Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease.

Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease.

Neural network dose prediction for cervical brachytherapy: Overcoming data scarcity for applicator-specific models.

BACKGROUND: 3D neural network dose predictions are useful for automating brachytherapy (BT) treatment planning for cervical cancer. Cervical BT can be delivered with numerous applicators, which necessitates developing models that generalize to multiple applicator types. The variability and scarcity of data for any given applicator type poses challenges for deep learning. PURPOSE: The goal of this work was to compare three methods of neural network training-a single model trained on all applicator data, fine-tuning the combined model to each applicator, and individual (IDV) applicator models-to determine the optimal method for dose prediction. METHODS: Models were produced for four applicator types-tandem-and-ovoid (T&O), T&O with 1-7 needles (T&ON), tandem-and-ring (T&R) and T&R with 1-4 needles (T&RN). First, the combined model was trained on 859 treatment plans from 266 cervical cancer patients treated from 2010 onwards. The train/validation/test split was 70%/16%/14%, with approximately 49%/10%/19%/22% T&O/T&ON/T&R/T&RN in each dataset. Inputs included four channels for anatomical masks (high-risk clinical target volume [HRCTV], bladder, rectum, and sigmoid), a mask indicating dwell position locations, and applicator channels for each applicator component. Applicator channels were created by mapping the 3D dose for a single dwell position to each dwell position and summing over each applicator component with uniform dwell time weighting. A 3D Cascade U-Net, which consists of two U-Nets in sequence, and mean squared error loss function were used. The combined model was then fine-tuned to produce four applicator-specific models by freezing the first U-Net and encoding layers of the second and resuming training on applicator-specific data. Finally, four IDV models were trained using only data from each applicator type. Performance of these three model types was compared using the following metrics for the test set: mean error (ME, representing model bias) and mean absolute error (MAE) over all dose voxels and ME of clinical metrics (HRCTV D90% and D2cc of bladder, rectum, and sigmoid), averaged over all patients. A positive ME indicates the clinical dose was higher than predicted. 3D global gamma analysis with the prescription dose as reference value was performed. Dice similarity coefficients (DSC) were computed for each isodose volume. RESULTS: Fine-tuned and combined models showed better performance than IDV applicator training. Fine-tuning resulted in modest improvements in about half the metrics, compared to the combined model, while the remainder were mostly unchanged. Fine-tuned MAE = 3.98%/2.69%/5.36%/3.80% for T&O/T&R/T&ON/T&RN, and ME over all voxels = -0.08%/-0.89%/-0.59%/1.42%. ME D2cc were bladder = -0.77%/1.00%/-0.66%/-1.53%, rectum = 1.11%/-0.22%/-0.29%/-3.37%, sigmoid = -0.47%/-0.06%/-2.37%/-1.40%, and ME D90 = 2.6%/-4.4%/4.8%/0.0%. Gamma pass rates (3%/3 mm) were 86%/91%/83%/89%. Mean DSCs were 0.92%/0.92%/0.88%/0.91% for isodoses ≤ 150% of prescription. CONCLUSIONS: 3D BT dose was accurately predicted for all applicator types, as indicated by the low MAE and MEs, high gamma scores and high DSCs. Training on all treatment data overcomes challenges with data scarcity in each applicator type, resulting in superior performance than can be achieved by training on IDV applicators alone. This could presumably be explained by the fact that the larger, more diverse dataset allows the neural network to learn underlying trends and characteristics in dose that are common to all treatment applicators. Accurate, applicator-specific dose predictions could enable automated, knowledge-based planning for any cervical brachytherapy treatment.

Deep Learning Estimation of 10-2 Visual Field Map Based on Macular Optical Coherence Tomography Angiography Measurements.

PURPOSE: To develop deep learning (DL) models estimating the central visual field (VF) from optical coherence tomography angiography (OCTA) vessel density (VD) measurements. DESIGN: Development and validation of a deep learning model. METHODS: A total of 1051 10-2 VF OCTA pairs from healthy, glaucoma suspects, and glaucoma eyes were included. DL models were trained on en face macula VD images from OCTA to estimate 10-2 mean deviation (MD), pattern standard deviation (PSD), 68 total deviation (TD) and pattern deviation (PD) values and compared with a linear regression (LR) model with the same input. Accuracy of the models was evaluated by calculating the average mean absolute error (MAE) and the R2 (squared Pearson correlation coefficients) of the estimated and actual VF values. RESULTS: DL models predicting 10-2 MD achieved R2 of 0.85 (95% confidence interval [CI], 74-0.92) for 10-2 MD and MAEs of 1.76 dB (95% CI, 1.39-2.17 dB) for MD. This was significantly better than mean linear estimates for 10-2 MD. The DL model outperformed the LR model for the estimation of pointwise TD values with an average MAE of 2.48 dB (95% CI, 1.99-3.02) and R2 of 0.69 (95% CI, 0.57-0.76) over all test points. The DL model outperformed the LR model for the estimation of all sectors. CONCLUSIONS: DL models enable the estimation of VF loss from OCTA images with high accuracy. Applying DL to the OCTA images may enhance clinical decision making. It also may improve individualized patient care and risk stratification of patients who are at risk for central VF damage.

A fully integrated wearable ultrasound system to monitor deep tissues in moving subjects.

Recent advances in wearable ultrasound technologies have demonstrated the potential for hands-free data acquisition, but technical barriers remain as these probes require wire connections, can lose track of moving targets and create data-interpretation challenges. Here we report a fully integrated autonomous wearable ultrasonic-system-on-patch (USoP). A miniaturized flexible control circuit is designed to interface with an ultrasound transducer array for signal pre-conditioning and wireless data communication. Machine learning is used to track moving tissue targets and assist the data interpretation. We demonstrate that the USoP allows continuous tracking of physiological signals from tissues as deep as 164 mm. On mobile subjects, the USoP can continuously monitor physiological signals, including central blood pressure, heart rate and cardiac output, for as long as 12 h. This result enables continuous autonomous surveillance of deep tissue signals toward the internet-of-medical-things.

A Generalized Explanation Framework for Visualization of Deep Learning Model Predictions.

Attribution-based explanations are popular in computer vision but of limited use for fine-grained classification problems typical of expert domains, where classes differ by subtle details. In these domains, users also seek understanding of "why" a class was chosen and "why not" an alternative class. A new GenerAlized expLanatiOn fRamEwork (GALORE) is proposed to satisfy all these requirements, by unifying attributive explanations with explanations of two other types. The first is a new class of explanations, denoted deliberative, proposed to address the "why" question, by exposing the network insecurities about a prediction. The second is the class of counterfactual explanations, which have been shown to address the "why not" question but are now more efficiently computed. GALORE unifies these explanations by defining them as combinations of attribution maps with respect to various classifier predictions and a confidence score. An evaluation protocol that leverages object recognition (CUB200) and scene classification (ADE20 K) datasets combining part and attribute annotations is also proposed. Experiments show that confidence scores can improve explanation accuracy, deliberative explanations provide insight into the network deliberation process, the latter correlates with that performed by humans, and counterfactual explanations enhance the performance of human students in machine teaching experiments.

Cascade R-CNN: High Quality Object Detection and Instance Segmentation.

In object detection, the intersection over union (IoU) threshold is frequently used to define positives/negatives. The threshold used to train a detector defines its quality. While the commonly used threshold of 0.5 leads to noisy (low-quality) detections, detection performance frequently degrades for larger thresholds. This paradox of high-quality detection has two causes: 1) overfitting, due to vanishing positive samples for large thresholds, and 2) inference-time quality mismatch between detector and test hypotheses. A multi-stage object detection architecture, the Cascade R-CNN, composed of a sequence of detectors trained with increasing IoU thresholds, is proposed to address these problems. The detectors are trained sequentially, using the output of a detector as training set for the next. This resampling progressively improves hypotheses quality, guaranteeing a positive training set of equivalent size for all detectors and minimizing overfitting. The same cascade is applied at inference, to eliminate quality mismatches between hypotheses and detectors. An implementation of the Cascade R-CNN without bells or whistles achieves state-of-the-art performance on the COCO dataset, and significantly improves high-quality detection on generic and specific object datasets, including VOC, KITTI, CityPerson, and WiderFace. Finally, the Cascade R-CNN is generalized to instance segmentation, with nontrivial improvements over the Mask R-CNN.

Learning Complexity-Aware Cascades for Pedestrian Detection.

The problem of pedestrian detection is considered. The design of complexity-aware cascaded pedestrian detectors, combining features of very different complexities, is investigated. A new cascade design procedure is introduced, by formulating cascade learning as the Lagrangian optimization of a risk that accounts for both accuracy and complexity. A boosting algorithm, denoted as complexity aware cascade training (CompACT), is then derived to solve this optimization. CompACT cascades are shown to seek an optimal trade-off between accuracy and complexity by pushing features of higher complexity to the later cascade stages, where only a few difficult candidate patches remain to be classified. This enables the use of features of vastly different complexities in a single detector. In result, the feature pool can be expanded to features previously impractical for cascade design, such as the responses of a deep convolutional neural network (CNN). This is demonstrated through the design of pedestrian detectors with a pool of features whose complexities span orders of magnitude. The resulting cascade generalizes the combination of a CNN with an object proposal mechanism: rather than a pre-processing stage, CompACT cascades seamlessly integrate CNNs in their stages. This enables accurate detection at fairly fast speeds.

Semantic Fisher Scores for Task Transfer: Using Objects to Classify Scenes.

The transfer of a neural network (CNN) trained to recognize objects to the task of scene classification is considered. A Bag-of-Semantics (BoS) representation is first induced, by feeding scene image patches to the object CNN, and representing the scene image by the ensuing bag of posterior class probability vectors (semantic posteriors). The encoding of the BoS with a Fisher vector (FV) is then studied. A link is established between the FV of any probabilistic model and the Q-function of the expectation-maximization (EM) algorithm used to estimate its parameters by maximum likelihood. This enables 1) immediate derivation of FVs for any model for which an EM algorithm exists, and 2) leveraging efficient implementations from the EM literature for the computation of FVs. It is then shown that standard FVs, such as those derived from Gaussian or even Dirichlet mixtures, are unsuccessful for the transfer of semantic posteriors, due to the highly non-linear nature of the probability simplex. The analysis of these FVs shows that significant benefits can ensue by 1) designing FVs in the natural parameter space of the multinomial distribution, and 2) adopting sophisticated probabilistic models of semantic feature covariance. The combination of these two insights leads to the encoding of the BoS in the natural parameter space of the multinomial, using a vector of Fisher scores derived from a mixture of factor analyzers (MFA). A network implementation of the MFA Fisher Score (MFA-FS), denoted as the MFAFSNet, is finally proposed to enable end-to-end training. Experiments with various object CNNs and datasets show that the approach has state-of-the-art transfer performance. Somewhat surprisingly, the scene classification results are superior to those of a CNN explicitly trained for scene classification, using a large scene dataset (Places). This suggests that holistic analysis is insufficient for scene classification. The modeling of local object semantics appears to be at least equally important. The two approaches are also shown to be strongly complementary, leading to very large scene classification gains when combined, and outperforming all previous scene classification approaches by a sizable margin.

Automated High-Frequency Observations of Physical Activity Using Computer Vision.

PURPOSE: To test the validity of the Ecological Video Identification of Physical Activity (EVIP) computer vision algorithms for automated video-based ecological assessment of physical activity in settings such as parks and schoolyards. METHODS: Twenty-seven hours of video were collected from stationary overhead video cameras across 22 visits in nine sites capturing organized activities. Each person in the setting wore an accelerometer, and each second was classified as moderate-to-vigorous physical activity or sedentary/light activity. Data with 57,987 s were used to train and test computer vision algorithms for estimating the total number of people in the video and number of people active (in moderate-to-vigorous physical activity) each second. In the testing data set (38,658 s), video-based System for Observing Play and Recreation in Communities (SOPARC) observations were conducted every 5 min (130 observations). Concordance correlation coefficients (CCC) and mean absolute errors (MAE) assessed agreement between (1) EVIP and ground truth (people counts+accelerometry) and (2) SOPARC observation and ground truth. Site and scene-level correlates of error were investigated. RESULTS: Agreement between EVIP and ground truth was high for number of people in the scene (CCC = 0.88; MAE = 2.70) and moderate for number of people active (CCC = 0.55; MAE = 2.57). The EVIP error was uncorrelated with camera placement, presence of obstructions or shadows, and setting type. For both number in scene and number active, EVIP outperformed SOPARC observations in estimating ground truth values (CCC were larger by 0.11-0.12 and MAE smaller by 41%-48%). CONCLUSIONS: Computer vision algorithms are promising for automated assessment of setting-based physical activity. Such tools would require less manpower than human observation, produce more and potentially more accurate data, and allow for ongoing monitoring and feedback to inform interventions.

Fluoroscopic tumor tracking for image-guided lung cancer radiotherapy.

Accurate lung tumor tracking in real time is a keystone to image-guided radiotherapy of lung cancers. Existing lung tumor tracking approaches can be roughly grouped into three categories: (1) deriving tumor position from external surrogates; (2) tracking implanted fiducial markers fluoroscopically or electromagnetically; (3) fluoroscopically tracking lung tumor without implanted fiducial markers. The first approach suffers from insufficient accuracy, while the second may not be widely accepted due to the risk of pneumothorax. Previous studies in fluoroscopic markerless tracking are mainly based on template matching methods, which may fail when the tumor boundary is unclear in fluoroscopic images. In this paper we propose a novel markerless tumor tracking algorithm, which employs the correlation between the tumor position and surrogate anatomic features in the image. The positions of the surrogate features are not directly tracked; instead, we use principal component analysis of regions of interest containing them to obtain parametric representations of their motion patterns. Then, the tumor position can be predicted from the parametric representations of surrogates through regression. Four regression methods were tested in this study: linear and two-degree polynomial regression, artificial neural network (ANN) and support vector machine (SVM). The experimental results based on fluoroscopic sequences of ten lung cancer patients demonstrate a mean tracking error of 2.1 pixels and a maximum error at a 95% confidence level of 4.6 pixels (pixel size is about 0.5 mm) for the proposed tracking algorithm.

Natural image statistics and low-complexity feature selection.

Low-complexity feature selection is analyzed in the context of visual recognition. It is hypothesized that high-order dependences of bandpass features contain little information for discrimination of natural images. This hypothesis is characterized formally by the introduction of the concepts of conjunctive interference and decomposability order of a feature set. Necessary and sufficient conditions for the feasibility of low-complexity feature selection are then derived in terms of these concepts. It is shown that the intrinsic complexity of feature selection is determined by the decomposability order of the feature set and not its dimension. Feature selection algorithms are then derived for all levels of complexity and are shown to be approximated by existing information-theoretic methods, which they consistently outperform. The new algorithms are also used to objectively test the hypothesis of low decomposability order through comparison of classification performance. It is shown that, for image classification, the gain of modeling feature dependencies has strongly diminishing returns: best results are obtained under the assumption of decomposability order 1. This suggests a generic law for bandpass features extracted from natural images: that the effect, on the dependence of any two features, of observing any other feature is constant across image classes.

Layered dynamic textures.

A novel video representation, the layered dynamic texture (LDT), is proposed. The LDT is a generative model, which represents a video as a collection of stochastic layers of different appearance and dynamics. Each layer is modeled as a temporal texture sampled from a different linear dynamical system. The LDT model includes these systems, a collection of hidden layer assignment variables (which control the assignment of pixels to layers), and a Markov random field prior on these variables (which encourages smooth segmentations). An EM algorithm is derived for maximum-likelihood estimation of the model parameters from a training video. It is shown that exact inference is intractable, a problem which is addressed by the introduction of two approximate inference procedures: a Gibbs sampler and a computationally efficient variational approximation. The trade-off between the quality of the two approximations and their complexity is studied experimentally. The ability of the LDT to segment videos into layers of coherent appearance and dynamics is also evaluated, on both synthetic and natural videos. These experiments show that the model possesses an ability to group regions of globally homogeneous, but locally heterogeneous, stochastic dynamics currently unparalleled in the literature.

Discriminant saliency, the detection of suspicious coincidences, and applications to visual recognition.

A discriminant formulation of top-down visual saliency, intrinsically connected to the recognition problem, is proposed. The new formulation is shown to be closely related to a number of classical principles for the organization of perceptual systems, including infomax, inference by detection of suspicious coincidences, classification with minimal uncertainty, and classification with minimum probability of error. The implementation of these principles with computational parsimony, by exploitation of the statistics of natural images, is investigated. It is shown that Barlow's principle of inference by the detection of suspicious coincidences enables computationally efficient saliency measures which are nearly optimal for classification. This principle is adopted for the solution of the two fundamental problems in discriminant saliency, feature selection and saliency detection. The resulting saliency detector is shown to have a number of interesting properties, and act effectively as a focus of attention mechanism for the selection of interest points according to their relevance for visual recognition. Experimental evidence shows that the selected points have good performance with respect to 1) the ability to localize objects embedded in significant amounts of clutter, 2) the ability to capture information relevant for image classification, and 3) the richness of the set of visual attributes that can be considered salient.

Super Diffusion for Salient Object Detection.

One major branch of saliency object detection methods are diffusion-based which construct a graph model on a given image and diffuse seed saliency values to the whole graph by a diffusion matrix. While their performance is sensitive to specific feature spaces and scales used for the diffusion matrix definition, little work has been published to systematically promote the robustness and accuracy of salient object detection under the generic mechanism of diffusion. In this work, we firstly present a novel view of the working mechanism of the diffusion process based on mathematical analysis, which reveals that the diffusion process is actually computing the similarity of nodes with respect to the seeds based on diffusion maps. Following this analysis, we propose super diffusion, a novel inclusive learning-based framework for salient object detection, which makes the optimum and robust performance by integrating a large pool of feature spaces, scales and even features originally computed for non-diffusion-based salient object detection. A closed-form solution of the optimal parameters for the integration is determined through supervised learning. At the local level, we propose to promote each individual diffusion before the integration. Our mathematical analysis reveals the close relationship between saliency diffusion and spectral clustering. Based on this, we propose to re-synthesize each individual diffusion matrix from the most discriminative eigenvectors and the constant eigenvector (for saliency normalization). The proposed framework is implemented and experimented on prevalently used benchmark datasets, consistently leading to state-of-the-art performance.

Modeling, clustering, and segmenting video with mixtures of dynamic textures.

A dynamic texture is a spatio-temporal generative model for video, which represents video sequences as observations from a linear dynamical system. This work studies the mixture of dynamic textures, a statistical model for an ensemble of video sequences that is sampled from a finite collection of visual processes, each of which is a dynamic texture. An expectationmaximization (EM) algorithm is derived for learning the parameters of the model, and the model is related to previous works in linear systems, machine learning, time-series clustering, control theory, and computer vision. Through experimentation, it is shown that the mixture of dynamic textures is a suitable representation for both the appearance and dynamics of a variety of visual processes that have traditionally been challenging for computer vision (e.g. fire, steam, water, vehicle and pedestrian traffic, etc.). When compared with state-of-the-art methods in motion segmentation, including both temporal texture methods and traditional representations (e.g. optical flow or other localized motion representations), the mixture of dynamic textures achieves superior performance in the problems of clustering and segmenting video of such processes.

On the plausibility of the discriminant center-surround hypothesis for visual saliency.

It has been suggested that saliency mechanisms play a role in perceptual organization. This work evaluates the plausibility of a recently proposed generic principle for visual saliency: that all saliency decisions are optimal in a decision-theoretic sense. The discriminant saliency hypothesis is combined with the classical assumption that bottom-up saliency is a center-surround process to derive a (decision-theoretic) optimal saliency architecture. Under this architecture, the saliency of each image location is equated to the discriminant power of a set of features with respect to the classification problem that opposes stimuli at center and surround. The optimal saliency detector is derived for various stimulus modalities, including intensity, color, orientation, and motion, and shown to make accurate quantitative predictions of various psychophysics of human saliency for both static and motion stimuli. These include some classical nonlinearities of orientation and motion saliency and a Weber law that governs various types of saliency asymmetries. The discriminant saliency detectors are also applied to various saliency problems of interest in computer vision, including the prediction of human eye fixations on natural scenes, motion-based saliency in the presence of ego-motion, and background subtraction in highly dynamic scenes. In all cases, the discriminant saliency detectors outperform previously proposed methods from both the saliency and the general computer vision literatures.

Supervised learning of semantic classes for image annotation and retrieval.

A probabilistic formulation for semantic image annotation and retrieval is proposed. Annotation and retrieval are posed as classification problems where each class is defined as the group of database images labeled with a common semantic label. It is shown that, by establishing this one-to-one correspondence between semantic labels and semantic classes, a minimum probability of error annotation and retrieval are feasible with algorithms that are 1) conceptually simple, 2) computationally efficient, and 3) do not require prior semantic segmentation of training images. In particular, images are represented as bags of localized feature vectors, a mixture density estimated for each image, and the mixtures associated with all images annotated with a common semantic label pooled into a density estimate for the corresponding semantic class. This pooling is justified by a multiple instance learning argument and performed efficiently with a hierarchical extension of expectation-maximization. The benefits of the supervised formulation over the more complex, and currently popular, joint modeling of semantic label and visual feature distributions are illustrated through theoretical arguments and extensive experiments. The supervised formulation is shown to achieve higher accuracy than various previously published methods at a fraction of their computational cost. Finally, the proposed method is shown to be fairly robust to parameter tuning.

Automated Ecological Assessment of Physical Activity: Advancing Direct Observation.

Technological advances provide opportunities for automating direct observations of physical activity, which allow for continuous monitoring and feedback. This pilot study evaluated the initial validity of computer vision algorithms for ecological assessment of physical activity. The sample comprised 6630 seconds per camera (three cameras in total) of video capturing up to nine participants engaged in sitting, standing, walking, and jogging in an open outdoor space while wearing accelerometers. Computer vision algorithms were developed to assess the number and proportion of people in sedentary, light, moderate, and vigorous activity, and group-based metabolic equivalents of tasks (MET)-minutes. Means and standard deviations (SD) of bias/difference values, and intraclass correlation coefficients (ICC) assessed the criterion validity compared to accelerometry separately for each camera. The number and proportion of participants sedentary and in moderate-to-vigorous physical activity (MVPA) had small biases (within 20% of the criterion mean) and the ICCs were excellent (0.82-0.98). Total MET-minutes were slightly underestimated by 9.3-17.1% and the ICCs were good (0.68-0.79). The standard deviations of the bias estimates were moderate-to-large relative to the means. The computer vision algorithms appeared to have acceptable sample-level validity (i.e., across a sample of time intervals) and are promising for automated ecological assessment of activity in open outdoor settings, but further development and testing is needed before such tools can be used in a diverse range of settings.

Parametric Regression on the Grassmannian.

We address the problem of fitting parametric curves on the Grassmann manifold for the purpose of intrinsic parametric regression. We start from the energy minimization formulation of linear least-squares in Euclidean space and generalize this concept to general nonflat Riemannian manifolds, following an optimal-control point of view. We then specialize this idea to the Grassmann manifold and demonstrate that it yields a simple, extensible and easy-to-implement solution to the parametric regression problem. In fact, it allows us to extend the basic geodesic model to (1) a "time-warped" variant and (2) cubic splines. We demonstrate the utility of the proposed solution on different vision problems, such as shape regression as a function of age, traffic-speed estimation and crowd-counting from surveillance video clips. Most notably, these problems can be conveniently solved within the same framework without any specifically-tailored steps along the processing pipeline.

Prognostic markers in treated hypertensive diabetic patients. 28-month follow-up.

INTRODUCTION: Diabetes mellitus has a prevalence of about 6 to 10% in western populations, with a rising tendency due to inappropriate increases in calorie intake and decreased physical activity. In diabetic patients hypertension (HT) has a prevalence of over 60% and cerebro- and cardiovascular disease is responsible for two-thirds of the mortality in these patients. PATIENTS AND METHODS: We studied prospectively and consecutively 97 patients (age 63 +/- 8; 39-89) with treated type 2 diabetes and HT. The objective was to identify cardio- and cerebrovascular risk markers. The majority of the patients were evaluated by clinical and laboratory examination, 24h ambulatory blood pressure monitoring (ABPM), HbA1c, total cholesterol, HDL-C and triglycerides, microalbuminuria, echocardiogram (left ventricular mass index) and carotid-femoral pulse wave velocity. Later, the patients were re-evaluated using the same diagnostic methodology after a mean follow-up of 28 months. RESULTS: The population was at high risk for cardio- and cerebrovascular disease (60% dyslipidemic, 39% with previous cerebro- or cardiovascular accidents, 73% nondipper, 69% with decreased vascular distensibility [<12 m/sec] and 35% with microalbuminuria) despite treatment. Diabetes was controlled in only 55% of cases and blood pressure (BP) in 10%, although by ABPM it was controlled in 40% of cases. Simultaneous control of diabetes and HT was present in only one third of the patients. At the end of follow-up these values had not changed significantly, which can only be considered positive in respect of reduction in microalbuminuria (due to ACEIs and AIIRAs). Thirty cardio- and cerebrovascular events occurred (5 deaths), related to inadequate control of diabetes at initial evaluation (p=0.012), night-time systolic BP (SBP) and nondipper status (p=0.02) and vascular distensibility at the end of the study (p=0.03). On multiple linear regression (stepwise) analysis the only variable which was significantly associated with cardio- and cerebrovascular mortality and morbidity was night-time SBP. CONCLUSIONS: Overall analysis of the data confirmed the elevated risk of these patients and the importance of more frequent and aggressive control. The study also confirms the importance of evaluation by ABPM in these patients, which may lead to more efficacious, tailor-made treatment.