Super-twisting-based meal detector for type 1 diabetes management: Improvement and assessment in a real-life scenario.

BACKGROUND AND OBJECTIVE: Hybrid automated insulin delivery systems rely on carbohydrate counting to improve postprandial control in type 1 diabetes. However, this is an extra burden on subjects, and it introduces a source of potential errors that could impact control performances. In fact, carbohydrates estimation is challenging, prone to errors, and it is known that subjects sometimes struggle to adhere to this requirement, forgetting to perform this task. A possible solution is the use of automated meal detection algorithms. In this work, we extended a super-twisting-based meal detector suggested in the literature and assessed it on real-life data. METHODS: To reduce the false detections in the original meal detector, we implemented an implicit discretization of the super-twisting and replaced the Euler approximation of the glucose derivative with a Kalman filter. The modified meal detector is retrospectively evaluated in a challenging real-life dataset corresponding to a 2-week trial with 30 subjects using sensor-augmented pump control. The assessment includes an analysis of the nature and riskiness of false detections. RESULTS: The proposed algorithm achieved a recall of 70 [13] % (median [interquartile range]), a precision of 73 [26] %, and had 1.4 [1.4] false positives-per-day. False positives were related to rising glucose conditions, whereas false negatives occurred after calibrations, missing samples, or hypoglycemia treatments. CONCLUSIONS: The proposed algorithm achieves encouraging performance. Although false positives and false negatives were not avoided, they are related to situations with a low risk of hypoglycemia and hyperglycemia, respectively.

Black-box Model Identification of Physical Activity in Type-l Diabetes Patients.

In this paper we consider the problem of predicting future values of glucose in type-1 diabetes. In particular, we investigate the benefit of including physical activity, measured by an off-the-shelf wearable device, to other physiologic signals frequently used to predict blood-glucose concentration, namely injected insulin, carbohydrates intake, and past glucose samples measured by a Continuous Glucose Monitoring (CGM) sensor. Derivation of individualized predictors is crucial to cope with the wide inter- and intra-subject variability: learning and updating patient-specific models of the glucose-insulin system and using them to design personalized control actions has the potential to improve substantially patients' quality oflife. On data collected by 6 subjects for 5 days, we identify a black-box liner model that uses insulin and meal as inputs and glucose as output. Prediction Error Method (PEM) is used for parameter estimation. The personalized model is employed to derive patient-tailored predictors. This procedure is then repeated using a further physiological input, accounting for physical activity. The prediction accuracy of the two models, including or not physical activity, was compared on the basis of two metrics commonly used in system identification, namely Coefficient of Determination (COD) and Root Mean Squared Error. The models identified with physical activity have better performance, increasing the 3-hr prediction COD by mean ± standard deviation of 18.5% ± 30.1%.

Gait analysis contribution to problems identification and surgical planning in CP patients: an agreement study.

BACKGROUND: Previous studies have demonstrated that the use of gait analysis (GA) modifies decision making and changes planned surgical treatment, confirming some clinical indications or defining alternative choices, excluding or delaying already planned surgery in children with cerebral palsy (CP). AIM: To assess the difference in defining functional problems and treatment relevance using clinical assessment or gait analysis in CP children. DESIGN: The study has been designed for assessing the rate of agreement on muscle-skeletal diagnosis, and on surgical recommendations in diplegic CP patients, when decided by two different blinded clinicians based on a) clinical assessment, and b) GA in addition to clinical assessment. POPULATION: Twenty-five diplegic children who have been evaluated by GA before surgery and at a follow up of at least 6 months. Methods. Two separate lists of problems and consequent surgical interventions were outlined for all the patients by two blinded experts from clinical and GA assessment. The two sets of nominal-scale ratings for all patients of the two groups were statistically evaluated for agreement. RESULTS: A fair and a slight agreement was found respectively between the two sets of problems and the two sets of surgical plans. Main differences in problems identified were relative to the presence of generalized spasticity and bony deformities as detected by means of GA instead of local problems and soft tissues spasticity/retraction clinically identified. As a consequence, by means of GA, surgery was indicated only in 65% of patients. CONCLUSION: The availability of a GA laboratory helps in diagnostic reasoning in CP children indicated for surgery. Low agreement found appears to be a result of a different clinical approach of the surgeons. CLINICAL REHABILITATION IMPACT: The use of GA in the analysis of motor problems in CP children provides a basis for an objective reasoning for clinical decision making and for assessing functional outcome. Further efforts are required to build a body of knowledge about a consensus on the identification of walking problems in CP children.

Rehabilitation of brachial plexus injuries in adults and children.

Management of brachial plexus injury sequelae is a challenging issue in neurorehabilitation. In the last decades great strides have been made in the areas of early diagnosis and surgical techniques. Conversely, rehabilitation of brachial plexus injury is a relatively unexplored field. Some critical aspects regarding brachial plexus injury rehabilitation have to be acknowledged. First, brachial plexus injury may result in severe and chronic impairments in both adults and children, thus requiring an early and long-lasting treatment. Second, nerve damage causes a multifaceted clinical picture consisting of sensorimotor disturbances (pain, muscle atrophy, muscle weakness, secondary deformities) as well as reorganization of the Central Nervous System that may be associated with upper limb underuse, even in case of peripheral injured nerves repair. Finally, psychological problems and a lack of cooperation by the patient may limit rehabilitation effects and increase disability. In the present paper the literature concerning brachial plexus injury deficits and rehabilitation in both adults and children was reviewed and discussed. Although further research in this field is recommended, current evidence supports the potential role of rehabilitation in reducing both early and long-lasting disability. Furthermore, the complexity of the functional impairment necessitates an interdisciplinary approach incorporating various health professionals in order to optimizing outcomes.

Equinus foot classification in cerebral palsy: an agreement study between clinical and gait analysis assessment.

BACKGROUND: Excessive ankle plantar flexion (equinus foot) is a common problem in cerebral palsy (CP) and several treatment options can be considered depending on the equinus type. Few attempts have been made to classify different forms of equinus foot for specific treatment. AIM: This study is aimed at defining equinus foot types in CP patients according to the Ferrari classification, integrating clinical and instrumental assessments. The hypothesis is that clinical differentiation of equinus foot can be evidenced by recurrent anomalies identifiable through gait analysis (GA), which can make the assessment, usually based only on clinician semeiotics, more objective. DESIGN: Clinical and instrumental assessments were performed separately by a senior CP physiatrist and a senior GA physiatrist, the latter was blind to the clinical diagnosis of equinus type. SETTING: Outpatients POPULATION: Twenty patients, 16 diplegics and 4 hemiplegics (mean age 11 years, SD 4 years 11 months). METHODS: Clinical assessment by means of Modified Ashworth Scale, Gross Motor Function Measure (GMFM), Observational Gait Analysis (OGA), and measurement of lower limb muscle strength by dynamometer were used to classify the equinus type. Gait analysis assessed the kinematics and EMG of affected lower limbs. RESULTS: Ten different equinus types were identified. Since various forms of equinus can be present in the same patient, we were able to classify a total of 61 types of equinus in 36 feet. Substantial agreement was found between Clinical and Gait Analysis equinus assignment matched in 50 out of 61 types (Index of agreement with Fleiss' Kappa 79.3 % ). In some case only Gait Analysis was able to identify the equinus type, while in others it did not confirm clinical assignment. CONCLUSION: Gait analysis is able to distinguish different equinus types according to Ferrari classification, making the clinical decision less arbitrary. CLINICAL REHABILITATION IMPACT: Correct objective diagnosis of equinus foot in CP patients is of paramount importance when choosing suitable rehabilitative interventions.

A modified constraint-induced movement therapy (CIT) program improves paretic arm use and function in children with cerebral palsy.

AIM: Constraint-induced movement therapy (CIT) is a rehabilitation intervention put forward by Taub and colleagues for sensorimotor disorders in children with hemiparesis, comprising consisting of the restraint of the unaffected arm and concurrent intensive training of the affected arm for six hours/day for two weeks. The aim of this study was to evaluate the effectiveness of a modified CIT program (mCIT) characterized by restraining the unaffected hand with a cotton mitten during daily activities and a reduced intensity training program for two h/week for five weeks. METHODS: Ten children (age: 1-9 years) with hemiparetic cerebral palsy were enrolled in a randomized, cross-over study in which the effects of a mCIT and a conventional physiotherapy program were compared. The amount of use and the functional performance of the affected arm were evaluated by means of two specifically devised tests (Use and Function Test). A further test evaluated functional performance during bimanual tasks. These measures showed a good inter-rater and inter-session reliability. All tests were administered before, at the end and four weeks after treatment. RESULTS: Significant differences between the two therapeutic approaches were evidenced in both affected arm use (P=0.008) and function (P=0.018). These improvements maintained at the follow-up (Use Test P=0.07; paretic arm function P=0.012). Bimanual function performance showed a trend towards improvement in both post-treatment and follow-up testing. The conventional physiotherapy group did not show any improvement in any outcome measure. CONCLUSIONS: The mCIT program proposed in the present study showed to be a promising rehabilitative procedure in children with congenital arm paresis after cerebral palsy.

Cell proliferation as an independent predictor of survival for patients with advanced nasopharyngeal carcinoma.

Commonly used clinical and pathologic criteria are often of limited value in predicting the outcome of patients with undifferentiated nasopharyngeal carcinoma, and new parameters related to the biology of growth of neoplastic cells are still required for better definition of the aggressiveness of these tumors. The prognostic significance of DNA ploidy, measured by image cytometry on isolated cells, and of the mitotic index, proliferating cell nuclear antigen, and p53 protein, all measured by image cytometry in histologic sections, were evaluated on archival tumor tissues from 53 patients with Stage III or IV nasopharyngeal carcinomas. Patients were staged according to the criteria of the International Union Against Cancer and were irradiated according to a conventional radiotherapy schedule. No significant associations were found between biologic parameters and clinical features. Only the stage and the mitotic index were related to patient survival, and, when examined in a proportional hazard regression analysis, both provided independent information. When patients with compromised skull and/or cranial nerves (T4 tumors), who had a very short survival, were eliminated from the analysis, only the mitotic index and proliferating cell nuclear antigen allowed discrimination of a subset of patients with poor prognoses. This study shows that the assessment of cell proliferative activity can provide useful information for better predicting the clinical course of high-risk patients with nasopharyngeal carcinomas and improve therapeutic strategies.

In vivo CHCl3 bioactivation, toxicokinetics, toxicity, and induced compensatory cell proliferation in B6C3F1 male mice.

Chloroform carcinogenicity has often been associated with acute tissue damage and consequent compensatory cell proliferation. However, available data do not fully support this hypothesis, and other biological factors may play a role in the tumor induction by chloroform. The purpose of this study was to characterize the in vivo CHCl3 metabolism and the time course of toxic effects and of cell proliferation in the liver and kidney of B6C3F1 male mice dosed i.p. or by gavage with 150 mg CHCl3/kg body wt. Microsomal phospholipid adducts attributed to (14)CHCl3 metabolism by both oxidative and reductive pathways were detected in both liver and kidney. The levels and composition of the adducts were similar in the liver and kidney of treated animals. In the liver, although no necrosis was histologically detectable, a transient cell proliferation was found starting at 24 and peaking at 48 hr post-treatment. Kidney toxicity was evident by biochemical and cytochemical methods at 5 hr after dosing and progressed to severe necrosis at 48 and 96 hr. An intense kidney cell regeneration began 48 hr after CHCl3 treatment, became maximal at 96 hr, and was sustained for at least the following 3 days. These observations raise questions about the purely epigenetic action of chloroform in tumor induction since bioassays have found tumors in liver but not kidneys of CHCl3-treated B6C3F1 mice.

Cytometric measurement of cell proliferation in echo-guided biopsies from focal lesions of the liver.

Increased proliferative activity determined in surgical specimens of hepatocellular carcinoma (HCC) has been associated with tumor grade and patient survival. The measurement of cell proliferation in echo-guided biopsies of small focal liver lesions might provide useful information for the early recognition of malignancy and for predicting the aggressiveness of small HCCs. We assessed the diagnostic and prognostic value of cell proliferation in 91 echo-guided needle biopsies of focal liver lesions using the monoclonal antibody Ki-67, which detects a human nuclear antigen that is present in proliferating cells. Measurements were performed by image cytometry as the percentage of Ki-67 positive hepatocytes nuclei over total hepatocyte nuclei in the biopsy. At the histological examination, 27 lesions were diagnosed as chronic hepatitis, 10 as cirrhosis, 11 as macroregenerative nodule, and 43 as HCC in cirrhotic liver. Although the highest Ki-67 values (> 20%) were found in less-differentiated HCCs, most well-differentiated HCCs and nine borderline nodules were completely devoid of Ki-67-positive hepatocytes. A sustained Ki-67 labeling (up to 16%) was found in hepatitis and cirrhosis, similar to that found in several malignant tumors. In the HCC subset, Ki-67 labeling was strongly correlated to the Edmondson-Steiner histological grade. However, survival analysis did not indicate a better outcome for those patients with low-proliferating tumors.

Structure of human cervical mucus correlation with plasma ovarian hormone levels.

In studying the structural changes of human cervical mucus during the ovulatory cycle, they have been observed to be directly related to ovarian hormone changes. Mucus structural changes, if taken according to their sequence during the cycle, clearly express the anatomic and functional events occurring in the ovary. If each structure is considered separately, only the mucus of the preovulatory period can be considered an indication of the corresponding ovarian processes, presenting peculiar morphologic characteristics. The observation of a similar morphologic appearance in the mucus of the early follicular and luteal phases leads one to believe, in spite of the influence of totally different hormone levels, in the likely existence of a mechanism of interference between estrogens and progesterone during the postovulatory period of the cycle.