Mandibular cortical bone evaluation on cone beam computed tomography images of patients with bisphosphonate related osteonecrosis of the jaws

Objectives The objective of this study was to develop a technique for detecting cortical bone dimensional changes in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). Study Design Subjects with BRONJ who had cone-beam computed tomography imaging were selected, with age- and gender-matched controls. Mandibular cortical bone measurements to detect bisphosphonate-related cortical bone changes were made inferior to mental foramen, in 3 different ways: within a fixed sized rectangle, in a rectangle varying with the cortical height, and a ratio between area and height. Results Twelve BRONJ cases and 66 controls were evaluated. The cortical bone measurements were significantly higher in cases than controls for all 3 techniques. The bone measurements were strongly associated with BRONJ case status (odds ratio 3.36-7.84). The inter-rater reliability coefficients were high for all techniques (0.71-0.90). Conclusions Mandibular cortical bone measurement is a potentially useful tool in the detection of bone dimensional changes caused by bisphosphonates. Long-term administration of bisphosphonates (BPs) affects bone quality and metabolism following accumulation in bone.1 Since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were published in 2003,2 there has been a search for factors that can predict the onset of the condition. Oral and intravenous BPs reduce bone resorption, increase mineral content of bone, and alter bony architecture.3, 4, 5 and 6 Previous studies have demonstrated these changes both radiographically and following histologic analysis.1, 3, 7, 8, 9 and 10 The BP-related jaw changes may present radiological features, such as thickening of lamina dura and cortical borders, diffuse sclerosis, and narrowing of the mandibular canal3 and 11; however, oral radiographs of patients taking BPs do not consistently show radiographic changes to the jaws.11 and 12 The challenge is to find imaging tools that could improve the detection of changes in the bone associated with BP use. Various skeletal radiographic features associated with BRONJ in conventional periapical and panoramic radiographs, computed tomography, magnetic resonance imaging, and nuclear bone scanning have been described.3, 8, 9, 10 and 11 There has also been a search for BP-related quantitative methods for the evaluation of radiographic images, to avoid observer subjectivity in interpretation. Factors thought to be important include trabecular and cortical structure, and bone mineralization.4 Consequently, measurable bone data have been reported in subjects taking BPs through many techniques, including bone density, architecture, and cortical bone thickness.1, 4, 7 and 13 Trabecular microarchitecture of postmenopausal women has been evaluated with noninvasive techniques, such as high-resolution magnetic resonance images showing less deterioration of the bone 1 year after initiation of oral BP therapy.4 A decrease in bone turnover and a trend for an increase in the bone wall thickness has been detected by histomorphometry in subjects taking BPs.1 Alterations in the cortical structure of the second metacarpal have been detected in digital x-ray radiogrammetry of postmenopausal women treated with BPs.7 Mandibular cortical width may be measured on dental panoramic radiographs, and it has been suggested as a screening tool for referring patients for bone densitometry for osteoporosis investigation.14 and 15 Inhibition of the intracortical bone remodeling in the mandible of mice taking BPs has been reported.16 Thus, imaging evaluation of the mandibular cortical bone could be a biologically plausible way to detect BP bone alterations. Computed tomography can assess both cortical and trabecular bone characteristics. Cone-beam computed tomography (CBCT) can provide 3-dimensional information, while using lower doses and costing less than conventional CT. The CBCT images have been studied as a tool for the measurement of trabecular bone in patients with BRONJ.13 Therefore, cortical bone measurements on CBCT of the jaws might also help to understand bone changes in patients with BRONJ. There is no standard in quantifying dimensional changes of mandibular cortical bone. We explored several different approaches to take into consideration possible changes in length, area, and volume. These led to the 3 techniques developed in this study. This article reports a matched case-control study in which mandibular cortical bone was measured on CBCT images of subjects with BRONJ and controls. The aim of the study was to explore the usefulness of 3 techniques for detecting mandibular cortical bone dimensional changes caused by BP.

Análise da distribuição de tensões em reabilitação com implantes cone morse em maxilar posterior: estudo pelo MEF 3D não linear

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The cone loading test to estimate deformability moduli of a tropical soil

The Cone Loading Test (CLT) consists of the execution of a load test on the piezocone probe in conjunction with the CPT test. The CLT yields the modulus ECLT, a parameter that can be used in the estimative of foundation settlement. It is also presented here the interpretation and the process to determine ECLT values from the stress-displacement curves obtained from cone loading tests. Several CLT tests were conducted at the experimental research site of São Paulo State University, Bauru-SP-Brazil. The geotechnical profile at the studied site is a brown to bright red slightly clayey fine sand, a tropical soil common to this region which is lateritic, unsaturated and collapsible. The results of CLT tests satisfactorily represent the behavior of the investigated soil. The penetrometric modulus ECLT for each depth was calculated considering the elastic behavior in the initial linear segment of the soil stress-strain curve. The ECLT moduli obtained for the various tests were compared to moduli obtained from PMT and DMT test results performed at same studied site. The shear modulus degradation curves obtained from the CLT tests are also presented. The comparison to PMT and DMT results indicates the CLT test is a viable complementary test to the CPT in the quest for better understanding stress-strain behavior of soils. Further, the CLT test provides a graphic visualization of the degradation of the shear modulus with increasing levels of strain. As a hybrid geotechnical test, CPT+CLT can be valuable in the investigation of non-conventional collapsible soils, whose literature lack reference parameters for the prediction of settlement in the design of foundations.

Determining spatial and temporal scales for management: lessons from whaling

Selection of the appropriate management unit is critical to the conservation of animal populations. Defining such units depends upon knowledge of population structure and upon the timescale being considered. Here, we examine the trajectory of eleven subpopulations of five species of baleen whales to investigate temporal and spatial scales in management. These subpopulations were all extirpated by commercial whaling, and no recovery or repopulation has occurred since. In these cases, time elapsed since commercial extinction ranges from four decades to almost four centuries. We propose that these subpopulations did not recover either because cultural memory of the habitat has been lost, because widespread whaling among adjacent stocks eliminated these as sources for repopulation, and/or because segregation following exploitation produced the abandonment of certain areas. Spatial scales associated with the extirpated subpopulations are frequently smaller than those typically employed in management. Overall, the evidence indicates that: (1) the time frame for management should be at most decadal in scope (i.e., <100 yr) and based on both genetic and nongenetic evidence of population substructure, and (2) at least some stocks should be defined on a smaller spatial scale than they currently are.

Evaluating Measurement Invariance with Censored Ordinal Data: A Monte Carlo Comparison of Alternative Model Estimators and Scales of Measurement

Evaluations of measurement invariance provide essential construct validity evidence. However, the quality of such evidence is partly dependent upon the validity of the resulting statistical conclusions. The presence of Type I or Type II errors can render measurement invariance conclusions meaningless. The purpose of this study was to determine the effects of categorization and censoring on the behavior of the chi-square/likelihood ratio test statistic and two alternative fit indices (CFI and RMSEA) under the context of evaluating measurement invariance. Monte Carlo simulation was used to examine Type I error and power rates for the (a) overall test statistic/fit indices, and (b) change in test statistic/fit indices. Data were generated according to a multiple-group single-factor CFA model across 40 conditions that varied by sample size, strength of item factor loadings, and categorization thresholds. Seven different combinations of model estimators (ML, Yuan-Bentler scaled ML, and WLSMV) and specified measurement scales (continuous, censored, and categorical) were used to analyze each of the simulation conditions. As hypothesized, non-normality increased Type I error rates for the continuous scale of measurement and did not affect error rates for the categorical scale of measurement. Maximum likelihood estimation combined with a categorical scale of measurement resulted in more correct statistical conclusions than the other analysis combinations. For the continuous and censored scales of measurement, the Yuan-Bentler scaled ML resulted in more correct conclusions than normal-theory ML. The censored measurement scale did not offer any advantages over the continuous measurement scale. Comparing across fit statistics and indices, the chi-square-based test statistics were preferred over the alternative fit indices, and ΔRMSEA was preferred over ΔCFI. Results from this study should be used to inform the modeling decisions of applied researchers. However, no single analysis combination can be recommended for all situations. Therefore, it is essential that researchers consider the context and purpose of their analyses.

Generalizing the dynamic field theory of spatial cognition across real and developmental time scales

Within cognitive neuroscience, computational models are designed to provide insights into the organization of behavior while adhering to neural principles. These models should provide sufficient specificity to generate novel predictions while maintaining the generality needed to capture behavior across tasks and/or time scales. This paper presents one such model, the Dynamic Field Theory (DFT) of spatial cognition, showing new simulations that provide a demonstration proof that the theory generalizes across developmental changes in performance in four tasks—the Piagetian A-not-B task, a sandbox version of the A-not-B task, a canonical spatial recall task, and a position discrimination task. Model simulations demonstrate that the DFT can accomplish both specificity—generating novel, testable predictions—and generality—spanning multiple tasks across development with a relatively simple developmental hypothesis. Critically, the DFT achieves generality across tasks and time scales with no modification to its basic structure and with a strong commitment to neural principles. The only change necessary to capture development in the model was an increase in the precision of the tuning of receptive fields as well as an increase in the precision of local excitatory interactions among neurons in the model. These small quantitative changes were sufficient to move the model through a set of quantitative and qualitative behavioral changes that span the age range from 8 months to 6 years and into adulthood. We conclude by considering how the DFT is positioned in the literature, the challenges on the horizon for our framework, and how a dynamic field approach can yield new insights into development from a computational cognitive neuroscience perspective.

Weekly Problems Scales: Instruments for Sexually Abused Youth and Their Nonoffending Parents in Treatment

This study’s purpose was to determine if efficient measures could be created to assess multiple problematic behaviors identified in youth who were sexually abused and in treatment. Because of the lack of easily administered brief instruments that assess multiple domains of interest in this population, complementary parent and child assessment measures were developed. The Weekly Problems Scale–Child Version (WPSC) and the Weekly Problems Scale–Parent Version (WPS-P) were created to monitor the weekly progress of the child and family in treatment and focus specifically on common areas of difficulties in this population. Exploratory factor analysis was conducted to assist in identifying the number of underlying dimensions in the scales. Results indicate that the WPS-C and WPS-P demonstrate adequate internal consistency, temporal stability, and construct validity. The WPS-C and WPSP display significant promise as research and clinical assessment tools for use with youth who are sexually abused and their nonoffending parents in treatment.

Heterochromatic Flicker Electroretinograms Reflecting Luminance and Cone Opponent Activity in Glaucoma Patients

PURPOSE. To measure heterochromatic flicker electroretinograms (ERGs) at high (36 Hz) and intermediate (12 Hz) temporal frequencies to evaluate luminance and cone opponent responses, respectively, in glaucoma eyes with (perimetric) and without (preperimetric) visual field defects. METHODS. Flicker ERGs were recorded from one randomly chosen dilated eye of 32 patients (mean age, 61 +/- 11 years; 15 men, 17 women) from the Erlangen Glaucoma Registry and from 24 healthy volunteers (mean age, 43 +/- 11 years; 14 men, 10 women). Red and green light-emitting diodes in a Ganzfeld stimulator were sine wave-modulated in counterphase. The responses were measured at 36 Hz, the frequency at which ERGs reflect activity of the luminance pathway, and at 12 Hz, the frequency at which ERGs reflect chromatic activity. RESULTS. Response amplitudes were similar in glaucoma patients and controls. Phase differences were observed in patients with visual field defects (perimetric) compared with the control group at 36 and 12 Hz in the first harmonic and second harmonic responses. Patients without visual field defects (preperimetric) showed phase differences for the second harmonic component at 36 Hz. No age effect on response amplitudes and phases was found in any of the subject groups (controls and patients). CONCLUSIONS. The responses displayed phase differences but not amplitude differences in perimetric glaucoma patients at both 36 and 12 Hz, suggesting that both magnocellular and parvocellular pathways are affected. Preperimetric glaucoma patients also showed phase differences. The response phase may be sensitive to early dysfunction of the inner retina. (ClinicalTrials.gov number, NCT00494923.) (Invest Ophthalmol Vis Sci. 2011;52:6757-6765) DOI:10.1167/iovs.11-7538

Cone contrast influence on components of the pattern onset/offset VECP

Transient visual evoked cortical potentials (VECP) were recorded from the scalp of healthy normal trichromats (n = 12). VECPs were elicited by onset/offset presentation of patterned stimuli of two kinds: isochromatic luminance-modulated, and equiluminant red-green modulated, sine wave gratings. The amplitude and latency of the major onset components of the onset/offset VECP were measured and plotted as a function of the logarithm of pooled cone contrast. The early onset components, achromatic C1 and chromatic N1, increase linearly with log contrast, but N1 has a higher contrast gain than C1. The late onset components, achromatic C2 and chromatic N2, have similar contrast gain, and similar response as a function of contrast level: both increase in the low-to-medium range of contrasts and saturate at high contrast levels. In the range of pooled cone contrast tested, C1 and N1 show similar latencies, whilst C2 shows shorter latencies than N2. We suggest that C1 and N1 are generated by the same visual mechanism with high red-green contrast gain and low luminance contrast gain, whilst C2 and N2 are generated by different visual mechanisms.

Absence of ocular interaction in flicker ERG responses reflecting cone opponent and luminance signals

The aim of the study was to investigate whether there is an ocular interaction in the flicker ERG responses reflecting luminance and cone opponency in normal human subjects. Flicker ERGs were recorded from one dilated eye of 10 healthy volunteers. Each subject was tested twice: once with and once without occluding the opposite eye. Red and green LEDs were modulated in counterphase in a Ganzfeld stimulator. ERG responses were recorded for different ratios of the modulation in the red and green LEDs and at 12 and 36 Hz. The amplitudes and phases of the fundamental components were compared between the conditions with and without occlusion. The 12-Hz flicker ERGs reflected activity of the cone opponent channel, whereas the 36-Hz data reflected luminance activity. There were no significant differences between the conditions with and without occluding the opposite eye for any of the stimulus protocols. Ocular interaction is absent in flicker ERGs reflecting cone opponent and luminance activity.

Cone photopigment variations in Cebus apella monkeys evidenced by electroretinogram measurements and genetic analysis

We investigated the color vision pattern in Cebus apella monkeys by means of electroretinogram measurements (ERG) and genetic analysis. Based on ERG we could discriminate among three types of dichromatic males. Among females, this classification is more complex and requires additional genetic analysis. We found five among 10 possible different phenotypes, two trichromats and three dichromats. We also found that Cebus present a new allele with spectral peak near 552 nm, with the amino acid combination SFT at positions 180, 277 and 285 of the opsin gene, in addition to the previously described SYT, AFT and AFA alleles. (C) 2009 Elsevier Ltd. All rights reserved.

Thyroid hormone action is required for normal cone opsin expression during mouse retinal development

PURPOSE. The expression of S- and M-opsins in the murine retina is altered in different transgenic mouse models with mutations in the thyroid hormone receptor (TR)-beta gene, demonstrating an important role of thyroid hormone (TH) in retinal development. METHODS. The spatial expression of S- and M-opsin was compared in congenital hypothyroidism and in two different TR mutant mouse models. One mouse model contains a ligand-binding mutation that abolishes TH binding and results in constitutive binding to nuclear corepressors. The second model contains a mutation that blocks binding of coactivators to the AF-2 domain without affecting TH binding. RESULTS. Hypothyroid newborn mice showed an increase in S- opsin expression that was completely independent of the genotype. Concerning M-opsin expression, hypothyroidism caused a significant decrease (P < 0.01) only in wild-type animals. When TR beta 1 and -beta 2 were T3-binding defective, the pattern of opsin expression was similar to TR beta ablation, showing increased S- opsin expression in the dorsal retina and no expression of M-opsin in the entire retina. In an unexpected finding, immunostaining for both opsins was detected when both subtypes of TR beta were mutated in the helix 12 AF-2 domain. CONCLUSIONS. The results show, for the first time, that the expression of S- and M-opsin is dependent on normal thyroid hormone levels during development.

No evidence of UV cone input to mono- and biphasic horizontal cells in the goldfish retina

Many animal species make use of ultraviolet (UV) light in a number of behaviors, such as feeding and mating. The goldfish (Carassius auratus) is among those with a UV photoreceptor and pronounced UV sensitivity. Little is known, however, about the retinal processing of this input. We addressed this issue by recording intracellularly from second-order neurons in the adult goldfish retina. In order to test whether cone-driven horizontal cells (HCs) receive UV cone inputs, we performed chromatic adaptation experiments with mono- and biphasic HCs. We found no functional evidence of a projection from the UV-sensitive cones to these neurons in adult animals. This suggests that goldfish UV receptors may contact preferentially triphasic HCs, which is at odds with the hypothesis that all cones contact all cone-driven HC types. However, we did find evidence of direct M-cone input to monophasic HCs, favoring the idea that cone-HC contacts are more promiscuous than originally proposed. Together, our results suggest that either UV cones have a more restricted set of post-synaptic partners than the other three cone types, or that the UV input to mono- and biphasic HCs is not very pronounced in adult animals.

Toward a Clinical Protocol for Assessing Rod, Cone, and Melanopsin Contributions to the Human Pupil Response

PURPOSE. To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol. METHODS. PLR was measured with an eye tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5 log cd/m(2) red (640 +/- 10 nm) and blue (467 +/- 17 nm) stimuli of various durations were presented after dark adaptation. In experiments 2 and 3, 1-second red and blue stimuli were presented at different intensity levels in the dark (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on the results of experiments 1 to 3, a clinical protocol was designed and tested on healthy control subjects and patients with retinitis pigmentosa and Leber`s congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin-driven sustained pupil response after termination of an intense blue stimulus was 1 second. PLR rod-and melanopsin-driven components are best studied with low-and high-intensity flashes, respectively, presented in the dark (experiment 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (experiment 3). With the clinical protocol, robust melanopsin responses could be seen in patients with few or no contributions from the rods and cones. CONCLUSIONS. It is possible to assess the rod, cone, and melanopsin contributions to the PLR with blue flashes at two or three intensity levels in the dark and one red flash on a blue background. (Invest Ophthalmol Vis Sci. 2011; 52: 6624-6635) DOI: 10.1167/iovs.11-7586