The mechanisms of adaptation for muscle fascicle length changes with exercise: Implications for spastic muscle.

We are proposing optimal training conditions that can lead to an increase in the number of serial sarcomeres (SSN) and muscle fascicle length (FL) in spastic muscles. Therapeutic interventions for increasing FL in clinical populations with neurological origin, in whom relative shortness of muscle fascicles contributed to the presentation of symptoms such as spasticity, contracture, and limited functional abilities, do not generally meet these conditions, and therefore, result in less than satisfactory outcomes. Based on a review of literature, we argue that protocols of exercise interventions that led to sarcomerogenesis, and increases in SSN and FL in healthy animal and human models satisfied three criteria: 1) all involved eccentric exercise at appropriately high velocity; 2) resulted in positive strain of muscle fascicles; and 3) momentary deactivation in the stretched muscle. Accordingly, to increase FL in spastic muscles, new exercise protocols in which the three presumed criteria are satisfied, must be developed, and long-term muscle architectural and functional adaptations to such trainings must be examined.

Remarkable impact of low BiYbO3 doping levels on the local structure and phase transitions of BaTiO3.

In situ Raman spectroscopy shows the simultaneous incorporation of small amounts of Bi3+ and Yb3+ into the lattice of BaTiO3 to break the average symmetry inferred from X-ray powder diffraction analysis and permittivity measurements. In particular, Bi3+ with a stereochemically active lone-pair of electrons induces severe lattice strain and the coexistence of different local crystal symmetries over a wide temperature range, effectively controlling the physical properties, such as the temperature dependence of the permittivity and the Curie temperature. These results show that compositional gradients based in small variations of these two dopants could successfully explain the enhanced thermal stability of the permittivity in core-shell type ceramics, whereas the lower capacitance of the shell can also cap the maximum permittivity at the Curie temperature.

Lateral gradients of phases, residual stress and hardness in a laser heated Ti0.52Al0.48N coating on hard metal.

The influence of a local thermal treatment on the properties of Ti-Al-N coatings is not understood. In the present work, a Ti0.52Al0.48N coating on a WC-Co substrate was heated with a diode laser up to 900 °C for 30 s and radially symmetric lateral gradients of phases, residual stress and hardness were characterized ex-situ using position-resolved synchrotron X-ray diffraction, Raman spectroscopy, transmission electron microscopy and nanoindentation. The results reveal (i) a residual stress relaxation at the edge of the irradiated area and (ii) a compressive stress increase of few GPa in the irradiated area center due to the Ti-Al-N decomposition, in particular due to the formation of small wurtzite (w) AlN domains. The coating hardness increased from 35 to 47 GPa towards the center of the heated spot. In the underlying heated substrate, a residual stress change from about - 200 to 500 MPa down to a depth of 6 µm is observed. Complementary, in-situ high-temperature X-ray diffraction analysis of stresses in a homogeneously heated Ti0.52Al0.48N coating on a WC-Co substrate was performed in the range of 25-1003 °C. The in-situ experiment revealed the origin of the observed thermally-activated residual stress oscillation across the laser heated spot. Finally, it is demonstrated that the coupling of laser heating to produce lateral thermal gradients and position-resolved experimental techniques opens the possibility to perform fast screening of structure-property relationships in complex materials.

Putative contributors to the secular increase in obesity: exploring the roads less traveled.

OBJECTIVE: To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices. DESIGN: A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity. DATA: Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available. RESULTS: For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations. CONCLUSION: Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Improving the detection of simulated masses in mammograms through two different image-processing techniques.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether contrast-limited adaptive histogram equalization (CLAHE) or histogram-based intensity windowing (HIW) improves the detection of simulated masses in dense mammograms. MATERIALS AND METHODS: Simulated masses were embedded in portions of mammograms of patients with dense breasts; the mammograms were digitized at 50 microm per pixel, 12 bits deep. In two different experiments, images were printed both with no processing applied and with related parameter settings of two image-processing methods. A simulated mass was embedded in a realistic background of dense breast tissue, with its position varied. The key variables in each trial included the position of the mass, the contrast levels of the mass relative to the background, and the selected parameter settings for the image-processing method. RESULTS: The success in detecting simulated masses on mammograms with dense backgrounds depended on the parameter settings of the algorithms used. The best HIW setting performed better than the best fixed-intensity window setting and better than no processing. Performance with the best CLAHE settings was no different from that with no processing. In the HIW experiment, there were no significant differences in observer performance between processing conditions for radiologists and nonradiologists. CONCLUSION: HIW should be tested in clinical images to determine whether the detection of masses by radiologists can be improved. CLAHE processing will probably not improve the detection of masses on clinical mammograms.

Measuring the genetic influence in modulating the human life span: gene-environment interaction and the sex-specific genetic effect.

New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene-environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographic information in the estimation of the genetic influence on life spans. Based on Cox's proportional hazard assumption, the model measures the risks for each gene as well as for gene-environment and gene-sex interactions, while controlling for confounding factors. A two-step MLE is introduced to obtain a non-parametric form of the baseline hazard function. The model is applied to genotypic data from Italian centenarian studies to estimate relative risks of candidate genes, risks due to interactions and initial frequencies of different genes in the population. Results from models that either do or do not take into consideration individual heterogeneity are compared. It is shown that ignoring the existence of heterogeneity can lead to a systematic underestimation of genetic effects and effects due to interactions.

Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2 in a polymeric matrix.

PURPOSE: The purpose of this study was to develop a polymeric sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2) and to evaluate local bone growth induced by the sustained release of BMP-2 in an animal model. METHODS: BMP-2 was incorporated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres to obtain different release rates. Two sustained and an immediate release implants were produced by suspending the BMP-2 loaded PLGA microspheres in aqueous sodium carboxymethylcellulose (CMC), lyophilizing, and cutting the dried materials to the size of the animal bone defects. The local in vivo release at the implantation site in rat calvarial defects was determined by gamma scintigraphy using radiolabeled BMP-2. The local bone induction in the critical size of rabbit calvarial defects was evaluated six weeks post implantation. RESULTS: The immediate release implant showed about 65% initial drug release within 24 h and the remaining BMP-2 quickly exhausted from the implantation site within 7 days. The sustained release implants, showing 45-55% initial release followed by a prolonged release for 21 days, released a greater amount of BMP-2 at the implantation site and maintained higher serum BMP-2 for the longer period of time compared to the immediate release implant. Significant bone growth was observed in all BMP-2 treated defects while the defects without treatment or with BMP-2-free implant showed minimal bone healing. 75-79% of rabbit calvarial defect area was healed with newly induced bone matrix by the sustained release implants in 6 weeks as compared to 45% recovery from the immediate release implant. CONCLUSION: The sustained delivery of BMP-2 based on the biodegradable PLGA microsphere system resulted in faster and more complete bone healing in the animal model.

Hypertrophic cardiomyopathy. Tools for identifying risk and alleviating symptoms.

Hypertrophic cardiomyopathy is characterized by left or right ventricular hypertrophy that is usually asymmetric and involves the interventricular septum. The condition has numerous genetic, anatomic, and clinical variations and continues to stimulate interest and investigation into causes and treatment options. New genetic forms of the disorder are being identified because of the rapid growth of molecular genetics. However, even with technological advances and a large database of information, risk stratification and treatment of hypertrophic cardiomyopathy remain difficult and controversial. Because of the high risk of sudden death, it is imperative that patients be advised against participation in competitive sports.

Effect of display luminance on the feature detection rates of masses in mammograms.

Our purpose in this study was to determine the importance of the luminance range of the display system for the detection of simulated masses in mammograms. Simulated masses were embedded in selected portions (512 x 512 pixels) of mammograms digitized at 50 micro pixels, 12 bits deep. The masses were embedded in one of four quadrants in the image. An observer experiment was conducted in which the observer's task was to determine in which quadrant the mass is located. The key variables involved in each trial included the position of the mass, the contrast level of the mass, and the luminance of the display. The contrast of the mass with respect to the background was fixed to one of four selected contrast levels. The digital images were printed to film, and displayed on a mammography lightbox. The display luminance was controlled by placing neutral density films between the laser printed films of mammographic backgrounds and the lightbox. The resulting maximum luminances examined in this study ranged from 34 cd/m2 to 2056 cd/m2. Twenty observers viewed 80 different images (20 observations at each of 4 different mass contrast levels) under each of the 5 luminance conditions for a total of 800 independent observations per observer. An analysis of variance yielded no statistically significant correlation between the luminance range of the display and the feature detection rate of the simulated masses in mammograms. However, the performance of the lower luminance display systems (less than 300 cd/m2), may be reduced due to the high levels of ambient light found in many reading environments.

Genes, demography, and life span: the contribution of demographic data in genetic studies on aging and longevity.

In population studies on aging, the data on genetic markers are often collected for individuals from different age groups. The purpose of such studies is to identify, by comparison of the frequencies of selected genotypes, "longevity" or "frailty" genes in the oldest and in younger groups of individuals. To address questions about more-complicated aspects of genetic influence on longevity, additional information must be used. In this article, we show that the use of demographic information, together with data on genetic markers, allows us to calculate hazard rates, relative risks, and survival functions for respective genes or genotypes. New methods of combining genetic and demographic information are discussed. These methods are tested on simulated data and then are applied to the analysis of data on genetic markers for two haplogroups of human mtDNA. The approaches suggested in this article provide a powerful tool for analyzing the influence of candidate genes on longevity and survival. We also show how factors such as changes in the initial frequencies of candidate genes in subsequent cohorts, or secular trends in cohort mortality, may influence the results of an analysis.

Posterior chamber phakic intraocular lens for hyperopia.

PURPOSE: A Phase I U.S. FDA clinical study of a plate haptic posterior chamber phakic intraocular lens (STAAR Surgical Implantable Contact Lens) for treatment of hyperopia was conducted at 4 sites in the United States. The purpose of this report is to assess the short-term safety and efficacy. METHODS: Ten patients with hyperopia between +2.50 and +10.875 D were implanted in one eye each with the posterior chamber plate phakic intraocular lens and were examined at baseline and 1 day, 1 week, 1, 3, and 6 months after surgery. Mean baseline hyperopia was +6.63 D. RESULTS: At 6 months postoperatively, 7 of 10 eyes (70%) had an uncorrected visual acuity of 20/20 or better and 10 of 10 (100%) had 20/40 or better. Eight of ten eyes (80%) had a spectacle-corrected visual acuity within 1 line of baseline; the other two eyes (20%) had an improvement of 3 lines. Mean 6-month postoperative spherical equivalent refraction was +0.20 +/- 0.61D (range, -0.50 to +1.50 D), a reduction of 6.025 D from baseline. Eight of 10 eyes (80%) were within +/-0.50 D of emmetropia, 9 eyes (90%) were within +/-1.00 D, and all eyes (100%) were within +/-1.50 D. No operative or postoperative complications or adverse reactions were observed. CONCLUSIONS: Results support the short-term safety, efficacy, and predictability of the STAAR Surgical Implantable Contact Lens (plate haptic posterior chamber phakic intraocular lens) in the treatment of hyperopia.

Contrast limited adaptive histogram equalization image processing to improve the detection of simulated spiculations in dense mammograms.

The purpose of this project was to determine whether Contrast Limited Adaptive Histogram Equalization (CLAHE) improves detection of simulated spiculations in dense mammograms. Lines simulating the appearance of spiculations, a common marker of malignancy when visualized with masses, were embedded in dense mammograms digitized at 50 micron pixels, 12 bits deep. Film images with no CLAHE applied were compared to film images with nine different combinations of clip levels and region sizes applied. A simulated spiculation was embedded in a background of dense breast tissue, with the orientation of the spiculation varied. The key variables involved in each trial included the orientation of the spiculation, contrast level of the spiculation and the CLAHE settings applied to the image. Combining the 10 CLAHE conditions, 4 contrast levels and 4 orientations gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 40 backgrounds. Twenty student observers were asked to detect the orientation of the spiculation in the image. There was a statistically significant improvement in detection performance for spiculations with CLAHE over unenhanced images when the region size was set at 32 with a clip level of 2, and when the region size was set at 32 with a clip level of 4. The selected CLAHE settings should be tested in the clinic with digital mammograms to determine whether detection of spiculations associated with masses detected at mammography can be improved.

Implantable contact lens for moderate to high myopia: phase 1 FDA clinical study with 6 month follow-up.

PURPOSE: To assess the short-term safety and efficacy of the implantable contact lens (ICL) to treat moderate to high myopia. SETTING: Phase 1 U.S. Food and Drug Administration clinical study of the ICL conducted at four sites in the United States. METHODS: Ten patients with myopia of 7.00 diopters (D) or greater had implantation of a Staar Surgical ICL and were examined preoperatively (baseline) and 1 day, 1 week, and 1, 3, and 6 months postoperatively. Mean preoperative myopia was 7.75 D (range 7.25 to 9.37 D). RESULTS: Six months postoperatively, 5 of 10 eyes (50%) had an uncorrected visual acuity (UCVA) of 20/20 or better, and all eyes had a UCVA of 20/30 or better. All eyes had a best spectacle-corrected visual acuity (BSCVA) of 20/20 or better and 6 eyes (60%), of 20/15 or better. Six eyes (60%) had an improvement of one or more lines of BSCVA. Mean postoperative spherical equivalent was -0.025 D +/- 0.47 (SD). Eight eyes (80%) were within +/- 0.250 D of emmetropia, and all were within +/- 1.125 D. No intraoperative or postoperative complications or adverse reactions were observed. CONCLUSIONS: The results support the short-term safety, efficacy, and predictability of ICL implantation to treat moderate to high myopia.

Does intensity windowing improve the detection of simulated calcifications in dense mammograms?

This study attempts to determine whether intensity windowing (IW) improves detection of simulated calcifications in dense mammograms. Clusters of five simulated calcifications were embedded in dense mammograms digitized at 50-microns pixels, 12 bits deep. Film images with no windowing applied were compared with film images with nine different window widths and levels applied. A simulated cluster was embedded in a realistic background of dense breast tissue, with the position of the cluster varied. The key variables involved in each trial included the position of the cluster, contrast level of the cluster, and the IW settings applied to the image. Combining the ten IW conditions, four contrast levels and four quadrant positions gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 160 backgrounds. The entire experiment consisted of 800 trials. Twenty student observers were asked to detect the quadrant of the image in which the mass was located. There was a statistically significant improvement in detection performance for clusters of calcifications when the window width was set at 1024 with a level of 3328, and when the window width was set at 1024 with a level of 3456. The selected IW settings should be tested in the clinic with digital mammograms to determine whether calcification detection performance can be improved.

Hepatic enhancement and metastatic lesion conspicuity on CT scans: influence of intravenous glucagon and oral CT contrast material.

PURPOSE: To determine the effect of glucagon and orally administered contrast material on hepatic enhancement and metastatic lesion conspicuity on computed tomographic (CT) scans. MATERIALS AND METHODS: Nine patients with a history of hepatic metastasis underwent two CT examinations with intravenously administered contrast material. Each patient was given orally administered CT contrast material for the first examination. No oral contrast material was given in the second examination. Five patients underwent the initial CT with intravenous administration of 1 mg of glucagon; the second examination was performed without glucagon. Four patients were administered glucagon before the second examination, but no glucagon was administered before the first. Attenuation in the liver, portal vein, and aorta was measured by observers blinded to whether the patient had been given glucagon. Lesion conspicuity was rated on a continuous scale. RESULTS: Greater mean hepatic enhancement was noted on scans of patients in whom oral contrast material was administered (mean, 52 HU) versus those in whom no oral contrast material was administered (mean, 47 HU; P = .019). Glucagon was not associated with greater hepatic enhancement. Neither oral contrast material nor glucagon had a significant effect on lesion conspicuity. CONCLUSION: Oral CT contrast material is associated with a small increase in hepatic enhancement that does not appear to be clinically important. Glucagon does not appear to affect hepatic enhancement or lesion conspicuity in humans.

Ablation zone centration after photorefractive keratectomy and its effect on visual outcome.

PURPOSE: To determine the relation between ablation zone decentration, measured by corneal topography, and visual and refractive outcome, contrast sensitivity, glare, and subjective reports of halos after photorefractive keratectomy (PRK). SETTING: Eye Foundation, University of Missouri-Kansas City School of Medicine. METHODS: This study comprised 70 eyes of 70 patients enrolled into Phase III of the clinical investigation of the VISX 20/20 excimer laser for the correction by PRK of 1.00 to 6.00 diopters of pre-existing sphere. All patients were treated with 5.0 mm ablation zones. Preoperative and postoperative corneal topography in 67 eyes was done using the EyeSys system. Ablation zone decentration was measured relative to the pupillary center at all postoperative visits as determined from the difference or change map. RESULTS: Mean distance between the ablation zone center and the pupillary center was 0.62 mm +/- 0.34 (SD) (range 0.07 to 1.67 mm). Twenty seven of 66 patients with corneal topography (40.9%) had decentrations less than 0.5 mm; decentrations in 6 eyes (9.1%) were 1.0 mm or more from the pupillary center. No correlation was observed between the magnitude of decentration and 1 year postoperative best spectacle-corrected acuity (r = -.04, P = .76), uncorrected acuity (r = -.03, P = .84), or spherical equivalent (r = -.07, P = .59); preoperative uncorrected acuity (r = .04, P = .73) or spherical equivalent (r = -.02, P = .90); or reduction in spherical equivalent (r = .02, P = .89). The magnitude of decentration was correlated with preoperative spectacle-corrected acuity (r = -.37, P = .002). There was no difference in contrast sensitivity, glare, or halos between the cases with less than 0.5 mm of decentration and those with 0.5 mm or more of decentration. CONCLUSIONS: The degree of ablation zone decentration did not affect postoperative Snellen visual acuity or contrast sensitivity.