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Biomedical subjects

R Elliott

Publications and source records attributed to R Elliott.

At least 73 records · Page 4Linked to original sources

Differential neural responses during performance of matching and nonmatching to sample tasks at two delay intervals.

Visual short-term memory in humans and animals is frequently assessed using delayed matching to sample (DMTS) and delayed nonmatching to sample (DNMTS) tasks across variable delay intervals. Although these tasks depend on certain common mechanisms, there are behavioral differences between them, and neuroimaging provides a means of assessing explicitly whether this is underpinned by differences at a neural level. Findings of delay-dependent deficits, after lesions in humans and animals, suggest that the neural implementation of these tasks may also critically depend on the delay interval. In this study we determined whether there were differential neural responses associated with DMTS and DNMTS tasks at two different delay intervals using functional magnetic resonance imaging. Ten healthy volunteers were studied under four test conditions: DMTS and DNMTS at 5 and 15 sec delay. The main effect of DMTS compared with DNMTS across both delay intervals was associated with significant activation in bilateral head of caudate and medial orbitofrontal cortex. By contrast, DNMTS compared with DMTS was associated with significant activation in mediodorsal thalamus, bilateral lateral orbitofrontal cortex, and left premotor cortex. The main effect of short compared with long delay, across both tasks, was associated with significantly greater activity in occipital and parietal cortices. By contrast, long compared with short delay was associated with significantly greater activity in temporal and ventrolateral frontal cortices. We conclude that DMTS and DNMTS are not equivalent and furthermore that the precise neural implementation of these tasks is a dynamic function of delay interval.

Adult↗

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand.

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.

Animals↗

Ventromedial prefrontal cortex mediates guessing.

Guessing is an important component of everyday cognition. The present study examined the neural substrates of guessing using a simple card-playing task in conjunction with functional magnetic resonance imaging (fMRI). Subjects were scanned under four conditions. In two, they were shown images of the back of a playing card and had to guess either the colour or the suit of the card. In the other two they were shown the face of a card and had to report either the colour or the suit. Guessing compared to reporting was associated with significant activations in lateral prefrontal cortex (right more than left), right orbitofrontal cortex, anterior cingulate, bilateral inferior parietal cortex and right thalamus. Increasing the guessing demands by manipulating the number of alternative outcomes was associated with activation of the left lateral and medial orbitofrontal cortex. These data suggest that while simple two choice guessing depends on an extensive neural system including regions of the right lateral prefrontal cortex, activation of orbitofrontal cortex increases as the probabilistic contingencies become more complex. Guessing thus involves not only systems implicated in working memory processes but also depends upon orbitofrontal cortex. This region is not typically activated in working memory tasks and its activation may reflect additional requirements of dealing with uncertainty.

Adult↗

Verbal communication: what do critical care nurses say to their unconscious or sedated patients?

The importance of using verbal communication in the care of critically ill patients has long been known. Both qualitative and quantitative studies have presented evidence of the benefits of effective communication. This non-participant observational study aimed to explore how much and what types of verbal communication critical care nurses use when caring for unconscious or sedated patients. Sixteen critical care nurses were observed in 4-hour episodes and their verbal communication was transcribed and timed at source. Seven categories of verbal communication and a 'core concept' emerged on analysis of the raw data. Medical investigations/interventions performed on the patients increased the amount of communication used. The participants in this study were found to use a greater variety and amount of verbal communication than participants in other studies. The findings of this study highlight the need for formal support systems and continued education for nurses about the benefits of verbal communication.

Analgesia↗

Genetic dissection of X-linked interspecific hybrid placental dysplasia in congenic mouse strains.

Interspecific hybridization in the genus Mus results in male sterility and X-linked placental dysplasia. We have generated several congenic laboratory mouse lines (Mus musculus) in which different parts of the maternal X chromosome were derived from M. spretus. A strict positive correlation between placental weight and length of the M. spretus-derived part of the X chromosome was shown. Detailed analysis was carried out with one congenic strain that retained a M. spretus interval between 12.0 and 30.74 cM. This strain consistently produced hyperplastic placentas that exhibited an average weight increase of 180% over the weight of control placentas. In derived subcongenic strains, however, increased placental weight could no longer be observed. Morphometric analysis of these placentas revealed persistence of abnormal morphology. Fully developed placental hyperplasia could be reconstituted by recombination of proximal and central M. spretus intervals with an intervening M. musculus region. These results may suggest that placental dysplasia of interspecific mouse hybrids is caused by multiple loci clustered on the X chromosome that act synergistically. Alternatively, it is possible that changes in chromatin structure in interspecific hybrids that influence gene expression are dependent on the length of the alien chromosome.

Animals↗

Radiation safety audits.

Radiation Safety Management Audits are an important tool for maintaining a good radiation safety program. They serve as a useful mechanism for program evaluation and improvement and can be instrumental in correcting problems, communicating strengths and weaknesses to manangement and involving the Radiation Safety Committee in the program operation. Effective audits can and should be done regardless of the size of the program. They need not be costly and, if organized properly, can be performed with a minimal time commitment. The remainder of this article will cover some successful audit tips.

Humans↗

Evolving guidelines for publication of qualitative research studies in psychology and related fields.

We present a set of evolving guidelines for reviewing qualitative research, to serve four functions: to contribute to the process of legitimizing qualitative research; to ensure more appropriate and valid scientific reviews of qualitative manuscripts, theses, and dissertations; to encourage better quality control in qualitative research through better self- and other-monitoring; and to encourage further developments in approach and method. Building on a review of existing principles of good practice in qualitative research, we used an iterative process of revision and feedback from colleagues who engage in qualitative research, resulting in a set of seven guidelines common to both qualitative and quantitative research and seven guidelines especially pertinent to qualitative investigations in psychology and related social sciences. The Evolving Guidelines are subject to continuing revision and should not be used in a rigid manner, in order to avoid stifling creativity in this rapidly evolving, rich research tradition.

Guidelines as Topic↗

Neural response during preference and memory judgments for subliminally presented stimuli: a functional neuroimaging study.

Preexposing subjects to visual stimuli is sufficient to establish a subsequent preference, even when previous exposure is subliminal, such that explicit recognition is at chance. This influence of previous exposure on preference judgments, known as the "mere exposure effect," is a form of unconscious memory. The present functional neuroimaging study examines the mechanism of this effect. Nine volunteer subjects were studied using functional imaging while making forced choice judgments about abstract stimuli on the basis of either preference or memory. Each judgment type was made under two conditions: under one condition one or the other stimulus had previously been presented subliminally, whereas under the second condition both stimuli were novel. Memory judgments were associated with activation of left frontopolar cortex and parietal areas, whereas preference judgments were associated with activation of medial prefrontal cortex and regions of occipital cortex. The modulation of preference by objective familiarity (implicit memory) was associated with right lateral frontal activation. Significant activation of hippocampal gyrus was seen in response to objective stimulus novelty, regardless of judgment type required. Our data thus demonstrate activations of a memory system independent of recollective experience. Dissociable activations within this system implicate a frontopolar involvement in explicit retrieval attempt and right lateral prefrontal cortex involvement in implicit memory expressed in preference judgments. Furthermore, the results suggest that hippocampal response to stimulus novelty can be independent of conscious reportability of familiarity.

Adult↗

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.

The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.

Amino Acid Sequence↗

The neural response in short-term visual recognition memory for perceptual conjunctions.

Short-term visual memory has been widely studied in humans and animals using delayed matching paradigms. The present study used positron emission tomography (PET) to determine the neural substrates of delayed matching to sample for complex abstract patterns over a 5-s delay. More specifically, the study assessed any differential neural response associated with remembering individual perceptual properties (color only and shape only) compared to conjunction between these properties. Significant activations associated with short-term visual memory (all memory conditions compared to perceptuomotor control) were observed in extrastriate cortex, medial and lateral parietal cortex, anterior cingulate, inferior frontal gyrus, and the thalamus. Significant deactivations were observed throughout the temporal cortex. Although the requirement to remember color compared to shape was associated with subtly different patterns of blood flow, the requirement to remember perceptual conjunctions between these features was not associated with additional specific activations. These data suggest that visual memory over a delay of the order of 5 s is mainly dependent on posterior perceptual regions of the cortex, with the exact regions depending on the perceptual aspect of the stimuli to be remembered.

Adult↗

Activation of different anterior cingulate foci in association with hypothesis testing and response selection.

Much everyday behavior is implicitly guided by hypotheses about the world which are monitored and updated in the light of changing circumstances. The process of translating these hypotheses into behavior typically involves implementing choices, often based on incompletely specified information. The present study aimed at modeling these processes to determine the neural substrates of hypothesis testing and, in particular, how these are modulated by the requirement to make choices. We used positron emission tomography to study six right-handed volunteers performing an insoluble hypothesis testing task in which subjects attempted to identify a rule determining which of two black and white checkerboard stimuli was correct. This task was compared with a control task matched for perceptuomotor requirements, but involving no hypothesis testing. Both tasks were performed with or without a requirement to make a choice. Structures activated in association with hypothesis testing included the cerebellum, left anterior cingulate, right precuneus, right thalamus, and left inferior frontal gyrus. The requirement to choose a response was associated with activation of the left anterior cingulate and right lateral orbitofrontal cortex. A significant modulation of activation associated with hypothesis testing was observed in the anterior cingulate region that was also activated by making a choice. These findings are discussed in terms of the neural substrates of complex "executive" tasks. We argue that the precise cognitive parameters of such tasks, and specifically the requirement to implement decisions in actual behavior, are critical in determining the associated neural response.

Adult↗

Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression.

BACKGROUND: It has been suggested that patients with unipolar depression show abnormal responses to negative feedback in the performance of cognitive tasks. Positron emission tomography (PET) has previously identified blood flow abnormalities in depressed patients during cognitive performance. We have also used PET to identify regions where there is differential neural response to performance feedback in normal volunteers. In this study we aimed to test the hypothesis that blood flow in these regions, the medial caudate and ventromedial prefrontal cortex, would be abnormal in depressed patients. METHODS: Six patients with unipolar depression and six matched controls were scanned using PET while performing cognitive tasks in the presence and absence of feedback. RESULTS: Compared with controls, depressed patients failed to show significant activation in the medial caudate and ventromedial orbitofrontal cortex. Blood flow was lower and a differential response, observed in normals, under different task and feedback conditions was not seen in the patients. DISCUSSION: The findings suggest that the behavioural response to feedback in depressed patients is associated with an abnormal neural response within the medial caudate and ventromedial orbitofrontal cortex, regions implicated in reward mechanisms. We argue that the observed abnormalities may depend on a combination of psychological factors, with both cognitive and emotive components.

Adult↗

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region.

We have recently reported isolation of the gene responsible for X-linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X-specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.

Abnormalities, Multiple↗

Oral cyclosporin in refractory inflammatory bowel disease.

BACKGROUND: The role of cyclosporin in patients with severe, refractory inflammatory bowel disease is unclear. METHODS: A seven year retrospective review of patients treated with oral cyclosporin for inflammatory bowel disease refractory to conventional medical therapy was undertaken. RESULTS: Twenty-eight patients (13 ulcerative colitis and 15 Crohn's disease) received oral cyclosporin for a mean of nine months (range 0.25-27 months). Within four weeks of starting cyclosporin, a complete clinical response occurred in 15 patients (nine with ulcerative colitis and six with Crohn's colitis), in whom conventional maintenance treatment was instituted concurrently. The clinical response was sustained during cyclosporin treatment in ten, but maintained after cyclosporin withdrawal in only five patients (18% of entire study group). Four of the five patients who relapsed after cyclosporin withdrawal had failed previously to respond to azathioprine. None of the five patients with continuing remission after cyclosporin withdrawal had received azathioprine in the past. There were three clinically significant infections and 14 cases of impaired renal function during treatment. CONCLUSIONS: Oral cyclosporin induces remission in some patients with severe ulcerative colitis or Crohn's colitis, but its benefits in cases refractory to azathioprine are over-shadowed by a high frequency of relapse after drug withdrawal.

Administration, Oral↗