In this paper we propose a method for construction of feed-forward neural classifiers based on regularization and adaptive architectures. Using a penalized maximum likelihood scheme, we derive a modified form of the entropic error measure and an algebraic estimate of the test error. In conjunction with optimal brain damage pruning, a test error estimate is used to select the network architecture. The scheme is evaluated on four classification problems. 相似文献
Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field
stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory
control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We
investigated the functional and morphological effects of α-latrotoxin (αLTX), a spider neurotoxin believed to cause massive
release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared
to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor Nω-nitro-L-arginine (L-NOARG: 0.3 mM) both αLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine,
no contraction was observed, and under these conditions αLTX and EFS induced relaxation. At low frequencies (<12 Hz), the
EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first
phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first
phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 μM ω-conotoxin GVIA,
blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence
of L-NOARG or ω-conotoxin GVIA, the αLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and
ω-conotoxin GVIA further reduced or abolished the relaxation. In preparationstreated with tetrodotoxin or scorpion venom,
believed to inactivate nerves by acting on sodium channels, αLTX and EFS had no effects. αLTX-induced relaxation was not associated
with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation.
A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation
was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and ω-conotoxin GVIA. Ultrastructural
analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle.
In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. αLTX caused
a major loss of both types of vesicle. The present data suggest that αLTX has the ability to release not only adrenergic and
cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra.
Received: 13 January 1997 / Accepted: 17 April 1997 相似文献
BACKGROUND: Inclusion or not of a treatment strategy in the publicly financed health care is really a matter of prioritisation. In Sweden priority setting decisions are governed by law in which it is stated that decisions should be guided by firstly the principle of need and secondly the principle of cost-effectiveness. OBJECTIVE: The purpose of the paper is to discuss and illustrate the roles of need and cost-effectiveness in decisions on inclusion or not of treatment strategies in the publicly financed health care. METHODS: The theoretical backgrounds of need and cost-effectiveness are discussed in short, both with respect to their meaning and to their potential roles in decisions on priority setting. Four treatment strategies, Viagra, Rivastigmine, statins, and lung transplants, are analysed with respect to whether either cost-effectiveness or need, or both, seem to have played a role in the decisions of inclusion or not in the basic health care package. RESULTS: Both need and cost-effectiveness are important and should be important aspects when making decisions on priority setting. From the examples of the four treatment strategies it seems that decisions are almost exclusively made with reference to the principle of need. CONCLUSIONS: The most evident conclusion to be drawn from this study is that decisions on priority setting are almost solely based on the principle of need. This implies that the principle of cost-effectiveness is given very little space, which is a problem as this means an obvious risk of inefficient resource use. 相似文献
Background: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues.
Methods: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 micro gram, in saline; clonidine, 8 micro gram/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined.
Results: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. 相似文献
NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand
for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241.
This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared 76Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised
by N-alkylation of the nitrogen of the amide group with [11C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake
of radioactivity in the occipital, temporal and frontal cortex. In the study with [76Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after
injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with
flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection.
The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands
for imaging of benzodiazepine receptors in the primate brain. [76Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage.
Received 19 April and in revised form 10 June 1997 相似文献
Background: Central neuraxial blockades find widespread applications. Severe complications are believed to be extremely rare, but the incidence is probably underestimated.
Methods: A retrospective study of severe neurologic complications after central neuraxial blockades in Sweden 1990-1999 was performed. Information was obtained from a postal survey and administrative files in the health care system. During the study period approximately 1,260,000 spinal blockades and 450,000 epidural blockades were administered, including 200,000 epidural blockades for pain relief in labor.
Results: The 127 complications found included spinal hematoma (33), cauda equina syndrome (32), meningitis (29), epidural abscess (13), and miscellaneous (20). Permanent neurologic damage was observed in 85 patients. Incidence of complications after spinal blockade was within 1:20-30,000 in all patient groups. Incidence after obstetric epidural blockade was 1:25,000; in the remaining patients it was 1:3600 (P < 0.0001). Spinal hematoma after obstetric epidural blockade carried the incidence 1:200,000, significantly lower than the incidence 1:3,600 females subject to knee arthroplasty (P < 0.0001). 相似文献