A Wearable Haptic Device for the Hand with Interchangeable End-Effectors.

This paper presents a 4-degrees-of-freedom (4-DoF) hand wearable haptic device for Virtual Reality (VR). It is designed to support different end-effectors, that can be easily exchanged so as to provide a wide range of haptic sensations. The device is composed of a static upper body, secured to the back of the hand, and the (changeable) end-effector, placed in contact with the palm. The two parts of the device are connected by two articulated arms, actuated by four servo motors housed on the upper body and along the arms. The paper summarizes the design and kinematics of the wearable haptic device and presents a position control scheme able to actuate a broad range of end-effectors. As a proof of concept, we present and evaluate three representative end-effectors during interactions in VR, rendering the sensation of interacting (E1) with rigid slanted surfaces and sharp edges having different orientations, (E2) with curved surfaces having different curvatures, and (E3) with soft surfaces having different stiffness characteristics. A few additional end-effector designs are discussed. A human-subjects evaluation in immersive VR shows the broad applicability of the device, able to render rich interactions with a diverse set of virtual objects.

Multicentric Carpotarsal Osteolysis Syndrome Associated Nephropathy: Novel Variants of MAFB Gene and Literature Review.

Multicentric carpo-tarsal osteolysis (MCTO) is a rare osteolysis syndrome mainly involving carpal and tarsal bones usually presenting in early childhood. MCTO has autosomal dominant inheritance with heterozygous mutation in the MAFB gene. The skeletal disorder is often associated with chronic kidney disease. Data on clinical characterization and best treatment option of MCTO-associated nephropathy are scarce and mostly limited to case reports. With the aim to better define the phenotype and long-term outcomes of MCTO-associated nephropathy, we launched an online survey through the Workgroup for hereditary glomerulopathies of the European Rare Kidney Disease Network (ERKNet). Overall, we collected clinical and genetic data of 54 MCTO patients, of which 42 previously described and 12 new patients. We observed a high rate of kidney involvement (70%), early age of kidney disease onset, nephrotic-range proteinuria, and a kidney survival around of 40% at long-term follow-up. Our finding confirmed the heterogeneity of clinical manifestations and widen the spectrum of phenotypes resulting from MCTO-associated nephropathy. Furthermore, we report the first case of complete remission after treatment with cyclosporine A. We demonstrated that multidisciplinary care is essential for MCTO patients and early referral to nephrologists is therefore warranted to facilitate prompt treatment.

Dyslipidemia in Children Treated with a BRAF Inhibitor for Low-Grade Gliomas: A New Side Effect?

BRAF inhibitors, in recent years, have played a central role in the disease control of unresectable BRAF-mutated pediatric low-grade gliomas (LGGs). The aim of the study was to investigate the acute and long-term effects of vemurafenib on the lipid metabolism in children treated for an LGG. In our cohort, children treated with vemurafenib (n = 6) exhibited alterations in lipid metabolism a few weeks after starting, as was demonstrated after 1 month (n = 4) by the high plasma levels of the total cholesterol (TC = 221.5 ± 42.1 mg/dL), triglycerides (TG = 107.8 ± 44.4 mg/dL), and low-density lipoprotein (LDL = 139.5 ± 51.5 mg/dL). Despite dietary recommendations, the dyslipidemia persisted over time. The mean lipid levels of the TC (222.3 ± 34.7 mg/dL), TG (134.8 ± 83.6 mg/dL), and LDL (139.8 ± 46.9 mg/dL) were confirmed abnormal at the last follow-up (45 ± 27 months, n = 6). Vemurafenib could be associated with an increased risk of dyslipidemia. An accurate screening strategy in new clinical trials, and a multidisciplinary team, are required for the optimal management of unexpected adverse events, including dyslipidemia.

Hyperseries in the non-Archimedean ring of Colombeau generalized numbers.

This article is the natural continuation of the paper: Mukhammadiev et al. Supremum, infimum and hyperlimits of Colombeau generalized numbers in this journal. Since the ring of Robinson-Colombeau is non-Archimedean and Cauchy complete, a classical series ∑ n = 0 + ∞ a n of generalized numbers is convergent if and only if a n → 0 in the sharp topology. Therefore, this property does not permit us to generalize several classical results, mainly in the study of analytic generalized functions (as well as, e.g., in the study of sigma-additivity in integration of generalized functions). Introducing the notion of hyperseries, we solve this problem recovering classical examples of analytic functions as well as several classical results.

Low C3 Serum Levels Predict Severe Forms of STEC-HUS With Neurologic Involvement.

Background: The correlation between the severity of hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) and involvement of the complement system has been examined in a small number of studies, with conflicting results. In the present study, we investigated whether serum C3 levels on admission are associated with neurologic involvement. Methods: To this purpose, 68 consecutive STEC-HUS patients were recruited and main clinical and laboratory variables ad hospital admission were compared between those with or without neurologic involvement. Results: STEC-HUS patients who developed neurologic involvement (NI) showed significant higher leukocyte count, C-reactive protein and hemoglobin, and lower sodium levels as compared with those without. Interestingly, baseline serum levels of C3 were significantly lower in patients with NI as compared with those without (p < 0.001). Moreover, when stratified according to need of Eculizumab rescue therapy due to severe NI, patients treated with this drug showed baseline C3 serum levels significantly lower than those who were not (p < 0.001). Low C3 was independent risk factor for NI in our patients' population when entered as covariate in a multivariate logistic regression analysis including other major variables previously proposed as possible predictors of poor prognosis in STEC-HUS (for instance, leukocyte count, c-reactive protein, sodium levels) (HR 6.401, 95%CI 1.617-25.334, p = 0.008 for C3). To underline the role of complement in the worsening of STEC-HUS patients' clinical conditions and outcomes, all patients were divided into two groups according to the baseline lower vs. normal serum levels of C3 and the main data on care needs were assessed. Interestingly more patients with lower C3 serum levels required renal replacement therapy (p = 0.024), anti-hypertensive therapy (p = 0.011), Intensive Care Unit admission (p = 0.009), and longer hospitalization (p = 0.003), thus displaying significantly more severe disease features as compared with those with normal C3 serum levels. Conclusions: Our data suggests that children with STEC-HUS with decreased C3 concentrations at admission are more likely to develop neurologic involvement and are at increased risk of having severe clinical complications.

Mid-Aortic Syndrome: A Rare Cause of Renovascular Hypertension in Childhood Treated Percutaneously with an Unusual Vascular Access.

INTRODUCTION: Mid-Aortic Syndrome (MAS) is a rare vascular malformation characterized by segmental narrowing of the abdominal aorta and stenosis of its principal branches. Patients affected by MAS typically present malignant renovascular hypertension, with variable clinical symptoms like claudication, abdominal angina, and headache. Moreover, they can develop other complications, such as hypertensive encephalopathy, congestive heart failure and vascular brain accidents. Hypertension with MAS is often resistant to multidrug therapy, requiring a surgical approach to treat the clinical symptoms, prevent or block organ damage and normalize the blood pressure. CASE REPORT: Here, the case of a 4-year-old boy showing elevated blood pressure with left ventricular hypertrophy leading to idiopathic MAS, who was successfully treated with percutaneous transcatheter renal angioplasty (PTRA) using an unusual, anterograde access, is reported. DISCUSSION AND CONCLUSION: In children and adolescents, vascular malformations like MAS must be considered as a possible cause of hypertension. PTRA is a successful therapeutic strategy in children with severe renovascular hypertension. Anterograde access, using an axillary artery, can be a valid approach for PTRA when femoral access is difficult to achieve.

Caring About the Human Operator: Haptic Shared Control for Enhanced User Comfort in Robotic Telemanipulation.

Haptic shared control enables a human operator and an autonomous controller to share the control of a robotic system using haptic active constraints. It has been used in robotic teleoperation for different purposes, such as navigating along paths minimizing the torques requested to the manipulator or avoiding possibly dangerous areas of the workspace. However, few works have focused on using these ideas to account for the user's comfort. In this article, we present an innovative haptic-enabled shared control approach aimed at minimizing the user's workload during a teleoperated manipulation task. Using an inverse kinematic model of the human arm and the rapid upper limb assessment (RULA) metric, the proposed approach estimates the current user's comfort online. From this measure and an a priori knowledge of the task, we then generate dynamic active constraints guiding the users towards a successful completion of the task, along directions that improve their posture and increase their comfort. Studies with human subjects show the effectiveness of the proposed approach, yielding a 30% perceived reduction of the workload with respect to using standard guided human-in-the-loop teleoperation.

A Haptic Shared-Control Architecture for Guided Multi-Target Robotic Grasping.

Although robotic telemanipulation has always been a key technology for the nuclear industry, little advancement has been seen over the last decades. Despite complex remote handling requirements, simple mechanically linked master-slave manipulators still dominate the field. Nonetheless, there is a pressing need for more effective robotic solutions able to significantly speed up the decommissioning of legacy radioactive waste. This paper describes a novel haptic shared-control approach for assisting a human operator in the sort and segregation of different objects in a cluttered and unknown environment. A three-dimensional scan of the scene is used to generate a set of potential grasp candidates on the objects at hand. These grasp candidates are then used to generate guiding haptic cues, which assist the operator in approaching and grasping the objects. The haptic feedback is designed to be smooth and continuous as the user switches from a grasp candidate to the next one, or from one object to another one, avoiding any discontinuity or abrupt changes. To validate our approach, we carried out two human-subject studies, enrolling 15 participants. We registered an average improvement of 20.8%, 20.1%, and 32.5% in terms of completion time, linear trajectory, and perceived effectiveness, respectively, between the proposed approach and standard teleoperation.

A pediatric neurologic assessment score may drive the eculizumab-based treatment of Escherichia coli-related hemolytic uremic syndrome with neurological involvement.

BACKGROUND: Thrombotic microangiopathy (TMA) is a clinical syndrome encompassing a large group of rare but severe disorders including thrombotic thrombocytopenic purpura (TTP) and both typical and atypical forms of hemolytic uremic syndrome (HUS). The key role of the complement system is well known in TTP and atypical HUS, but recent reports describe its involvement in the pathogenesis of HUS secondary to gastrointestinal infections due to Shiga toxin-producing Escherichia coli (STEC). METHODS: TMA mainly affects the kidney, but extra-renal complications are frequently described. The involvement of the central nervous system (CNS) represents often a life-threatening condition and it can result in serious long-term disability in HUS patients who overcome the acute phase of illness. In the present study, we retrospectively analyzed a pediatric cohort of a single tertiary pediatric hospital in Southern Italy, in which this complication occurred in 12/54 children (22% of cases), of whom five with severe neurological involvement had been successfully treated with eculizumab. RESULTS: The great clinical variability of brain injury in our cohort has led us to retrospectively build a "neurological score" useful to assess the clinical severity of neurologic involvement. Subjects with higher neurologic score due to the most severe CNS involvement resulted in the group of patients early treated with eculizumab, obtaining a good clinical response (four out five patients). In conclusion, the early treatment with eculizumab in children with severe neurological involvement during STEC-HUS was associated with complete regression of both acute kidney injury (AKI) and neurological lesions observed at magnetic resonance imaging (MRI). CONCLUSIONS: A "neurological score" may be a useful tool to drive the early treatment of CNS complications in STEC-HUS with eculizumab, although future perspective controlled studies are urgently needed to validate this therapeutic approach.

From Uganda to Italy: a case of nephrotic syndrome secondary to Plasmodium infection, Quartan malarial nephropathy and kidney failure.

Gentile F, Martino M, Santangelo L, Giordano P, Torres DD, Carbone V, Di Palma AM, Rossini M, Gesualdo L, Giordano P, Giordano M. From Uganda to Italy: a case of nephrotic syndrome secondary to Plasmodium infection, Quartan malarial nephropathy and kidney failure. Turk J Pediatr 2019; 61: 776-779. Malaria (M), the first parasitic infection, is sometimes associated with nephrotic syndrome (NS) in tropical areas. Kidney involvement during quartan malaria is represented by immune-complex mediated glomerulonephritis (GN). Generally, NS develops several weeks after onset of quartan fever and its clinical course proceeds slowly to end-stage kidney disease (ESKD) even after eradication of the infection. We describe a case of Plasmodium malariaeassociated nephrotic syndrome and chronic proliferative glomerulopathy in a boy from Uganda. Renal biopsy revealed chronic proliferative GN with capillary wall thickening producing a double contour, segmental sclerosis and tubular atrophy. Blood Giemsa smear contained rare ring-form trophozoites and gametocytes of Plasmodium spp. This case highlights the importance of obtaining remote travel histories from immigrants presenting with nephrotic syndrome especially due to the current immigration crisis in Europe. Malaria has low prevalence or less known in our continent and requires more medical attention by European doctors.

Indications and results of renal biopsy in children: a 36-year experience.

BACKGROUND: This study was conducted to investigate retrospectively the indications for renal biopsy (RB) in native kidneys and to analyze pathological findings in a single tertiary pediatric hospital in Southern Italy for the last 36 years. METHODS: All patients who underwent RB at our hospital from 1979 to 2014 were included. All renal tissue specimens were studied under light and immunofluorescent microscopy, while electron microscopy was performed only for specific clinical indications. RESULTS: The study group included 213 patients (female 43.2%) who underwent 225 percutaneous native kidney biopsies. Median age was 10.4 years (range 0.6-24 years). The most frequent indication for RB was nephrotic syndrome (44.4%), followed by proteinuria (27.6%), asymptomatic hematuria (17.3%) and acute kidney injury (9.8%). Gross hematuria appeared after biopsy in less than 5% of the patients, but none of them needed blood transfusion. Adequate renal tissue sample was obtained in 95.5% of the renal biopsies. Primary glomerulonephritis (GN) was the most common finding (61.4%), followed by secondary GN (21.4%), tubulointerstitial diseases (3.7%) and hereditary nephropathy (2.8%), while in 10.7% of the cases, normal renal tissues were found. According to histopathological diagnosis, the most common causes of primary GN were IgA nephropathy (20.9%), followed by minimal change disease (18.1%) and focal segmental glomerulosclerosis (11.6%). CONCLUSIONS: The epidemiology of glomerular disease in our single-center cohort is similar to that shown in other national and international reports. Moreover, our study shows that percutaneous ultrasound-guided RB is a safe, reliable and effective technique in children.

Comparison of Percutaneous Mitral Valve Repair Versus Conservative Treatment in Severe Functional Mitral Regurgitation.

Percutaneous mitral valve repair (PMVR) using the MitraClip System is feasible and entails clinical improvement even in patients with high surgical risk and severe functional mitral regurgitation (MR). The aim of this study was to assess survival rates and clinical outcome of patients with severe, functional MR treated with optimal medical therapy (OMT) compared with those who received MitraClip device. Sixty patients treated with OMT were compared with a propensity-matched cohort of 60 patients who underwent PMVR. Baseline demographics and echocardiographic variables were similar between the 2 groups. The mean age of patients was 75 years, and 67% were men. The median logistic EuroSCORE and EuroSCORE II were 17% and 6%, respectively, because of the presence of several co-morbidities. The mechanism of MR was functional in all cases with an ischemic etiology in 52% of patients. Median left ventricle ejection fraction was 34%. All the patients were symptomatic for dyspnea with 63% and 12% in the New York Heart Association class III and IV, respectively. In PMVR group, the procedure was associated with safety and very low incidence of procedural complications with no occurrence of procedural and inhospital mortality. After a median follow-up of 515 days (248 to 828 days), patients treated with PMVR demonstrated overall survival, survival freedom from cardiac death and survival free of readmission due to cardiac disease curves higher than patients treated conservatively (log-rank test p = 0.007, p = 0.002, and p = 0.04, respectively). In conclusion, PMVR offers a valid option for selected patients with high surgical risk and severe, functional MR and entails better survival outcomes compared with OMT.

Aneurysmal bone cyst does not hinder the success of kidney transplantation. A case report.

Uremic osteodystrophy is an expected complication in subjects with chronic renal insufficiency. It develops gradually and progressively already during the conservative treatment and then during the dialysis treatment. It can present a wide histopathological spectrum including typical alterations (from osteitis fibrosa to osteomalacia and/or mixed lesions) or, more rarely, isolated bone lesions indicative of a brown tumor of the bone. These conditions must be clearly identified in the pretransplant phase, especially if a bone lesion indicative of a pathological condition possibly evolving into a neoplasm is detected fortuitously. We report the case of a 19-yr-old boy with renal insufficiency and candidate for a pre-emptive renal transplantation from a living donor, in whom the diagnosis of ABC of the pubic symphysis - asymptomatic and fortuitously detected while performing instrumental investigations - was suspected through the imaging studies (CT scan, MRI) and was confirmed by the histological examination. This made it possible to perform the renal transplant. The immunosuppressive treatment, which was subsequently administered, was based on steroids, calcineurin inhibitors (tacrolimus), and mycophenolate and did not determine any modification in the radiological aspect of the bone lesion, even after more than one yr from the transplant.

Human-Centered Design and Evaluation of Haptic Cueing for Teleoperation of Multiple Mobile Robots.

In this paper, we investigate the effect of haptic cueing on a human operator's performance in the field of bilateral teleoperation of multiple mobile robots, particularly multiple unmanned aerial vehicles (UAVs). Two aspects of human performance are deemed important in this area, namely, the maneuverability of mobile robots and the perceptual sensitivity of the remote environment. We introduce metrics that allow us to address these aspects in two psychophysical studies, which are reported here. Three fundamental haptic cue types were evaluated. The Force cue conveys information on the proximity of the commanded trajectory to obstacles in the remote environment. The Velocity cue represents the mismatch between the commanded and actual velocities of the UAVs and can implicitly provide a rich amount of information regarding the actual behavior of the UAVs. Finally, the Velocity+Force cue is a linear combination of the two. Our experimental results show that, while maneuverability is best supported by the Force cue feedback, perceptual sensitivity is best served by the Velocity cue feedback. In addition, we show that large gains in the haptic feedbacks do not always guarantee an enhancement in the teleoperator's performance.

Modeling direction discrimination thresholds for yaw rotations around an earth-vertical axis for arbitrary motion profiles.

Understanding the dynamics of vestibular perception is important, for example, for improving the realism of motion simulation and virtual reality environments or for diagnosing patients suffering from vestibular problems. Previous research has found a dependence of direction discrimination thresholds for rotational motions on the period length (inverse frequency) of a transient (single cycle) sinusoidal acceleration stimulus. However, self-motion is seldom purely sinusoidal, and up to now, no models have been proposed that take into account non-sinusoidal stimuli for rotational motions. In this work, the influence of both the period length and the specific time course of an inertial stimulus is investigated. Thresholds for three acceleration profile shapes (triangular, sinusoidal, and trapezoidal) were measured for three period lengths (0.3, 1.4, and 6.7 s) in ten participants. A two-alternative forced-choice discrimination task was used where participants had to judge if a yaw rotation around an earth-vertical axis was leftward or rightward. The peak velocity of the stimulus was varied, and the threshold was defined as the stimulus yielding 75 % correct answers. In accordance with previous research, thresholds decreased with shortening period length (from ~2 deg/s for 6.7 s to ~0.8 deg/s for 0.3 s). The peak velocity was the determining factor for discrimination: Different profiles with the same period length have similar velocity thresholds. These measurements were used to fit a novel model based on a description of the firing rate of semi-circular canal neurons. In accordance with previous research, the estimates of the model parameters suggest that velocity storage does not influence perceptual thresholds.

Predicting direction detection thresholds for arbitrary translational acceleration profiles in the horizontal plane.

In previous research, direction detection thresholds have been measured and successfully modeled by exposing participants to sinusoidal acceleration profiles of different durations. In this paper, we present measurements that reveal differences in thresholds depending not only on the duration of the profile, but also on the actual time course of the acceleration. The measurements are further explained by a model based on a transfer function, which is able to predict direction detection thresholds for all types of acceleration profiles. In order to quantify a participant's ability to detect the direction of motion in the horizontal plane, a four-alternative forced-choice task was implemented. Three types of acceleration profiles (sinusoidal, trapezoidal and triangular) were tested for three different durations (1.5, 2.36 and 5.86 s). To the best of our knowledge, this is the first study which varies both quantities (profile and duration) in a systematic way within a single experiment. The lowest thresholds were found for trapezoidal profiles and the highest for triangular profiles. Simulations for frequencies lower than the ones actually measured predict a change from this behavior: Sinusoidal profiles are predicted to yield the highest thresholds at low frequencies. This qualitative prediction is only possible with a model that is able to predict thresholds for different types of acceleration profiles. Our modeling approach represents an important advancement, because it allows for a more general and accurate description of perceptual thresholds for simple and complex translational motions.