Biomedical subjects
Publications and source records attributed to David Rose.
We report a case of false aneurysm of the left ventricle occurring subsequently to the placing of a vent sump line through the apex during an aortic valve procedure; the diagnosis was made twelve months later during a routine echocardiographic examination. The lesion was successfully repaired. This case recommend the use of other routes of venting in order to reduce the incidence of such complications.
Binocular disparity and motion parallax provide information about the spatial structure and layout of the world. Descriptive similarities between the two cues have often been noted which have been taken as evidence of a close relationship between them. Here, we report two experiments which investigate the effect of surface orientation and modulation frequency on (i) a threshold detection task and (ii) a supra-threshold depth-matching task using sinusoidally corrugated surfaces defined by binocular disparity or motion parallax. For low frequency corrugations, an orientation anisotropy was observed in both domains, with sensitivity decreasing as surface orientation was varied from horizontal to vertical. In the depth-matching task, for surfaces defined by binocular disparity the greatest depth was seen for oblique orientations. For surfaces defined by motion parallax, perceived depth was found to increase as surface orientation was varied from horizontal to vertical. In neither case was perceived depth for supra-threshold surfaces related to threshold performance in any simple manner. These results reveal clear differences between the perception of depth from binocular disparity or motion parallax, and between perception at threshold and supra-threshold levels of performance.
BACKGROUND: The technique of off-pump coronary artery bypass graft (OPCABG) surgery differs considerably from on-pump CABG. This study investigates the impact of surgical training on clinical outcome in patients undergoing OPCABG. METHODS: All 251 OPCABG cases performed by one service over an 18-month period were analyzed. The 83 operations (33%) performed by two trainees under supervision were compared with the 168 operations (67%) performed by an experienced consultant surgeon. Patient and disease characteristics, intraoperative and postoperative data, morbidity and mortality were analyzed using univariate and multivariate analysis. Data were extracted from a prospective database. RESULTS: Patients operated on by the consultant were more likely to have had unstable angina (p = 0.003, odds ratio [OR] = 3.5), impaired left ventricular function (ejection fraction < 0.3; p = 0.005, OR = 2.4), or previous cardiac surgery (p = 0.03). They were more likely to receive three or more grafts (p = 0.017, OR = 2.0). Operative mortality was 2.4% (consultant) and 0% (trainees; p = 0.31). Postoperative morbidity, such as reoperation for bleeding (consultant 3% versus trainees 1.2%), stroke (0.6% versus 1.2%), and hemofiltration (3.6% versus 0%) was similar between the two patient groups. Stay in the intensive care unit was not significantly different in the two groups. CONCLUSIONS: In our experience, trainee surgeons are less likely to operate on patients with unstable angina or cardiac dysfunction. Operative morbidity and mortality are, however, similar in patients operated on by either an experienced consultant surgeon or trainees. We believe OPCABG can be taught safely to trainees under supervision.
INTRODUCTION: The failure of pharmaceutical drug candidates due to toxicity, especially hepatotoxicity, is an important and continuing problem for drug development. The current manuscript explores new toxicogenomics approaches to better understand the hepatotoxic potential of human pharmaceutical compounds and to assess their toxicity earlier in the drug development process by means of a toxicity screen. RESOURCES: Data consisted of two commercial knowledgebases that employed a hybrid experimental design in which human drug toxicity information was extracted from the literature, dichotomized and merged with rat-based gene expression measures. One knowledgebase used gene expression from rat primary hepatocytes while the other employed whole rats. Approximately 100 compounds were used in each. METHODS: Toxicity classification rules were built using a stochastic gradient boosting machine learner, with classification error estimated using a modified bootstrap estimate of true error. Several types of clustering methods were also applied, some based on sets of compounds and others based on sets of genes. RESULTS: Robust classification rules were constructed for both in vitro (hepatocytes) and in vivo (liver) data, based on a high dose, 24-hour design. There appeared to be little overlap between the two classifiers, at least in terms of their gene lists. Robust classifiers could not be fitted when earlier timepoints and/or low dose data were included, indicating that experimental design is important for these systems. CONCLUSIONS: In light of these findings, a working compound screen based on these toxicity classifiers appears feasible, with classifier operating characteristics used to tune a screen for a specific implementation. To ensure robust and optimal performance, issues such as site variability of microarrays and generalizability of findings should be addressed as indicated.
Knowledge of the molecular events that occur during hematopoietic stem/progenitor cell (HSPC) development is vital to our understanding of blood cell production. To study the functional groups of genes characteristic of HSPCs we isolated a subpopulation of CD34+ bone marrow (BM) cells from nonhuman primates that persisted in vivo after a sublethal dose of total body irradiation (TBI). CD34+ cells isolated during the phase of maximal hematopoietic suppression show a transcriptional profile characteristic of metabolically inactive cells, with strong coordinate downregulation of a large number of genes required for protein production and processing. Consistent with this profile, these CD34+ cells were not able to generate hematopoietic colonies. Transcriptional profiling of these CD34+ cells in conjunction with a pathway analysis method reveals several classes of functionally related genes that are upregulated in comparison to the CD34+ cells obtained prior to TBI. These families included genes known to be associated with self-renewal and maintenance of HSPCs (including bone morphogenetic proteins), resistance to apoptosis (Bcl-2) as well as genes characteristic of a variety of nonhematopoietic tissues (gamma-aminobutyric acid/glycine receptor, complement receptor C1qRp). In contrast, during the period of hematopoietic recovery, the CD34+ cells expressed higher level of genes encoding factors regulating maturation and differentiation of HSPCs. Our data indicate that the primitive BM CD34+ cell population that persists after radiation possesses a transcriptional profile suggestive of pluripotency.
We examined whether it is possible to identify the emotional content of behaviour from point-light displays where pairs of actors are engaged in interpersonal communication. These actors displayed a series of emotions, which included sadness, anger, joy, disgust, fear, and romantic love. In experiment 1, subjects viewed brief clips of these point-light displays presented the right way up and upside down. In experiment 2, the importance of the interaction between the two figures in the recognition of emotion was examined. Subjects were shown upright versions of (i) the original pairs (dyads), (ii) a single actor (monad), and (iii) a dyad comprising a single actor and his/her mirror image (reflected dyad). In each experiment, the subjects rated the emotional content of the displays by moving a slider along a horizontal scale. All of the emotions received a rating for every clip. In experiment 1, when the displays were upright, the correct emotions were identified in each case except disgust; but, when the displays were inverted, performance was significantly diminished for some emotions. In experiment 2, the recognition of love and joy was impaired by the absence of the acting partner, and the recognition of sadness, joy, and fear was impaired in the non-veridical (mirror image) displays. These findings both support and extend previous research by showing that biological motion is sufficient for the perception of emotion, although inversion affects performance. Moreover, emotion perception from biological motion can be affected by the veridical or non-veridical social context within the displays.
The superiority of the modified 16-item Rey memory test over the original 15-item test has yet to be established in relation to the detection of feigned memory deficits. This study compares the effectiveness of these two versions of the test in combination with a standard memory test. Sixty-four participants, equally divided into "controls" and "simulators", and 32 "memory-impaired" volunteers completed the WAIS-III Digit Span test and either the 15-item or 16-item Rey test. The median scores of the simulators were worse than those of both the controls and the memory-impaired subjects on two types of score on the 16-item test compared to just one on the 15-item test. However, combining the total score from the 16-item test with the digits forward span accurately detected 63% of simulators (with only 6% of nonsimulators wrongly classified as simulators). This performance was better than that obtained from any of the test scores taken singly or from any other combination of a digit span score with a Rey score. It is concluded that the addition of a standard memory test to the Rey memory test improves the detection of individuals feigning memory impairment.
The management of rectal cancer has been revolutionised over the last 20 years through improvements in staging, surgery and the use of radiotherapy and combination chemoradiotherapy. The traditional approach involved surgery followed by pathological assessment of the specimen reporting the completeness of excision. Incomplete excision in many cases led to local recurrence of the cancer within the pelvis with the disabling symptoms of pelvic pain, bowel fistulation and bowel and bladder dysfunction. Indeed, many patients died with local recurrence alone and salvage therapy in these patients was rarely successful. However, the recognition of the advantage of pre-operative therapy for patients in whom surgery would not provide local cure has been a major advance. The ability to downstage/downsize the tumour before curative surgery has improved outcome. However, these pre-operative therapies are toxic and not without their own complications, therefore the select use, targeted at the appropriate patient, represents the 'gold-standard'. The development of magnetic resonance imaging staging that accurately predicts operability has completed this triad approach which is focused through the weekly multidisciplinary team meeting. National acceptance of these techniques and standards can only improve the outcome for patients with this disease.
Hippocampal activation was investigated, comparing allocentric and egocentric spatial memory. Healthy participants were immersed in a virtual reality circular arena, with pattern-rendered walls. In a viewpoint-independent task, they moved toward a pole, which was then removed. They were relocated to another position and had to move to the prior location of the pole. For viewpoint-dependent memory, the participants were not moved to a new starting point, but the patterns were rotated to prevent them from indicating the final position. Hippocampal and parahippocampal activation were found in the viewpoint-independent memory encoding phase. Viewpoint-dependent memory did not result in such activation. These results suggest differential activation of the hippocampal formation during allocentric encoding, in partial support of the spatial mapping hypothesis as applied to humans.
We present a new computational method for identifying regulated pathway components in transcript profiling (TP) experiments by evaluating transcriptional activity in the context of known biological pathways. We construct a graph representing thousands of protein functional relationships by integrating knowledge from public databases and review articles. We use the notion of distance in a graph to define pathway neighborhoods. The pathways perturbed in an experiment are then identified as the subgraph induced by the genes, referred to as activity centers, having significant density of transcriptional activity in their functional neighborhoods. We illustrate the predictive power of this approach by performing and analyzing an experiment of TP53 overexpression in NCI-H125 cells. The detected activity centers are in agreement with the known TP53 activation effects and our independent experimental results. We also apply the method to a serum starvation experiment using HEY cells and investigate the predicted activity of the transcription factor MYC. Finally, we discuss interesting properties of the activity center approach and its possible applications beyond the comparison of two experiments.
To determine factors that predispose or protect healthcare workers from severe acute respiratory syndrome (SARS), we conducted a retrospective cohort study among 43 nurses who worked in two Toronto critical care units with SARS patients. Eight of 32 nurses who entered a SARS patient's room were infected. The probability of SARS infection was 6% per shift worked. Assisting during intubation, suctioning before intubation, and manipulating the oxygen mask were high-risk activities. Consistently wearing a mask (either surgical or particulate respirator type N95) while caring for a SARS patient was protective for the nurses, and consistent use of the N95 mask was more protective than not wearing a mask. Risk was reduced by consistent use of a surgical mask, but not significantly. Risk was lower with consistent use of a N95 mask than with consistent use of a surgical mask. We conclude that activities related to intubation increase SARS risk and use of a mask (particularly a N95 mask) is protective.
The military is interested in finding a hemostatic dressing that is effective in controlling hemorrhage from combat wounds, relatively inexpensive, and easy to transport. The fibrin dressing has existed for decades, but the military has been reluctant to use the dressing because it is not Food and Drug Administration approved, fairly expensive, and difficult to apply on certain wounds. Newer dressings such as the microporous polysaccharide hemosphere (TraumaDEX), mineral zeolite (QuikClot), poly-N-acetylglucosamine (HemCon), and microporous hydrogel-forming polyacrylamide (BioHemostat) dressings have addressed these deficiencies in that they are relatively inexpensive, easy to transport, and easy to apply. However, the effectiveness of these new dressings on wounds sustained in combat is still questionable according to studies and anecdotal reports from Operation Iraqi Freedom. More research is needed to draw definite conclusions about the effectiveness of these dressings in a combat setting.
BACKGROUND: Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. METHODS: SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. RESULTS: The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. CONCLUSIONS: SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation.
The locations of visual objects and events in the world are represented in a number of different coordinate frameworks. For example, a visual transient is known to attract (exogenous) attention and facilitate performance within an egocentric framework. However, when attention is allocated voluntarily to a particular visual feature (ie endogenous attention), the location of that feature appears to be variously encoded either within an allocentric framework or in a spatially invariant manner. In three experiments we investigated the importance of location for the allocation of endogenous attention and whether egocentric and/or allocentric spatial frameworks are involved. Primes and targets were presented in four conditions designed to vary systematically their spatial relationships in egocentric and allocentric coordinates. A reliable effect of egocentric priming was found in all three experiments, which suggests that endogenous shifts of attention towards targets defined by a particular feature operate in an egocentric representation of visual space. In addition, allocentric priming was also found for targets primed by their colour or shape. This suggests that attending to targets primed by nonspatial attributes results in facilitation that is localised in more than one coordinate frame of spatial reference.
'Preattentive' vision is typically considered to include several low-level processes, including the perception of depth from binocular disparity and motion parallax. However, doubt was cast on this model when it was shown that a secondary attentional task can modulate the motion aftereffect (Chaudhuri, 1990 Nature 344 60-62). Here we investigate whether attention can also affect the depth aftereffect (Blakemore and Julesz, 1971 Science 171 286-288). Subjects adapted to stationary or moving random-dot patterns segmented into depth planes while attention was manipulated with a secondary task (character processing at parametrically varied rates). We found that the duration of the depth aftereffect can be affected by attentional manipulations, and both its duration and that of the motion aftereffect varied with the difficulty of the secondary task. The results are discussed in the context of dynamic feedback models of vision, and support the penetrability of low-level sensory processes by attentional mechanisms.
Performance of a wide range of simple visual tasks improves with practice. Here we ask whether such learning occurs for the fundamental visual task of luminance contrast detection. In two experiments we find that contrast sensitivity increases following extensive practice at detecting briefly presented sinusoidal luminance gratings and that learning is maintained after six months. Learning is spatial frequency tuned, specific to retinal location and can be specific to one eye, but is not selective for orientation. The selectivity of learning implies that it is based on plasticity in early visual, as opposed to central cognitive, processing mechanisms.
The Ebbinghaus illusion has traditionally been considered as either a sensory or a cognitive illusion, or some combination of these two. Cognitive contrast explanations take support from the way the illusion varies with the degree of shape similarity between the test and inducing elements; we show, however, that contour interaction explanations may account for this result too. We therefore tested these alternative theories by measuring the illusion with different test shapes as well as different inducer shapes, in all combinations. We found that for angular or hexagonal test shapes there is no similarity effect, and for some shape combinations there is no significant illusion, in contradiction to both of the traditional hypotheses. Instead, we suggest that an integrated model of visual processing is needed to account for the illusion.
Reported outcomes after child brain injury are variable, creating difficulties for predicting individual needs and service provision. In the UK, prognosis for children surviving early brain injury is characteristically optimistic. Communication between hospital and community agencies is poor. There is little regard for facilitating optimal recovery, and even less for supporting the child's further learning and development. The problem persists in spite of accumulating clinical and scientific evidence over the last 100 years. The consequences are wide-ranging and detrimental to the physical and mental health of the child and family. The disabled child becomes a progressively handicapped adult. Long-term outcome in old age may be unnecessarily compromised. The social and economic costs will be correspondingly and unnecessarily high.