Unpacking the gestures of chemistry learners: What the hands tell us about correct and incorrect conceptions of stereochemistry.

In this study, adults, who were naïve to organic chemistry, drew stereoisomers of molecules and explained their drawings. From these explanations, we identified nine strategies that participants expressed during those explanations. Five of the nine strategies referred to properties of the molecule that were explanatorily irrelevant to solving the problem; the remaining four referred to properties that were explanatorily relevant to the solution. For each problem, we tallied which of the nine strategies were expressed within the explanation for that problem, and determined whether the strategy was expressed in speech only, gesture only, or in both speech and gesture within the explanation. After these explanations, all participants watched the experimenter deliver a two-minute training module on stereoisomers. Following the training, participants repeated the drawing+explanation task on six new problems. The number of relevant strategies that participants expressed in speech (alone or with gesture) before training did not predict their post-training scores. However, the number of relevant strategies participants expressed in gesture-only before training did predict their post-training scores. Conveying relevant information about stereoisomers uniquely in gesture prior to a brief training is thus a good index of who is most likely to learn from the training. We suggest that gesture reveals explanatorily relevant implicit knowledge that reflects (and perhaps even promotes) acquisition of new understanding.

A triple-blind, placebo-controlled randomised trial of the ilioinguinal-transversus abdominis plane (I-TAP) nerve block for elective caesarean section.

This study investigated the efficacy of a new ilioinguinal-transversus abdominis plane block when used as a component of multimodal analgesia. We conducted a prospective, triple-blind, placebo-controlled randomised study of 100 women undergoing elective caesarean section. All women had spinal anaesthesia with hyperbaric bupivacaine, 15 µg fentanyl and 150 µg morphine, as well as 100 mg diclofenac and 1.5 g paracetamol rectally. Women were randomly allocated to receive the ilioinguinal-transversus abdominis plane block or a sham block at the end of surgery. The primary outcome was the difference in fentanyl patient-controlled analgesia dose at 24 h. Secondary outcomes included postoperative pain scores, adverse effects and maternal satisfaction. The cumulative mean (95%CI) fentanyl dose at 24 h was 71.9 (55.6-92.7) µg in the ilioinguinal-transversus abdominis group compared with 179.1 (138.5-231.4) µg in the control group (p < 0.001). Visual analogue scale pain scores averaged across time-points were 1.9 (1.5-2.3) mm vs. 5.0 (4.3-5.9) mm (p = 0.006) at rest, and 4.7 (4.1-5.5) mm vs. 11.3 (9.9-13.0) mm (p = 0.001) on movement, respectively. Post-hoc analysis showed that the ilioinguinal-transversus abdominis group was less likely to use ≥ 1000 µg fentanyl compared with the control group (2% vs. 16%; p = 0.016). There were no differences in opioid-related side-effects or maternal satisfaction with analgesia. The addition of the ilioinguinal-transversus abdominis plane block provides superior analgesia to our usual multimodal analgesic regimen.

Teachers' gestures and students' learning: sometimes "hands off" is better.

During mathematics instruction, teachers often make links between different representations of mathematical information, and they sometimes use gestures to refer to the representations that they link. In this research, we investigated the role of such gestures in students' learning from lessons about links between linear equations and corresponding graphs. Eighty-two middle-school students completed a pretest, viewed a video lesson, and then completed a posttest comparable to the pretest. In all of the video lessons, the teacher explained the links between equations and graphs in speech. The lessons varied in whether the teacher referred to the equations in gesture and in whether she referred to the graphs in gesture, yielding four conditions: neither equations nor graphs, equations only, graphs only, and both equations and graphs. In all conditions, the gestures were redundant with speech, in the sense that the referents of the gestures were also mentioned in speech (e.g., pointing to "2" while saying "2"). Students showed substantial learning in all conditions. However, students learned less when the teacher referred to the equations in gesture than when she did not. This was not the case for gesture to graphs. These findings are discussed in terms of the processing implications of redundancy between gesture and speech, and the possibility of "trade-offs" in attention to the visual representations. The findings underscore the need for a more nuanced view of the role of teachers' gestures in students' comprehension and learning.

Modality and intermittency effects on time estimation.

The modality of a stimulus and its intermittency affect time estimation. The present experiment explores the effect of a combination of modality and intermittency, and its implications for internal clock explanations. Twenty-four participants were tested on a temporal bisection task with durations of 200-800ms. Durations were signaled by visual steady stimuli, auditory steady stimuli, visual flickering stimuli, and auditory clicks. Psychophysical functions and bisection points indicated that the durations of visual steady stimuli were classified as shorter and more variable than the durations signaled by the auditory stimuli (steady and clicks), and that the durations of the visual flickering stimuli were classified as longer than the durations signaled by the auditory stimuli (steady and clicks). An interpretation of the results is that there are different speeds for the internal clock, which are mediated by the perceptual features of the stimuli timed, such as differences in time of processing.

RNA profiling of cyclooxygenases 1 and 2 in colorectal cancer.

Cyclooxygenases (particularily Cox-2) are involved in carcinogenesis and metastatic cancer progression. The expression profiles of the cyclooxygenases and the roles they play in established tumours of similar stage remains unclear. We report that Cox-1 and Cox-2 expression is highly variable in Dukes' C tumours, and changes in Cox-1 expression may be of importance.

Cyclo-oxygenase 2 inhibition in colorectal cancer therapy.

BACKGROUND: Cyclo-oxygenase inhibition for the treatment of colorectal neoplasia has been studied with renewed interest since the discovery of cyclo-oxygenase (Cox) 2 and the introduction of specific Cox-2 inhibitors. These drugs have implications for both the prevention of colorectal carcinoma and the potential treatment of the disease. METHODS AND RESULTS: A Medline database search was performed for articles using the keywords "colonic, colon or rectal and neoplasia or cancer" and "cyclo-oxygenase or Cox-2." Cross-references of relevant historical papers were also included. There is substantial evidence that Cox-2 plays a role in the development and progression of colorectal cancer. The specific inhibition of this enzyme has been shown to inhibit cancer growth in in vitro and in vivo models. The mechanisms of action for these effects are poorly understood and potential clinical applications at present remain under investigation. CONCLUSION: Cox-2 inhibitors have great promise as useful additions to current cancer treatments. There is a need for randomized clinical trials to define a role for these drugs in chemoprevention, recurrence prophylaxis, and adjuvant therapy for colorectal and other solid tumours.

Animal cognition: 1900-2000.

During the 20th century there has been considerable progress in the study of animal cognition, based on essential ideas that were developed earlier. These essential ideas include the metaphors of the animal, the questions, the sources of hypotheses, and the types of explanations. The progress cannot be generally characterized as continuous improvement, cyclic changes, or discrete steps, but the quality of the empirical results has increased substantially since the first experiments in the field. Improvements in research methods have been primarily responsible for this progress. These have included improvements in animal husbandry, stimulus control, apparatus design, the measurement of behavior, experimental procedures, and data analysis. In the last third of the century the computer has led to major improvements in all stages of the research process in animal cognition. Although they have greatly improved the quality of the empirical results, they have not led to a general theory of animal cognition. In the near future the available research methods are likely to lead to further progress in the developments of quantitative theories of animal cognition.

The mouse lens fiber-cell intrinsic membrane protein MP19 gene (Lim2) and granule membrane protein GMP-17 gene (Nkg7): Isolation and sequence analysis of two neighboring genes.

PURPOSE: The lens fiber cell intrinsic membrane protein MP19 appears to play a key role in lens fiber cell structure or communication, and thus cataractogenesis. The goal of this study was to isolate and characterize the entire gene structure of the MP19 gene, termed Lim2, and to investigate gene sequences surrounding this lens-specific gene. METHODS: A 129/SvJ mouse genomic DNA library was screened using radioisotope labeled bovine MP19 cDNA. From this screening, an 11 kb genomic fragment was isolated which contained the entire Lim2 gene, and a neighboring gene, Nkg7, which codes for a 17 kDa granulocyte membrane protein termed GMP-17. The nucleotide sequence of this entire fragment was obtained using double strand automated sequencing techniques. Using CAT and green fluorescent protein reporter constructs, Lim2 5'-upstream promoter sequences were analyzed. RESULTS: An 11,182 base pair genomic clone containing the entire murine Lim2 gene and another downstream gene, Nkg7, was obtained and completely sequenced. These two genes are only 1,182 base pairs apart, from the poly(A) signal of the Lim2 gene to the published transcriptional start site of Nkg7. Interestingly, the protein coded for by Nkg7, GMP-17, is very similar to the product of the lens Lim2 gene, MP19, in many respects. Both proteins are transmembrane proteins, with each having 4 transmembrane loops. The amino acid sequence of the two proteins is 34% identical, and 49% with respect to similar amino acids. The size of mouse Lim2 is 5,896 base pairs from the transcriptional start site to the poly(A) signal, and contains five exons and four introns. Exons 2-5 of the Lim2 gene encode a polypeptide of 173 amino acids, having over 92% identity to human MP19. Using chloramphenicol acetyltransferase (CAT) and green fluorescent protein (GFP) reporter constructs, it was determined that about 160 bp of sequence upstream from the start of transcription is both necessary and sufficient for efficient expression levels as well as tissue specificity of expression. CONCLUSIONS: The mouse Lim2 gene is very similar to the human LIM2 gene, both having the same number of exons and introns. The coding nucleotide sequences from both species are 88% identical, and 92% identical at the amino acid level. In the immediate 5'-upstream region of these two genes, several highly conserved regions are observed. Due to the similarity of the MP19 and GMP-17 proteins, it is interesting to speculate that the lens MP19 and the lymphocyte-associated GMP-17 may have originated from one primordial gene which, through genetic drift, resulted in two separate proteins having similar functions in two widely separated tissue types.

Lim2(To3) transgenic mice establish a causative relationship between the mutation identified in the lim2 gene and cataractogenesis in the To3 mouse mutant.

PURPOSE: Lim2 is the gene encoding the ocular lens-specific intrinsic membrane protein MP19. We previously reported finding a single nonconservative G->T transversion in exon two of the Lim2 gene. This mutation was linked to the cataract in the To3 (Total opacity number 3) mouse mutant, confirming Lim2 as an ideal candidate gene for the To3 cataract. The aim of the present study was to substantiate a causative relationship between the mutation in the Lim2 gene and cataractogenesis in the To3 mouse mutant. To this end a Lim2To3 transgene cassette was engineered and introduced into fertilized normal mouse embryos to test its ability to induce cataractogenic lens development. METHODS: A Lim2 genomic clone was isolated and purified from a murine 129/SvJ genomic library. A restriction endonuclease map of the gene was generated using classical Southern techniques. The murine Lim2 promoter was characterized by transfecting primary chicken lens epithelial cells with Lim2 promoter-CAT reporter constructs and assaying promoter activity and specificity. This genomic clone was then used in conjunction with PCR to generate a Lim2To3 transgene cassette. After sequencing of the PCR engineered portion, the Lim2To3 transgene was then used to generate Lim2To3 transgenic mice via pronuclear injection. Founder mice and their offspring from outcrosses and intercrosses were characterized by ophthalmic examination, PCR and Southern DNA analysis, RT-PCR mRNA analysis, and histology of lens sections. RESULTS: Two mice, from independent microinjections, were identified as positive for presence of the Lim2To3 transgene cassette as well as presence of bilateral congenital cataracts and reduced eye size and mass. One of these founders was incapable of germline transmission of the transgene to offspring and was not characterized further. The other was capable of germline transmission and was characterized as described above. PCR DNA analysis revealed a perfect concordance between presence of the Lim2To3 transgene cassette and congenital cataract in offspring of this founder. Transgenic hemizygotes exhibited cataract and a reduction in eye and lens size and mass, while transgenic "homozygotes" presented with a more severe cataract and microphthalmic reduction in eye and lens size and mass. Southern analysis revealed approximately 2 copies of the transgene cassette integrated into a single chromosomal site in the founder and all hemizygous offspring. RT-PCR analysis revealed a very low ratio of Lim2To3 transgenic mRNA compared to endogenous normal Lim2. Finally, histology revealed that lens development was abnormal in mutant transgenic animals by embryonic day E15. By E19, just prior to birth, gross disorganization of secondary fibers was observed in mutants. CONCLUSIONS: These transgenic experiments firmly establish a causative relationship between the previously identified mutation in the Lim2 gene and cataractogenesis in the To3 mouse mutant. The low levels of mutant mRNA produced by the transgene cassette as compared to endogenous levels of normal Lim2 mRNA provides evidence that this dominant mutation results in a mutant MP19 protein with altered function rather than simply loss of function.

Stimulus and temporal cues in classical conditioning.

In 2 experiments, separate groups of rats were given stimulus conditioning, temporal conditioning, untreated control and (in Experiment 2) learned irrelevance control procedures, followed by a compound with both stimulus and temporal cues. Stimulus conditioning consisted of a random 15-s duration conditioned stimulus (CS) followed by food; temporal conditioning consisted of food-food intervals of fixed 90 s (Experiment 1) or fixed 75 + random 15 s (Experiment 2). The stimulus group abruptly increased responding after CS onset, and the temporal group gradually increased responding over the food-food interval. When the food-food interval was fixed 90 s, the temporal cue exerted stronger control in the compound, whereas when the food-food interval was fixed 75 + random 15 s, the stimulus cue exerted stronger control. The strength of conditioning, temporal gradients of responding, and cue competition effects appear to reflect simultaneous timing of multiple intervals.

Using the Internet for postgraduate medical education.

Obtaining information from the Internet can be fun. As the Internet is unregulated, the quality of this information can vary enormously and time can be wasted searching poor quality websites. Despite this, use of the Internet for postgraduate medical education is increasing.

Evaluation of quantitative theories of timing.

Scalar timing theory is a clear, complete, modular, and precise theory of timing that explains much of the data from many timing procedures, but not all of the data from all of the procedures. The multiple-time-scale theory of timing provides an alternative representation of time that has not yet been tested with respect to its fit to timing data.

A mutation in the connexin 50 (Cx50) gene is a candidate for the No2 mouse cataract.

PURPOSE: The No2 cataractous mouse mutant displays a bilateral, congenital, hereditary nuclear opacity of the ocular lens. The aim of this work was to identify and subsequently screen an optimal candidate gene for a mutation correlated and consistent with the observed phenotype. METHODS: The No2 cataract was mapped in relation to genes and microsatellite markers by crossing to the wild mouse strain Mus spretus and then backcrossing to the inbred strain C3H/ HeH. The Cx50 (MP70) protein coding region and flanking sequences were amplified from normal parental as well as heterozygous and homozygous mutant genomic DNAs. These PCR products were then sequenced directly. Sequence data was corroborated by restriction analysis of PCR products. RESULTS: Mapping of the No2 cataract placed it in the vicinity of Gja8, the gene encoding connexin 50 (MP70), a major component of lens fiber gap junctions. Amplification and subsequent sequencing of the Cx50 protein coding regions revealed a single A-->C transversion within codon 47. This sequence change resulted in the creation of an HhaI restriction endonuclease restriction site, allowing for corroboration of the sequence data via restriction analysis using this enzyme. The sequence alteration is also predicted to result in the nonconservative substitution of alanine (Ala) for the normally encoded aspartic acid (Asp) at this position within the polypeptide. CONCLUSIONS: The identified mutation in Gja8 is both correlated and consistent with the cataract observed in the No2 mouse mutant, making it an ideal candidate for the cataract. This study provides the first evidence that a mutation in a lens connexin can result in congenital hereditary cataract, highlighting the importance of lens connexins in maintaining lens transparency.

Temporal search as a function of the variability of interfood intervals.

We attempted to determine whether timing theories developed primarily to explain performance in fixed-interval reinforcement schedules are also applicable to variable intervals. Groups of rats were trained in lever boxes on peak procedures with a 30-, 45-, or 60-s interval, or a 30- to 60-s uniform distribution (Experiment 1); a 60-s fixed and 1- to 121-s uniform distribution between and within animals (Experiment 2); and a procedure in which the interval between food and next available food gradually changed from a fixed 60 s to a uniform distribution between 0 and 120 s (Experiment 3). In uniform interval schedules rats made lever responses at particular times since food, as measured by the distribution of food-food intervals, the distribution of postreinforcement pauses, and the mean response rate as a function of time since food. Qualitative features of this performance are described by a multiple-oscillator connectionist theory of timing.

Granule cell development in the cerebellum is punctuated by changes in Sox gene expression.

Development of the vertebrate cerebellum is unusual compared to most other regions of the brain since it involves two germinal regions. Most cell types arise from the luminal, ventricular zone as in other brain regions, but granule cells arise from the second germinal layer, the external granular layer (EGL). Our analysis of the temporal and positional expression of three members of the Sox gene family of transcription factors in the cerebellum shows that granule cell development is unusual compared to most other neurons of the central nervous system (CNS). We show that granule cell precursors lose expression of cSox2 and cSox3 as they migrate to form the EGL. The EGL is the first example of a germinal layer in the CNS which does not exhibit expression of these genes. Throughout most of the CNS cSox11 expression is very low in the ventricular zone but increases dramatically as cells cease proliferation and migrate to form the subventricular zone. We also find that cSox11 expression increases when cells of the cerebellum migrate to form the EGL, but levels of expression as high as that in the subventricular zone are only seen when cells cease proliferation and migrate inwards to form the deep EGL. These observations demonstrate that cells of the proliferative superficial EGL differ qualitatively from cells of the ventricular zone in their expression of Sox genes whereas the post-proliferative cells of the deep EGL appear analogous, in their expression of Sox genes, to cells of the subventricular zone.

A comparison between children's and adults' ability to detect conceptual information conveyed through representational gestures.

The present study compares children's and adults' ability to detect information that is conveyed through representational hand gestures. Eighteen children (M = 10 years, 1 month) and 18 college undergraduates watched videotaped stimuli of children verbally and gesturally explaining their reasoning in a problem-solving situation. A recall procedure was used to assess whether children and adults could detect information conveyed in the stimulus children's gesture and speech. Results showed that children and adults recalled information that was conveyed through representational gestures. In addition, "mismatching" gesture negatively affected the precision of speech recall for adults. However, this negative effect on speech recall was absent for children.

Are separate theories of conditioning and timing necessary?

Conditioning and timing studies have evolved under separate traditions, which is exemplified in both traditional theories (e.g. the Rescorla-Wagner model of conditioning vs. Scalar Timing Theory) and in a dual process model (Gibbon, J., Balsam, P., 1981. In: Autoshaping and Conditioning Theory. Academic Press, New York.). Other lines of theoretical development in both timing and conditioning fields have resulted in the emergence of 'hybrid' theories in which conditioning and timing processes are integrated. Simulations were conducted with a recent hybrid theory of timing (Machado, A., 1997. Psychol. Rev. 104, 241-265). The simulations were of classical conditioning procedures in which the local or global predictability of food was varied by manipulating the variability of the CS-US relationship, variability of the CS duration, and variability of the intertrial interval. The hybrid model provided good qualitative fits to indices of conditioning (discrimination ratios) and timing (local rates of responding), indicating that it may be possible to model both conditioning and timing results with a single process in which an internal representation of time and a strength of association are integrated. However, the failure of the model to provide good quantitative fits of the data indicates the need for a consideration of alternative perceptual representations of time and/or principles of association within the framework of the hybrid model.

Quantitative models of animal learning and cognition.

This article reviews the prerequisites for quantitative models of animal learning and cognition, describes the types of models, provides a rationale for the development of such quantitative models, describes criteria for their evaluation, and makes recommendations for the next generation of quantitative models. A modular approach to the development of models is described in which a procedure is considered as a generator of stimuli and a model is considered as a generator of responses. The goal is to develop models that, in combination with many different procedures, produce sequences of times of occurrence of events (stimuli and responses) that are indistinguishable from those produced by the animal under many experimental procedures and data analysis techniques.