Fate of biomedical research protocols and publication bias in France: retrospective cohort study

Objectives To describe the fate of protocols approved by the French research ethics committees, a national system created by the French 1988 Huriet-Sérusclat Act; to assess publication bias at a national level.Design Retrospective cohort study.Setting Representative sample of 25/48 French research ethics committees in 1994.Protocols 649 research protocols approved by committees, with follow-up information.Main outcome measures Protocols'' initial characteristics (design, study size, investigator) abstracted from committees'' archives; follow-up information (rates of initiation, completion, and publication) obtained from mailed questionnaire to principal investigators.Results Completed questionnaires were available for 649/976 (69%) protocols. Of these, 581 (90%) studies were initiated, 501/581 (86%) were completed, and 190/501 (38%) were published. Studies with confirmatory results were more likely to be published as scientific papers than were studies with inconclusive results (adjusted odds ratio 4.59, 95% confidence interval 2.21 to 9.54). Moreover, studies with confirmatory results were published more quickly than studies with inconclusive results (hazard ratio 2.48, 1.36 to 4.55).Conclusion At a national level, too many research studies are not completed, and among those completed too many are not published. We suggest capitalising on research ethics committees to register and follow all authorised research on human participants on a systematic and prospective basis.     

Means for efficient electron beam generation in wide-aperture open-discharge light sources

The interaction of a plasma in the accelerating gap of an open discharge with a strong external electric field and with the cathode surface has been investigated theoretically and experimentally. In a pulsed nanosecond discharge, the ion inertia and plasma screening of the electric field cause a fast growth of the electric field E in the cathode region and a decrease in the length of the latter. Along with a reduction of the electron multiplication factor at high electric fields, this leads to a substantial decrease in the ion flux toward the cathode, which allows one to develop highly efficient open-discharge light sources with a long lifetime and low cathode sputtering. In this respect, continuous and quasi-continuous discharges are less advantageous because of the smaller increase in the electric field in the cathode region. The Townsend coefficients of charge multiplication and electron emission at high electric fields typical of open discharges have been measured for the first time. Fast ions and atoms extracted from the plasma of the accelerating gap significantly affect the cathode emission properties. In particular, photoemission is enhanced by more than one order of magnitude and becomes the main mechanism for electron generation. This also increases the efficiency and lifetime of open-discharge light sources.     

Aging-related changes in the sensitivity of the system of respiratory control and the intensity of free-radical processes in humans

Results of a comparative study of the sensitivity of the system of respiratory control to increases in the CO₂ concentration and the intensity of free-radical processes in young and elderly subjects are described. It is shown that normal (natural) aging is accompanied by a decrease in the sensitivity of the respiratory system to hypercapnic stimulation and a parallel significant decrease in the activity of catalase in the blood of examined subjects. Mechanisms responsible for the modifications of the sensitivity of the system of respiratory control to hypercapnia are discussed; these shifts can be at least partly related to changes in the intensity of production of free radicals observed in elderly subjects. Neirofiziologiya/Neurophysiology, Vol. 40, No. 1, pp. 53–57, January–February, 2008.     

Oculomotor activities in monkeys with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced syndrome of parkinsonism

In twoMacaca rhesus monkeys that received repeated N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections (single dose 0.2 mg/kg, i.m.; cumulative dose 11.2–13.3 mg), changes in characteristics of spontaneous saccadic eye movements and vestibulo-ocular reflex (VOR) were evaluated. With the development of severe behavioral disturbances, amplitude of spontaneous saccadic eye movements gradually decreased. Pronounced changes in duration of saccadic eye movements, frequency of spontaneous saccades, and their pattern were observed. No changes in parameters of VOR slow component were recorded, but high total MPTP doses suppressed fast phase of the reflex.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 184–190, May–June, 1993.     

Effect of intracellular administration of L-tyrosine and L-phenylalanine upon voltage-dependent calcium current in PC 12 pheochromocytoma cells

Using the voltage clamp technique under conditions of intracellular perfusion, we investigated changes in high-threshold voltage-dependent calcium current (I_Ca) in the surface membrane of PC 12 cells caused by intracellular administration of the aromatic amino acids L-tyrosine and L-phenylalanine. Administration of L-tyrosine (20 mmole/1) prevented decrease in I_Ca caused by perfusion of the cell with an artificial saline solution and had a transient restorative effect upon the cell. Administration of L-phenylalanine (20 mM) quickened the decrease in amplitude of I_Ca observed in the control. These effect of aromatic amino acids are maintained when ATP (2 mM) in the intracellular solution is replaced by an equivalent quantity of ADP. The tyrosine hydroxylase blocker -methyl D,L-tyrosine (20 MM) had an effect upon I_Ca analogous to that of L-tyrosine.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 1, pp. 105–111, January–February, 1991.     

Electrophysiological analysis of corticofugal influences on preoptic neurons

Evoked potential (EPs) and responses of the medial (MPO) and lateral (LPO) preoptic region (RPO) and adjacent structures of the hypothalamus to stimulation of the prefrontal (area 8) and cingulate (area 24) cortex, piriform lobe (periamygdaloid cortex), and hippocampus (area CA3) were investigated in acute experiments on cats under ketamine anesthesia. The most pronounced EPs were observed in the RPO after stimulating the piriform and cingulate cortex. A close relation was found between neuronal responses and EP components. The majority of neurons responding to stimulation of various cortical structures were localized in the LPO, where primarily excitatory responses dominate. The MPO contained somewhat fewer neurons responding to cortical stimulation, and the dominant response here was primarily inhibitory. The ratio of inhibitory and excitatory responses in the LPO was 0.6:1 and in the MPO 5.8:1. Primarily in-inhibitory responses dominated also in the LPO zone adjacent to the bed nucleus stria terminalis (BST) and primarily excitatory in the region surrounding the supraoptic nucleus (SO) (respective ratios 4.9:1 and 0.7:1). The RPO is a broad convergence zone, where 3/4 of the neurons responded to stimuli of two and more cortical regions.A. M. Gorky Medical Institute, Ukrainian Minstry of Health, Donetsk. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 709–719, November–December, 1991.     

Thalamic inputs to the motor cortex studied in cats by retrograde axonal horseradish peroxidase transport

Thalamic afferent inputs of the motor cortex (area 4) were studied in cats by retrograde axonal transport of horseradish peroxidase (HRP). The main concentration of HRP-labeled neurons was found in rostral zones of the relay nuclei (of the ventrolateral and ventrobasal complex). A few labeled neurons were found in the mediodorsal association nucleus, where their distribution is quite local. HRP-labeled neurons of nonspecific intralaminar nuclei, projecting into the motor cortex, are present only in single numbers and show no tendency toward grouping in any parts of these nuclei. The results are evidence that the motor cortex receives heterogeneous afferentation from various thalamic nuclei, and it is evidently this which guarantees the reliability of transmission of incoming information.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 250–255, March–April, 1985.     

Postsynaptic components of paroxysmal neuronal response in the strychninized neocortex

Neuronal response in the strychninized cortical suprasylvian gyrus was investigated in experiments on immobilized and unanesthetized cats using intracellular techniques. Paroxysmal depolarizing shifts (PDS) in neuronal membrane potential were recorded, consisting of a bursting discharge and slow depolarization wave. It was found when using intracortical stimulation that PDS can accumulate and change in shape and size. Bursting discharges in PDS were induced by large-scale EPSP which could be distinguished from paroxysmal response. Data from presumably intradendritic readings demonstrated the presence of large-scale EPSP during the generation of epileptiform discharges in the cortex. In a proportion of cells, PDS were accompanied by hyperpolarizing potentials — apparently IPSP, since they undergo reversal with intercellular administration of Cl^–. The contribution of excitatory and inhibitory synaptic influences to paroxysmal neuronal response is discussed.I. I. Mechnikov State University, Odessa. Translated from Neirofiologiya, Vol. 22, No. 5, pp. 642–649, September–October, 1990.     

The targeted force steps developed by a human wrist: Cyclic components in the motor program

The targeted flexor isometric force steps developed by a wrist and corresponding EMG activity of the flexor muscles were studied in healthy volunteers. In 82.3–97.5% of trials, the main component of the force trajectory (before the postcorrections of the force level) showed complex dynamics: several (from two to five)dF/dt peaks were observed at this section of the trajectory. The distribution of time intervals from the initiation of the force trajectory todF/dt peaks was polymodal in all cases. The mean interval between successivedF/dt peaks varied from 56.7 msec to 84.4 msec in different individuals (the average group value was 70.5 msec). All tested subjects exhibited amplitude modulation of integrated EMG at the section reflecting the force step development; the averaged interval between the successive first-order EMG peaks calculated for the group of five persons was 78.6 msec. Strict temporal correlation ofdF/dt peaks and EMG peaks was found (coefficient of correlation averaged 0.94). It is concluded that the motor command ensuring performance of isometric force step includes a cyclic component; this feature must be taken into account when mechanisms controlling such motor events are interpreted. The frequency of the component is near the upper limit of a normal tremor frequency band. At the same time, it is impossible to regard the cyclic component in the motor command as a result of simple superposition of tremor on the targeted force development because the cyclic component is clearly synchronized with the force step initiation.Neirofiziologiya/Neurophysiology, Vol. 25, No. 6, pp. 455–462, November–December, 1993.     

Effect of fura-2 on calcium transients and its dependence on the kinetics and location of endogenous buffers (a model study)

Distortions in fura-2 recordings of intracellular free calcium concentration ([Ca²⁺]i transient elevations) were investigated by computer simulation of calcium diffusion and buffering in a spherical cell. The peak value of [Ca²⁺]i, averaged over the volume of the cell, was shown to depend linearly on the fura-2 concentration within a 0–50-µM range of the latter. The model predicts that fura-2 significantly decreases the peak amplitude of calcium transients if the indicator is used in a large concentration, the fixed endogenous buffer is slow, or/and the concentration of endogenous buffer in submembrane shells is low. Inclusion in our model of calibration equations for a fluorescent measurement-based [Ca²⁺]i calculation revealed more significant discrepancies between fura-2 recordings and actual [Ca²⁺]i, as compared with the discrepancies between theoretical [Ca²⁺]i in the presence of fura-2 and without the dye in the cell.Neirofiziologiya/Neurophysiology, Vol. 27, No. 4, pp. 288–298, July–August, 1995.