Computing of temporal information in spiking neural networks with ReRAM synapses.

Resistive switching random-access memory (ReRAM) is a two-terminal device based on ion migration to induce resistance switching between a high resistance state (HRS) and a low resistance state (LRS). ReRAM is considered one of the most promising technologies for artificial synapses in brain-inspired neuromorphic computing systems. However, there is still a lack of general understanding about how to develop such a gestalt system to imitate and compete with the brain's functionality and efficiency. Spiking neural networks (SNNs) are well suited to describe the complex spatiotemporal processing inside the brain, where the energy efficiency of computation mostly relies on the spike carrying information about both space (which neuron fires) and time (when a neuron fires). This work addresses the methodology and implementation of a neuromorphic SNN system to compute the temporal information among neural spikes using ReRAM synapses capable of spike-timing dependent plasticity (STDP). The learning and recognition of spatiotemporal spike sequences are experimentally demonstrated. Our simulation study shows that it is possible to construct a multi-layer spatiotemporal computing network. Spatiotemporal computing also enables learning and detection of the trace of moving objects and mimicking of the hierarchy structure of the biological visual cortex adopting temporal-coding for fast recognition.

Publisher Correction: Memristive neural network for on-line learning and tracking with brain-inspired spike timing dependent plasticity.

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Memristive neural network for on-line learning and tracking with brain-inspired spike timing dependent plasticity.

Brain-inspired computation can revolutionize information technology by introducing machines capable of recognizing patterns (images, speech, video) and interacting with the external world in a cognitive, humanlike way. Achieving this goal requires first to gain a detailed understanding of the brain operation, and second to identify a scalable microelectronic technology capable of reproducing some of the inherent functions of the human brain, such as the high synaptic connectivity (~104) and the peculiar time-dependent synaptic plasticity. Here we demonstrate unsupervised learning and tracking in a spiking neural network with memristive synapses, where synaptic weights are updated via brain-inspired spike timing dependent plasticity (STDP). The synaptic conductance is updated by the local time-dependent superposition of pre- and post-synaptic spikes within a hybrid one-transistor/one-resistor (1T1R) memristive synapse. Only 2 synaptic states, namely the low resistance state (LRS) and the high resistance state (HRS), are sufficient to learn and recognize patterns. Unsupervised learning of a static pattern and tracking of a dynamic pattern of up to 4 × 4 pixels are demonstrated, paving the way for intelligent hardware technology with up-scaled memristive neural networks.

Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas.

Although high-dose methotrexate (HD-MTX) is the most effective drug against primary CNS lymphomas (PCNSL), outcome-determining variables related to its administration schedule have not been defined. The impact on toxicity and outcome of the area under the curve (AUC(MTX)), dose intensity (DI(MTX)) and infusion rate (IR(MTX)) of MTX and plasmatic creatinine clearance (CL(crea)) was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-based combinations. Anticonvulsants were administered in 31 pts (69%). Age >60 years, anticonvulsant therapy, slow IR(MTX) (1100 micromol hl(-1) were independently associated with a better survival. Slow CL(crea) and high AUC(MTX) are favourable outcome-determining factors in PCNSL, while slow CL(crea) is significantly related to higher toxicity. AUC(MTX) significantly correlates with age, anticonvulsant therapy, IR(MTX), and DI(MTX). These findings, which seem to support the choice of an MTX dose >/=3 gm(-2) in a 4-6-h infusion, every 3-4 weeks, deserve to be assessed prospectively in future trials. MTX dose adjustments in patients with fast CL(crea) should be investigated.

Relevance of intraocular involvement in the management of primary central nervous system lymphomas.

BACKGROUND: Reported data regarding intraocular lymphoma (IOL) management are anecdotal. Cases of IOL included in an international multicentre series of 378 immunocompetent patients with primary central nervous system lymphomas (PCNSLs) were reviewed. PATIENTS AND METHODS: Staging included slit-lamp examination in 170 patients: IOL was diagnosed in 22 cases (13%). A concomitant brain lesion was detected in 21 cases. Planned treatment was chemotherapy followed by radiotherapy in 13 cases, chemotherapy alone in three and radiotherapy, followed by or not by chemotherapy in five; one patient was not treated. Chemotherapy included high-dose methotrexate in 12 cases. Ten patients received intrathecal chemotherapy. Radiotherapy consisted of whole brain irradiation, followed by or not by a tumour bed boost; ocular irradiation was planned in 15 cases. Irradiation in one patient without brain lesions was limited to the orbits only (50 Gy). RESULTS: IOL was positively correlated to systemic symptoms and meningeal disease. Fifteen patients (71%) achieved an objective response; 16 patients experienced a failure (2-year failure-free survival 34+/-10%). Failures involved the eyes in eight cases, with a 2-year time to ocular relapse of 59+/-11%. Ocular failure was less common in patients treated with chemotherapy plus ocular irradiation and was associated with a significantly shorter survival. Seven patients are alive [median follow-up 53 months, 2-year overall survival (OS): 39+/-11%] , five of whom were treated with ocular irradiation. The patient with isolated IOL is alive and disease-free at 14 months. OS of the entire series was similar to that of PCNSL patients with negative slit-lamp examination. CONCLUSIONS: IOL is usually associated with concomitant brain disease and shows a survival similar to that of the rest of PCNSLs. Chemotherapy combined with ocular irradiation resulted in better control of ocular disease, which seems to be associated with survival. In view of the potential role of ocular irradiation, the use of chemotherapy alone in phase II trials should be critically reconsidered in PCNSL patients with ocular disease.

A multicenter study of treatment of primary CNS lymphoma.

OBJECTIVE: To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma. METHODS: Planned treatment was radiotherapy (RT) in 98 patients, chemotherapy (CHT) in 32, RT followed by CHT in 36, and CHT followed by RT in 197 patients. High-dose methotrexate (HD-MTX; 1 to 8 g/m2) was used in 169 patients and intrathecal CHT in 109. RESULTS: One hundred sixteen patients are alive (median follow-up 24 months), with a 2-year overall survival of 37%. Patients treated with CHT followed by RT had improved survival with respect to patients treated with RT alone. Patients receiving HD-MTX-based primary CHT survived longer than those treated with other drugs. HD-MTX associated with other cytostatics, in particular HD-cytarabine, produced better results than HD-MTX alone. No correlation between MTX dose and survival was found. In patients receiving HD-MTX, consolidation RT or intrathecal CHT did not improve survival. Age, performance status, lactate dehydrogenase serum level, CSF protein level, site of disease, and use of HD-MTX were all predictors of survival. CONCLUSIONS: Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.

Taxanes in lung cancer: a review with focus on the European experience.

The introduction of new agents in the treatment of lung cancer raised in the past few years new interest in clinical research on this topic. The use of taxanes as paclitaxel and docetaxel may represent a significant progress in the treatment of lung cancer. Taxanes used as single agents show a substantial activity in lung cancer and, because of their unique mechanism of action, it is possible to combine these drugs with other non-cross-resistant agents. Taxanes share a radiosensitizing effect and their use with concurrent radiotherapy appears to become a new standard. This review will focus on the European clinical experience in the treatment of lung cancer with the two compounds.

[Is there progress in the chemotherapy of small cell lung cancer?]. / Gibt es einen Fortschritt in der Chemotherapie des kleinzelligen Bronchuskarzinoms?

Small cell lung cancer (SCLC) is a frequent neoplastic disease which has shown an increasing incidence during recent years, particularly in women. Because of the high sensitivity of chemotherapy, remission is usually achieved with standard regimens. However, relapses are common and 5-year survival is < 10%. Over the last few years intensive chemotherapy with or without stem cell support has been developed and has brought about an improvement of overall survival in SCLC patients. This therapeutic approach is reviewed.

Endothelin A receptor blockade causes adverse left ventricular remodeling but improves pulmonary artery pressure after infarction in the rat.

BACKGROUND: Endothelin A (ETA) receptor antagonists have been shown to improve ventricular remodeling and survival in rats when started 10 days after infarction. Whether starting them earlier would have a more or less beneficial effect is uncertain. METHODS AND RESULTS: Rats surviving an acute myocardial infarction (MI) for 24 hours (n=403) were assigned to saline or the ETA receptor antagonist LU 127043 or its active enantiomer LU 135252 for 4 weeks. Chronic LU treatment had no effect on survival, with 46% of LU rats and 47% of saline-treated rats with large MI surviving to the end of the study. LU treatment led to scar thinning, further left ventricular (LV) dilatation, an increase in LV end-diastolic pressure, and an increase in wet lung weight (P<0.05). Despite this detrimental effect on LV function, LU led to a significant decrease in RV systolic (50+/-2 to 44+/-2 mm Hg, P<0.05 vs saline) and right atrial pressures. LU treatment also prevented the increase in pulmonary ET-1 found in saline-treated rats with large MI but did not modify the increase in cardiac ET-1 in hearts with large MI. CONCLUSIONS: The early use of the ETA receptor antagonists LU 127043 or its active enantiomer LU 135252 after infarction in the rat leads to impaired scar healing and LV dilatation and dysfunction. This is accompanied by a decrease in RV systolic and right atrial pressures and a decrease in pulmonary but not cardiac ET-1 levels. It would thus appear that the early use of ETA receptor antagonists after infarction may be detrimental.

[Autoimmune processes as paraneoplastic manifestations in familial breast carcinoma]. / Autoimmunprozesse als paraneoplastische Manifestationen bei familiärem Mammakarzinom.

In two patients, mother and daughter, with breast cancer a paraneoplastic syndrome of probably autoimmune pathogenesis developed in the course of the neoplastic disease. In the mother the cancer occurred when she was aged 51, first in the left and then, 4 years later, in the right breast. A local recurrence 18 years later caused a pericardial effusion and further tumour recurrences were associated with symptoms like those in Sjögren's syndrome, as well as bullous pemphigoid and polyneuropathy. Antinuclear antibodies, extractable nuclear antigen antibodies and rheuma factors were demonstrated in serum. Both symptoms and antibody titres regressed under treatment with tamoxifen and various cytostatic drugs. The patient died aged 74 years.--The daughter underwent a lumpectomy for breast cancer when aged 39 years, followed by mastectomy for local recurrence after 2 years. A further 2 years later she was found to be anaemic with a positive Coombs test (1:1024) and antibodies against IgG and complement. Metastases developed later. In her case, too, clinical and serological findings clearly regressed under treatment with tamoxifen and chemotherapy. She died, aged 45 years, from the consequences of further metastases.

Adjuvant chemotherapy after orchiectomy in high-risk patients with clinical stage I non-seminomatous testicular cancer.

In patients with clinical stage I non-seminomatous germ cell tumor the relapse rate seen after orchiectomy alone is approximately 30%. If retroperitoneal lymph node dissection is adopted the relapse rate in patients with histologically negative retroperitoneal nodes is reduced to approximately 10%. Nevertheless, follow-up is still mandatory and 70-80% of clinical stage I patients undergo unnecessary surgery. Metastases and relapses are mostly seen in patients with histological evidence of vascular invasion, growth beyond the testicular capsule and/or embryonal carcinoma in the primary tumor. We conducted a prospective trial of two cycles of cisplatin-based adjuvant chemotherapy for 43 patients with clinical stage I non-seminomatous germ cell tumors and at least one of these risk factors (vascular invasion n = 5, pT > 1 n = 21, embryonal carcinoma n = 42). After a median follow-up of 42 months (12-82 months) 40/41 patients (97.5%) who received the planned chemotherapy remain relapse-free. One patient had surgical excision of a mature teratoma in the ipsilateral iliac region 26 months after orchiectomy and is now disease-free without further treatment after 25+ months. No life-threatening toxicity from chemotherapy was encountered. Two patients who refused the chemotherapy relapsed. In patients with high-risk clinical stage I non-seminomatous testicular cancer two cycles of adjuvant chemotherapy are highly effective in preventing relapses and may be used as an alternative to a 'wait and watch' program or retroperitoneal lymph node dissection, particularly in patients with a compromised follow-up.