Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.

Early Postnatal Use of Glibenclamide in Permanent Neonatal Diabetes Secondary to Antenatally Diagnosed KJCN11 Mutation.

INTRODUCTION: Heterozygous activating mutations in KCNJ11 cause both permanent and transient neonatal diabetes. A minority of patients also have neurological features. Early genetic diagnosis has important therapeutic implications as treatment with sulfonylurea provides good metabolic control and exerts a protective effect on neuromuscular function. CASE PRESENTATION: A term female infant with normal birth weight (2.73 kg, z-score: -1.69) was admitted to the Neonatal Unit at Addenbrookes Hospital. She had been antenatally diagnosed with KCNJ11 mutation-R201C inherited from her glibenclamide-treated mother who continued sulfonylurea treatment throughout pregnancy. A continuous glucose-monitoring system inserted at 20 h of age showed progressive rise of blood glucose concentrations, prompting treatment with glibenclamide on day 2 of life. Initial attempts to treat with an extemporaneous solution of glibenclamide (starting dose 0.2 mg/kg/day) resulted in inconsistent response and significant hypoglycaemia and hyperglycaemia. A licenced liquid formulation of glibenclamide (AMGLIDIA) at a starting dose of 0.05 mg/kg/day was used with stabilization of blood glucose profile within 24 h. Other than a mild transient elevation in transaminase, treatment was well tolerated. At most recent review (age 12 months), the patient remains well with age-appropriate neurodevelopment. Overall glucose control is reasonable with estimated HbA1c of 7.6% (59.9 mmol/mol). CONCLUSION: Early postnatal glibenclamide treatment of insulin-naive patients with KATP-dependent neonatal diabetes is safe, provides good metabolic control, and has a potential protective effect on neurological function. The formulation of the medicine needs to be carefully considered in the context of the very small doses required in this age group.

Safe and effective use of a hybrid closed-loop system from diagnosis in children under 18 months with type 1 diabetes.

The management of type 1 diabetes in infancy presents significant challenges. Hybrid closed loop systems have been shown to be effective in a research setting and are now available for clinical use. There are relatively little reported data regarding their safety and efficacy in a real world clinical setting. We report two cases of very young children diagnosed with type 1 diabetes at ages 18 (Case 1) and 7 months (Case 2), who were commenced on hybrid closed-loop insulin delivery using the CamAPS FX™ system from diagnosis. At diagnosis, total daily dose (TDD) was 6 and 3.3 units for Case 1 and 2, respectively. Closed loop was started during the inpatient stay and weekly follow up was provided via video call on discharge. Seven months from diagnosis, Case 1 has an HbA1C of 49 mmol/mol, 61% time in range (TIR, 3.9-10 mmol/L) with 2% time in hypoglycemia (<3.9 mmol/L) with no incidents of very low blood glucose (BG; <3 mmol/L, 54 mg/dL) over 6 months. Given the extremely small TDD of insulin in Case 2, we elected to use diluted insulin (insulin aspart injection, NovoLog, Novo Nordisk Inc., Plainsboro, NJ, Diluting Medium for NovoLog®). Six months from diagnosis, the estimated HbA1c is 50 mmol/mol, TIR 76% with 1% hypoglycemia and no incidents of very low BG (<3 mmol/L, 54 mg/dL) over 6 months. We conclude that the use hybrid closed-loop can be safe and effective from diagnosis in children under 2 years of age with type 1 diabetes.

Confidence Estimation for Medical Image Registration Based On Stereo Confidences.

In this paper, we propose a novel method to estimate the confidence of a registration that does not require any ground truth, is independent from the registration algorithm and the resulting confidence is correlated with the amount of registration error. We first apply a local search to match patterns between the registered image pairs. Local search induces a cost space per voxel which we explore further to estimate the confidence of the registration similar to confidence estimation algorithms for stereo matching. We test our method on both synthetically generated registration errors and on real registrations with ground truth. The experimental results show that our confidence measure can estimate registration errors and it is correlated with local errors.

Cardiac MR perfusion image processing techniques: a survey.

First-pass cardiac MR perfusion (CMRP) imaging has undergone rapid technical advancements in recent years. Although the efficacy of CMRP imaging in the assessment of coronary artery diseases (CAD) has been proven, its clinical use is still limited. This limitation stems, in part, from manual interaction required to quantitatively analyze the large amount of data. This process is tedious, time-consuming, and prone to operator bias. Furthermore, acquisition and patient related image artifacts reduce the accuracy of quantitative perfusion assessment. With the advent of semi- and fully automatic image processing methods, not only the challenges posed by these artifacts have been overcome to a large extent, but a significant reduction has also been achieved in analysis time and operator bias. Despite an extensive literature on such image processing methods, to date, no survey has been performed to discuss this dynamic field. The purpose of this article is to provide an overview of the current state of the field with a categorical study, along with a future perspective on the clinical acceptance of image processing methods in the diagnosis of CAD.

Fully automated attenuation measurement and motion correction in FLIP image sequences.

Fluorescence loss in photobleaching (FLIP) is a method to study compartment connectivity in living cells. A FLIP sequence is obtained by alternatively bleaching a spot in a cell and acquiring an image of the complete cell. Connectivity is estimated by comparing fluorescence signal attenuation in different cell parts. The measurements of the fluorescence attenuation are hampered by the low signal to noise ratio of the FLIP sequences, by sudden sample shifts and by sample drift. This paper describes a method that estimates the attenuation by modeling photobleaching as exponentially decaying signals. Sudden motion artifacts are minimized by registering the frames of a FLIP sequence to target frames based on the estimated model and by removing frames that contain deformations. Linear motion (sample drift) is reduced by minimizing the entropy of the estimated attenuation coefficients. Experiments on 16 in vivo FLIP sequences of muscle cells in Drosophila show that the proposed method results in fluorescence attenuations similar to the manually identified gold standard, but with standard deviations of approximately 50 times smaller. As a result of this higher precision, cell compartment edges and details such as cell nuclei become clearly discernible. The main value of this method is that it uses a model of the bleaching process to correct motion and that the model based fluorescence intensity and attenuation estimates can be interpreted easily. The proposed method is fully automatic, and runs in approximately one minute per sequence, making it suitable for unsupervised batch processing of large data series.

Action unit classification using active appearance models and conditional random fields.

In this paper, we investigate to what extent modern computer vision and machine learning techniques can assist social psychology research by automatically recognizing facial expressions. To this end, we develop a system that automatically recognizes the action units defined in the facial action coding system (FACS). The system uses a sophisticated deformable template, which is known as the active appearance model, to model the appearance of faces. The model is used to identify the location of facial feature points, as well as to extract features from the face that are indicative of the action unit states. The detection of the presence of action units is performed by a time series classification model, the linear-chain conditional random field. We evaluate the performance of our system in experiments on a large data set of videos with posed and natural facial expressions. In the experiments, we compare the action units detected by our approach with annotations made by human FACS annotators. Our results show that the agreement between the system and human FACS annotators is higher than 90% and underlines the potential of modern computer vision and machine learning techniques to social psychology research. We conclude with some suggestions on how systems like ours can play an important role in research on social signals.

Articulated planar reformation for change visualization in small animal imaging.

The analysis of multi-timepoint whole-body small animal CT data is greatly complicated by the varying posture of the subject at different timepoints. Due to these variations, correctly relating and comparing corresponding regions of interest is challenging.In addition, occlusion may prevent effective visualization of these regions of interest. To address these problems, we have developed a method that fully automatically maps the data to a standardized layout of sub-volumes, based on an articulated atlas registration. We have dubbed this process articulated planar reformation, or APR. A sub-volume can be interactively selected for closer inspection and can be compared with the corresponding sub-volume at the other timepoints, employing a number of different comparative visualization approaches. We provide an additional tool that highlights possibly interesting areas based on the change of bone density between timepoints. Furthermore we allow visualization of the local registration error, to give an indication of the accuracy of the registration. We have evaluated our approach on a case that exhibits cancer-induced bone resorption.

Fully automatic registration and segmentation of first-pass myocardial perfusion MR image sequences.

RATIONALE AND OBJECTIVES: Derivation of diagnostically relevant parameters from first-pass myocardial perfusion magnetic resonance images involves the tedious and time-consuming manual segmentation of the myocardium in a large number of images. To reduce the manual interaction and expedite the perfusion analysis, we propose an automatic registration and segmentation method for the derivation of perfusion linked parameters. MATERIALS AND METHODS: A complete automation was accomplished by first registering misaligned images using a method based on independent component analysis, and then using the registered data to automatically segment the myocardium with active appearance models. We used 18 perfusion studies (100 images per study) for validation in which the automatically obtained (AO) contours were compared with expert drawn contours on the basis of point-to-curve error, Dice index, and relative perfusion upslope in the myocardium. RESULTS: Visual inspection revealed successful segmentation in 15 out of 18 studies. Comparison of the AO contours with expert drawn contours yielded 2.23 ± 0.53 mm and 0.91 ± 0.02 as point-to-curve error and Dice index, respectively. The average difference between manually and automatically obtained relative upslope parameters was found to be statistically insignificant (P = .37). Moreover, the analysis time per slice was reduced from 20 minutes (manual) to 1.5 minutes (automatic). CONCLUSION: We proposed an automatic method that significantly reduced the time required for analysis of first-pass cardiac magnetic resonance perfusion images. The robustness and accuracy of the proposed method were demonstrated by the high spatial correspondence and statistically insignificant difference in perfusion parameters, when AO contours were compared with expert drawn contours.

Detection of pollen grains in multifocal optical microscopy images of air samples.

Pollen is a major cause of allergy and monitoring pollen in the air is relevant for diagnostic purposes, development of pollen forecasts, and for biomedical and biological researches. Since counting airborne pollen is a time-consuming task and requires specialized personnel, an automated pollen counting system is desirable. In this article, we present a method for detecting pollen in multifocal optical microscopy images of air samples collected by a Burkard pollen sampler, as a first step in an automated pollen counting procedure. Both color and shape information was used to discriminate pollen grains from other airborne material in the images, such as fungal spores and dirt. A training set of 44 images from successive focal planes (stacks) was used to train the system in recognizing pollen color and for optimization. The performance of the system has been evaluated using a separate set of 17 image stacks containing 65 pollen grains, of which 86% was detected. The obtained precision of 61% can still be increased in the next step of classifying the different pollen in such a counting system. These results show that the detection of pollen is feasible in images from a pollen sampler collecting ambient air. This first step in automated pollen detection may form a reliable basis for an automated pollen counting system.

Sign language recognition by combining statistical DTW and independent classification.

To recognize speech, handwriting or sign language, many hybrid approaches have been proposed that combine Dynamic Time Warping (DTW) or Hidden Markov Models (HMM) with discriminative classifiers. However, all methods rely directly on the likelihood models of DTW/HMM. We hypothesize that time warping and classification should be separated because of conflicting likelihood modelling demands. To overcome these restrictions, we propose to use Statistical DTW (SDTW) only for time warping, while classifying the warped features with a different method. Two novel statistical classifiers are proposed (CDFD and Q-DFFM), both using a selection of discriminative features (DF), and are shown to outperform HMM and SDTW. However, we have found that combining likelihoods of multiple models in a second classification stage degrades performance of the proposed classifiers, while improving performance with HMM and SDTW. A proof-of-concept experiment, combining DFFM mappings of multiple SDTW models with SDTW likelihoods, shows that also for model-combining, hybrid classification can provide significant improvement over SDTW. Although recognition is mainly based on 3D hand motion features, these results can be expected to generalize to recognition with more detailed measurements such as hand/body pose and facial expression.

Automatic initialization algorithm for carotid artery segmentation in CTA images.

Analysis of CT datasets is commonly time consuming because of the required manual interaction. We present a novel and fast automatic initialization algorithm to detect the carotid arteries providing a fully automated approach of the segmentation and centerline detection. First, the volume of interest (VOI) is estimated using a shoulder landmark. The carotid arteries are subsequently detected in axial slices of the VOI by applying a circular Hough transform. To select carotid arteries related signals in the Hough space, a 3-D, direction dependent hierarchical clustering is used. To allow a successful detection for a wide range of vessel diameters, a feedback architecture was introduced. The algorithm was designed and optimized using a training set of 20 patients and subsequently evaluated using 31 test datasets. The detection algorithm, including VOI estimation, correctly detects 88% of the carotid arteries. Even though not all carotid arteries have been correctly detected, the results are very promising.

A new algorithm for the registration of portal images to planning images in the verification of radiotherapy, as validated in prostate treatments.

The manual verification of a radiotherapy treatment, where a portal image is matched onto a planning image, is very time consuming and subject to inter- and intraobserver variability. Therefore, a fully automatic matching procedure (image registration) is required. Existing automatic matching algorithms are confounded, however, by irrelevant information in the portal images (i.e., air in the intestines). Therefore, we have developed a new method, which is an extension of chamfer matching and uses, apart from the distance to the nearest edge, additional information on the correspondence of the gradient angle and magnitude of the edges, making the method less sensitive to confounding information in the images. To validate the automatic matching procedure in clinical practice, we applied the new method on 157 images of 29 randomly selected patients treated for carcinoma of the prostate. Three experts manually matched these images in consensus. Subsequently, the same observers assessed the results of the automatic registration. When regular chamfer matching is used for the fully automatic matching procedure, only 5% of the image pairs could be matched correctly, whereas the new method successfully registered 80% by using additional information on the angle of the edges. From the results of the validation study it can be concluded that a significant reduction in workload for the physicians and technicians can be achieved with this method.