Matheuristics for Multi-UAV Routing and Recharge Station Location for Complete Area Coverage.

This paper presents matheuristics for routing a heterogeneous group of capacitated unmanned air vehicles (UAVs) for complete coverage of ground areas, considering simultaneous minimization of the coverage time and locating the minimal number of refueling stations. Whereas coverage path planning (CPP) is widely studied in the literature, previous works did not combine heterogeneous vehicle performance and complete area coverage constraints to optimize UAV tours by considering both objectives. As this problem cannot be easily solved, we designed high-level path planning that combines the multiobjective variable neighborhood search (MOVNS) metaheuristic and the exact mathematical formulation to explore the set of nondominated solutions. Since the exact method can interact in different ways with MOVNS, we evaluated four different strategies using four metrics: execution time, coverage, cardinality, and hypervolume. The experimental results show that applying the exact method as an intraroute operator into the variable neighborhood descent (VND) can return solutions as good as those obtained by the closest to optimal strategy but with higher efficiency.

Safe coordination of robots in cyclic paths.

This paper presents a MILP (mixed integer linear programming) based formulation for the coordination of multiple robots. We consider robots that must follow closed intersecting paths persistently. We propose an off-line planning of velocity profiles preventing the need of online collision avoidance maneuvers or path replanning. Our robot model considers minimum and maximum speed constraints, which allows our strategy to be applied to fixed-wing aerial robots. We also deal with three important other issues which are usually disregarded in the related literature: minimum spatial separation; acceleration limits; and uncertainties on the speeds and positions. Simulations with up to 48 robots show the efficiency of our strategy. A real experiment with 3 actual e-puck robots is presented in order to demonstrate the robustness of our formulation in a real world scenario.

Multi-UAV Routing for Area Coverage and Remote Sensing with Minimum Time.

This paper presents a solution for the problem of minimum time coverage of ground areas using a group of unmanned air vehicles (UAVs) equipped with image sensors. The solution is divided into two parts: (i) the task modeling as a graph whose vertices are geographic coordinates determined in such a way that a single UAV would cover the area in minimum time; and (ii) the solution of a mixed integer linear programming problem, formulated according to the graph variables defined in the first part, to route the team of UAVs over the area. The main contribution of the proposed methodology, when compared with the traditional vehicle routing problem's (VRP) solutions, is the fact that our method solves some practical problems only encountered during the execution of the task with actual UAVs. In this line, one of the main contributions of the paper is that the number of UAVs used to cover the area is automatically selected by solving the optimization problem. The number of UAVs is influenced by the vehicles' maximum flight time and by the setup time, which is the time needed to prepare and launch a UAV. To illustrate the methodology, the paper presents experimental results obtained with two hand-launched, fixed-wing UAVs.

Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions.

High cholesterol levels are an established risk factor for cardiovascular disease (CVD), the world's leading cause of death. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) are prescribed to lower serum cholesterol levels and reduce the risk of CVD. Despite the success of statins, many patients abandon treatment owing to neuromuscular adverse drug reactions (ADRs). Genome-wide association studies have identified the single-nucleotide polymorphism (SNP) rs4149056 in the SLCO1B1 gene as being associated with an increased risk for statin-induced ADRs. By studying slow-channel syndrome transgenic mouse models, we determined that statins trigger ADRs in mice expressing the mutant allele of the rs137852808 SNP in the nicotinic acetylcholine receptor (nAChR) α-subunit gene CHRNA1. Mice expressing this allele show a remarkable contamination of end-plates with caveolin-1 and develop early signs of neuromuscular degeneration upon statin treatment. This study demonstrates that genes coding for nAChR subunits may contain variants associated with statin-induced ADRs.

Subcutaneous IGF-1 is not beneficial in 2-year ALS trial.

BACKGROUND: Previous human clinical trials of insulin-like growth factor type I (IGF-1) in amyotrophic lateral sclerosis (ALS) have been inconsistent. This phase III, randomized, double-blind, placebo-controlled study was undertaken to address whether IGF-1 benefited patients with ALS. METHODS: A total of 330 patients from 20 medical centers were randomized to receive 0.05 mg/kg body weight of human recombinant IGF-1 given subcutaneously twice daily or placebo for 2 years. The primary outcome measure was change in their manual muscle testing score. Secondary outcome measures included tracheostomy-free survival and rate of change in the revised ALS functional rating scale. Intention to treat analysis was used. RESULTS: There was no difference between treatment groups in the primary or secondary outcome measures after the 2-year treatment period. CONCLUSIONS: Insulin-like growth factor type I does not provide benefit for patients with amyotrophic lateral sclerosis.

Nerve conduction abnormalities in aging mice deficient for myelin-associated glycoprotein.

Ultrastructural, biochemical, and electrophysiological analyses were done on 12-14-month-old mice deficient for myelin-associated glycoprotein (MAG) to further characterize the neuropathy that develops as they age. Electron microscopy demonstrated normal myelin compaction and axonal degeneration in a large number of myelinated nerve fibers. Western blots showed that the proteins of compact myelin, P0 glycoprotein, and myelin basic protein were not significantly altered in the mutants; however, the Schwann cell protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase, was reduced to less than half the control level. Also, both total and phosphorylated high-molecular-weight neurofilament proteins (TNFH and PNFH, respectively) were significantly decreased, as was the PNFH:TNFH ratio. Electrophysiological evaluation revealed a mild, but statistically significant, reduction of conduction velocity and a nonsignificant mild decrease in compound muscle action potential amplitudes. This constellation of findings in aging MAG-null mice is consistent with an axonopathy that resembles axonal Charcot-Marie-Tooth (CMT2) disease in many respects. Thus, mutation of a myelin-associated gene expressed by Schwann cells can induce axonal degeneration and cause a neuropathy with minimal signs of demyelination.

Cutaneous silent periods in patients with Fabry disease.

We assessed the cutaneous silent period (CSP) in 24 patients with Fabry disease with small-fiber sensory neuropathy and 12 normal subjects to test the hypothesis that small-diameter afferents are responsible for producing the CSP. Sensory nerve conduction studies and quantitative sensory testing for cold and vibration detection thresholds were also measured. Overall, Fabry patients had impaired thermal, but not vibration, detection thresholds, with greatest impairment in the feet. In the upper extremity, CSP latencies, duration, and suppression of electromyographic activity (EMG) did not differ. In the lower extremity, patients had reduced suppression of EMG during the CSP compared to normal controls. CSP durations exhibited a bimodal distribution in patients, including a subset of seven patients with durations shorter than all controls. This subset had profound loss of thermal sensation in the feet, but this was also true of some patients who had normal CSPs. Patients with shortened CSPs had modestly elevated vibration thresholds and reduced sensory potentials in comparison to patients with normal CSPs. Reduced CSPs in Fabry patients are associated with, but not entirely explained by, the severity of small-fiber neuropathy as measured by quantitative sensory testing. The possibility that large-diameter fibers provide a minor contribution to producing the CSP should be considered.

[Chronic inflammatory neuropathies]. / Neuropatías crónicas inflamatorias.

INTRODUCTION: The group of chronic inflammatory neuropathies is made up of a variety of neuropathies of autoimmune or infectious origin. DEVELOPMENT: We describe three types of neuropathies and their treatment: demyelinating chronic neuropathy, motor multifocal neuropathy and demyelinating neuropathy associated with monoclonal gammapathy. These three types of neuropathy have uniform characteristics and features, which permit precise identification and suggest that they are separate entities. CONCLUSIONS: In the management of any type of neuropathy it is essential to make the correct diagnosis. Initial investigations should include detailed electrophysiological examination to detect the presence of demyelination, lumbar puncture and, if pleocytosis is found, the possibility of associated acquired immunodeficiency syndrome should be investigated. Also, before immunosuppressive treatment is begun, a systematic medical examination should be done to detect any other coexisting illness which might affect use of the different drugs involved.

[Plasmapheresis, immunotherapy and chemotherapy in polyneuropathies]. / Plasmaféresis, inmunoterapia y quimioterapia en las polineuropatías.

INTRODUCTION: Although the precise cause of many of the polyneuropathies evaluated clinically is unknown, there is substantial evidence that many are caused by autoimmune disorders. Currently treatment is directed towards production of immunomodulation or immunosuppression. DEVELOPMENT AND CONCLUSIONS: The degree of subjective symptoms such as fatigue, pain or other sensory symptoms are not good criteria for determination of the need for immunosuppressive treatment. Treatment should be orientated towards serious neuropathic defects, not minimal deficits. It is therefore important to record the defect precisely, so as to be able to determine objectively the effect of therapy. For this, tables or diagrams using established scales, such as that of the Medical Research Council, are recommended. Similarly, evaluation and follow-up by the physical therapy and occupational therapy departments should be considered when deciding the treatment to be used for autoimmune neuropathies such as corticosteroids, plasmapheresis, ev immunoglobulin, cytopathic agents and alpha interferon.

[Important aspects of the diagnosis and management of peripheral neuropathies]. / Aspectos importantes en el diagnóstico y manejo de las neuropatías periféricas.

INTRODUCTION: The peripheral neuropathies represent a diverse group of disorders of the peripheral nervous system of very varied aetiology. It is therefore important to classify them, so as to reduce the number of possible diagnoses and to identify the correct cause. OBJECTIVE: To review the most important principles of the initial examination and the management of peripheral neuropathies. DEVELOPMENT: The clinical features of these diseases may be debilitating and incapacitating, and may be part of a symptom complex of very serious diseases. It is necessary to carry out systematic evaluation of the symptoms, signs and laboratory tests so as to establish the correct diagnosis and begin treatment. Some of the most important elements used in the process of classification are: functional findings, topography or the anatomical pattern of the deficits, and the physiological or pathological findings. Treatment of the peripheral neuropathies may be divided into four groups: elimination of the casual agent, treatment of symptoms, modulation of the immune system and rehabilitation. CONCLUSION: The possibilities of diagnosis and treatment continue to increase as the mechanisms responsible become clearer.

Molecular mimicry in chronic inflammatory demyelinating polyneuropathy and melanoma.

Polyclonal immunoglobulin M antibodies to the monosialoganglioside GM2, sulfoglucuronyl glycolipids, and sulfatide were detected by thin-layer chromatography and enzyme-linked immunosorbent assay in the serum of a patient with melanoma and chronic inflammatory demyelinating polyneuropathy. Both the patient's serum and polyclonal antibodies against GM2 reacted strongly with a biopsy of melanomatous tissue from the patient, suggesting a process of molecular mimicry.

Central motor conduction time: reproducibility and discomfort of different methods.

Central motor conduction time, a useful measure for studying central motor pathways, is calculated by determining the difference between the latency of motor-evoked potentials and peripheral conduction time. The intraindividual trial-to-trial variability of central motor conduction time and the discomfort associated with three methods of measuring peripheral motor conduction time (F-wave latency, cervical magnetic stimulation, and cervical needle stimulation) were studied in 5 healthy subjects with the use of transcranial magnetic stimulation to elicit motor-evoked potentials. Central motor conduction time was calculated by using measurements, made on 3 separate days, from the same three muscles on each hand. A visual analog pain scale was used to determine the level of discomfort for each method. Intraindividual trial-to-trial variability of central motor conduction time was similar for all methods, with coefficients of variation of 13% for the F-wave latency, 15% for cervical magnetic stimulation, and 11% for cervical needle stimulation. The last method was significantly more painful than the other two methods; there was no significant difference in discomfort between the F-wave method and cervical magnetic stimulation. To assess peripheral motor conduction time, when determining central motor conduction time, either the F-wave method or cervical magnetic stimulation is preferable to cervical needle stimulation.

Peripheral neuropathy in children with HIV infection.

Peripheral neuropathy is infrequently reported in children with HIV infection, but may be underrecognized. To provide a better understanding of the patterns of peripheral neuropathy in these children, we surveyed the charts of 50 children with HIV infection referred to the EMG laboratory at the National Institutes of Health for evaluation of suspected peripheral neuropathy. Twelve children had an abnormal nerve conduction study. The findings suggested a distal sensory or sensorimotor axonal neuropathy in seven children, median nerve compression at the carpal tunnel in three, a demyelinating neuropathy in one child, and a lumbosacral polyradiculopathy in one adolescent. Distal symmetric polyneuropathy occurred mostly in older-aged children.

Inclusion body myositis: no evidence for a neurogenic component.

Because electrophysiologic, clinical, and histopathologic observations have suggested that inclusion body myositis (IBM) may have a coexistent neurogenic component, we used macro-electromyography (macro-EMG) to search for changes in the motor unit territory and signs of reinnervation. We studied 11 patients, aged 53 to 77 years (mean, 65.2 years), with typical, nonfamilial IBM lasting a mean of 8.5 years, and eight healthy volunteers aged 54 to 70 years (mean, 64.6 years), as control subjects. Nerve conduction studies showed focal abnormalities in 5 of the patients, but no evidence of a polyneuropathy. Concentric needle EMG in various proximal and distal muscles of the upper and lower limbs revealed short- or long-duration complex motor unit potentials (MUPs) or a mixture of both types of MUPs. Macro-EMG studies in the tibialis anterior muscle showed smaller macro-MUP amplitudes and areas in patients than in normal subjects. Four patients had abnormal macro-EMG studies with an increased number of small macro-MUPs, 1 patient had an equivocal study with large-amplitude but normal-area macro-MUPs, and the remaining 6 patients had normal studies. These findings are consistent with a primary muscle disorder similar to those seen in other myopathies. We conclude that macro-EMG does not support a coexistent neurogenic component in patients with IBM compared with normal subjects of similar age.

Electrophysiologic and histologic studies in clinically unaffected muscles of patients with prior paralytic poliomyelitis.

Macro-electromyography (macro-EMG) studies have provided important information about the size of the motor units and the degree of reinnvervation in clinically affected muscles of patients with a history of poliomyelitis and postpolio syndrome. The study of clinically unaffected muscles and correlation of their electrophysiologic characteristics with the muscle architecture could provide meaningful information about the ongoing subclinical denervation. We performed macro-EMG and concomitantly measured fiber density in the clinically unaffected gastrocnemius muscle of 10 patients with postpolio syndrome and 10 normal subjects of similar age. We also performed biopsies on the gastrocnemius muscle of 8 of the patients. The median amplitude and area of the macro-motor unit potentials (macro-MUPs) were increased in 8 of the 10 patients, and occasionally were five times as large as the mean median value for the normal subjects. Seven biopsy specimens showed moderate to very large fiber-type grouping. In 5 patients, there was correlation between the electrophysiologic and histologic indices of reinnervation. Amplitude and area of the macro-MUPs were associated with the muscle fiber cross-sectional area. We conclude that clinically unaffected muscles of patients with postpolio syndrome often have large motor units as the result of effective reinnervation after the original motor neuron loss. In spite of possible differences in the cytoarchitecture of muscles affected to different degrees, macro-EMG and fiber density measurements are reliable noninvasive techniques for studying the extent and effectiveness of reinnervation in patients with postpolio syndrome.

Mixed nerve action potentials in acquired demyelinating polyneuropathy.

Uncertainty about motor and sensory contributions in abnormal nerves has limited the use of mixed nerve action potentials (MNAPs). We recorded MNAPs in 21 patients with an acquired demyelinating neuropathy, 18 age-matched control subjects, and 10 patients with an axonal polyneuropathy. Bipolar and unipolar recordings from median and ulnar nerves were made above the elbow after electrical stimulation of the nerves at the wrist. Antidromic digital sensory action potentials and motor conduction velocity were also recorded for both nerves. In 19 median and 12 ulnar nerves from demyelinating polyneuropathy patients, compared with control subjects, MNAP amplitudes were significantly reduced (mean, 6 microV vs. 31 microV), MNAP velocities were mildly reduced (mean, 50 m/s vs. 62 m/s), motor conduction velocities were significantly reduced (mean, 33 m/s vs. 57 m/s), and MNAPs were significantly dispersed, with markedly prolonged rise times (mean 2.0 ms vs. 1.0 ms). Compared with the axonal polyneuropathy group, MNAP amplitudes from the median nerve were similarly reduced (mean, 8 microV vs. 9 microV), MNAP velocities were only slightly slower (mean, 52 m/s vs. 58 m/s), but the rise times were significantly prolonged (mean, 2.0 ms vs 1.2 ms). We conclude that, in acquired demyelinating neuropathies, the onset and, in some cases, the whole MNAP is from afferent fibers, which can be abnormally dispersed, and that, over the same segment MNAP velocity is less affected than motor conduction velocity.

Distal vacuolar myopathy in nephropathic cystinosis.

Nephropathic cystinosis is a lysosomal storage disorder leading to renal failure by age 10 years. Prolonged patient survival following renal transplantation has allowed the development of previously unknown long-term complications. Muscle involvement has been reported in a single posttransplant cystinosis patient, but the range of clinical, electrophysiologic, and histologic features has not been fully described. Thirteen of 54 post-renal-transplant patients that we examined developed weakness and wasting in the small hand muscles, with or without facial weakness and dysphagia. Tendon reflexes were preserved and sensory examinations were normal. Electrophysiologic studies in 11 affected patients showed normal nerve conduction velocities and preserved sensory action potentials. The voluntary motor units in the affected distal muscles had reduced amplitude and brief duration, confirmed with quantitative electromyography in 4 patients. Biopsy of the severely affected abductor digiti minimi or extensor carpi radialis brevis muscles in 2 patients revealed marked fiber size variability, prominent acid phosphatase-positive vacuoles, and absence of fiber type grouping or inflammatory cells. Crystals of cystine were detected in perimysial cells but not within the muscle cell vacuoles. The muscle cystine content of clinically affected muscles was markedly elevated. We conclude that a distal vacuolar myopathy is a common late complication of untreated nephropathic cystinosis. Although the cause is unclear, the general lysosomal defect in this disease may also affect the lysosomes within muscle fibers.