Effects of antiresorptive agents on bone micro-architecture assessed by Trabecular Bone Score in women age 50 and older. The Manitoba Prospective Study

Antiresorptive agents such as bisphosphonates induce a rapid increase of BMD during the 1st year of treatment and a partial maintenance of bone architecture. Trabecular Bone Score (TBS), a new grey-level texture measurement that can be extracted from the DXA image, correlates with 3D parameters of bone micro-architecture. Aim: To evaluate the longitudinal effect of antiresorptive agents on spine BMD and on site-matched spine microarchitecture as assessed by TBS. Methods: From the BMD database for Province of Manitoba, Canada, we selected women age >50 with paired baseline and follow up spine DXA examinations who had not received any prior HRT or other antiresorptive drug.Women were divided in two subgroups: (1) those not receiving any HRT or antiresorptive drug during follow up (=non-users) and (2) those receiving non-HRT antiresorptive drug during follow up (=users) with high adherence (medication possession ratio >75%) from a provincial pharmacy database system. Lumbar spine TBS was derived by the Bone Disease Unit, University of Lausanne, for each spine DXA examination using anonymized files (blinded from clinical parameters and outcomes). Effects of antiresorptive treatment for users and non-users on TBS and BMD at baseline and during mean 3.7 years follow-up were compared. Results were expressed % change per year. Results: 1150 non-users and 534 users met the inclusion criteria. At baseline, users and non-users had a mean age and BMI of [62.2±7.9 vs 66.1±8.0 years] and [26.3±4.7 vs 24.7±4.0 kg/m²] respectively. Antiresorptive drugs received by users were bisphosphonates (86%), raloxifene (10%) and calcitonin (4%). Significant differences in BMD change and TBS change were seen between users and nonusers during follow-up (p<0.0001). Significant decreases in mean BMD and TBS (−0.36± 0.05% per year; −0.31±0.06% per year) were seen for non-users compared with baseline (p<0.001). A significant increase in mean BMD was seen for users compared with baseline (+1.86±0.0% per year, p<0.0018). TBS of users also increased compared with baseline (+0.20±0.08% per year, p<0.001), but more slowly than BMD. Conclusion: We observed a significant increase in spine BMD and a positive maintenance of bone micro-architecture from TBS with antiresorptive treatment, whereas the treatment naïve group lost both density and micro-architecture. TBS seems to be responsive to treatment and could be suitable for monitoring micro-architecture. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: M.-A. Krieg: None declared, A. Goertzen: None declared, W. Leslie: None declared, D. Hans Consulting fees from Medimaps.

Modelling Bone Mineral Density in Swiss Breast Cancer Patients Treated with Letrozole, Tamoxifen and Sequences of Letrozole and Tamoxifen in the BIG 1-98 Study (SAKK 21/07).

Background: Bone health is a concern when treating early stage breast cancer patients with adjuvant aromatase inhibitors. Early detection of patients (pts) at risk of osteoporosis and fractures may be helpful for starting preventive therapies and selecting the most appropriate endocrine therapy schedule. We present statistical models describing the evolution of lumbar and hip bone mineral density (BMD) in pts treated with tamoxifen (T), letrozole (L) and sequences of T and L. Methods: Available dual-energy x-ray absorptiometry exams (DXA) of pts treated in trial BIG 1-98 were retrospectively collected from Swiss centers. Treatment arms: A) T for 5 years, B) L for 5 years, C) 2 years of T followed by 3 years of L and, D) 2 years of L followed by 3 years of T. Pts without DXA were used as a control for detecting selection biases. Patients randomized to arm A were subsequently allowed an unplanned switch from T to L. Allowing for variations between DXA machines and centres, two repeated measures models, using a covariance structure that allow for different times between DXA, were used to estimate changes in hip and lumbar BMD (g/cm2) from trial randomization. Prospectively defined covariates, considered as fixed effects in the multivariable models in an intention to treat analysis, at the time of trial randomization were: age, height, weight, hysterectomy, race, known osteoporosis, tobacco use, prior bone fracture, prior hormone replacement therapy (HRT), bisphosphonate use and previous neo-/adjuvant chemotherapy (ChT). Similarly, the T-scores for lumbar and hip BMD measurements were modeled using a per-protocol approach (allowing for treatment switch in arm A), specifically studying the effect of each therapy upon T-score percentage. Results: A total of 247 out of 546 pts had between 1 and 5 DXA; a total of 576 DXA were collected. Number of DXA measurements per arm were; arm A 133, B 137, C 141 and D 135. The median follow-up time was 5.8 years. Significant factors positively correlated with lumbar and hip BMD in the multivariate analysis were weight, previous HRT use, neo-/adjuvant ChT, hysterectomy and height. Significant negatively correlated factors in the models were osteoporosis, treatment arm (B/C/D vs. A), time since endocrine therapy start, age and smoking (current vs. never).Modeling the T-score percentage, differences from T to L were -4.199% (p = 0.036) and -4.907% (p = 0.025) for the hip and lumbar measurements respectively, before any treatment switch occurred. Conclusions: Our statistical models describe the lumbar and hip BMD evolution for pts treated with L and/or T. The results of both localisations confirm that, contrary to expectation, the sequential schedules do not seem less detrimental for the BMD than L monotherapy. The estimated difference in BMD T-score percent is at least 4% from T to L.

Tiller size/density compensation in grazed Tifton 85 bermudagrass swards

The objective of this study was to evaluate the occurrence of the tiller size/density compensation mechanism in Tifton 85 bermudagrass swards grazed by sheep under continuous stocking. Treatments corresponded to four sward steady state conditions (5, 10, 15, and 20 cm of sward surface height), maintained by sheep grazing. The experimental design was a complete randomized block with four replicates. Pasture responses evaluated include: tiller population density, tiller mass, leaf mass and leaf area per tiller, and herbage mass. Tiller volume, leaf area index, tiller leaf/stem ratio, and tiller leaf area/volume ratio were calculated and simple regression analyses between tiller population density and tiller mass were performed. Measurements were made in December, 1998, and January, April, and July, 1999. The swards showed a tiller size/density compensation mechanism in which high tiller population densities were associated with small tillers and vice-versa, except in July, 1999. Regression analyses revealed that linear coefficients were steeper than the theoretical expectation of -3/2. Increments in herbage mass were attributable to increases in tiller mass in December and January. Leaf area/volume ratio values of Tifton 85 tillers were much lower than those commonly found for temperate grass species.

Symptomatic complex partial status epilepticus manifesting as utilization behavior of a mobile phone.

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Traces of functions in Fock spaces on lattices of critical density

Following a scheme of Levin we describe the values that functions in Fock spaces take on lattices of critical density in terms of both the size of the values and a cancelation condition that involves discrete versions of the Cauchy and Beurling-Ahlfors transforms.

Planning under partial observability by classical replanning: theory and experiments

Planning with partial observability can be formulated as a non-deterministic search problem in belief space. The problem is harder than classical planning as keeping track of beliefs is harder than keeping track of states, and searching for action policies is harder than searching for action sequences. In this work, we develop a framework for partial observability that avoids these limitations and leads to a planner that scales up to larger problems. For this, the class of problems is restricted to those in which 1) the non-unary clauses representing the uncertainty about the initial situation are nvariant, and 2) variables that are hidden in the initial situation do not appear in the body of conditional effects, which are all assumed to be deterministic. We show that such problems can be translated in linear time into equivalent fully observable non-deterministic planning problems, and that an slight extension of this translation renders the problem solvable by means of classical planners. The whole approach is sound and complete provided that in addition, the state-space is connected. Experiments are also reported.

Use of solaria to predict weed density and floristic composition in no-till cropping systems

The objective of this work was to evaluate the efficiency of a new method, developed for predicting density and floristic composition of weed communities in field crops. Based on the use of solaria (100 mm transparent plastic tarps lying on the soil) to stimulate weed seedlings emergence, the method was tested in Tandil, Argentina, from 1998 to 2001. The system involved corn and sunflower in commercial no-till system. Major weeds in the experiments included Digitaria sanguinalis, Setaria verticillata and S. viridis, which accounted for 98% of the weed community in the three years of experiments since 1998. Large numbers of Tagetes minuta, Chenopodium album and Ammi majus were present in 2001. Comparison of weed communities under solaria with communities in field crops indicated that the method is useful for predicting the presence and density of some major weed species, at both high and low densities, of individuals in areas of 10 ha using only five solaria. Low density of weed species makes the method particularly useful to help deciding the time for herbicide applications to avoid soil contamination.

In-vivo performance of high-density collagen gel tubes for urethral regeneration in a rabbit model.

Congenital malformations or injuries of the urethra can be treated using existing autologous tissue, but these procedures are sometimes associated with severe complications. Therefore, tissue engineering may be advantageous for generating urethral grafts. We evaluated engineered high-density collagen gel tubes as urethral grafts in 16 male New Zealand white rabbits. The constructs were either acellular or seeded with autologous smooth muscle cells, isolated from an open bladder biopsy. After the formation of a urethral defect by excision, the tissue-engineered grafts were interposed between the remaining urethral ends. No catheter was placed postoperatively. The animals were evaluated at 1 or 3 months by contrast urethrography and histological examination. Comparing the graft caliber to the control urethra at 3 months, a larger caliber was found in the cell-seeded grafts (96.6% of the normal caliber) than in the acellular grafts (42.3%). Histology of acellular and cell-seeded grafts did not show any sign of inflammation, and spontaneous regrowth of urothelium could be demonstrated in all grafts. Urethral fistulae, sometimes associated with stenosis, were observed, which might be prevented by urethral catheter application. High-density collagen gel tubes may be clinically useful as an effective treatment of congenital and acquired urethral pathologies.

Microclimatic characterization and productivity of coffee plants grown under shade of pigeon pea in Southern Brazil

Recent studies on coffee (Coffea arabica L.) cultivation in agroforestry systems in Southern Brazil have shown the potential of partial shading to improve management of this crop. The objective of this work was to evaluate microclimatic conditions and their effects on coffee production of plants shaded with pigeon pea (Cajanus cajan) in comparison to unshaded ones, from May 2001 to August 2002 in Londrina, State of Paraná, Brazil. The appraised microclimatic characteristics were: global radiation, photosynthetic and radiation balance; air, leaf and soil temperatures; and soil humidity. Shading caused significant reduction in incident global solar radiation, photosynthetically active radiation and net radiation, and attenuated maximum leaf, air and soil temperatures, during the day. Shade also reduced the rate of cooling of night air and leaf temperatures, especially during nights with radiative frost. Soil moisture at 0-10 cm depth was higher under shade. The shaded coffee plants produced larger cherries due to slower maturation, resulting in larger bean size. Nevertheless, plants under shade emitted less plagiotropic branches, with smaller number of nodes per branch, and fewer nodes with fruits, resulting in a large reduction in coffee production. These results show the need to find an optimal tree density and management that do not compromise coffee production and protect against extreme temperatures.

Postsynaptic density protein PSD-95 expression in Alzheimer's disease and okadaic acid induced neuritic retraction.

In order to understand how plasticity is related to neurodegeneration, we studied synaptic proteins with quantitative immunohistochemistry in the entorhinal cortex from Alzheimer patients and age-matched controls. We observed a significant decrease in presynaptic synaptophysin and an increase in postsynaptic density protein PSD-95, positively correlated with beta amyloid and phosphorylated Tau proteins in Alzheimer cases. Furthermore, Alzheimer-like neuritic retraction was generated in okadaic acid (OA) treated SH-SY5Y neuroblastoma cells with no decrease in PSD-95 expression. However, in a SH-SY5Y clone with decreased expression of transcription regulator LMO4 (as observed in Alzheimer's disease) and increased neuritic length, PSD-95 expression was enhanced but did not change with OA treatment. Therefore, increased PSD-95 immunoreactivity in the entorhinal cortex might result from compensatory mechanisms, as in the SH-SY5Y clone, whereas increased Alzheimer-like Tau phosphorylation is not related to PSD-95 expression, as suggested by the OA-treated cell models.

Investigation of High Density Polyethylene Pipe for Highway Applications, HR-373, Phase 1, 1996

In the past, culvert pipes were made only of corrugated metal or reinforced concrete. In recent years, several manufacturers have made pipe of lightweight plastic - for example, high density polyethylene (HDPE) - which is considered to be viscoelastic in its structural behavior. It appears that there are several highway applications in which HDPE pipe would be an economically favorable alternative. However, the newness of plastic pipe requires the evaluation of its performance, integrity, and durability; A review of the Iowa Department of Transportation Standard Specifications for Highway and Bridge Construction reveals limited information on the use of plastic pipe for state projects. The objective of this study was to review and evaluate the use of HDPE pipe in roadway applications. Structural performance, soil-structure interaction, and the sensitivity of the pipe to installation was investigated. Comprehensive computerized literature searches were undertaken to define the state-of-the-art in the design and use of HDPE pipe in highway applications. A questionnaire was developed and sent to all Iowa county engineers to learn of their use of HDPE pipe. Responses indicated that the majority of county engineers were aware of the product but were not confident in its ability to perform as well as conventional materials. Counties currently using HDPE pipe in general only use it in driveway crossings. Originally, we intended to survey states as to their usage of HDPE pipe. However, a few weeks after initiation of the project, it was learned that the Tennessee DOT was in the process of making a similar survey of state DOT's. Results of the Tennessee survey of states have been obtained and included in this report. In an effort to develop more confidence in the pipe's performance parameters, this research included laboratory tests to determine the ring and flexural stiffness of HDPE pipe provided by various manufacturers. Parallel plate tests verified all specimens were in compliance with ASTM specifications. Flexural testing revealed that pipe profile had a significant effect on the longitudinal stiffness and that strength could not be accurately predicted on the basis of diameter alone. Realizing that the soil around a buried HDPE pipe contributes to the pipe stiffness, the research team completed a limited series of tests on buried 3 ft-diameter HDPE pipe. The tests simulated the effects of truck wheel loads above the pipe and were conducted with two feet of cover. These tests indicated that the type and quality of backfill significantly influences the performance of HDPE pipe. The tests revealed that the soil envelope does significantly affect the performance of HDPE pipe in situ, and after a certain point, no additional strength is realized by increasing the quality of the backfill.

Basic density and pulp yield relationship with some chemical parameters in eucalyptus trees

The objective of this work was to evaluate the use of basic density and pulp yield correlations with some chemical parameters, in order to differentiate an homogeneous eucalyptus tree population, in terms of its potential for pulp production or some other technological applications. Basic density and kraft pulp yield were determined for 120 Eucalyptus globulus trees, and the values were plotted as frequency distributions. Homogenized samples from the first and fourth density quartiles and first and fourth yield quartiles were submitted to total phenols, total sugars and methoxyl group analysis. Syringyl/guaiacyl (S/G) and syringaldehyde/vanillin (S/V) ratios were determined on the kraft lignins from wood of the same quartiles. The results show the similarity between samples from high density and low yield quartiles, both with lower S/G (3.88-4.12) and S/V (3.99-4.09) ratios and higher total phenols (13.3-14.3 g gallic acid kg-1 ). Woods from the high yield quartile are statistically distinguished from all the others because of their higher S/G (5.15) and S/V (4.98) ratios and lower total phenols (8.7 g gallic acid kg-1 ). Methoxyl group and total sugars parameters are more adequate to distinguish wood samples with lower density.

Effect of Density on Marshall Stability of Hot-Mix Asphaltic Concrete, MLR-82-01, 1982

The Iowa D.O.T. specifications do not require 100 percent of 50 blow Marshall density (generally 94%) for field compaction. However, stabilities are determined in the Laboratory on specimens compacted to 100 percent of Marshall density. The purpose of this study is to determine the stabilities of specimens compacted to various densities which are below 100 percent of the 50 blow Marshall density.

Investigation of Electromagnetic Gauges for Determination of In-Place Density of HMA Pavements, TR-576, 2009

This study evaluated the use of electromagnetic gauges to determine the adjusted densities of HMA pavements. Field measurements were taken with two electromagnetic gauges, the Pavement Quality Indicator (PQI) 301 and the Pavetracker Plus 2701B. Seven projects were included in the study with 3 to 5 consecutive paving days. For each day/lot 20 randomly selected locations were tested along with seven core locations. The analysis of PaveTracker and PQI density consisted of determining which factors are statistically significant, and core density residuals and a regression analysis of core as a function of PaveTracker and PQI readings. The following key conclusions can be stated: 1. Core density, traffic and binder content were all found to be significant for both electromagnetic gauges studied, 2. Core density residuals are normally distributed and centered at zero for both electromagnetic gauges, 3. For PaveTracker readings, statistically one third of the lots do not have an intercept that is zero and two thirds of the lots do not rule out a scaler correction factor of zero, 4. For PQI readings, statistically the 95% confidence interval rules out the intercept being zero for all seven projects and six of the seven projects do not rule out the scaler correction factor being zero, 5. The PQI 301 gauge should not be used for quality control or quality assurance, and 6. The Pavetracker 2701B gauge can be used for quality control but not quality assurance. This study has found that with the limited sample size, the adjusted density equations for both electromagnetic gauges were determined to be inadequate. The PaveTracker Plus 2701B was determined to be better than the PQI 301. The PaveTracker 2701B could still be applicable for quality assurance if the number of core locations per day is reduced and supplemented with additional PaveTracker 2701B readings. Further research should be done to determine the minimum number of core locations to calibrate the gauges each day/lot and the number of additional PaveTracker 2701B readings required.