肿瘤临床治疗中应关注肝脏

抗肿瘤细胞毒性药物有不同程度毒副作用,有些严重毒副反应是限制药物剂量或使用的直接原因。肝脏是药物代谢的主要器官,也是药物损伤的主要靶器官。随着临床肿瘤治疗关注治疗带来的副作用与关注疗效同等重要的发展,本文对抗肿瘤细胞毒性药物与肝损伤、发生机制、诊断、分型和临床治疗进展进行了阐述。     

Do complex models increase prediction of complex behaviours? Predicting driving ability in people with brain disorders

Prediction of complex behavioural tasks via relatively simple modelling techniques, such as logistic regression and discriminant analysis, often has limited success. We hypothesized that to more accurately model complex behaviour, more complex models, such as kernel-based methods, would be needed. To test this hypothesis, we assessed the value of six modelling approaches for predicting driving ability based on performance on computerized sensory–motor and cognitive tests (SMCTests?) in 501 people with brain disorders. The models included three models previously used to predict driving ability (discriminant analysis, DA; binary logistic regression, BLR; and nonlinear causal resource analysis, NCRA) and three kernel methods (support vector machine, SVM; product kernel density, PK; and kernel product density, KP). At the classification level, two kernel methods were substantially more accurate at classifying on-road pass or fail (SVM 99.6%, PK 99.8%) than the other models (DA 76%, BLR 78%, NCRA 74%, KP 81%). However, accuracy decreased substantially for all of the kernel models when cross-validation techniques were used to estimate prediction of on-road pass or fail in an independent referral group (SVM 73–76%, PK 72–73%, KP 71–72%) but decreased only slightly for DA (74–75%) and BLR (75–76%). Cross-validation of NCRA was not possible. In conclusion, while kernel-based models are successful at modelling complex data at a classification level, this is likely to be due to overfitting of the data, which does not lead to an improvement in accuracy in independent data over and above the accuracy of other less complex modelling techniques.     

Thought sequences

Abstract

Thought sequences are ordered series of verbal-like expressions that pass spontaneously through one's mind and which are characterised by well-demarcated beginnings and ends. The present paper notes the significance of and interest in thought sequences and presents a framework for their analysis. Given the scope of the enterprise, different levels of analysis are noted which set the boundaries for the present investigation, and define guidelines for further research. Here, the focus of interest is the structural (as distinct from either functional or computational) relationships between pairs of consecutive expressions. The informational bases for these relationships are reviewed and a typology of them is drawn. The typology reveals marked internal structure and it suggests that the variety of couplings of thought sequences constitutes a space spanned by a small number of variables. Methodological issues regarding the use of introspection in cognitive research are also discussed.     

Comprehensive driving assessment: neuropsychological testing and on-road evaluation of brain injured patients

The study investigates the correspondence between neuropsychological test results and on-road driving performance among 55 patients with a CT-verified brain damage or documented neurological disorder (cerebrovascular accident: 43, traumatic brain injury: 5, multiple sclerosis: 4, other: 3). 5 patients showed unimpaired test profiles and passed the on-road evaluation. 18 patients showed severe neuropsychological deficits contrary to driving and were not recommended for on-road evaluation. Of the remaining 32 patients with some neuropsychological deficits, all 100% in the minor impaired group (n = 8) passed the driving evaluation, compared to 69% in the mildly impaired (n = 16) and 38% in the moderately impaired group (n = 8). Measures of reduced visuoconstructive ability, reaction time, visual attention, and awareness of cognitive impairments, were found to discriminate between groups. It is concluded that neuropsychological assessment of targeted functions provide an ecological valid prediction of driving skill after brain damage, but that on-road evaluation is needed as supplement in cases with ambiguous test findings.     

The differential effects of thalamus and basal ganglia on facial emotion recognition

This study examined if subcortical stroke was associated with impaired facial emotion recognition. Furthermore, the lateralization of the impairment and the differential profiles of facial emotion recognition deficits with localized thalamic or basal ganglia damage were also studied. Thirty-eight patients with subcortical strokes and 19 matched normal controls volunteered to participate. The participants were individually presented with morphed photographs of facial emotion expressions over multiple trials. They were requested to classify each of these morphed photographs according to Ekman's six basic emotion categories. The findings indicated that the clinical participants had impaired facial emotion recognition, though no clear lateralization pattern of impairment was observed. The patients with localized thalamic damage performed significantly worse in recognizing sadness than the controls. Longitudinal studies on patients with subcortical brain damage should be conducted to examine how cognitive reorganization post-stroke would affect emotion recognition.     

Using perfusion fMRI to measure continuous changes in neural activity with learning

In this study, we examine the suitability of a relatively new imaging technique, arterial spin labeled perfusion imaging, for the study of continuous, gradual changes in neural activity. Unlike BOLD imaging, the perfusion signal is stable over long time-scales, allowing for accurate assessment of continuous performance. In addition, perfusion fMRI provides an absolute measure of blood flow so signal changes can be interpreted without reference to a baseline. The task we used was the serial response time task, a sequence learning task. Our results show reliable correlations between performance improvements and decreases in blood flow in premotor cortex and the inferior parietal lobe, supporting the model that learning procedures that increase efficiency of processing will be reflected in lower metabolic needs in tissues that support such processes. More generally, our results show that perfusion fMRI may be applied to the study of mental operations that produce gradual changes in neural activity.     

Timing in cognition and EEG brain dynamics: discreteness versus continuity

This article provides an overview of recent developments in solving the timing problem (discreteness vs. continuity) in cognitive neuroscience. Both theoretical and empirical studies have been considered, with an emphasis on the framework of operational architectonics (OA) of brain functioning (Fingelkurts and Fingelkurts in Brain Mind 2:291-29, 2001; Neurosci Biobehav Rev 28:827-836, 2005). This framework explores the temporal structure of information flow and interarea interactions within the network of functional neuronal populations by examining topographic sharp transition processes in the scalp EEG, on the millisecond scale. We conclude, based on the OA framework, that brain functioning is best conceptualized in terms of continuity-discreteness unity which is also the characteristic property of cognition. At the end we emphasize where one might productively proceed for the future research.     

Unilateral brain damage effects on processing homonymous and polysemous words

Using an auditory semantic priming paradigm, the present study investigated the abilities of left-hemisphere-damaged (LHD) non-fluent aphasic, right-hemisphere-damaged (RHD) and normal control individuals to access, out of context, the multiple meanings of three types of ambiguous words, namely homonyms (e.g., "punch"), metonymies (e.g., "rabbit"), and metaphors (e.g., "star"). In addition, the study tested certain predictions of the "suppression deficit" and "coarse semantic coding" hypotheses that have been proposed to account for the linguistic deficits typically observed after RH damage. Homonymous, metonymous, and metaphorical words were used as primes followed after a short (100 ms) or a long (1000 ms) inter-stimulus interval (ISI) by dominant-meaning-related, subordinate-meaning-related or unrelated target words. No significant group effects were found, and for both ISIs, dominant- and subordinate-related targets were facilitated relative to unrelated control targets for the homonymy and metonymy conditions. In contrast, for the metaphor condition, only targets related to the dominant meaning were facilitated. These findings provide only partial support for the "suppression deficit" hypothesis and no support for the "coarse semantic coding" hypothesis (as interpreted herein) indicating that patients with focal LH or RH damage can access the multiple meanings of ambiguous words and exhibit processing abilities comparable to those of older normal control subjects, at least at the single-word level.     

Positive facial affect facilitates the identification of famous faces

Several convergent lines of evidence have suggested that the presence of an emotion signal in a visual stimulus can influence processing of that stimulus. In the current study, we picked up on this idea, and explored the hypothesis that the presence of an emotional facial expression (happiness) would facilitate the identification of familiar faces. We studied two groups of normal participants (overall N=54), and neurological patients with either left (n=8) or right (n=10) temporal lobectomies. Reaction times were measured while participants named familiar famous faces that had happy expressions or neutral expressions. In support of the hypothesis, naming was significantly faster for the happy faces, and this effect obtained in the normal participants and in both patient groups. In the patients with left temporal lobectomies, the effect size for this facilitation was large (d=0.87), suggesting that this manipulation might have practical implications for helping such patients compensate for the types of naming defects that often accompany their brain damage. Consistent with other recent work, our findings indicate that emotion can facilitate visual identification, perhaps via a modulatory influence of the amygdala on extrastriate cortex.     

Kicking coordination captures differences between full-term and premature infants with white matter disorder

This study explores the relation of white matter disorder (WMD) to intralimb coordination patterns in premature infants with very low birth weight (VLBW). We specifically measured the temporal-spatial characteristics of intralimb coordination patterns of the legs. Three groups of infants were compared at one month corrected age (CA): 10 premature infants born VLBW and WMD (PTWMD), 10 premature infants born VLBW without WMD (PT) and 10 full term infants (FT). Using kinematic variables, we discriminate among VLBW infants with WMD from the two comparison groups. Infants born with WMD maintain patterns of tight coupling among leg joints (all flexion or all extension) while PT and FT term infants have begun to decouple leg joints by this age (combinations of flexion with extension). The coupling pattern is captured through joint correlations, discrete relative phase, and phase plane portraits. The PTWMD infants also demonstrate aberrant patterns of coordination evident through both temporal and spatial characteristics of the kicks. This is the first evidence that movement disorder associated with brain lesions can be identified and quantified with kinematic variables as early as one month of age.