although computer modeling accurately simulates experimental crash tests, it may not be applicable for predicting head injury in actual MVCs. Many complicating factors surrounding actual MVCs make accurate computer modeling difficult. Future modeling efforts should consider variables such as age of the occupant and should account for a wider variety of crash scenarios.