Search

Background: There is no universally accepted definition for surgical prehabilitation. The objectives of this scoping review were to (1) identify how surgical prehabilitation is defined across randomised controlled trials and (2) propose a common definition., Methods: The final search was conducted in February 2023 using MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and Cochrane. We included randomised controlled trials (RCTs) of unimodal or multimodal prehabilitation interventions (nutrition, exercise, and psychological support) lasting at least 7 days in adults undergoing elective surgery. Qualitative data were analysed using summative content analysis., Results: We identified 76 prehabilitation trials of patients undergoing abdominal (n=26, 34%), orthopaedic (n=20, 26%), thoracic (n=14, 18%), cardiac (n=7, 9%), spinal (n=4, 5%), and other (n=5, 7%) surgeries. Surgical prehabilitation was explicitly defined in more than half of these RCTs (n=42, 55%). Our findings consolidated the following definition: 'Prehabilitation is a process from diagnosis to surgery, consisting of one or more preoperative interventions of exercise, nutrition, psychological strategies and respiratory training, that aims to enhance functional capacity and physiological reserve to allow patients to withstand surgical stressors, improve postoperative outcomes, and facilitate recovery.', Conclusions: A common definition is the first step towards standardisation, which is needed to guide future high-quality research and advance the field of prehabilitation. The proposed definition should be further evaluated by international stakeholders to ensure that it is comprehensive and globally accepted., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Heterogeneity of reported outcomes can impact the certainty of evidence for prehabilitation. The objective of this scoping review was to systematically map outcomes and assessment tools used in trials of surgical prehabilitation., Methods: MEDLINE, EMBASE, PsychInfo, Web of Science, CINAHL, and Cochrane were searched in February 2023. Randomised controlled trials of unimodal or multimodal prehabilitation interventions (nutrition, exercise, psychological support) lasting at least 7 days in adults undergoing elective surgery were included. Reported outcomes were classified according to the International Society for Pharmacoeconomics and Outcomes Research framework., Results: We included 76 trials, mostly focused on abdominal or orthopaedic surgeries. A total of 50 different outcomes were identified, measured using 184 outcome assessment tools. Observer-reported outcomes were collected in 86% of trials (n=65), with hospital length of stay being most common. Performance outcomes were reported in 80% of trials (n=61), most commonly as exercise capacity assessed by cardiopulmonary exercise testing. Clinician-reported outcomes were included in 78% (n=59) of trials and most frequently included postoperative complications with Clavien-Dindo classification. Patient-reported outcomes were reported in 76% (n=58) of trials, with health-related quality of life using the 36- or 12-Item Short Form Survey being most prevalent. Biomarker outcomes were reported in 16% of trials (n=12) most commonly using inflammatory markers assessed with C-reactive protein., Conclusions: There is substantial heterogeneity in the reporting of outcomes and assessment tools across surgical prehabilitation trials. Identification of meaningful outcomes, and agreement on appropriate assessment tools, could inform the development of a prehabilitation core outcomes set to harmonise outcome reporting and facilitate meta-analyses., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Childhood maltreatment is a risk factor for the development of post-traumatic stress disorders and psychosis. However, the association between post-traumatic stress disorder (PTSD), including complex PTSD, and psychotic symptoms is unknown. We investigated whether the presence of PTSD and complex PTSD was associated with psychotic symptom severity within survivors of developmental trauma., Methods: As part of the Investigating Mechanisms underlying Psychosis Associated with Childhood Trauma (IMPACT) study, from Aug 20, 2020, to Jan 24, 2021, and from Sept 9, 2022, to Feb 21, 2023, using study advertisement on online platforms we recruited adult (≥18 years) participants who had experienced developmental trauma without a psychiatric diagnosis in the UK and South Korea. We measured whether participants met diagnostic thresholds for PTSD and complex PTSD using the self-reported International Trauma Questionnaire, and psychotic symptoms using the self-reported Community Assessment of Psychic Experiences. We used linear regression, adjusting for sociodemographic variables such as age, sex, ethnicity, educational attainment, and socioeconomic status, to examine whether there was an association between PTSD and complex PTSD and psychotic symptoms. The study is registered in the UK (University College London Research Ethics Committee [14317/001] and the National Health Service Research Ethics Committee [22/YH/0096]) and South Korea (Institutional Review Board of Seoul National University Bundang Hospital [B-2011-648-306]), and is ongoing., Findings: Of the 2675 participants who took part in the study, 1273 had experienced developmental trauma and were included in the study in the UK (n=475) and South Korea (n=798), comprising 422 (33%) men and 851 (67%) women with a mean age of 26·9 years (SD 6, range 18-40), mostly of White British (n=328) or South Korean (n=798) ethnicity. We found no significant association between PTSD and psychotic symptom severity (total severity β=-2·40 [SE 3·28], p=0·47), compared with participants who did not meet PTSD or complex PTSD caseness. We found a significant relationship between complex PTSD and psychotic symptom severity (total severity β=22·62 [SE 1·65], p<0·0001), including for positive (β=12·07 [SE 0·99], p<0·0001) and negative symptoms (β=10·5 [SE 0·95], p<0·0001), compared with participants who did not meet PTSD or complex PTSD caseness., Interpretation: Health systems must assess individuals with previous developmental trauma for complex PTSD and treat those affected. These individuals should also be assessed for psychotic symptoms, and if necessary, preventative measures should be taken to reduce risk of conversion. Further work should assess whether treating complex PTSD modifies the risk of conversion to psychosis., Funding: UKRI Future Leaders Fellowship, British Medical Association Margaret Temple Award for Schizophrenia Research, and the National Research Foundation of Korea-Korea Government., Competing Interests: Declaration of interests EK has participated in advisory or speaker meetings organized by Janssen Korea, Otsuka Korea, Boehringer Ingelheim, and Bukwang Pharm Company and was the principal investigator of research projects from Otsuka company. All other authors declare no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Alzheimer's disease (AD) is characterised by episodic memory impairment, but people also experience memory distortions, including false memories, which can impact on safety and reduce functioning. Understanding the neural networks that underpin false memories could help to predict the need for intervention and guide development of cognitive strategies to reduce memory errors. However, there is a relative absence of research into how the neuropathology of AD contributes to false memory generation. This paper systematically reviews the methodology and outcomes of studies investigating the neuroimaging correlates of false memory in AD. Four studies using structural imaging and three studies using functional imaging were identified. Studies were heterogenous in methodology and received mostly 'weak' quality assessment ratings. Combined, and consistent with neuroimaging findings in non-AD populations, results from identified studies provide preliminary support for the hypothesis that medial temporal lobe and prefrontal cortex dysfunction may lead to generation of false memories in AD. However, the small number of studies and significant heterogeneity within them means further study is necessary to assess replicability of results., Competing Interests: Declaration of Competing Interest None to report., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Differences in structural white and gray matter in survivors of traumatic experiences have been related to the development and maintenance of Posttraumatic Stress Disorder (PTSD). However, there are very few studies on diffusion tensor imaging and region based morphometry comparing patients with PTSD to two control groups, namely healthy individuals with or without trauma experience. It is also unknown if differences in white and gray matter are associated. In this cross-sectional study, we examined white- and gray matter differences between 44 patients with PTSD, 49 trauma control and 61 healthy control subjects. We compared the groups applying Tract-Based Spatial Statistics (TBSS) for a whole brain white matter analysis as well as region of interest analyses for white and gray matter. First, trauma control subjects in comparison to patients with PTSD and healthy control subjects showed significantly a) higher fractional anisotropy (FA) in the left corticospinal tract and inferior fronto-occipital fasciculus than patients with PTSD, b) higher FA in the left inferior fronto-occipital-, right inferior- and right superior longitudinal fasciculi, c) higher FA in the forceps minor and d) higher volume of the left and right anterior insulae. Second, we show significant correlations between the FA in the forceps minor and the gray matter volume in the left and right anterior insulae. Third, the mean FA value in the forceps minor correlated negatively with symptom severity of PTSD and depression as well as trait anxiety, whereas the gray matter volume in the left anterior insula correlated negatively with symptom severity in PTSD. Our findings underline the importance of brain structures critically involved in emotion regulation and salience mapping. While previous studies associated these processes primarily to functional and task-based differences in brain activity, we argue that morphometrical white and gray matter differences could serve as targets in neuroscientifically-informed prevention and treatment interventions for PTSD., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Implicit social biases play a critical role in shaping our attitudes towards other people. Such biases are thought to arise, in part, from a comparison between features of one's own self-image and those of another agent, a process known as 'bodily resonance'. Recent data have demonstrated that implicit bias can be remarkably plastic, being modulated by brief immersive virtual reality experiences that place participants in a virtual body with features of an out-group member. Here, we provide a mechanistic account of bodily resonance and implicit bias in terms of a putative self-image network that encodes associations between different features of an agent. When subsequently perceiving another agent, the output of this self-image network is proportional to the overlap between their respective features, providing an index of bodily resonance. By combining the self-image network with a drift diffusion model of decision making, we simulate performance on the implicit association test (IAT) and show that the model captures the ubiquitous implicit bias towards in-group members. We subsequently demonstrate that this implicit bias can be modulated by a simulated illusory body ownership experience, consistent with empirical data; and that the magnitude and plasticity of implicit bias correlates with self-esteem. Hence, we provide a simple mechanistic account of bodily resonance and implicit bias which could contribute to the development of interventions for reducing the negative evaluation of social out-groups., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Mercury (Hg) exposure was evaluated in bald eagles (Haliaeetus leucocephalus) in the lower Penobscot River watershed (PRW) in Maine to assess whether Hg discharges from a chlor-alkali plant (HoltraChem) influenced Hg concentrations in nestling tissues. Mean Hg concentrations in nestling blood and breast feathers sampled in marine and estuarine areas potentially contaminated with Hg from HoltraChem (the potential Hg impact zone) were significantly greater than those from reference sites spanning the Maine coast. To place Hg exposure in the potential Hg impact zone into a broader context, Hg exposure in bald eagle nestlings from four habitat types in the PRW was assessed. Mercury concentrations varied significantly across habitat types within the PRW, generally following the pattern: marine=estuarine

White matter plasticity occurs throughout life due to learning and can be a protective factor against as well as a vulnerability factor for the development of mental disorders. In this systematic review we summarize findings on structural white matter changes in children and adults with posttraumatic stress disorder (PTSD) and relate them to theoretical accounts of the pathophysiology of PTSD with a focus on the disturbed processing of contexts and associated problems in emotional and cognitive processing and PTSD symptomatology. We particularly examine studies reporting fractional anisotropy (FA) measured with diffusion tensor imaging (DTI). We further subdivided the studies in adult-onset PTSD with traumatic experience in adulthood, adult-onset PTSD with traumatic experience in childhood and children with PTSD. We included 30 studies comprising almost 1700 participants with 450 adults and 300 children suffering from PTSD. Our systematic review showed that for children with PTSD and adult-onset PTSD with childhood trauma, a decrease in FA in the corpus collosum, most prominently in the anterior and posterior midbody, the isthmus and splenium were reported. For adult-onset PTSD with traumatic experience in adulthood, changes in FA in the anterior and posterior part of the cingulum, the superior longitudinal fasciculus and frontal regions were found. Using GingerAle, we also performed a coordinate-based meta-analysis of 14 studies of adult-onset PTSD with traumatic experience in adulthood and did not find any significant clusters. Our results suggest that changes in white matter microstructure vary depending on traumatic experience and are associated with changes in brain circuits related to the processing of contexts. Finally, we present methodological considerations for future studies.

When remembering the past, we typically recall 'events' that are bounded in time and space. However, as we navigate our environment our senses receive a continuous stream of information. How do we create discrete long-term episodic memories from continuous input? Although previous research has provided evidence for a role of spatial boundaries in the online segmentation of our sensory experience within working memory, it is not known how this segmentation contributes to subsequent long-term episodic memory. Here we show that the presence of a spatial boundary at encoding (a doorway between two rooms) impairs participants' later ability to remember the order that objects were presented in. A sequence of two objects presented in the same room in a virtual reality environment is more accurately remembered than a sequence of two objects presented in adjoining rooms. The results are captured by a simple model in which items are associated to a context representation that changes gradually over time, and changes more rapidly when crossing a spatial boundary. We therefore provide the first evidence that the structure of long-term episodic memory is shaped by the presence of a spatial boundary and provide constraints on the nature of the interaction between working memory and long-term memory., (Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting., Methods: For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238., Findings: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain)., Interpretation: Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic., Funding: UK National Institute for Health Research Health Technology Assessment Programme., (Copyright © 2015 Pickard et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited., Methods: Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task., Results: Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory., Conclusions: These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Three recent studies (Pearson, 2012; Pearson, Ross, & Webster, 2012) purported to test the revised dual representation theory of posttraumatic stress disorder (Brewin, Gregory, Lipton, & Burgess, 2010) by manipulating the amount of additional information accompanying traumatic stimulus materials and assessing the effect on subsequent intrusive memories. Here we point out that these studies involve a misunderstanding of the meaning of "contextual" within the theory, such that the manipulation would be unlikely to have had the intended effect and the results are ambiguous with respect to the theory. Past and future experimental tests of the theory are discussed., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A dual representation model of intrusive memory proposes that personally experienced events give rise to two types of representation: an image-based, egocentric representation based on sensory-perceptual features; and a more abstract, allocentric representation that incorporates spatiotemporal context. The model proposes that intrusions reflect involuntary reactivation of egocentric representations in the absence of a corresponding allocentric representation. We tested the model by investigating the effect of alcohol on intrusive memories and, concurrently, on egocentric and allocentric spatial memory., Methods: With a double-blind independent group design participants were administered alcohol (.4 or .8 g/kg) or placebo. A virtual environment was used to present objects and test recognition memory from the same viewpoint as presentation (tapping egocentric memory) or a shifted viewpoint (tapping allocentric memory). Participants were also exposed to a trauma video and required to detail intrusive memories for 7 days, after which explicit memory was assessed., Results: There was a selective impairment of shifted-view recognition after the low dose of alcohol, whereas the high dose induced a global impairment in same-view and shifted-view conditions. Alcohol showed a dose-dependent inverted "U"-shaped effect on intrusions, with only the low dose increasing the number of intrusions, replicating previous work. When same-view recognition was intact, decrements in shifted-view recognition were associated with increases in intrusions., Conclusions: The differential effect of alcohol on intrusive memories and on same/shifted-view recognition support a dual representation model in which intrusions might reflect an imbalance between two types of memory representation. These findings highlight important clinical implications, given alcohol's involvement in real-life trauma., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

In previous studies, children disoriented in small enclosures used room shape, but not wall colours, to find hidden objects. Their reorientation was said to depend solely on a "geometric module" informationally encapsulated with respect to colour. We argue that previous studies did not fully evaluate children's use of colour owing to a bias in the enclosures' design. In this study, disoriented 18-24 month olds searched for toys in small square enclosures with two blue and two white walls. Children successfully reoriented using wall colour. This shows that they can make location judgments based on the left/right sense of the colours of adjoining landmarks. Performance was no different when symmetric colourful shapes were added to walls, but improved with asymmetric shapes which could be used without left/right judgments. The relatively poor use of colour in previous studies may be explained partly by a bias in their design, and partly by children's limited ability to discriminate the left/right sense of nongeometric features.

We studied the development of spatial frames of reference in children aged 3-6 years, who retrieved hidden toys from an array of identical containers bordered by landmarks under four conditions. By moving the child and/or the array between presentation and test, we varied the consistency of the hidden toy with (i) the body, and (ii) the testing room. The toy's position always remained consistent with (iii) the array and bordering landmarks. We found separate, additive performance advantages for consistency with body and room. These effects were already present at 3 years. A striking finding was that the room effect, which implies allocentric representations of the room and/or egocentric representations updated by self-motion, was much stronger in the youngest children than the body effect, which implies purely egocentric representations. Children as young as 3 years therefore had, and greatly favoured, spatial representations that were not purely egocentric. Viewpoint-independent recall based only on the array and bordering landmarks emerged at 5 years. There was no evidence that this later-developing ability, which implies object-referenced (intrinsic) representations, depended on verbal encodings. These findings indicate that core components of adult spatial competence, including parallel egocentric and nonegocentric representations of space, are present as early as 3 years. These are supplemented by later-developing object-referenced representations.

Polychlorinated biphenyls (PCBs) were measured in marine sediments and the coastal food web in Saglek Bay, Labrador, to investigate the influence of a local PCB source. Saglek Bay has been the site of a military radar station since the late 1950s and there was PCB-contaminated soil at a beach prior to cleanup in 1997-1999. PCB concentrations in marine sediments during 1997-1999 ranged from 0.24 to 62000 ng/g (dry weight) and decreased exponentially with distance from the contaminated beach. Given this gradient, spatial trends of PCBs in the food web were examined over four zones, according to distance from the contaminated beach: within 1.5 km--zone one, 1.5-4.5 km--zone two, 4.5-7.5 km--zone three, and greater than 7.5 km--zone four. PCB concentrations in a bottom-feeding fish (shorthorn sculpin, Myoxocephalus scorpius), decreased significantly from zone one to zone two, three, four, and distant Labrador reference sites. PCB concentrations in the eggs of a diving seabird (black guillemot, Cepphus grylle) were as high as 48000 ng/g during 1997-1999 and average concentrations in zones one and two were 84 and 13 times higher than in zone four. Marine invertebrates closely reflected the concentrations of PCBs in the associated sediment. In contrast to the benthic-based food web, anadromous arctic char (Salvelinus alpinus) showed no evidence of PCB accumulation from the contaminated sediments. Relatively high PCB concentrations were discovered in some great black-backed gulls (Larus marinus) and ringed seals (Phoca hispida) but appear to relate more to their high trophic level than sampling location. Those species that fed on or near the seabed and had limited foraging ranges were strongly influenced by the local contamination. Total PCB concentrations in the benthic-based food web were significantly higher than background levels for a distance of at least 7.5 km from the contaminated beach. This area is small in the context of widely distributed contamination from long-range transport but the area's high concentrations are comparable to levels associated with adverse effects elsewhere. Our findings should be useful to better assess the environmental impacts of PCB contamination at other coastal sites in the Arctic.

Anthropogenic contaminants have been a concern in the Canadian arctic for over 30 years due to relatively high concentrations of bioaccumulating and biomagnifying organochlorine contaminants (OCs) and toxic metals found in some arctic biota and humans. However, few studies have addressed the potential effects of these contaminants in Canadian arctic wildlife. Prior to 1997, biological effects data were minimal and insufficient at any level of biological organization. The present review summarizes recent studies on biological effects related to contaminant exposure, and compares new tissue concentration data to threshold effects levels. Weak relationships between cadmium, mercury and selenium burdens and health biomarkers in common eider ducks (Somateria mollissima borealis) in Nunavut were found but it was concluded that metals were not influencing the health of these birds. Black guillemots (Cepphus grylle) examined near PCB-contaminated Saglek Bay, Labrador, had enlarged livers, elevated EROD and liver lipid levels and reduced retinol (vitamin A) and retinyl palmitate levels, which correlated to PCB levels in the birds. Circulating levels of thyroid hormones in polar bears (Ursus maritimus) were correlated to PCB and HO-PCB plasma concentrations, but the impact at the population level is unknown. High PCB and organochlorine pesticide concentrations were found to be strongly associated with impaired humoral and cell-mediated immune responses in polar bears, implying an increased infection risk that could impact the population. In beluga whale (Delphinapterus leucas), cytochromes P450 (phase I) and conjugating (phase II) enzymes have been extensively profiled (immunochemically and catalytically) in liver, demonstrating the importance of contaminants in relation to enzyme induction, metabolism and potential contaminant bioactivation and fate. Concentrations of OCs and metals in arctic terrestrial wildlife, fish and seabirds are generally below effects thresholds, with the possible exception of PCBs in burbot (Lota lota) in some Yukon lakes, Greenland shark (Somniosus microcephalus), glaucous and great black-backed gulls (Larus hyperboreus and L. marinus), and TEQs of dioxin-like chemicals in seabird eggs. PCB and DDT concentrations in several arctic marine mammal species exceed effects thresholds, although evidence of stress in these populations is lacking. There is little evidence that contaminants are having widespread effects on the health of Canadian arctic organisms, with the possible exception of polar bears. However, further research and better understanding of organohalogen exposure in arctic biota is needed considering factors such as tissue levels that exceed effects thresholds, exposure to "new" organohalogen contaminants of concern, contaminated regions, and climate change.

Subjects in a darkroom saw an array of five phosphorescent objects on a circular table and, after a short delay, indicated which object had been moved. During the delay the subject, the table or a phosphorescent landmark external to the array was moved (a rotation about the centre of the table) either alone or together. The subject then had to indicate which one of the five objects had been moved. A fully factorial design was used to detect the use of three types of representations of object location: (i) visual snapshots; (ii) egocentric representations updated by self-motion; and (iii) representations relative to the external cue. Improved performance was seen whenever the test array was oriented consistently with any of these stored representations. The influence of representations (i) and (ii) replicates previous work. The influence of representation (iii) is a novel finding which implies that allocentric representations play a role in spatial memory, even over short distances and times. The effect of the external cue was greater when initially experienced as stable. Females out-performed males except when the array was consistent with self-motion but not visual snapshots. These results enable a simple egocentric model of spatial memory to be extended to address large-scale navigation, including the effects of allocentric knowledge, landmark stability and gender.

Geometric alterations to the boundaries of a virtual environment were used to investigate the representations underlying human spatial memory. Subjects encountered a cue object in a simple rectangular enclosure, with distant landmarks for orientation. After a brief delay, during which they were removed from the arena, subjects were returned to it at a new location and orientation and asked to mark the place where the cue had been. On some trials the geometry (size, aspect ratio) of the arena was varied between presentation and testing. Responses tended to lie somewhere between a location that maintained fixed distances from nearby walls and a location that maintained fixed ratios of the distances between opposing walls. The former were more common after expansions and for cued locations nearer to the edge while the latter were more common after contractions and for locations nearer to the center. The spatial distributions of responses predicted by various simple geometric models were compared to the data. The best fitting model was one derived from the response properties of 'place cells' in the rat hippocampus, which matches the 'proximities' 1/(d+c) of the cue to the four walls of the arena, where d is the distance to a wall and c is a global constant. Subjects also tended to adopt the same orientation at presentation and testing, although this was not due to using a view matching strategy, which could be ruled out in 50% of responses. Disoriented responses were most often seen where the cued location was near the center of the arena or where the long axis of a rectangular arena was changed between presentation and testing, suggesting that the geometry of the arena acts as a weak cue to orientation. Overall, the results suggest a process of visual landmark matching to determine orientation, combined with an abstract representation of the proximity of the cued location to the walls of the arena consistent with the neural representation of location in the hippocampus.

The vanilloid receptor type 1 (VR1) is a novel membrane receptor activated by heat or chemical ligands conveying information about chemosensitive and thermosensitive pain. We have overexpressed and purified wild type VR1 (wtVR1) as well as several mutant forms using the yeast strain Saccharomyces cerevisiae with the goal of obtaining sufficient protein for structural studies. To facilitate the rapid assaying of protein production and purification we used PCR to construct mutant VR1-green fluorescent protein fusion genes. All recombinant inserts were engineered with 12 HIS tags on the C-terminus for metal affinity column purification. The yield of purified protein from 16L fermentation was about 1mg following a single-step purification procedure. By taking advantage of the calcium permeability of VR1 we measured changes in [Ca(2+)](i) in capsaicin-stimulated fura-2 loaded yeast cells expressing VR1.

Psychophysiologic studies use air puff as an aversive stimulus to document abnormal fear conditioning in children of parents with anxiety disorders. This study used functional magnetic resonance imaging (fMRI) to examine changes in amygdala activity during air-puff conditioning among adults. Blood oxygen level-dependent (BOLD) signal was monitored in seven adults during 16 alternating presentations of two different colored lights (CS+ vs. CS-), one of which was consistently paired with an aversive air puff. A region-of-interest analysis demonstrated differential change in BOLD signal in the right but not left amygdala across CS+ versus CS- viewing. The amygdala is engaged by pairing of a light with an air puff. Given that prior studies relate air-puff conditioning to risk for anxiety in children, these methods may provide an avenue for directly studying the developmental neurobiology of fear conditioning.

Urethral melanoma is very rare and pathological diagnosis is important. The prognosis remains poor irrespective of the treatment modality. Rare cases of long-term survival have been reported, one of them following conservative management. An initial attempt at conservative resection is worth considering to offer a better quality of life to the patient for as long as possible. We describe a technique of organ-sparing resection in the management of urethral melanoma along with the follow-up protocol that we adapted., (Copyright 2001 The British Association of Plastic Surgeons.)

Women have played an active role as physicians and surgeons from earliest history. In the United States, medical education for women began in 1847 and flourished as medical schools proliferated to meet the growing population demand. The Flexner Report in 1910 resulted in about half the medical schools in the U.S. closing; many of them had admitted women. The number of women medical students increased beginning in the 1970s, until now, 43% of medical school graduates are women. The number of women residents has increased concomitantly from 22% in 1980 to 36% in 1997. Women residents in surgical training programs lag behind. Thoracic surgery has the lowest percent of women residents, at 5%. Unless an attempt is made to actively recruit women, thoracic surgery training programs are in danger of drawing from an increasingly smaller portion of medical school graduates.

Extradural abscess is a rare but recognized complication of extradural anaesthesia. Previous reports have been associated with a short time interval between extradural catheterization and presentation. We report a patient with rheumatoid arthritis, receiving steroid therapy, in whom an extradural abscess did not present until 23 days after the insertion of a thoracic extradural catheter to provide postoperative analgesia.

Very-low-calorie diets (VLCDs) provide a rapid decrease in total body weight, but limited data are available regarding the extent of fat loss and whether body fat distribution is altered. The purpose of this study was to investigate body composition, body fat distribution, and resting metabolic rate in obese men and women and to compare bioelectrical impedance analysis (BIA) with hydrodensitometry before and after 12 weeks of treatment in a VLCD program. Body composition was assessed by hydrodensitometry and BIA. Circumference measures were used to determine waist:hip and waist:thigh ratios. Seventeen subjects lost a mean of 24.2 kg. A mean of 75.5% of the weight loss was adipose tissue as measured by hydrodensitometry. BIA underestimated body fat percentage compared with hydrodensitometry in this obese population. Waist:hip and waist:thigh ratios showed a small but significant decrease, implying a decreased risk for diabetes and cardiovascular disease after weight loss. Resting metabolic rate, as measured by oxygen consumption, dropped 23.8% during the 12 weeks of the VLCD. The findings indicate that a VLCD can provide a rapid weight loss of more than 75% fat and a concomitant decrease in waist:hip and waist:thigh ratios. The findings also indicate that BIA may not be a useful tool in assessing fat loss in obese subjects. Finally, it appears that the decrease in resting metabolic rate that occurs during treatment with VLCD does not correlate with changes in lean body mass.

Quantitative HPLC analysis of saline-soluble proteins obtained from human coronary and thoracic aorta plaque and from whole internal mammary artery were performed. Protein extracts were characterized by anion exchange and reverse-phase HPLC and the integrated chromatographs revealed significant differences in both peak retention times and areas for protein species from coronary artery compared to thoracic aorta artery plaque. Coronary artery plaque proteins possessed a high degree of cationic charge and polarity compared to those present in thoracic aorta plaque and normal mammary artery. This suggests that specific protein markers may be expressed in plaque of different anatomical origin, and that the processing of protein may be distinct to plaque sites. In contrast, characterization of molecular weight by gel electrophoresis resolved no major differences between plaque types. These findings indicate that proteins in human plaque lesions of different anatomical origin can be resolved by HPLC methodology and that they exhibit different charge and polarity. Such an HPLC approach may prove useful in the quantitative identification and ultimate isolation of specific protein markers present in plaque during atherogenesis, and in the study of mechanisms of protein involvement in plaque formation.