Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.     

Microscopic examination of the microstructure and deformation of conventional and auxetic foams

Auxetic materials have a negative Poisson’s ratio, that is, they expand laterally when stretched longitudinally. One way of obtaining a negative Poisson’s ratio is by using a re-entrant cell structure. Auxetic foam was fabricated from a conventional polymeric foam. Assuming similar mechanical properties for the solid material comprising the foams, the principle variable affecting the properties of the foam is the geometry of the cells. This means that the unusual mechanical properties of auxetic foams are attributed to the deformation characteristics of re-entrant microstructures. In this paper, the results of optical- and scanning electron-microscopic studies of the geometrical parameters for the different foams examined are presented. Examples of the microstructural deformation mechanisms observed are also presented. Comparison between the conventional foams and their auxetic conversions are also made. This revised version was published online in November 2006 with corrections to the Cover Date.     

Shifts produced by mode filters on curved intensity contours

The author considers the shifts produced by mode filters on curved boundaries and contours. It is shown that these are similar to those produced by mean and median filters, the cases of linear intensity variations and of step edges being somewhat different and at opposite extremes of a continuum. Thus, shifts are intrinsic to basic neighbourhood averaging techniques, and can be avoided only by specially designed operators     

On the Yustova threshold plates

A response to criticism of threshold plates for the study of color vision developed at the Mendeleev All-Russia Research Institute of Metrology and published in 1994 is presented. The critics base their conclusions on colorimetric testing and the examination of the plates. In response to the article by M. V. Danilova and J. D. Mollon [4]. __________ Translated from Izmeritel’naya Tekhnika, No. 1, pp. 37–39, January, 2007.     

The design of experiments when there are errors in all the variables

The Error-in-Variables Model (EVM) applies to a large class of problems in parameter estimation in which there is error in all the variables. This property makes it of more general applicability than the widely used technique of ordinary Least Squares. While there is a voluminous literature on EVM there is nothing on a general method for designing experiments when EVM applies. In this paper we present an extension of the concept of D-optimality to provide such a general method. It is illustrated by applying it to the estimation of copolymer reactivity ratios and to fitting an ellipse.     

Complex frequency technique for linear and second harmonic optical properties of metallic surfaces

We describe a complex frequency technique for evaluating the linear and quadratic dielectric responses of metal surfaces, illustrated by application to the surface of jellium. The electric susceptibilities are shorter-range functions of the spatial coordinates at complex frequency, whereas their general behaviour is complicated, long-range and highly oscillatory at real frequency. As a result the linear and the second harmonic electric charges induced by an optical perturbation are then numerically easier to calculate at complex frequency. As the functions which characterize the optical behaviour of the metal surface are analytic in the upper complex frequency half-plane, the dielectric response at real frequency can be deduced by analytic continuation from the results at complex frequency. We illustrate and discuss this approach, which should be useful for studying more realistic models of a surface in which the crystal potential is included, and where a direct calculation of the dielectric response is difficult to obtain at real frequency.     

MR monitoring of focused ultrasonic surgery of renal cortex: experimental and simulation studies

The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.     

A pixellated grating array using photoelectrochemical etching on aGaAs waveguide

We have demonstrated and evaluated a grating array outcoupler fabricated by photoelectrochemical (PEC) etching, a manufacturable and practical approach for fabrication of grating-based III-V semiconductor waveguide devices. An array of submicron period gratings was etched into photolithographically delineated areas in a single PEC step. The fabricated devices are: 10-μm wide rib waveguides with 0.35-μm first-order outcoupling gratings; and 10-μm wide rib waveguides with 10 μm×10 μm pixellated areas of gratings. Device characterization demonstrates the effectiveness of outcoupling grating fabrication using PEC and that the pixellated grating outcoupler is an effective and simple means of generating an optical beam array