Combined Analysis of Neutrino and Antineutrino Oscillations at T2K.

T2K reports its first results in the search for CP violation in neutrino oscillations using appearance and disappearance channels for neutrino- and antineutrino-mode beams. The data include all runs from January 2010 to May 2016 and comprise 7.482×10^{20} protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135 µ-like events, and 7.471×10^{20} protons on target in antineutrino mode, which yielded 4 e-like and 66 µ-like events. Reactor measurements of sin^{2}2θ_{13} have been used as an additional constraint. The one-dimensional confidence interval at 90% for the phase δ_{CP} spans the range (-3.13, -0.39) for normal mass ordering. The CP conservation hypothesis (δ_{CP}=0, π) is excluded at 90% C.L.

Measurement of Muon Antineutrino Oscillations with an Accelerator-Produced Off-Axis Beam.

T2K reports its first measurements of the parameters governing the disappearance of ν[over ¯]_{µ} in an off-axis beam due to flavor change induced by neutrino oscillations. The quasimonochromatic ν[over ¯]_{µ} beam, produced with a peak energy of 0.6 GeV at J-PARC, is observed at the far detector Super-Kamiokande, 295 km away, where the ν[over ¯]_{µ} survival probability is expected to be minimal. Using a data set corresponding to 4.01×10^{20} protons on target, 34 fully contained µ-like events were observed. The best-fit oscillation parameters are sin^{2}(θ[over ¯]_{23})=0.45 and |Δm[over ¯]_{32}^{2}|=2.51×10^{-3} eV^{2} with 68% confidence intervals of 0.38-0.64 and 2.26-2.80×10^{-3} eV^{2}, respectively. These results are in agreement with existing antineutrino parameter measurements and also with the ν_{µ} disappearance parameters measured by T2K.

Measurement of Coherent π

We report the first measurement of the flux-averaged cross section for charged current coherent π^{+} production on carbon for neutrino energies less than 1.5 GeV, and with a restriction on the final state phase space volume in the T2K near detector, ND280. Comparisons are made with predictions from the Rein-Sehgal coherent production model and the model by Alvarez-Ruso et al., the latter representing the first implementation of an instance of the new class of microscopic coherent models in a neutrino interaction Monte Carlo event generator. We observe a clear event excess above background, disagreeing with the null results reported by K2K and SciBooNE in a similar neutrino energy region. The measured flux-averaged cross sections are below those predicted by both the Rein-Sehgal and Alvarez-Ruso et al.

A survey of the content of BSc courses in pharmacology in UK universities--is it time for a core curriculum?

The 18 UK universities offering three--of four--year BSc pharmacology courses were surveyed by questionnaire to determine course content, laboratory-practical content and project or dissertation requirements. In this article David Dewhurst and Clive Page provide an overview of the study, which highlighted the fact that there is no core curriculum. There was considerable variation in course content [only a limited number of common topics were taught in depth (> 15 h timetabled time)] and the time spent doing 'wet' laboratory practicals varied considerably (range 0-145 h). A research project in the final year was the norm (although the time allocation varied considerably), but some universities used a library-based dissertation as an alternative.

Some characteristics of the long-latency component of the evoked muscle response induced by administration of catechol to the anaesthetized rat: a neurophysiological and neuropharmacological investigation.

Administration of catechol to rats anaesthetized with urethane produces a central excitatory state during which an EMG consisting of three temporally distinct components (M1, M2 and M3) can be recorded from forelimb and hindlimb muscles to electrical stimulation of cutaneous afferents. The probability of occurrence of all three components was measured in flexor and extensor muscles of fore- and hindlimb and showed that the long latency component (M3) occurred less frequently in hindlimb muscles than forelimb and that its probability of occurrence in hindlimb extensors was significantly reduced as compared to flexors. A possible reflex pathway for this long latency component of the EMG is suggested. Phenobarbitone (5 mg kg-1 i.v.) had no significant effect on the probability of occurrence of M1, M2 or M3. These results suggest that the long latency component (M3) is not due to activation of a spino-bulbo-spinal reflex as has been previously suggested. Cholinoceptor blocking drugs were found to reduce significantly the probability of occurrence of M2 and M3 and anticholinesterases to increase the probability of M2. None of the drugs was found to affect the short latency M1 component of the EMG. These results are discussed in relation to the possible reflex pathways of all three components of the EMG.

Non involvement of gamma-aminobutyric acid in catechol-induced seizures.

The effects of certain anticonvulsant agents, namely, valproate, diazepam and phenobarbitone were investigated on catechol-induced spontaneous and evoked convulsions, in anaesthetized rats and mice. Valproate and diazepam significantly reduced the intensity of spontaneous convulsions and the frequency of occurrence of the longer-latency components (M2 and M3) of the evoked muscle response. Phenobarbitone significantly reduced spontaneous convulsions and the M3 component of the evoked muscle response. None of the drugs affected the short latency M1 component indicating a supra-spinal site of action of these drugs. Agents which modify gamma-aminobutyric acid (GABA)-mediated transmission were without effect on the frequency of occurrence of M1, M2 or M3. The results suggest that the convulsant action of catechol is not dependent on antagonism of GABA-mediated inhibition.

A pharmacological investigation of the electrically evoked convulsive activity induced by administration of catechol in the anaesthetized rat.

1 The response evoked by electrical stimulation at the wrist has been recorded from muscles of the forelimb of anaesthetized rats induced to convulse by administration of catechol.2 This response can be divided into three temporally distinct components, the characteristics of which have been described.3 The probability of occurrence of the two early components of the response has been measured before and after administration of various drugs. The results show that the first component is not affected by cholinoceptor or adrenoceptor blocking drugs or anticholinesterase agents. The probability of occurrence of the second component is significantly reduced by cholinoceptor blocking drugs and increased by physostigmine.4 The implications of these results in explaining the convulsant actions of catechol are discussed.

Sites and mechanisms of action of catechol (1,2-dihydroxybenzene) in the rat olfactory cortex slice.

Synaptic transmission in the isolated olfactory cortex slice from the rat was monitored by recording the surface field potentials evoked on lateral olfactory tract (LOT) stimulation. Catechol (approximately 0.05 to 2 mM) caused a concentration-dependent, partially reversible increase in the amplitudes of all field potentials. In a series of conditioning experiments, catechol (1 mM) potentiated postsynaptic inhibition by a mechanism which was at least partially picrotoxin-insensitive. When the relationship between the stimulus input and evoked output was investigated in picrotoxin-treated slices, for a given tract action potential amplitude, catechol (0.25 and 0.5 mM) increased the amplitude of the field potential known as the N-wave; in contrast, for a given N-wave amplitude, the latency of the population spike was increased. Catechol (1 mM) increased the K+-evoked release of endogenous aspartate by a tetrodotoxin-insensitive mechanism whereas the release of glutamate and gamma-aminobutyric acid (GABA) was unaffected. Catechol (1 mM) had no effect on submaximal depolarizations evoked by L-aspartate, L-glutamate or GABA. It is concluded that catechol potentiates excitatory transmission at the LOT-superficial pyramidal cell synapse, possibly by increasing evoked transmitter release. Other synaptic actions of catechol may be consequent upon this increased excitatory input but the results do not exclude the possibility of separate and distinct actions on polysynaptic transmission.

A pharmacological study of the spontaneous convulsive activity induced by 1,2-dihydroxybenzene (catechol) in the anaesthetized mouse.

1. The convulsive activity induced by catechol has been examined in anaesthetized mice either by determining the CD50 for the convulsions in drug-treated and control animals, or by studying the effects of various drugs on the total whole body activity. 2. The results indicate that catecholamines play no part in the mechanism of action of catechol. Drugs which alter cerebral catecholamine levels had no effect on the convulsions, nor did the alpha- and beta-adrenoceptor blocking drugs. 3. 5-Hydroxytryptamine (5-HT) could possibly be important, though results with drugs which either change brain 5-HT levels, or block 5-HT receptors were inconsistent. 4. gamma-Aminobutyric acid also appears not to be involved in the mechanism of action of catechol. 5. The results strongly suggest that catechol primarily activates a central cholinergic system, in that muscarinic and nicotinic receptor blocking drugs inhibit, and anticholinesterases potentiate the convulsions.

Possible role of excitatory amino acids in the convulsant action of catechol.

The effects of several excitatory amino acid receptor antagonists on sensory-evoked electromyographic activity induced by catechol have been studied in urethane-anaesthetised rats. 2-Amino-5-phosphono-valearic acid (1.2 mumol/kg i.c.), cis-2,3-piperidine dicarboxylic acid (1.4 mumol/kg i.c.), gamma-D-glutamyl-glycine (2.0 mumol/kg i.c.), 2-amino-7-phosphono-heptanoic acid (230 mumol/kg i.v.) and MK-801 (5 mg/kg i.p.) all significantly decreased the frequency of occurrence of those components of the sensory evoked EMG dependent on supraspinal structures, but were without effect on the spinal component.

A visually-driven postural after-effect.

Viewing a large-scale moving scene typically causes a free standing observer to lean in the direction of the seen motion. It was also noted that when the visual motion ceases, the observer drifts back toward the upright position, but instead of this body movement stopping at the vertical, it tends to continue so that the observer remains leaning in the opposite direction for several seconds before finally returning to the upright. The two experiments reported here were designed to investigate the determinants of this postural after-effect in relation to a pitch vection stimulus. Our findings clearly showed that the after-effect was dependent upon (1) the establishment of a prior visually-induced body lean, and (2) sight of the static display on the cessation of motion. The notion of an internalised representation of body position was invoked to account for these results.

A multiple electrode cochlear implant.

The University of Melbourne Departments of Otolaryngology and Electrical Engineering (UMDOLEE) receiving and stimulating component of a multiple-electrode cochlear implant hearing prosthesis produces constant stimulation. It has a stimulating pulse shape that minimizes the production of toxic substances and loss of metal from the electrodes, and this is achieved with a biphasic rectangular waveform where the first phase is negative with respect to ground. The duration of each stimulus phase in 180 msec, which is long enough to allow low levels of current stimulation, and short enough to permit rates of 1000 pulses/second to be achieved. In order to be consistent with our present understanding of the perception of pitch, the device permits the independent stimulation of a number of electrodes. Furthermore, to electrically isolate the stimulus to small areas, there is the capacity to vary the current and set the threshold independently at individual electrodes. The phase and amplitude of the pulses to neighbouring electrodes with also be varied to assist in localizing the current flow. The pattern to stimulation to individual or groups of electrodes can also be altered to enable studies to be carried out to determine ways of conveying frequency and intensity information over a more normal dynamic range.

Unity and diversity in psychiatry: some philosophical issues.

OBJECTIVE: The aim of this paper is to provide a defence of diversity in psychiatry and, correspondingly, to show that strict 'biologism' (or any other 'total' approach to psychiatry) is inappropriate. METHOD: Arguments are developed using as a basis the writings of well known philosophers such as Stephen Toulmin, Joel Feinberg and Charles Taylor. The authors examine the concepts of explanation and causation and consider the consequences for psychiatry which might follow the acceptance of mind-brain identity. There is also a discussion of the concept of a person. RESULT: If the same phenomenon is subject to explanation from diverse psychiatric perspectives, it does not follow that these modes of explanation must exclude or be in competition with each other. They may in fact be necessary to each other if psychiatry is to provide a full picture of mental functioning and human conduct. The thesis of mind-brain identity does not eliminate the variety of discourses within psychiatry, and hence it does not provide a rationale for 'biologism'. CONCLUSION: There is a need for a co-operative multidimensional approach in psychiatry.

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a marker of tumour cellularity and prognostic indicator in primary breast cancer.

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a cytosolic marker of tumour cellularity has been assessed, together with its use as a prognostic indicator for primary breast cancer in 87 patients over 4 years. 6-PGDH activity shows a good correlation with histologically-assessed tumour cellularity in a sample of 114 patients (correlation coefficient = 0.83). Patients whose primary breast tumour had a high 6-PGDH activity showed poor relapse-free survival times when compared to those with low 6-PGDH activities (Log Rank chi 2 = 6.87, P less than 0.01). This compared with a Log Rank chi 2 of 2.22, P less than 0.20 for oestrogen positive and negative patients. These results suggest that 6-PGDH activity is a better prognostic indicator in primary breast cancer than oestrogen receptor status.