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Adaptive smoothing via contextual and local discontinuities.

A novel adaptive smoothing approach is proposed for noise removal and feature preservation where two distinct measures are simultaneously adopted to detect discontinuities in an image. Inhomogeneity underlying an image is employed as a multiscale measure to detect contextual discontinuities for feature preservation and control of the smoothing speed, while local spatial gradient is used for detection of variable local discontinuities during smoothing. Unlike previous adaptive smoothing approaches, two discontinuity measures are combined in our algorithm for synergy in preserving nontrivial features, which leads to a constrained anisotropic diffusion process that inhomogeneity offers intrinsic constraints for selective smoothing. Thanks to the use of intrinsic constraints, our smoothing scheme is insensitive to termination times and the resultant images in a wide range of iterations are applicable to achieve nearly identical results for various early vision tasks. Our algorithm is formally analyzed and related to anisotropic diffusion. Comparative results indicate that our algorithm yields favorable smoothing results, and its application in extraction of hydrographic objects demonstrates its usefulness as a tool for early vision.

Algorithms↗

Randomised trial of an integrated educational strategy to reduce investigation rates in young women with dysfunctional uterine bleeding.

OBJECTIVES: To assess the effectiveness of an integrated educational strategy to change clinician behaviour and reduce the number of hysteroscopies and/or dilatation and curettages for women 40 years or less with dysfunctional uterine bleeding (DUB). DESIGN: Randomised controlled trial with six-month follow-up. SETTING: Public teaching hospital gynaecology units with 12,000-13,000 relevant procedures per year. PARTICIPANTS: Six public gynaecology units made up of 62 gynaecologists or trainees allocated at random to intervention group - three, or control group - 3. Intervention An educational strategy that included dissemination of evidence-based guidelines via a problem-based interactive workshop facilitated by an opinion leader and a laminated algorithm and guidelines. MAIN OUTCOME MEASURES: The number of hysteroscopies and/or dilatation and curettages performed for DUB on women 40 years or less, clinician behaviour change and perceived booking rates of the procedure. RESULTS: At six months, there was no significant effect on the number of hysteroscopies and/or dilatation and curettages performed but there was an increase in evidence-based behaviour. CONCLUSIONS: While the evidence-based educational strategy for the appropriate investigation of young women with DUB resulted in clinician behaviour change when applied to theoretical cases, it did not result in a reduction in hysteroscopy/D&C rates at six months.

Adult↗

An automatic method for identifying appropriate gradient magnitude for 3D boundary detection of confocal image stacks.

Gradients play an important role in 2D image processing. Many edge detection algorithms are gradient-based. We are interested in 3D boundary detection which can be considered as an extension of 2D edge detection in 3D space. In this paper, an algorithm to automatically and quantitatively measure the suitability of gradient magnitudes in detection of 3D boundary points of confocal image stacks is presented. A Measurement Function is defined to evaluate the suitability of each gradient magnitude chosen to be the threshold for 3D boundary detection. The application of Gauss's Divergence Theorem provides a solution to calculate the Measurement Function numerically. The gradient magnitude at which the maximum of the Measurement Function is achieved can be utilized as the most appropriate threshold for gradient-based boundary detection and other operations like volume visualization.

Journal Article↗

Autotransfusion after open heart surgery: the oxygen delivery capacity of shed mediastinal blood is maintained.

Autotransfusion of mediastinal shed blood after open heart surgery has become a common and accepted procedure in reducing the need for homologous transfusion during the last 15 years. The objectives of the present study were to investigate the oxygen delivery capacity of autotransfused shed mediastinal blood, compared to patient-blood, during cardiopulmonary bypass and in the postoperative period. Ten consecutive patients undergoing elective cardiac surgery were studied. Mediastinal shed blood was collected in the cardiotomy reservoir and retransfused during the first 18 postoperative hours. The oxygen delivery capacity of the blood to the tissues was calculated by use of the oxygen status algorithm (OSA 2.0) programme and measurement of the 2,3-diphosphoglycerate (2,3-DPG) concentration. Autotransfusion volume ranged from 450-1530 ml per patient (median 824 ml). Shed blood had a mean haemoglobin level of 8.8 g/dl and 7.4 g/dl at 1 h and 6 h of autotransfusion, respectively. There were no significant changes of 2,3-DPG concentration in the patient-blood during cardiopulmonary bypass or after autotransfusion compared to preoperative values. P50 for oxygen (3.6 and 3.6 kPa) and 2,3-DPG concentrations (5.3 and 5.1 mikromol/ml erythrocyte) in shed mediastinal blood (1h and 6h postoperatively) were not significantly different compared to patient-blood. The results demonstrate that the oxygen delivery capacity of shed mediastinal blood is maintained and that the oxygen affinity of patient-blood is not influenced by autotransfusion.

2,3-Diphosphoglycerate↗

Autotransfusion after open heart surgery: quality of shed mediastinal blood compared to banked blood.

The need to conserve a patient's own blood and avoid homologous transfusion is now well recognized. Therefore, techniques designed to reduce requirements for homologous blood transfusions have been developed. One of the methods is autotransfusion of shed mediastinal blood after open-heart surgery. The objectives of the present study were to investigate osmotic fragility and oxygen transport capacity of shed mediastinal blood compared to patient blood and stored packed red blood cells (SAGM). Shed mediastinal blood from ten consecutive patients undergoing elective cardiac surgery (coronary bypass grafting) was studied and compared to patient blood, 10 units of 3 weeks old and 10 units of 5 weeks old stored packed red blood cells (SAGM). Oxygen transport capacity was investigated by calculation of p50 for oxygen by use of the oxygen status algorithm (OSA 2.0) programme and measurement of 2,3-diphosphoglycerate (2,3-DPG) concentrations. The osmotic fragility was determined using increasing concentrations of saline. 2,3-DPG concentrations in shed mediastinal blood (5.3 mikromol/ml erythrocyte) were within the range measured in patient blood, but significantly higher than SAGM blood (P < 0.001). P50 for oxygen (3.5 kPa) in shed mediastinal blood was not significantly different compared to patient blood, but significantly higher (P < 0.01) compared with stored SAGM blood. The osmotic fragility in shed mediastinal blood was not significantly different compared to patient blood, but significantly lower (P < 0.001) than the osmotic fragility in stored SAGM blood. This suggests that red cells saved from shed mediastinal blood have better oxygen transport capacity and may have longer survival compared to stored blood.

Aged↗

Model-based estimation of vascular parameters: evaluation of robustness and suitability of models.

Left ventricular performance depends not only on myocardial state, but also on the properties of the systemic arterial tree. These properties can be assessed from recordings of aortic root pressure and flow by the use of appropriate vascular models. Noninvasive estimates of aortic root pressure and flow can be obtained by the combined use of calibrated external subclavian artery pulse tracing and Doppler echocardiography. With recent advances in computer technology, estimation of model parameters are thus accessible in the clinical setting. We discuss the suitability of different parametric vascular models together with methods for adapting these models to the measured aortic root pressure. We compared the results obtained with simple vascular models (three-component modified Windkessel models) with those of five-component models. The simpler models gave less accurate approximation of the measured pressure waveform, but for a representative set of aortic root pressure and flow data, the simpler models provided adequate estimates of the peripheral arterial resistance, the total arterial compliance, and the proximal aortic area compliance. Furthermore, the simpler models are robust for measurement noise with simple estimation algorithms. Distal arterial pressure and flow waveforms are more oscillatory, and for these the five-component model has more robust estimation schemes with more accurate estimated parameters. Hence, we conclude that for clinical noninvasive assessment of aortic vascular properties, the simpler three-component models provide adequate information. For assessment of the peripheral arteries with large oscillations in the flow, the three-component models can give more than 10% error in the compliance estimate and more complex models can be appropriate.

Aorta↗

Bone structure effect on root resorption.

OBJECTIVES: To explore if alveolar bone shape and density might promote external apical root resorption. SETTING AND SAMPLE POPULATION: Panoramic radiographs of 700 patients who had orthodontic treatment at Temple University were reviewed and 22 patients with radiographic evidence of root resorption on the lower incisors were selected for the study. Exclusion criteria included a history of systemic diseases, craniofacial abnormalities, tooth injury, endodontically treated teeth, and impacted teeth. METHODS: Pre-treatment (T1) and post-treatment (T2) cephalometric radiographs were converted into digital format and enhanced to reduce contrast variability and improve edge definition. Tooth length, root length, root area, alveolar area around the root including cortical area, area of medullary bone, and area of the symphysis were measured using an interactive software algorithm. A region of interest within the symphysis was also defined and trabecular space area and fractal dimension calculated as an estimate of bone density. RESULTS: Root area and tooth length were correlated negatively with changes in root area, tooth area, and root length. Larger teeth demonstrated a greater amount of root resorption. Dentoalveolar complex dimensions remained relatively unchanged during tooth movement. The amount of alveolar bone around the root, thickness of cortical bone, density of the trabecular network, and fractal dimension showed no significant correlation with the extent of the external apical root resorption. CONCLUSIONS: The results of this study suggest that the density and morphology of the dentoalveolar complex are not significant factors in the etiology of external apical root resorption.

Adolescent↗

Monte Carlo evaluation of 6 MV intensity modulated radiotherapy plans for head and neck and lung treatments.

Intensity modulated radiotherapy (IMRT) beams may have strong fluence variations and are advantageous at disease sites such as lung and head and neck (H&N), where neighboring tissues have very different electron densities. We use Monte Carlo (MC) dose calculations to evaluate the dosimetric effects of these inhomogeneities for 10 clinical IMRT treatment plans for five lung patients and four H&N patients. All beams are 6 MV photons. "Standard plans" were first produced on a clinical treatment planning system which optimizes beam intensity distributions to meet dose and dose-volume constraints and calculates dose using a measurement-based pencil-beam algorithm with an equivalent pathlength inhomogeneity correction. Patient anatomy and electron densities were obtained from patient-specific CT images. The dose distribution of each beam was recalculated with the MC method, using the same CT images, beam geometry, beam weighting and optimized fluence intensity distributions as the corresponding standard plan. For the lung cases, the MC calculated dose distributions are characterized by reduced penetrations and increased penumbra due to larger secondary electron range in the low-density media, which is not accurately accounted for in the pencil beam algorithm. For the lung cases, the PTV was underdosed; except for one dose-volume index, underdose was less than 10%. Individual H&N fields are affected to different degrees by tissue inhomogeneities, depending on specific anatomy, especially the size and location of air cavities in relation to the beam orientation and field size. For four H&N plans, PTV coverage changed by less than 2%; for the fifth, there was less than 10% difference between the standard and the MC plans. Critical normal tissue DVHs (cord, lung, brainstem) are changed by <10% at the high dose end and mean lung doses are changed by <6%.

Algorithms↗

Monte Carlo evaluation of Compton scatter subtraction in single photon emission computed tomography.

In single photon emission computed tomography (SPECT), Compton scattering produces a background that degrades the image quality and contributes erroneously to quantitative measurements. A clinically implementable compensation algorithm has previously been reported that subtracts a Compton scatter image, acquired in an energy window set below the energy of the photopeak, from the primary image acquired in the photopeak window. We present an evaluation and justification of the assumptions made in the previous empirical development of the subtraction algorithm. A Monte Carlo model of the SPECT system in which the Compton scattered vents may be followed independently of the nonscattered events was used to evaluate this subtraction technique. Simulation shows that the assumptions made in the experimental application of this algorithm were valid. Specifically (1) the "scatter" energy window used in the experiment (91-125 keV for imaging Tc-99m) contains only scattered events, (2) the shape of the line spread function (LSF) for the events in the scatter window is a reasonable approximation to the shape of the scatter in the photopeak window, and (3) the ratio of the number of scattered events in the photopeak window to the number of events in the scatter window is 0.57, close to the value of 0.5 derived heuristically. Thus, Monte Carlo simulation validates the basic assumptions underlying the empirical implementation of the scatter subtraction algorithm.

Humans↗

Global phylogeny of Mycobacterium tuberculosis based on single nucleotide polymorphism (SNP) analysis: insights into tuberculosis evolution, phylogenetic accuracy of other DNA fingerprinting systems, and recommendations for a minimal standard SNP set.

We analyzed a global collection of Mycobacterium tuberculosis strains using 212 single nucleotide polymorphism (SNP) markers. SNP nucleotide diversity was high (average across all SNPs, 0.19), and 96% of the SNP locus pairs were in complete linkage disequilibrium. Cluster analyses identified six deeply branching, phylogenetically distinct SNP cluster groups (SCGs) and five subgroups. The SCGs were strongly associated with the geographical origin of the M. tuberculosis samples and the birthplace of the human hosts. The most ancestral cluster (SCG-1) predominated in patients from the Indian subcontinent, while SCG-1 and another ancestral cluster (SCG-2) predominated in patients from East Asia, suggesting that M. tuberculosis first arose in the Indian subcontinent and spread worldwide through East Asia. Restricted SCG diversity and the prevalence of less ancestral SCGs in indigenous populations in Uganda and Mexico suggested a more recent introduction of M. tuberculosis into these regions. The East African Indian and Beijing spoligotypes were concordant with SCG-1 and SCG-2, respectively; X and Central Asian spoligotypes were also associated with one SCG or subgroup combination. Other clades had less consistent associations with SCGs. Mycobacterial interspersed repetitive unit (MIRU) analysis provided less robust phylogenetic information, and only 6 of the 12 MIRU microsatellite loci were highly differentiated between SCGs as measured by GST. Finally, an algorithm was devised to identify two minimal sets of either 45 or 6 SNPs that could be used in future investigations to enable global collaborations for studies on evolution, strain differentiation, and biological differences of M. tuberculosis.

Algorithms↗

Three dimensional reconstruction of a human breast carcinoma using routine laboratory equipment and immunohistochemistry.

AIMS: To establish a three dimensional reconstruction of an invasive breast carcinoma using basic laboratory equipment to evaluate and characterise the spatial arrangement of the parenchymal cells of the breast. METHODS: One hundred and twenty eight sequential 4 microm sections (20 microm apart) of the tumour were stained immunohistochemically with an epithelial specific marker (AE1/AE3) or tumour specific marker (c-erbB-2) to reconstruct two different three dimensional images of the normal and malignant parenchymal cells. Sections were digitally imaged using a microscope, scanner, and digital camera linked to a conventional personal computer. Accurate alignment of the digitalised images was carried out using a semiautomatic graphical method of manual interaction, using the cross correlation coefficient as a goodness of fit measure, and an automatic search algorithm using the Fibonacci search algorithm for automatic alignment. The volume was reconstructed using maximum, minimum point projection and "back to front" opacity blending. RESULTS: The quality of the reconstructed images was distinct and perfect, providing a comprehensive and explicit view of the normal and malignant parenchymal tissues of the breast that is not possible by viewing two dimensional histological sections. Specifically, this approach showed the spatial arrangement of the tumour cells and their relation to the surrounding tissues at a high resolution. CONCLUSION: This simple and reproducible approach enables the spread and infiltration of invasive carcinoma to be understood and could also be used to analyse the spatial relation between atypical hyperplastic and malignant in situ lesions of the breast.

Biomarkers, Tumor↗

Breast lesions: evaluation with US strain imaging--clinical experience of multiple observers.

PURPOSE: To prospectively determine the accuracy of using an ultrasonographic (US) strain imaging technique known as lesion size comparison to differentiate benign from malignant breast lesions. MATERIALS AND METHODS: Institutional Review Board approval and patient informed consent were obtained for this HIPPA-compliant study. US strain imaging was performed prospectively for 89 breast lesions in 88 patients. Lesions were imaged by using freehand compression and a real-time strain imaging algorithm. Five observers obtained manual measurements of lesion height, width, and area from B-mode and strain images. By using these size measurements, individual observer and group performances were assessed by using the area under the receiver operating characteristic curve (A(z)). The performance of a single size parameter versus that of a combination of size parameters was evaluated by using univariate and multivariate logistic regression. RESULTS: Group A(z) values showed that width ratio and area ratio yielded the best results for differentiating benign and malignant breast lesions, and they were not statistically different from one another (P = .499). For the group, the performance of area and width, which was superior to that of height and aspect ratio, was statistically significant for all cases (P < .011) except for those that compared area with aspect ratio (P = .118). By using a group threshold of 1.04 for width ratio and 1.13 for area ratio, the sensitivity and specificity of the technique were 96% and 21%, respectively, for width and 96% and 24%, respectively, for area. The best observer achieved a sensitivity of 96% and a specificity of 61% by using the area ratio. For all but one observer, combined size parameters did not improve observer performance (P > .258). Significant interobserver performance variability was observed (P < .001). CONCLUSION: Results suggest that US strain imaging has the potential to aid diagnosis of breast lesions. However, manually tracing lesion boundaries for size ratio differentiation in a busy clinical setting did not match the diagnostic performance levels previously reported. Focusing on measurements of lesion width, along with additional observer training or automated processes, may yield a suitable method for routine clinical application.

Adult↗

Increasing myocardial contraction and blood pressure in C57BL/6 mice during early postnatal development.

Knowledge of the developmental changes of cardiovascular parameters in the genetic background of a mouse strain is important for understanding phenotypic changes in transgenic or knockout mouse models for heart disease. We studied arterial blood pressure and myocardial contractility in mice of the common background strain C57BL/6, aged 21 days [postnatal day 21 (P21)] to 580 days. Heart rate increased during maturation from 396 beats/min at P21 to 551 beats/min at postnatal day 50 (P50), and mean arterial blood pressure increased in parallel from 86 to 110 mmHg and remained constant afterward. Echocardiographically determined left ventricular myocardial wall dimensions (R = 0.79, P < 0.0001) and left ventricular mass calculated using the area-length algorithm correlated strongly with histomorphometrical measurements (R = 0.93, P < 0.001). Sarcomere shortening records from isolated ventricular myocytes used as a measure for myocardial contractility revealed a negative shortening-frequency relation under a pacing frequency of 2 Hz and a positive relation above 2 Hz. Shortening amplitudes recorded from P21 myocytes were smaller, and the shortening-frequency relation was less steep than in adult myocytes. A stimulation pause was followed by a negative "staircase" at pacing frequency of < or =6 Hz and a positive staircase at > or =6 Hz. P21 myocytes developed positive staircases at 8 and 10 Hz, and adult myocytes also developed them at 6 Hz. Blood pressure increase during maturation until P50 may originate from increasing single cardiomyocyte contractility.

Aging↗

Localization of cortical areas activated by thinking.

These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work in the form of operations on internal information, done by an awake subject. The rCBF was measured in 254 cortical regions in 11 subjects with the intracarotid 133Xe injection technique. In normal man, changes in the regional cortical metabolic rate of O2 leads to proportional changes in rCBF. One control study was taken with the subjects at rest. Then the rCBF was measured during three different simple algorithm tasks, each consisting of retrieval of a specific memory followed by a simple operation on the retrieved information. Once started, the information processing went on in the brain without any communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined that they started at their front door and then walked alternatively to the left or the right each time they reached a corner. The rCBF increased only in homotypical cortical areas during thinking. The areas in the superior prefrontal cortex increased their rCBF equivalently during the three types of thinking. In the remaining parts of the prefrontal cortex there were multifocal increases of rCBF. The localizations and intensities of these rCBF increases depended on the type of internal operation occurring. The rCBF increased bilaterally in the angular cortex during 50-3 thinking. The rCBF increased in the right midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and posterior superior parietal cortex, increased their rCBF exclusively during route-finding thinking. We observed no decreases in rCBF. All rCBF increases extended over a few square centimeters of the cortex. The activation of the superior prefrontal cortex was attributed to the organization of thinking. The activation of the angular cortex in 50-3 thinking was attributed to the retrieval of the numerical memory and memory for subtractions. The activation of the right midtemporal cortex was attributed to the retrieval of the nonverbal auditory memory.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Mapping↗

Genetic variation in white matter hyperintensity volume in the Framingham Study.

BACKGROUND AND PURPOSE: In a previous study of normal elderly male twins, the heritability of quantitative white matter hyperintensity (WMH) volume has been estimated to be high (0.73). We investigated heritability of WMH in a family-based sample of the Framingham Heart Study for sex differences and the impact of age. METHODS: Brain magnetic resonance scans were performed on 2012 individuals in the cohort and offspring of the Framingham study. This report was limited to 1330 stroke-free and dementia-free members (mean age 61.0 years) of the Framingham offspring. Individuals with a history of multiple sclerosis, stroke, dementia, or other neurological condition including traumatic brain injury were excluded from this analysis. WMH volume and total cranial volume (TCV) were quantified using a previously published algorithm. Because of extreme skewing, measures of WMH were log-transformed before analysis. Variance components methods were used to estimate heritability of WMH after adjusting for sex, age, age2, and TCV. RESULTS: In the full dataset, WMH heritability was 0.55 (P<0.0001). Heritability among women was 0.78 (P<0.0001) whereas heritability among men was 0.52 (P<0.0003). Heritability varied as average age increased, with a peak of 0.68 (P<0.0001) in individuals aged 55 or older. CONCLUSIONS: Using a family-based study design comprising generally healthy individuals, this study found high heritability of WMH overall and similar heritability for both men and women. In addition, the heritability of WMH remained high among individuals in whom the prevalence of cerebrovascular brain injury was generally low, suggesting that WMH is also likely to be an excellent genetic marker of brain aging.

Adult↗

Hierarchical bayesian models for regularisation in sequential learning

We show that a hierarchical Bayesian modeling approach allows us to perform regularization in sequential learning. We identify three inference levels within this hierarchy: model selection, parameter estimation, and noise estimation. In environments where data arrive sequentially, techniques such as cross validation to achieve regularization or model selection are not possible. The Bayesian approach, with extended Kalman filtering at the parameter estimation level, allows for regularization within a minimum variance framework. A multilayer perceptron is used to generate the extended Kalman filter nonlinear measurements mapping. We describe several algorithms at the noise estimation level that allow us to implement on-line regularization. We also show the theoretical links between adaptive noise estimation in extended Kalman filtering, multiple adaptive learning rates, and multiple smoothing regularization coefficients.

Journal Article↗

Blood flow estimation error with intravascular ultrasound due to in-plane component of flow.

Previously, we presented a real-time method to measure blood flow perpendicular to the image plane of an intravascular ultrasound (IVUS) imaging system using a slow-time FIR (finite impulse response) filter bank. Any in-plane flow introduces error in the flow measurement using the filter bank algorithm. Simulations show that for a flow angle of +/- 10 degrees and velocities between 200 mm/s and 300 mm/s, the energy within the lowest frequency band filter is 6.92 to 7.80 times higher than for perpendicular flow in the worst case. We present a variation of the FIR filter bank algorithm, applying filter coefficients in a tilted fashion to slow-time signals (i.e., combining slow-time and fast-time). An appropriate tilt, which depends on the flow angle and velocity, corrects for the increased energy under the frequency bands. In this case, the energy under the lowest frequency band filter for an angle of +/- 10 degrees and velocities ranging from 200 mm/s to 300 mm/s is 2.09 to 2.94 times higher than for perpendicular flow, yielding greater than a factor of three improvement in the worst case over the original slow-time method. Moreover, the average energy over the vessel determined with the appropriate tilt is within 2-3% of the true value.

Algorithms↗

Sex differences in circulating human leptin pulse amplitude: clinical implications.

Leptin, a product of fat cells, provides a signal of nutritional status to the central nervous system. Leptin concentrations have ultradian and diurnal fluctuations. We conducted this study to assess sex differences in the levels of organization of frequently sampled leptin concentrations in healthy, normal weight women and men. Leptin levels were sampled every 7 min for 24 h in 14 healthy, normal weight individuals (6 women and 8 men). The 14 leptin time series containing a total of 2898 leptin measurements were assessed by 1) algorithms that characterize statistically significant pulsatility, 2) Spectral (Fourier) analysis, 3) analysis of time intervals and variability, and 4) approximate entropy. We found that frequently sampled plasma leptin concentrations have a 24-h profile that is numerically more than twice as high in women as in men, and leptin pulse amplitude is likewise more than twice as high in women. However, healthy men and women have nearly identical concentration-independent and frequency-related 24-h and ultradian patterns. Leptin concentrations have nonrandom fluctuations over 24 h, independent of their absolute value and underlying 24-h periodicity, that are similar in men and women. Ultradian periodicities detected by Fourier time series have similar values in men and women. The strongest distinction between the sexes in the level of organization of leptin concentration is not at the level of pulse organization or oscillation frequency, but, rather, in the mass or amount of leptin released (or removed) per unit time, indicating that women might be more resistant to the effects of leptin than men. Because leptin is clinically relevant to the regulation of body weight, future studies should examine whether the relative leptin resistance exhibited by women might contribute to their increased susceptibility to disorders whose pathophysiology involves dysregulation of food intake and body weight.

Adult↗