Density Histograms Research Articles

Selective Arterial Embolization of Renal Angiomyolipoma: Efficacy, Tumor Volume Reduction and Complications

Objective: To evaluate the efficacy and complications of selective arterial embolization in renal angiomyolipoma and to identify predictive factors for tumor rupture.Materials and Methods: Overall, 21 patients with 25 renal angiomyolipoma (AML) underwent selective arterial embolization (SAE) between January 2008 and June 2019, comprising 15 cases involving prophylaxis embolization of a tumor >4 cm diameter and 10 involving embolization for a ruptured tumor. Multidetector computed tomography (MDCT) was performed pre- and post-SAE, using the 2D tumor diameter in the ruptured AMLs. Three-dimensional volumetry and density histogram were performed for determining the total tumor volume, fat, and angiomyogenic component reduction in the unruptured AMLs. The predictive factors for tumor rupture, the treatment outcome and complications were analyzed. Results: The clinical success rate was 84% (21/25 cases) and the technical success rate was 96% (24/25 cases). The 3D volume post-SAE within 1-3 months showed a greater decrement of the enhanced angiomyogenic component than the fat component, with median percentages of -62.2% and -18.4%, respectively (p-value = 0.333). Minor complications were post-embolization syndrome (5 case, 20%) and minimal renal infarction (4 cases, 16%). Renal abscesses were the major complications (3 cases, 12%). A factor associated with tumor rupture was the presence of an intra-tumoral aneurysm (p-value < 0.05).Conclusion: SAE is an effective treatment for renal AML with a high technical and clinical success rate and limited complications. Three-dimensional volume measurement and density histogram analysis might be better tools than two-dimensional CT to evaluate post-SAE response, which is crucial for management planning.

Size Structure of Cupressus sempervirens L. and Pistacia lentiscus L. Popula- tions in Wadi Alkuf, East of Libya


 
 
 Wadi Alkuf is one of the richest of all the phytogeographical regions of Al-Jabal Al- Akhder. The present work aims to study the size structure of Cupressus sempervirens L. and Pista- cia lentiscus L. populations in relation to their physiographic and soil conditions in Wadi Alkuf, northeast of Libya. Eighteen terraces (25 m × 25 m) were selected at Wadi Alkuf of Al-Jabal Al- Akhder at three different levels (six downstream, midstream, and upstream). The number of indi- viduals of each species was counted while the height (H) and mean crown diameter (D) were meas- ured. The size index of each individual was calculated and then used to classify the population into 7 size classes: 1 m to 7 m. The height, mean diameter, height to diameter ratio, size index, and vol- ume per individual in each size class were determined. Generally, the height to diameter ratio was more than unity for C. sempervirens L., this means that the diameter of these species tend to expand vertically rather than horizontally, while the height to diameter ratio was less than unity for P. len- tiscus L, this means that the diameter of these species tends to expand horizontally rather than verti- cally. The total size structure of C. sempervirens L. in the study area is characterized by the prepon- derance of the young individuals comparing with the old ones, while that of P. lentiscus L. showed a reverse pattern (i.e., preponderance of mature individual compared with the young ones). Five forms of size distributions along the different elevations were recognized: more or less inverse J- shaped distribution, positively skewed distribution, bell-shaped distribution, more or less J-shaped distribution, and more or less stationary size distribution biased to large size. The study’s results show that density histograms of size distributions are good indicators of future trends in population numbers for the studied species. The field observations were consistent with the results of the inves- tigation of soil properties. The soil downstream has the highest values of pH, EC, HCO-3, SO4-2, Cl- and Na+, while that of the upstream has the lowest values except for K+.
 
 

Release the Pressure! Does Jugular Venous Pressure Predict Rejection in Cardiac Biopsy?

<h3>Purpose</h3> Rejection in heart transplant recipients is often diagnosed by surveillance biopsies as most patients are asymptomatic. Nevertheless, rejection, if left untreated, can produce progressive diastolic dysfunction followed by systolic heart failure. This in turn will cause an increase in central venous pressure due to decreased ventricular compliance. With this in mind we sought out to determine if elevated central venous pressures measured invasively at the time of the biopsy correlated with the presence of rejection. <h3>Methods</h3> Patients undergoing an endomyocardial biopsy between June and October 2020 were included. The invasive JVP was measured before and after the procedure by measuring the height of the blood column in the side port of the sheath open to the atmospheric pressure. The biopsy results were reported according to the 2004 ISHLT revision. Differences in median JVP for each biopsy result group (0, 1R, 2R, 3R) were compared using a Mann-Whitney test. The histogram density for each biopsy group was graphed using a Kernel density plot. <h3>Results</h3> Eighty-four patients underwent one or more endomyocardial biopsies, with a total of 374 biopsies performed. Of all procedures, 187 were grade 0 for rejection, 168 were grade 1R and 18 were grade 2R. One patient had Grade 3R rejection (not shown in illustration) The median JVP was not statistically different between the three groups and the numerical difference was not clinically meaningful (figure 1 A). The Kernel density plot (figure 1 B) demonstrates the similarities between the groups. The lack of correlation between invasive JVP and rejection persists if data from the first 2 weeks post heart transplant are excluded. <h3>Conclusion</h3> In our dataset, there was no clinical or statistical difference in median invasive JVP and rejection grade between the biopsy result groups. One limitation is that we only had one patient with severe rejection (3R). Overall, our findings reinforce the need for surveillance biopsies.

Histogram of kidney stones on non-contrast computed tomography to predict successful stone dusting during retrograde intrarenal surgery.

To predict successful dusting of kidney stones during retrograde intrarenal surgery (RIRS) using stone density parameters and histograms measured with non-contrast computed tomography imaging. Medical records of 49 patients who underwent retrograde intrarenal surgery between January 2018 and January 2019 at Kyung Hee University Hospital were reviewed, and the data of 55 stones were evaluated. Patient age, sex, mean stone density, the highest and lowest measured Hounsfield unit (HU), standard deviation and range of the measured HUs, volume of the most measured HU, and success of dusting were evaluated. Histograms of the measured HUs were created and cutoff values for successful dusting were analyzed. Thirty-two stones were successfully dusted during surgery. Dusted stones had a wider range of HU and higher standard deviation. The volume of the most measured HU was smaller in the dusted stones. Successful dusting could be predicted when the volume of the most measured HU was < 8.9mm3, with range ≥ 853, or when the volume of the most measured HU was < 8.9mm3, with range < 853, and the mean stone density was < 355. The histograms of HUs of the dusted stones were wide and rugged, while those of dusting failed stones were narrow and peaked. Evaluation of stone HU histograms showed differences in distribution and proportion. This will help predict surgical outcomes and prepare for intraoperative complications.

A numerical study of entropy and residual entropy estimators based on smooth density estimators for non-negative random variables

In this paper, we are interested in estimating the entropy of a non-negative random variable. Since the underlying probability density function is unknown, we propose the use of the Poisson smoothed histogram density estimator to estimate the entropy. To study the per- formance of our estimator, we run simulations on a wide range of densities and compare our entropy estimators with the existing estimators based on different approaches such as spacing estimators. Furthermore, we extend our study to residual entropy estimators which is the entropy of a random variable given that it has been survived up to time $t$.

Atmospheric reentry hemisphere prediction for prograde orbits using logical disjunction

A unique logic-based algorithm for atmospheric reentry hemisphere prediction is presented for spacecraft in low-eccentricity, prograde low Earth orbits at altitudes of 300 km and lower. Using two-line element (TLE) data for initial orbit conditions, coupled with coarse estimates for spacecraft aerodynamic characteristics, the algorithm relies on logical disjunction operations based on a dual analysis of histogram and two-weighted Gaussian probability density function (PDF) fits of predicted reentry latitude data. The algorithm requires the execution of a series of parametric simulations to determine the reentry hemisphere for variations in spacecraft aerodynamic coefficients and drag reference area. When implemented, the algorithm yields accurate hemisphere predictions on average 15 days from reentry as demonstrated by historical reentry cases from 1979 to 2018. All reentry cases were selected to demonstrate the algorithm’s ability to deliver accurate reentry hemisphere predictions for spacecraft with varying physical size and mass, and reentering during different periods of solar cycle activity.

Evaluating the Effect of Intensity Standardisation on Longitudinal Whole Brain Atrophy Quantification in Brain Magnetic Resonance Imaging

Atrophy quantification is fundamental for understanding brain development and diagnosing and monitoring brain diseases. FSL-SIENA is a well-known fully automated method that has been widely used in brain magnetic resonance imaging studies. However, intensity variations arising during image acquisition may compromise evaluation, analysis and even diagnosis. In this work, we studied whether intensity standardisation could improve longitudinal atrophy quantification using FSL-SIENA. We evaluated the effect of six intensity standardisation methods—z-score, fuzzy c-means, Gaussian mixture model, kernel density estimation, histogram matching and WhiteStripe—on atrophy detected by FSL-SIENA. First, we evaluated scan–rescan repeatability using scans taken during the same session from OASIS (n=122). Except for WhiteStripe, intensity standardisation did not compromise the scan–rescan repeatability of FSL-SIENA. Second, we compared the mean annual atrophy for Alzheimer’s and control subjects from OASIS (n=122) and ADNI (n=147) yielded by FSL-SIENA with and without intensity standardisation, after adjusting for covariates. Our findings were threefold: First, the use of histogram matching was counterproductive, primarily as its assumption of equal tissue proportions does not necessarily hold in longitudinal studies. Second, standardising with z-score and WhiteStripe before registration affected the registration performance, thus leading to erroneous estimates. Third, z-score was the only method that consistently led to increased effect sizes compared to when omitted (no standardisation: 0.39 and 0.43 for OASIS and ADNI; z-score: 0.45 for both datasets). Overall, we found that incorporating z-score right after registration led to reduced inter-subject inter-scan intensity variability and benefited FSL-SIENA. Our work evinces the relevance of appropriate intensity standardisation in longitudinal cerebral atrophy assessments using FSL-SIENA.

Relationship between Emphysema Progression at CT and Mortality in Ever-Smokers: Results from the COPDGene and ECLIPSE Cohorts.

Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (clinicaltrials.gov, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; clinicaltrials.gov, NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results A total of 5143 participants (2613 men [51%]; mean age, 60 years ± 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years ± 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years ± 0.6 in COPDGene and 3.0 years ± 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16; P = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13; P = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31; P < .001) for the same increase in the rate of change in lung density perc15. Conclusion In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee and Park in this issue.

Distribution pattern of left ventricular ejection fraction in patients with decompensated heart failure depends on sex results of a latent class analysis

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): unrestricted grant from Boehringer Ingelheim Background &amp; Aims Since 2016, heart failure (HF) is classified using left ventricular ejection fraction (LVEF) thresholds of 40% and 50%. However, HF phenotypes may develop across the entire LVEF spectrum depending on individual patient characteristics including the risk and comorbidity profile. Using latent class analysis, we explored the sex-specific distribution of in-hospital LVEF in patients hospitalized for acute heart failure (AHF) at a tertiary care center in Germany. Methods Consecutive patients (≥18 years) hospitalized for AHF were recruited and phenotyped prospectively on a 7/24 basis. Exclusion criteria were high output heart failure, cardiogenic shock, and being listed for high urgency cardiac transplantation. LVEF was determined by transthoracic echocardiography using Simpson´s biplane or monoplane method. First, we estimated the distribution of LVEF in both sexes using histogram and kernel density estimation methods (bandwidth was selected by biased cross-validation). Then, Gaussian Mixture Models were fitted with increasing number of components. To identify the optimal number of subgroups we calculated the Bayesian Information Criterion (BIC). The minimum of the BIC criterion suggests the optimal number of subgroups for the final model. This analysis was performed on subsets including only male and only female patients. Results Out of 629 patients (39.8% female) admitted with AHF between 09/2014 and 12/2017, 93% patients received in-hospital echocardiography, and in 79.2% LVEF could be quantitatively assessed. The BIC suggested two subgroups each for male (Fig. A) and female patients (Fig. B). In the male two-subgroup model, mean ± SD LVEF values were 30 ± 9% and 59 ± 8%, thus covering 48% and 52% of the men, respectively (Fig. C). In the female two-subgroup model, respective LVEF values were 36 ± 13% and 65 ± 8%, thus covering 47% and 53% of patients (Fig. D). The "male" model suggested 45% as cut-point, whilst the "female" model suggested 51% as cut-point differentiating between lower and higher LVEF. Conclusions Using non-parametric and parametric statistical approaches, specific subgroups of patients hospitalized with AHF were identified among male and female patients hospitalized for AHF, which each time comprised subgroups with impaired vs. more preserved LVEF. Future analyses in larger AHF cohorts as well as in populations with chronic stable HF are warranted which take also into consideration sex differences in HF aetiology. Figure A) Minimum number of components (BIC) in men. B) Minimum BIC in women. C) LVEF distribution in men (2 components). D) LVEF distribution in women (2 components). The orange line indicates the respective cut-points between low and high LVEF. Abstract Figure.

Uni- and multivariate probability density models for numeric subgroup discovery

Subgroup Discovery is a supervised, exploratory data mining paradigm that aims to identify subsets of a dataset that show interesting behaviour with respect to some designated target attribute. The way in which such distributional differences are quantified varies with the target attribute type. This work concerns continuous targets, which are important in many practical applications. For such targets, differences are often quantified using z-score and similar measures that compare simple statistics such as the mean and variance of the subset and the data. However, most distributions are not fully determined by their mean and variance alone. As a result, measures of distributional difference solely based on such simple statistics will miss potentially interesting subgroups. This work proposes methods to recognise distributional differences in a much broader sense. To this end, density estimation is performed using histogram and kernel density estimation techniques. In the spirit of Exceptional Model Mining, the proposed methods are extended to deal with multiple continuous target attributes, such that comparisons are not restricted to univariate distributions, but are available for joint distributions of any dimensionality. The methods can be incorporated easily into existing Subgroup Discovery frameworks, so no new frameworks are developed.

Kinetic and rheological investigation of cyclopentane hydrate formation in waxy water-in-oil emulsions

Hydrates and waxes are supposed to coexist in the deep-water pipelines under suitable conditions of low temperature and high pressure. Understanding the effect of precipitated wax crystals on hydrate formation and rheological properties of hydrate slurry is crucial to the flow assurance in offshore petroleum production. In this work, a stress-controlled rheometer was used to carry out the rheological experiments for investigating the impact of wax crystals on hydrate formation and yield property of hydrate slurry. The effects of wax content and water cut on cyclopentane (CP) hydrate nucleation and growth were investigated in terms of the measured viscosity data. Log-normal distribution could well fit the probability density histogram of CP hydrate critical time. The logarithmic mean values of CP hydrate critical time decreased with increasing water cut but increased with increasing wax content in water-in-oil (w/o) emulsions. Semi-empirical models were proposed to describe the inhibitory effect of wax crystals on CP hydrate nucleation kinetics by considering the inhibition of mass transfer based on the Freundlich and Langmuir adsorption functions, respectively. Hydrate slurry viscosity rate showed the two-stage characteristics in wax-free w/o emulsions, while four stages could be clearly observed in waxy w/o emulsions. The maximum values of hydrate slurry viscosity rate and calculated hydrate effective volume fraction decreased with increasing wax content. Hydrate growth time was gradually extended as wax content increased. Furthermore, the measured yield stress and yield strain increased with increasing wax content at different water cuts, which was associated with the multiple effect of capillary bridge between hydrate particles, spatial network of wax crystals and coalescence of water droplets. At last, compared to the stress ramp rate, the influence of annealing time on yield stress was more significant.

Comparative analysis of density histograms and visual scores in incremental and volumetric high-resolution computed tomography of the chest in idiopathic pulmonary fibrosis patients

BackgroundVolumetric high-resolution computed tomography (HRCT) of the chest has recently replaced incremental CT in the diagnostic workup of idiopathic pulmonary fibrosis (IPF). Concomitantly, visual and quantitative scores have been proposed for disease extent assessment to ameliorate disease management.PurposeTo compare the performance of density histograms (mean lung attenuation, skewness, and kurtosis) and visual scores, along with lung function correlations, in IPF patients submitted to incremental or volumetric thorax HRCT.Material and methodsClinical data and CT scans of 89 newly diagnosed and therapy-naive IPF patients were retrospectively evaluated.ResultsForty-six incremental and 43 volumetric CT scans were reviewed. No differences of density histograms and visual scores estimates were found by comparing two HRCT techniques, with an optimal inter-operator agreement (concordance correlation coefficient >0.90 in all instances). Single-breath diffusing lung capacity for carbon monoxide (DLCOsb) was inversely related with the Best score (r = −00.416; p = 0.014), the Kazerooni fibrosis extent (r = −0.481; p = 0.004) and the mean lung attenuation (r = −0.382; p = 0.026), while a positive correlation was observed with skewness (r = 0.583; p = 0.001) and kurtosis (r = 0.543; p = 0.001) in the incremental HRCT sub-group. Similarly, in the volumetric CT sub-cohort, DLCOsb was significantly associated with skewness (r = 0.581; p = 0.007) and kurtosis (r = 0.549; p = 0.018). Correlations with visual scores were not confirmed. Forced vital capacity significantly related to all density indices independently on HRCT technique.ConclusionsDensity histograms and visual scores similarly perform in incremental and volumetric HRCT. Density quantification displays an optimal reproducibility and proves to be superior to visual scoring as more strongly correlated with lung function.

EPID-20. NOVEL GLIOBLASTOMA POPULATION-BASED HISTOLOGIC STAIN NORMALIZATION

Abstract Histopathologic evaluation has been an integral part of clinical diagnosis for central nervous system tumors, providing information essential for classification, management, and treatment of the disease. Hematoxylin and eosin (H&amp;E) staining is routinely used in histology, providing detail of tissue morphology, structure, and cellular composition. MOTIVATION: Slide staining is rife with color intensity variations, mainly due to differences in materials and staining protocols among others. These variations introduce inaccuracies in downstream computational analysis and quantification of disease, disabling the generalization of computational models. To overcome these variations, current approaches arbitrarily select a slide within the cohort to normalize all slides of the cohort, leading to non-reproducible results in other cohorts. We develop a population-based whole slide image (WSI) normalization method based on overall region driven stain vectors and color histogram, weighted by corresponding percent contribution to overall slide (PCOS). METHODS: We identified a cohort of 509 H&amp;E stained WSIs with corresponding anatomical annotations from the Ivy Glioblastoma Atlas Project. These WSIs and annotations were reviewed by two neuropathologists for correctly annotated regions. Each region was weighted according to PCOS, WSIs with PCOS &amp;lt; 0.05% were discarded. Then, the optical densities and histograms calculated. Resulting color histogram and optical density was applied to the WSI cohort. Finally, stain intensity variability pre- and post- normalization was compared. RESULTS: Normalizing WSIs based on our approach, results in a significant (p &amp;lt; 0.01, Wilcoxon) improvement in color intensity variation for eight of nine regions tested, with the exception of “Pseudopalisading Cells with no visible Necrosis” (p = 0.8). DISCUSSION: This novel transformative technique is insensitive to artificially staining background density and straightforward to apply. Furthermore, the approach shows promise towards a viable and robust tool for stain normalization in large WSIs cohorts, with the potential towards a stain normalization standard generalizable to other diseases.

Using mathematics to diagnose, cure, and predict cardiac arrhythmia.

Mathematics can be used to analyze and model cardiac arrhythmia. I discuss three different problems. (1) Diagnosis of atrial fibrillation based on the time intervals between subsequent beats. The probability density histograms of the differences of the intervals between consecutive beats have characteristic shapes for atrial fibrillation. (2) Curing atrial fibrillation by ablation of the core of rotors. Recent clinical studies have proposed that ablating the core of rotors in atrial tissue can cure atrial fibrillation. However, the claims are controversial. One problem that arises relates to difficulties associated with developing algorithms to identify the core of rotors. In model tissue culture systems, heterogeneity in the structure makes it difficult to unambiguously locate the core of rotors. (3) Risk stratification for sudden cardiac death (SCD). Despite numerous clinical studies, there is still a need for improved criteria to assess the risk of SCD. I discuss the possibility of using the dynamics of premature ventricular complexes to help make predictions. The development of wearable devices to record and analyze cardiac rhythms offers new prospects for the diagnosis and treatment of cardiac arrhythmia.

An evaluation of pose-normalization algorithms for point clouds introducing a novel histogram-based approach

Building Information Modeling is growing more relevant as digital models are not only used during the construction phase but also throughout the building’s life cycle. The digital representation of geometric, physical and functional properties enables new methods for planning, execution and operation. Digital models of existing buildings are commonly derived from surveying data such as laser scanning which needs to be processed either manually or automatically throughout various steps. Aligning point clouds along the coordinate system’s main axes (also commonly known as pose normalization) is a task benefitting any point cloud processing workflow, be it manual or automated. With the goal of automating this task, we compare various existing methods and present our own approach based on point density histograms. We conclude this paper by comparing and discussing all methods in terms of speed and robustness.

Quantitative-analysis of computed tomography in COVID-19 and non COVID-19 ARDS patients: A case-control study.

PurposeThe aim of this study was to assess whether the computed tomography (CT) features of COVID-19 (COVID+) ARDS differ from those of non-COVID-19 (COVID−) ARDS patients.Materials and methodsThe study is a single-center prospective observational study performed on adults with ARDS onset ≤72 h and a PaO2/FiO2 ≤ 200 mmHg. CT scans were acquired at PEEP set using a PEEP-FiO2 table with VT adjusted to 6 ml/kg predicted body weight.Results22 patients were included, of whom 13 presented with COVID-19 ARDS. Lung weight was significantly higher in COVID− patients, but all COVID+ patients presented supranormal lung weight values. Noninflated lung tissue was significantly higher in COVID− patients (36 ± 14% vs. 26 ± 15% of total lung weight at end-expiration, p < 0.01). Tidal recruitment was significantly higher in COVID− patients (20 ± 12 vs. 9 ± 11% of VT, p < 0.05). Lung density histograms of 5 COVID+ patients with high elastance (type H) were similar to those of COVID− patients, while those of the 8 COVID+ patients with normal elastance (type L) displayed higher aerated lung fraction.

Regional variations of jaw bone characteristics in an ovariectomized rat model

Postmenopausal osteoporosis causes severe loss of bone quantity and quality in limb bone but has a lesser effect on jaw bone. Thus, the objective of this study was to examine whether ovariectomy (OVX) and mastication alter the regional variation of jaw bone characteristics. Sprague-Dawley female rats (6 months) were given a bilateral OVX or a sham operation (SHAM) (n = 10 for each group). After 2 months post-OVX, the hemi-mandible from each rat was dissected. A micro-computed tomography based mean, standard deviation (SD), the lower and upper 5th percentile (Low5 and High5) values of tissue mineral density (TMD) histograms were assessed for whole bone (WB), alveolar bone (AB), cortical bone (CB), and trabecular bone (TB) regions. Morphology of TB and periodontal ligament (PDL) was also obtained. Layers of AB were segmented up to 400 μm from the PDL. Mechanical properties at the tissue level were measured by nanoindentation at the same site by a single loading-unloading cycle of indentation in hydration. The AB and TB regions had significantly lower TMD Mean, Low5, and High5 but higher SD than the CB region for both sham and OVX groups (p < 0.01). TMD parameters of the OVX group rapidly increased up to 60 μm away from the PDL and were significantly higher than those of the sham group starting at 280 μm and farther in the CB region (p < 0.05). All values of morphological and nanoindentation parameters were not significantly different between sham and OVX groups (p > 0.06). Estrogen deficiency induced by OVX did not deteriorate bone characteristics including mineral density, morphology, and nanoindentation parameters in rat mandibles. Masticatory loading had an effect on the TMD parameters at the limited region of AB. These results provide insight into why osteoporosis-associated jaw bone fractures are extremely rare.

¿El descortezamiento de un árbol medicinal impacta en su estructura poblacional-espacial? El caso de Hintonia latiflora en México

Se documenta la estructura poblacional y el patrón de distribución y correlación espacial entre etapas de desarrollo de Hintonia latiflora, especie amenazada en México por la cosecha comercial de su corteza. Se establecieron seis unidades de muestreo (tres cosechadas y tres no cosechadas) de 20 m × 100 m para el censo de todas las plantas y se categorizaron en tres etapas de desarrollo con base en la altura total y diámetro basal; todos los individuos fueron ubicados por sus coordenadas cartesianas. La estructura poblacional se analizó mediante un histograma de densidad; , mientras que el sesgo y la curtosis se usaron para determinar el efecto del aprovechamiento sobre las categorías de tamaño. Los patrones espaciales univariantes y bivariantes se determinaron usando la función L1(t) y L12(t) de Ripley, respectivamente, y la significancia estadística fue a 99% mediante simulaciones Monte Carlo. La densidad entre sitios cosechados vs. no cosechados fue estadísticamente diferente (p &lt; 0.013), pero la estructura poblacional fue semejante, con un patrón de distribución asimétrico positivo (S3 = 0.947 y S3 = 1.063) y leptocúrtico (S4 = 2.006 y S4 = 2.400). El patrón de distribución univariante en todos los casos fue agregado (L(t) &gt; 0), mientras que la correlación espacial en poblaciones sujetas a descortezamiento reflejó una combinación entre independencia y atracción espacial a diferentes distancias. Esta información aporta bases para el manejo sostenible de H. latiflora y representa el primer estudio en México que analiza el impacto del descortezamiento de un recurso medicinal sobre su estructura poblacional-espacial.

Expression of the type 3 inositol 1, 4, 5-trisphosphate receptor according to the chronic liver disease etiology in hepatocellular carcinoma.

e16604 Background: The expression of type 3 isoform of the inositol 1, 4, 5-trisphosphate receptor (ITPR-3), an intracellular calcium (Ca2+) channel reported in liver cancer cells, is important in the Ca2+ signalling. Thus, it may be involved in the many events of hepatocarcinogenesis. Here, we investigated the ITPR-3 expression in hepatocellular carcinoma (HCC) and its association with clinicopathological parameters and long-term outcomes, according to the etiology of underlying chronic liver disease (CLD). Methods: Clinical and laboratory data from patients (n = 53) who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were retrospectively collected. After pathological reviewing of their explanted liver samples, ITPR-3 expression in both tumor and underlying cirrhosis were assessed by immunohistochemistry, and quantified using density histograms in the ImageJ software. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analysed. Results: Hepatitis C virus (HCV) (n = 31), alcohol abuse (n = 16) and cryptogenic cirrhosis (n = 6) were the underlying CLD etiology, and the groups were, in general, well balanced regarding clinicopathological indices. Median EFS was 78.9 months (range, 63.6-94.1). The ITPR-3 expression profile was cytoplasmatic, predominantly perinuclear, and was stronger in tumor than in adjacent cirrhosis, considering all etiologies together (intensity 9.1% higher in tumors, p &lt; 0.001) However, analyzing each etiologic group, the cryptogenic was the only one in which there was no difference between tumor and underlying CLD. Comparing the ITPR-3 expression only in tumors, there was no difference regarding the etiology of CLD. The tumor ITPR-3 higher intensity was correlated with higher serum aspartate alanine-transferases (ALT) levels (p = 0.018) and lower mitotic index ( &lt; 5 per 10 high power fields) (p = 0.009). There was no association between receptor expression and event occurrence or EFS. Conclusions: The ITPR-3 was expressed in HCC, regardless of the underlying CLD etiology. Its correlation with mitotic index, a cell proliferation marker, was demonstrated, but there were no associations with clinical outcomes. Apart from cryptogenic cirrhosis, ITPR-3 expression was more intense in tumors than in underlying cirrhosis. These findings suggest that ITPR-3 could have a role in carcinogenesis. However, the prognostic and therapeutic implications need to be investigated.

The predictive role of plasma mutant allele fraction to antiangiogenic drugs in patients with mCRC: An expanded analysis of surrogate biomarkers of response to first-line treatment with bevacizumab.

3541 Background: So far, no biomarkers of response to anti-angiogenic drugs are available in colorectal cancer (CRC) treatment. Liquid biopsy tracks dynamic mutational changes in CRC patients (pts). RAS mutant allele fraction in plasma (plMAF) is an independent prognostic marker in metastatic CRC (mCRC). We explored the predictive value of plMAF in RAS mutant pts treated in 1st line with chemotherapy +/- bevacizumab (bev). Methods: A multicentric prospective/retrospective analysis was conducted. We collected data from 226 mCRC pts and selected the subset not eligible for metastasis resection with basal plMAF sample evaluable for RAS mutant MAF quantification with digital PCR (BEAMing). Pts were stratified as high (≥ 5.8%) or low ( &lt; 5.8%) plMAF. We investigated associations between clinicopathological variables and progression-free survival (PFS) stratified by plMAF RAS levels using Cox regression models and survival data were calculated by Kaplan-Meier method. Computational analysis of baseline CT scan data extracted 93 radiomics features of all the lesions per patient including 1) 1st class from density histogram distribution and texture analysis by 2) 2nd order and 3) higher order feature classes. The radiomic features distribution between pts with high and low pIMAF was assessed with Student’s t-test analysis. Results: From October 17 to May 19, 63 basal plasma samples were analysed with BEAMing. 42 pts (67.7%) were classified as high and 21 pts (32,3%) as low plMAF. In high plMAF subgroup, a statistically significant longer PFS favouring FOLFOX+bev was observed, compared to FOLFOX alone (10.7 vs 6.9 mts; HR: 0.30; p = 0.002). In low RAS plMAF subgroup, no differences in terms of PFS were observed in either arm (8.9 vs 8.7 mts; HR: 0.7; p = 0.6). Multivariate PFS model showed no association between RAS plMAF and clinicopathological variables, except for high RAS plMAF and treatment benefit with FOLFOX+bev. The CT-radiomics signature, that may translate tumor vascularization, differentiated patients with high vs low pIMAF (p = 0.002). 58 patients (92%) had similar radiomic score; 5 patients with high plMAF (8%) presented very heterogeneous radiomic score distribution. Conclusions: Tumor-borne RAS plMAFs may constitute a potential predictive biomarker of efficacy for anti-angiogenic drugs in mCRC. Next steps will include the identification of -histological, transcriptomic and radiomic- surrogate biomarkers of response that reflect tumor irrigational status.