Mechanisms Suppressing Superheavy Element Yields in Cold Fusion Reactions.

Superheavy elements are formed in fusion reactions which are hindered by fast nonequilibrium processes. To quantify these, mass-angle distributions and cross sections have been measured, at beam energies from below-barrier to 25% above, for the reactions of ^{48}Ca, ^{50}Ti, and ^{54}Cr with ^{208}Pb. Moving from ^{48}Ca to ^{54}Cr leads to a drastic fall in the symmetric fission yield, which is reflected in the measured mass-angle distribution by the presence of competing fast nonequilibrium deep inelastic and quasifission processes. These are responsible for reduction of the compound nucleus formation probablity P_{CN} (as measured by the symmetric-peaked fission cross section), by a factor of 2.5 for ^{50}Ti and 15 for ^{54}Cr in comparison to ^{48}Ca. The energy dependence of P_{CN} indicates that cold fusion reactions (involving ^{208}Pb) are not driven by a diffusion process.

Comparison of recipient outcomes following transplant from local versus imported pancreas donors.

The shortage of deceased donor organs for solid organ transplantation continues to be an ongoing dilemma. One approach to increase the number of pancreas transplants is to share organs between procurement regions. To assess for the effects of organ importation, we reviewed the outcomes of 1014 patients undergoing deceased donor pancreas transplant at a single center. We performed univariate and multivariate analyses of the association of donor, recipient and surgical characteristics with patient outcomes. Organ importation had no effect on graft or recipient survival for recipients of solitary pancreas transplants. Similarly, there was no effect on technical failure rate, graft survival or long-term patient survival for simultaneous kidney-pancreas (SPK) recipients. In contrast, there was a significant and independent increased risk of death in the first year in SPK recipients of imported organs. SPK recipients had longer hospitalizations and increased hospital costs. This increased medical complexity may make these patients more susceptible to short-term complications resulting from the longer preservation times of import transplants. These findings support the continued use of organ sharing to reduce transplant wait times but highlight the importance of strategies to reduce organ preservation times.

To move or not: previous experience in a runway avoidance task determines the appearance of hippocampal Type 2 sensory processing theta.

Rats in a runway avoidance task responded to a test shock probe with a period of immobility lasting from 2 to 6s. The shock avoidance-trained group displayed hippocampal theta during the immobility response. The inescapable shock group, in contrast, displayed large amplitude irregular activity (LIA). Following reversal training to escapable shock, all shock avoidance-trained rats responded with LIA and inescapable shock trained rats, reversed to shock avoidance, displayed theta.

Hippocampal formation theta activity and movement selection.

Hippocampal theta activity results from activation in the ascending synchronizing system. It occurs during sensory/signal processing prior to and coincident with voluntary movements in mammals. The experiments summarized here suggest that it is involved in the organization of motor behaviour. (1) Procaine (a local anaesthetic) infused into the medial septum (MS) abolishes hippocampal theta activity and running behaviour elicited by electrical posterior hypothalamic (PH) stimulation. This indicates that movement elicited by PH stimulation, is dependent on ascending hypothalamo-septal circuitry. (2) Theta can also be recorded in immobile rats prior to the initiation of lateral dodging movements they make in response to conspecific rats attempting to steal their food. Following infusion of atropine into the MS, theta recorded during immobility is abolished and the rats are severely impaired at initiating movements in defence of their food. It is suggested that atropine-sensitive theta is involved in the initiation of movements made by rats in response to sensory stimuli. (3) Rats with fimbria-fornix transections were also less likely to engage in lateral dodging movements in defence of their food, were hyperactive, less thigmotaxic, and defecated more often, compared to control animals. Depth profile analysis of hippocampal field activity in lesioned animals revealed an absence of theta during electrical or chemical pons stimulation. These findings provide evidence that these neural systems are involved in signal processing relevant to movements underlying adaptive behaviour.

Anatomical, electrophysiological and pharmacological studies of ascending brainstem hippocampal synchronizing pathways.

The present review has provided evidence that very potent ascending brainstem hippocampal synchronizing pathways originate in the rostral pons region (RPO and PPT), and ascend to and synapse with several midline caudal diencephalic nuclei (posterior hypothalamic and supramammillary) which send projections to the medial septal region (MS/vDBB). The medial septal region in turn is a critical nodal point, sending projections to limbic structures such as the hippocampal formation, cingulate cortex, and entorhinal cortex. The pontine and diencephalic nuclei appear to play a critical role in determining the translation of increasing levels of activation into moment to moment changes in the frequency of hippocampal theta field and theta-related cellular discharges, relayed to the MS/vDBB nuclei. The MS/vDBB nuclei appear to play a critical role in translating increasing levels of ascending synchronizing activation into moment to moment changes in the amplitude of hippocampal theta field activity and the accompanying rate and pattern of phasic theta-ON cells. The MS/vDBB carries out this role through a balance of activity in the septohippocampal cholinergic and GABA-ergic projections. Cholinergic projections provide the afferent excitatory drive for hippocampal theta-ON cells and the GABA-ergic projections act to reduce the overall level of inhibition by inhibiting hippocampal GABA-ergic interneurons (theta-OFF cells). Both activities must be present for the generation of hippocampal theta and theta-related cellular activities. The balance between the cholinergic and GABA-ergic projections may determine whether hippocampal synchrony (theta) or asynchrony (LIA, large amplitude irregular activity) occurs. These same ascending pathways influence the electrophysiological and pharmacological properties of the neocortex as well. The functional significance of the ascending brainstem synchronizing pathways is the generalized regulation of activities in these cortical structures as they relate to sensorimotor behavior.

The extrinsic modulation of hippocampal theta depends on the coactivation of cholinergic and GABA-ergic medial septal inputs.

The long trains of theta field activity recorded from the hippocampal formation of urethane-anesthetized rats are thought to be primarily dependent on cholinergic afferents originating in the medial septum/vertical limb of the diagonal band of Broca (MS/vDBB). Recent anatomical studies have revealed the existence of a septal GABA-ergic input to the hippocampal formation which synapses mainly on intrinsic GABA-ergic interneurons. The present work investigated the possibility that some form of interaction between cholinergic and GABA-ergic MS/vDBB inputs might be required for the generation of hippocampal theta field and cellular activities in urethane-anesthetized rats. Reversible inactivation of the MS/vDBB completely abolished theta field and theta-on cell activities, but "released" theta-off cells. The theta field and theta-on cell activities induced by direct intrahippocampal microinfusions of carbachol were also abolished by MS/vDBB inactivation. We speculated that septal suppression was producing two effects: 1) removing excitatory, cholinergic input; and 2) removing inhibitory control of hippocampal GABA-ergic interneurons, thereby increasing the overall level of hippocampal inhibition. Sequential administration of both carbachol and the GABA-A antagonist, bicuculline, resulted in theta-like oscillations similar to those seen in hippocampal slices bath perfused with carbachol alone. Thus, following MS/vDBB inactivation hippocampal GABA-ergic systems are overactive; this enhances intrinsic inhibition and blocks carbachol theta. By reducing the overall level of inhibition in the hippocampus with bicuculline, it is possible to reinstate its oscillatory properties. Conversely, increasing the level of inhibition in the hippocampus (with muscimol) results in the abolishment of theta field activity and the discharges of both theta-on and theta-off cells. Based on these findings we are proposing that cholinergic and GABA-ergic systems originating in the MS/vDBB act synergistically to modulate hippocampal theta. Cholinergic projections provide the afferent excitatory drive for hippocampal theta-on cells and septal GABA-ergic projections act to reduce the overall level of inhibition by inhibiting hippocampal GABA-ergic interneurons (hippocampal theta-off cells). Both activities must be present for the generation of hippocampal theta field and cellular activities. The balance between the cholinergic and GABA-ergic systems may determine whether hippocampal synchrony (theta) or asynchrony (LIA) occurs.

Ascending projections of the posterior nucleus of the hypothalamus: PHA-L analysis in the rat.

With the exception of a report by R.B. Veazey, D.G. Amaral, and W.M. Cowan (1982, J. Comp. Neurol. 207:135-156) that examined the projections of the posterior hypothalamic area in the monkey by using the autoradiographic technique, the ascending projections of the posterior nucleus (PH) of the hypothalamus have not been systematically examined in any species. The present report describes the ascending projections of PH in the rat by using the anterograde anatomical tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L). The major ascending route for PH fibers is the medial forebrain bundle. PH fibers project densely to several subcortical and cortical sites. The subcortical sites are the subthalamus/hypothalamus (zona incerta, the supramammillary nucleus, lateral, perifornical, dorsal, and anterior nuclei/areas), the thalamus (lateroposterior, laterodorsal, parafascicular, reuniens, paraventricular, central medial, paracentral, central lateral and intermediodorsal nuclei), the amygdala (central, lateral, and medial nuclei), the septal area (bed nucleus of stria terminalis, medial and lateral septum), and the basal forebrain (horizontal/vertical limbs of diagonal band nuclei and lateral preoptic area). The cortical sites are the perirhinal, insular, frontal (lateral agranular), prelimbic, and infralimbic cortices. The diversity of PH projections to subcortical and cortical "limbic-related" sites and to several structures with direct input to the hippocampus (supramammillary nucleus, reuniens, paraventricular and laterodorsal nuclei of the thalamus, medial and lateral septum, and perirhinal cortex) suggest that the PH may serve a critical role in various components of emotional behavior, including mnemonic processes associated with significant emotional events.

Diagnosis of pancreas rejection: cystoscopic transduodenal versus percutaneous computed tomography scan-guided biopsy.

BACKGROUND: The most common cause of graft failure after technically successful pancreas transplants is rejection. Laboratory parameters for detecting pancreas graft rejection are not consistently reliable and can lead to unnecessary antirejection treatment. Histopathologic evaluation is the gold standard in the differential diagnosis of pancreas graft dysfunction. Four biopsy techniques have been described: cystoscopic transduodenal (CB), percutaneous computed tomography scan-guided (PB), open, and laparoscopic biopsy. METHODS: We studied the two most common techniques, CB and PB, in pancreas transplant recipients with presumed rejection. Group 1 comprised 103 attempts at CB in 82 recipients (53 men, 29 women) with bladder-drained (BD) pancreas transplants, at 1 to 80 (median, 14) months after transplant. Group 2 comprised 93 attempts at PB in 68 recipients (41 men, 27 women), at 0.5 to 64 (median, 14) months after transplant. RESULTS: In group 1, of 103 attempts at CB, adequate tissue was obtained in 90 (87%): pancreas alone in 23 (22%), pancreas + duodenum in 35 (34%), duodenum alone in 32 (31%). Of the 58 pancreas biopsies, 23 (40%) showed acute rejection. Of the 67 duodenal biopsies, 16 (24%) showed acute rejection. Complications of CB included macrohematuria in 4 recipients (4%) and microhematuria in 32 (31%). We noted no biopsy-related pancreatitis. The mean cost of CB was $2561+/-246. In group 2, of 93 attempts at PB, adequate tissue (all pancreas) was obtained in 67 (72%); of these, 29 (43%) showed acute rejection. Of 23 inaccessible pancreases, 9 (39%) underwent CB; pancreatic tissue was obtained in four (45%), and results were consistent with rejection in all four. Complications of PB included biopsy-related pancreatitis (serum amylase > or = 25%) in five (7%) recipients, macrohematuria in one (1%), and abdominal hemorrhage in two (3%). The mean cost of PB was $1038+/-78. (1) CB and PB prevented unnecessary antirejection treatment in 44% of our recipients with successful biopsies; (2) CB had a higher success rate for obtaining tissue (including duodenal specimens) and a lower rate of major complications; (3) PB was easier and cheaper, did not require general anesthesia, and was performed as an outpatient procedure. CONCLUSIONS: We conclude that PB should become the biopsy technique of choice in recipients with presumed pancreas graft rejection. If PB fails, recipients with bladder-drained pancreas transplants should undergo CB. If CB fails, or in recipients with enteric-drained or duct-injected pancreas transplants, a laparoscopic or open biopsy should be considered.

Randomization tests: application to single-cell and other single-unit neuroscience experiments.

The application of randomization tests for statistical determination of the significance of experimental manipulations on single cells and other types of single units in neuroscience is described. Applications of standard parametric tests like analysis of variance (ANOVA) and t tests to data from single-subject experiments have been severely criticized for lack of validity and those criticisms are relevant to parametric statistical tests for data from other types of single-unit experiments. A broad class of statistical tests known as randomization tests, on the other hand, has been free of such criticism. Randomization tests have been applied to data from various types of single units in neuroscience, where their validity in the absence of random sampling makes them especially valuable. Until the advent of computers, the computational requirements of randomization tests rendered them impractical. Randomization test computer programs are now readily available. Procedures for access to a public domain program are given in the text.

Theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration.

The current review advances the argument that it is naïve to ascribe a unitary function to the hippocampal formation (HPC). Rather, it is more productive to consider the hippocampal formation as consisting of a number of subsystems, each subsystem defined by its own particular neural circuitry. Among examples of neural circuitry appearing in current hippocampal literature are theta, beta and gamma oscillations, sharp waves, place cells and head orientation cells. Data are reviewed supporting the case that theta band oscillation and synchrony is involved in mechanisms underlying sensorimotor integration. Specifically, the neural circuitry underlying the production of oscillation and synchrony (theta) in limbic cortex and associated structures function in the capacity of providing voluntary motor systems with continually updated feedback on their performance relative to changing environmental (sensory) conditions. A crucial aspect of this performance is the intensity with which the motor programs are initiated and maintained. The ascending brainstem HPC synchronizing pathways make the primary contribution in this regard. These pathways originate in the rostral pontine region, ascend and synapse with caudal diencephalic nuclei, which in turn send projections to the medial septal region. The medial septum functions as the node in the ascending pathways, sending both cholinergic and GABA-ergic projections to the HPC. An updated version of the sensorimotor integration model including anatomical details is presented and discussed.

Hippocampal formation is involved in movement selection: evidence from medial septal cholinergic modulation and concurrent slow-wave (theta rhythm) recording.

Hippocampal rhythmical slow-wave field activity which occurs in response to sensory stimulation is predominantly cholinergic (atropine-sensitive theta rhythm), can precede movement initiation, and co-occurs during non-cholinergic theta rhythm associated with ongoing movement (atropine-resistant). This relationship suggests that theta rhythm plays some role in movement control. The present naturalistic experiments tested the idea that atropine-sensitive theta rhythm plays a role in sensory integration and planning required for initiating appropriate movements. One of a pair of hungry rats, the victim, implanted with hippocampal field recording electrodes, a septal injection cannula, and a posterior hypothalamic stimulating electrode, was given food which the other, the robber, tries to steal. Since the victim dodges from the robber with a latency, distance, and velocity dependent upon the size of the food, elapsed eating time, and proximity of the robber, the movement requires sensory integration and planning. Although eating behavior seemed normal, atropine-sensitive theta rhythm and dodging were disrupted by an infusion of a cholinergic antagonist into the medial septum. When the victim in turn attempted to steal the food back, Type 1 theta rhythm was present and robbery attempts seemed normal. Prior to cholinergic blockade, posterior hypothalamic stimulation produced theta rhythm and dodges, even in the absence of the robber, but following injections, atropine-sensitive theta rhythm and dodging were absent as the animals dropped the food and ran. The results provide the first evidence to link atropine-sensitive theta rhythm and hippocampal structures to a role in sensory integration and planning for the initiation of movement.

State-dependent spike train dynamics of hippocampal formation neurons: evidence for theta-on and theta-off cells.

In these experiments the firing patterns of neurons located throughout the CA1-dentate region were recorded during the occurrence of either larger amplitude irregular activity (LIA) or slow wave theta activity, in the hippocampal formation of urethane-anesthetized rats. The main conclusion was that there were two distinct populations of neurons whose spike train dynamics varied systematically in relation to the ongoing EEG state and therefore probably played a role in the genesis of these slow wave rhythms. Within each of the two populations, called theta-on and theta-off cells, there were several subtypes labelled tonic and phasic. Tonic subtypes provided information about the change from one EEG state to another and phasic subtypes, in addition to showing this, provided specific information about frequency changes within the theta state. The importance of extending these observations to freely moving animals was discussed.

Medial septal modulation of hippocampal theta cell discharges.

The effect of small electrolytic lesions in various areas of the septum on the behavioral correlates and firing repertoires of hippocampal theta cells, was investigated in the freely moving rabbit. Lesions localized to the medial septum were found to abolish both slow wave theta and the rhythmic firing of CA1 and dentate layer theta cells, in both the type 1 theta (movement) and type 2 theta (sensory processing) behavior conditions. Small lesions of the diagonal band, lateral septum and fimbria/fornix regions only affected rhythmicity to the extent that they also involved the medial septal region. The same medial septal lesions that abolished rhythmicity were also shown to reduce the mean discharge rate of theta cells occurring during the type 1 movement condition by approximately 50%, while the discharge rate occurring during the type 2 sensory processing condition did not change significantly. Behavioral changes were also only observed for lesions involving the medial septum. The importance of afferent input from the medial septum in the generation of hippocampal theta cell rhythmicity was discussed.

An analysis of cholinoceptive neurons in the hippocampal formation by direct microinfusion.

Microinfusions of cholinergic agents were made in various sites in the dorsal hippocampal formation of urethane anaesthetized rats. Infusions of eserine or carbachol elicited hippocampal theta activity when made in areas containing high levels of cholinergic markers: the stratum oriens and radiatum of the CA1 and CA3, the stratum moleculare and stratum granulosum of the dentate gyrus and the infragranular region of the hilus. Subsequent infusions of atropine sulfate antagonized the theta activity. Control infusions of equal volumes of saline in active sites were without effect. Infusions of eserine or carbachol in the vicinity of the hippocampal fissure, the stratum lacunosum/moleculare of the CA1 or CA3, in the deep regions of the hilus, and in the lateral ventricle and overlying neocortex, were also without effect. Furthermore, in active sites, the latency to onset of theta and subsequent theta frequency, were both directly related to the total amount of carbachol infused. Thus, areas in which theta could be elicited with a cholinergic agonist (carbachol), or an anticholinesterase (eserine) and antagonized with atropine, were found to correspond well to areas previously found to contain a high density of cholinoceptive neurons, using autoradiographic and immunohistochemical techniques. These results provide further support for the involvement of acetylcholine as a neurotransmitter in the generation of type 2 theta in the hippocampal formation.

Preliminary observations on the physiology and pharmacology of hippocampal theta-off cells.

The discharge patterns of phasic linear and tonic non-linear hippocampal theta-off cells and the simultaneously occurring field activity [theta (theta) and large amplitude irregular activity] were studied in response to sensory input, electrical stimulation of the dorsomedial-posterior hypothalamus and systemic administration of cholinergic agents, in urethane-anesthetized rats. Sensory input, hypothalamic stimulation and the administration of eserine all produced a total reduction of the discharges of phasic linear theta-off cells when the resulting induced theta was of a frequency of 5 Hz and above. The discharges of tonic non-linear theta-off cells were also totally reduced during the same conditions, even at the lowest frequencies of induced theta. Administration of atropine SO4 abolished all theta activity previously elicited by electrical stimulation of the hypothalamus, sensory input and eserine. However, sensory input and hypothalamic stimulation still produced the reduction of discharge rates of both types of theta-off cells in the presence of atropine SO4. The linear relation between the discharge rate of phasic linear theta-off cells and levels of hypothalamic stimulation was also preserved in the presence of atropine. It was suggested that GABA may mediate the discharge properties of hippocampal theta-off cells.

Responses of phasic and tonic hippocampal theta-on cells to cholinergics: differential effects of muscarinic and nicotinic activation.

The discharge patterns of tonic and phasic hippocampal formation theta-on cells were recorded in response to systemic administration of cholinergic agents, in urethane-anesthetized rats. Eserine and carbachol resulted in long trains of slow-wave theta and accompanying activation of tonic and phasic theta-on cells. Both slow-wave theta and the characteristic accompanying discharge patterns of theta-on cells were blocked by administration of atropine SO4, providing evidence that the effects of eserine and carbachol were mediated by muscarinic receptors. The systemic administration of nicotine resulted in 20-30 s of slow-wave theta and during this time, both tonic and phasic theta-on cell discharges were suppressed.

Generators and topography of hippocampal theta (RSA) in the anaesthetized and freely moving rat.

Spontaneous and hypothalamically induced hippocampal rhythmical slow activity (RSA or theta) was studied acutely in rats anaesthetized with urethane or immobilized with D-tubocurarine. Systematic tracking of microelectrodes showed two foci of hippocampal RSA, one located in the basal part (stratum oriens) of CAl (mean amplitude 1 mV) and the other located in stratum moleculare of the dorsal blade of the fascia dentata (mean amplitude 2 mV). The hippocampal RSA recorded from the lower blade of the fascia dentata was always smaller than that found in the upper blade (mean amplitude 1 mV). The whole dorsal hippocampal extent within each generator zone was shown to be in synchrony, and the respective generator zones of both hippocampi were synchronous with one another. A null zone in stratum radiation was found interposed between the two generators and a zone of large amplitude fast activity (30-50 Hz) was localized to the hilus of the fascia dentata. Wave form analysis showed that the RSA recorded from the two generators was approximately 180 degrees out of phase. Amplitude and analysis of phase changes of RSA recorded in brain areas outside of the two generator zones suggested that such activity was due to physical spread from the two generators, with the possible exception of a restricted portion of CA3. The existence of the two generators, 180 degrees out of phase, was demonstrated in freely moving rats. Behavioural observations showed that the two generators were related systematically to concurrent motor behaviour. Preliminary observations suggest that, of the two generators, the one located in CAl may be the more variable.

Carbachol-induced EEG 'theta' in hippocampal formation slices: evidence for a third generator of theta in CA3c area.

The topography of carbachol-induced EEG theta activity was studied using the hippocampal formation slice preparation. Systematic tracking with electrodes exhibited two amplitude maxima of cholinergic-induced theta, one located in the stratum oriens of the CA1 pyramidal cells and the other in a region of CA3c pyramidal neurons. In addition, mapping experiments demonstrated EEG theta in the CA3a and CA3b cell body layers, but not in the subicular and parasubicular regions, or the ventral blade of the dentate gyrus. Furthermore, transected slice (trans-slice) preparations used in the present study revealed that the CA3c region could generate carbachol-induced theta independently of CA1 and dentate gyrus generator zones and conversely, CA1 and dentate gyrus areas were capable of generating cholinergic-induced theta rhythm independently of the CA3c region. These results provide strong evidence for 3 independent, anatomically separated generators of theta: one located in the stratum oriens of CA1 neurons, a second in the stratum moleculare of the dentate gyrus and a third one in the region of Ca3c cells. In addition, the results support previous in vivo suggestions that theta rhythm can be either elicited or blocked by cholinergic agents acting on sites within the hippocampal formation.

Phase shifting of CA1 and dentate EEG theta rhythms in hippocampal formation slices.

Carbachol-induced hippocampal EEG theta-rhythms were recorded simultaneously from the CA1 and dentate areas in rat hippocampal brain slices. Phase shifts ranging from 0 to 180 degrees between the CA1 and dentate theta generators were observed. The differences in slow wave theta phase relations between in vitro and in vivo preparations were interpreted as resulting from deafferentation of the hippocampal slices.

The development of carbachol-induced EEG 'theta' examined in hippocampal formation slices.

The development of carbachol-induced EEG theta (theta) activity was studied in the CA1 and dentate regions of hippocampal formation slices obtained from neonatal rats (4, 6, 8, 10, 12 and 14 days of age). When perfused with carbachol (50 microM), 4- and 6-day-old hippocampal slices exhibited only short-lasting irregular activity. The initial appearance of carbachol-induced rhythmic waves were observed in slices obtained from 8-day-old rats. From the time that theta appeared at 8 days of age, a steady increase in amplitude and frequency was noted. This observed in vitro developmental pattern of hippocampal theta-rhythm closely resembles the development of theta activity in in vivo preparations.