Impact of echocardiography on patient management in the intensive care unit: an audit of district general hospital practice.

BACKGROUND: Echocardiography has been shown to positively impact on the management of the critically ill patient. However, many published studies have a significant bias towards inclusion of cardiothoracic patients. We present an audit of the impact of echocardiography on the management of patients in a district general hospital intensive care unit (ICU). METHODS: We conducted a prospective audit of all echocardiograms, both transthoracic (TTE) and transoesophageal (TOE), performed on our ICU between October 1, 2005, and December 31, 2007. In addition to patient characteristics, we recorded the indication for the echocardiogram, and any change in management that occurred as a result of the study. RESULTS: Two hundred and fifty-eight echocardiograms were performed in 217 patients, of which 224 (86.8%) were performed by intensive care consultants. One hundred and eighty-seven studies (72.4%) were TTEs and 71 (27.8%) were TOEs. TTE provided diagnostic images in 91.3% of spontaneously breathing and 84.2% of mechanically ventilated patients. Management was changed directly as a result of information provided in 51.2% of studies. Changes included fluid administration, inotrope or drug therapy, and treatment limitation. CONCLUSIONS: Echocardiography may have a significant impact on the management of patients in the general ICU. We recommend that appropriate training in echocardiography should be incorporated into the intensive care curriculum in the UK.

Severe acute respiratory distress syndrome in pregnancy. Caesarean section in the second trimester to improve maternal ventilation.

We report the case of a 25-year-old woman in the second trimester of pregnancy with acute respiratory distress syndrome associated with miliary tuberculosis. Delivery of the baby by caesarean section at 24 weeks gestation resulted in an immediate and sustained improvement in respiratory function and maternal survival. We believe this to be the first report suggesting a role for caesarean section, performed with the aim of an improvement in maternal respiratory function, at such an early point in pregnancy.

Plasma lidocaine concentrations following insertion of 2% lidocaine gel into the uterine cavity after uterine balloon thermal ablation.

BACKGROUND: Uterine balloon thermal ablation is used to treat menorrhagia. We thought that intrauterine application of 2% lidocaine gel could reduce postoperative pain after this procedure. Before using this technique we wished to establish how much lidocaine is absorbed systemically from the uterine cavity after thermal ablation. METHODS: Ten ASA I-II patients (age 38-50 yr) underwent uterine balloon thermal ablation under general anaesthesia. They each had 11 ml of 2% lidocaine gel (Instillagel(TM)) inserted into the uterine cavity at the end of the procedure. Blood samples were taken at 5, 15, 30 and 60 min after insertion and lidocaine concentrations were measured using high-performance liquid chromatography. RESULTS: Mean (range) plasma lidocaine concentrations at 5, 15, 30 and 60 min were 40.3 (0-221.9), 66.3 (0-271.9), 64.9 (0-208) and 75 (0-212) ng ml(-1), respectively. CONCLUSION: There was minimal systemic absorption of lidocaine from the uterus following uterine balloon thermal ablation. Measured concentrations were well below the toxic plasma concentration for lidocaine (8-10 micro g ml(-1)).

The temporal resolution of neural codes: does response latency have a unique role?

This article reviews the nature of the neural code in non-human primate cortex and assesses the potential for neurons to carry two or more signals simultaneously. Neurophysiological recordings from visual and motor systems indicate that the evidence for a role for precisely timed spikes relative to other spike times (ca. 1-10 ms resolution) is inconclusive. This indicates that the visual system does not carry a signal that identifies whether the responses were elicited when the stimulus was attended or not. Simulations show that the absence of such a signal reduces, but does not eliminate, the increased discrimination between stimuli that are attended compared with when the stimuli are unattended. The increased accuracy asymptotes with increased gain control, indicating limited benefit from increasing attention. The absence of a signal identifying the attentional state under which stimuli were viewed can produce the greatest discrimination between attended and unattended stimuli. Furthermore, the greatest reduction in discrimination errors occurs for a limited range of gain control, again indicating that attention effects are limited. By contrast to precisely timed patterns of spikes where the timing is relative to other spikes, response latency provides a fine temporal resolution signal (ca. 10 ms resolution) that carries information that is unavailable from coarse temporal response measures. Changes in response latency and changes in response magnitude can give rise to different predictions for the patterns of reaction times. The predictions are verified, and it is shown that the standard method for distinguishing executive and slave processes is only valid if the representations of interest, as evidenced by the neural code, are known. Overall, the data indicate that the signalling evident in neural signals is restricted to the spike count and the precise times of spikes relative to stimulus onset (response latency). These coding issues have implications for our understanding of cognitive models of attention and the roles of executive and slave systems.

Crystal structure of the fission yeast mitochondrial Holliday junction resolvase Ydc2.

Resolution of Holliday junctions into separate DNA duplexes requires enzymatic cleavage of an equivalent strand from each contributing duplex at or close to the point of strand exchange. Diverse Holliday junction-resolving enzymes have been identified in bacteria, bacteriophages, archaea and pox viruses, but the only eukaryotic examples identified so far are those from fungal mitochondria. We have now determined the crystal structure of Ydc2 (also known as SpCce1), a Holliday junction resolvase from the fission yeast Schizosaccharomyces pombe that is involved in the maintenance of mitochondrial DNA. This first structure of a eukaryotic Holliday junction resolvase confirms a distant evolutionary relationship to the bacterial RuvC family, but reveals structural features which are unique to the eukaryotic enzymes. Detailed analysis of the dimeric structure suggests mechanisms for junction isomerization and communication between the two active sites, and together with site-directed mutagenesis identifies residues involved in catalysis.

Excess synchrony in motor cortical neurons provides redundant direction information with that from coarse temporal measures.

Previous studies have shown that measures of fine temporal correlation, such as synchronous spikes, across responses of motor cortical neurons carries more directional information than that predicted from statistically independent neurons. It is also known, however, that the coarse temporal measures of responses, such as spike count, are not independent. We therefore examined whether the information carried by coincident firing was related to that of coarsely defined spike counts and their correlation. Synchronous spikes were counted in the responses from 94 pairs of simultaneously recorded neurons in primary motor cortex (MI) while monkeys performed arm movement tasks. Direct measurement of the movement-related information indicated that the coincident spikes (1- to 5-ms precision) carry approximately 10% of the information carried by a code of the two spike counts. Inclusion of the numbers of synchronous spikes did not add information to that available from the spike counts and their coarse temporal correlation. To assess the significance of the numbers of coincident spikes, we extended the stochastic spike count matched (SCM) model to include correlations between spike counts of the individual neural responses and slow temporal dependencies within neural responses (approximately 30 Hz bandwidth). The extended SCM model underestimated the numbers of synchronous spikes. Therefore as with previous studies, we found that there were more synchronous spikes in the neural data than could be accounted for by this stochastic model. However, the SCM model accounts for most (R(2) = 0.93 +/- 0.05, mean +/- SE) of the differences in the observed number of synchronous spikes to different directions of arm movement, indicating that synchronous spiking is directly related to spike counts and their broad correlation. Further, this model supports the information theoretic analysis that the synchronous spikes do not provide directional information beyond that available from the firing rates of the same pool of directionally tuned MI neurons. These results show that detection of precisely timed spike patterns above chance levels does not imply that those spike patterns carry information unavailable from coarser population codes but leaves open the possibility that excess synchrony carries other forms of information or serves other roles in cortical information processing not studied here.

Consistency of encoding in monkey visual cortex.

Are different kinds of stimuli (for example, different classes of geometric images or naturalistic images) encoded differently by visual cortex, or are the principles of encoding the same for all stimuli? We examine two response properties: (1) the range of spike counts that can be elicited from a neuron in epochs representative of short periods of fixation (up to 400 msec), and (2) the relation between mean and variance of spike counts elicited by different stimuli, that together characterize the information processing capabilities of a neuron using the spike count code. In monkey primary visual cortex (V1) complex cells, we examine responses elicited by static stimuli of four kinds (photographic images, bars, gratings, and Walsh patterns); in area TE of inferior temporal cortex, we examine responses elicited by static stimuli in the sample, nonmatch, and match phases of a delayed match-to-sample task. In each area, the ranges of mean spike counts and the relation between mean and variance of spike counts elicited are sufficiently similar across experimental conditions that information transmission is unaffected by the differences across stimulus set or behavioral conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically significant but small differences, the median difference in transmitted information for these neurons was 0.9%]. Encoding therefore appears to be consistent across experimental conditions for neurons in both V1 and TE, and downstream neurons could decode all incoming signals using a single set of rules.

Effect of image orientation and size on object recognition: responses of single units in the macaque monkey temporal cortex.

This study examined how cells in the temporal cortex code orientation and size of a complex object. The study focused on cells selectively responsive to the sight of the head and body but unresponsive to control stimuli. The majority of cells tested (19/26, 73%) were selectively responsive to a particular orientation in the picture plane of the static whole body stimulus, 7/26 cells showed generalisation responding to all orientations (three cells with orientation tuning superimposed on a generalised response). Of all cells sensitive to orientation, the majority (15/22, 68%) were tuned to the upright image. The majority of cells tested (81%, 13/16) were selective for stimulus size. The remaining cells (3/16) showed generalisation across four-fold decrease in size from life-sized. All size-sensitive cells were tuned to life-sized stimuli with decreasing responses to stimuli reduced from life-size. These results do not support previous suggestions that cells responsive to the head and body are selective to view but generalise across orientation and size. Here, extensive selectivity for size and orientation is reported. It is suggested that object orientation and size-specific responses might be pooled to obtain cell responses that generalise across size and orientation. The results suggest that experience affects neuronal coding of objects in that cells become tuned to views, orientation, and image sizes that are commonly experienced. Models of object recognition are discussed.

I see a face-a happy face.

Information analysis shows that face-selective neurons in inferior temporal cortex encode different stimulus attributes early and late in their response to the same image.

Stochastic nature of precisely timed spike patterns in visual system neuronal responses.

It is not clear how information related to cognitive or psychological processes is carried by or represented in the responses of single neurons. One provocative proposal is that precisely timed spike patterns play a role in carrying such information. This would require that these spike patterns have the potential for carrying information that would not be available from other measures such as spike count or latency. We examined exactly timed (1-ms precision) triplets and quadruplets of spikes in the stimulus-elicited responses of lateral geniculate nucleus (LGN) and primary visual cortex (V1) neurons of the awake fixating rhesus monkey. Large numbers of these precisely timed spike patterns were found. Information theoretical analysis showed that the precisely timed spike patterns carried only information already available from spike count, suggesting that the number of precisely timed spike patterns was related to firing rate. We therefore examined statistical models relating precisely timed spike patterns to response strength. Previous statistical models use observed properties of neuronal responses such as the peristimulus time histogram, interspike interval, and/or spike count distributions to constrain the parameters of the model. We examined a new stochastic model, which unlike previous models included all three of these constraints and unlike previous models predicted the numbers and types of observed precisely timed spike patterns. This shows that the precise temporal structures of stimulus-elicited responses in LGN and V1 can occur by chance. We show that any deviation of the spike count distribution, no matter how small, from a Poisson distribution necessarily changes the number of precisely timed spike patterns expected in neural responses. Overall the results indicate that the fine temporal structure of responses can only be interpreted once all the coarse temporal statistics of neural responses have been taken into account.

Neurological recovery after prolonged verapamil-induced cardiac arrest.

A 15-year-old female survived a total of 65 minutes cardiac arrest following ingestion of verapamil and selective serotonin re-uptake inhibitors. We consider that the lack of neurological damage, despite evidence of significant renal and myocardial injury, may be related to the possible neuroprotective effect of a large dose of verapamil.

Response features determining spike times.

Interpreting messages encoded in single neuronal responses requires knowing which features of the responses carry information. That the number of spikes is an important part of the code has long been obvious. In recent years, it has been shown that modulation of the firing rate with about 25 ms precision carries information that is not available from the total number of spikes across the whole response. It has been proposed that patterns of exactly timed (1 ms precision) spikes, such as repeating triplets or quadruplets, might carry information that is not available from knowing about spike count and rate modulation. A model using the spike count distribution, the low-pass filtered PSTH (bandwidth below 30 Hz), and, to a small degree, the interspike interval distribution predicts the numbers and types of exactly-timed triplets and quadruplets that are indistinguishable from those found in the data. From this it can be concluded that the coarse (< 30 Hz) sequential correlation structure over time gives rise to the exactly timed patterns present in the recorded spike trains. Because the coarse temporal structure predicts the fine temporal structure, the information carried by the fine temporal structure must be completely redundant with that carried by the coarse structure. Thus, the existence of precisely timed spike patterns carrying stimulus-related information does not imply control of spike timing at precise time scales.

Visual recognition based on temporal cortex cells: viewer-centred processing of pattern configuration.

A model of recognition is described based on cell properties in the ventral cortical stream of visual processing in the primate brain. At a critical intermediate stage in this system, 'Elaborate' feature sensitive cells respond selectively to visual features in a way that depends on size (+/- 1 octave), orientation (+/- 45 degrees) but does not depend on position within central vision (+/- 5 degrees). These features are simple conjunctions of 2-D elements (e.g. a horizontal dark area above a dark smoothly convex area). They can arise either as elements of an object's surface pattern or as a 3-D component bounded by an object's external contour. By requiring a combination of several such features without regard to their position within the central region of the visual image, 'Pattern' sensitive cells at higher levels can exhibit selectivity for complex configurations that typify objects seen under particular viewing conditions. Given that input features to such Pattern sensitive cells are specified in approximate size and orientation, initial cellular 'representations' of the visual appearance of object type (or object example) are also selective for orientation and size. At this level, sensitivity to object view (+/- 60 degrees) arises because visual features disappear as objects are rotated in perspective. Processing is thus viewer-centred and the neurones only respond to objects seen from particular viewing conditions or 'object instances'. Combined sensitivity to multiple features (conjunctions of elements) independent of their position, establishes selectivity for the configurations of object parts (from one view) because rearranged configurations of the same parts yield images lacking some of the 2-D visual features present in the normal configuration. Different neural populations appear to be selectively tuned to particular components of the same biological object (e.g. face, eyes, hands, legs), perhaps because the independent articulation of these components gives rise to correlated activity in different sets of input visual features. Generalisation over viewing conditions for a given object can be established by hierarchically pooling outputs of view-condition specific cells with pooling operations dependent on the continuity in experience across viewing conditions. Different object parts are seen together and different views are seen in succession when the observer walks around the object. The view specific coding that characterises the selectivity of cells in the temporal lobe can be seen as a natural consequence of selective experience of objects from particular vantage points. View specific coding for the face and body also has great utility in understanding complex social signals, a property that may not be feasible with object-centred processing.

Crystal structure of an octameric RuvA-Holliday junction complex.

Holliday junctions occur as intermediates in homologous recombination and DNA repair. In bacteria, resolution of Holliday junctions is accomplished by the RuvABC system, consisting of a junction-specific helicase complex RuvAB, which promotes branch migration, and a junction-specific endonuclease RuvC, which nicks two strands. The crystal structure of a complex between the RuvA protein of M. leprae and a synthetic four-way junction has now been determined. Rather than binding on the open surface of a RuvA tetramer as previously suggested, the DNA is sandwiched between two RuvA tetramers, which form a closed octameric shell, stabilized by a conserved tetramer-tetramer interface. Interactions between the DNA backbone and helix-hairpin-helix motifs from both tetramers suggest a mechanism for strand separation promoted by RuvA.

Evidence accumulation in cell populations responsive to faces: an account of generalisation of recognition without mental transformations.

In this paper we analyse the time course of neuronal activity in temporal cortex to the sight of the head and body. Previous studies have already demonstrated the impact of view, orientation and part occlusion on individual cells. We consider the cells as a population providing evidence in the form of neuronal activity for perceptual decisions related to recognition. The time course on neural responses to stimuli provides an explanation of the variation in speed of recognition across different viewing circumstances that is seen in behavioural experiments. A simple unifying explanation of the behavioural effects is that the speed of recognition of an object depends on the rate of accumulation of activity from neurones selective for the object, evoked by a particular viewing circumstance. This in turn depends on the extent that the object has been seen previously under the particular circumstance. For any familiar object, more cells will be tuned to the configuration of the object's features present in the view or views most frequently experienced. Therefore, activity amongst the population of cells selective for the object's appearance will accumulate more slowly when the object is seen in an unusual view, orientation or size. This accounts for the increased time to recognise rotated views without the need to postulate 'mental rotation' or 'transformations' of novel views to align with neural representations of familiar views.

The 'Ideal Homunculus': decoding neural population signals.

Information processing in the nervous system involves the activity of large populations of neurons. It is possible, however, to interpret the activity of relatively small numbers of cells in terms of meaningful aspects of the environment. 'Bayesian inference' provides a systematic and effective method of combining information from multiple cells to accomplish this. It is not a model of a neural mechanism (neither are alternative methods, such as the population vector approach) but a tool for analysing neural signals. It does not require difficult assumptions about the nature of the dimensions underlying cell selectivity, about the distribution and tuning of cell responses or about the way in which information is transmitted and processed. It can be applied to any parameter of neural activity (for example, firing rate or temporal pattern). In this review, we demonstrate the power of Bayesian analysis using examples of visual responses of neurons in primary visual and temporal cortices. We show that interaction between correlation in mean responses to different stimuli (signal) and correlation in response variability within stimuli (noise) can lead to marked improvement of stimulus discrimination using population responses.