bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopaminergic Modulation of Working Memory for Spatial but Not Object Cues in Normal Humans
Authors: Luciana Monica , Collins Paul F.
Published: February 2008

It appears that functionally segregated visual pathways exist in the primate brain for the processing of visuospatial versus nonspatial information. Functional segregation has been demonstrated for the early associative processing of sensory information but may also exist at higher levels of cognitive analysis. Namely, connections between the dorsal visual system and dorsolateral prefrontal cortex (PFC) appear to mediate spatial working memory, which is modulated by dopamine receptor fields in the principal sulcal region of the PFC. It is speculated that nonspatial working memory may be modulated within connections between ventral visual processing regions and the inferior convexity of the PFC. Whether dopamine facilitates nonspatial memory through connections between the ventral visual system and ventral PFC has not been examined. In this study, normal humans completed spatial and nonspatial working memory tasks under pharmacological challenges with a dopamine receptor agonist (bromocriptine) and antagonist (haloperidol) in a double-blind placebcxontrolled repeated measures design. Findings indicated facilitation of spatial delayed working memory functions by bromocriptine and impairment of spatial working memory functions by haloperidol. Neither drug was effective in manipulating nonspatial memory performance. Control tasks were included to measure drug effects on basic sensorimotor and attentional processes. Findings suggest that separate processing mechanisms for remembering “What” versus “Where” an object is may exist at structural, but also neurochemical, levels in the human brain.
Mental Rotation Studied by Functional Magnetic Resonance Imaging at High Field (4 Tesla): Performance and Cortical Activation
Authors: Tagaris Georgios A. , Kim Seong-Gi , Strupp John P. , Andersen Peter , Uğurbil Kamil , Georgopoulos Apostolos P.
Published: February 2008

We studied the performance and cortical activation patterns during a mental rotation task (Shepard & Metzler, 1971) using functional magnetic resonance imaging (fMlU) at high field (4 Tesla). Twenty-four human subjects were imaged (fMRI group), whereas six additional subjects performed the task without being imaged (control group). All subjects were shown pairs of perspective drawings of 31, objects and asked to judge whether they were the same or mirror images. The measures of performance examined included (1) the percentage of errors, (2) the speed of performance, calculated as the inverse of the average response time, and (3) the rate of rotation for those object pairs correctly identified as “same.” We found the following: (1) Subjects in the fMRI group performed well outside and inside the magnet, and, in the latter case, before and during data acquisition. Moreover, performance over time improved in the same manner as in the control group. These findings indicate that exposure to high magnetic fields does not impair performance in mental rotation. (2) Functional activation data were analyzed from 16 subjects of the fMRI goup. Several cortical areas were activated during task performance. The relations between the measures of performance above and the magnitude of activation of specific cortical areas were investigated by anatomically demarcating these areas of interest and calculating a normalized activation for each one of them. (3) We used the multivariate technique of hierarchical tree modeling to determine functional clustering among areas of interest and performance measures. Two main branches were distinguished: One comprised areas in the right hemisphere and the extrastriate and superior parietal lobules bilaterally, whereas the other comprised areas of the left hemisphere and the frontal pole bilaterally; all three performance measures above clustered with the former branch. Specifically, performance outcome (“percentage of errors”) clustered with the parieto-occipital subcluster, whereas both the speed of performance and the rate of mental rotation clustered with the right precentral gyms. We conclude that the mental rotation paradigm used involves the cooperative interaction of functional groups of cortical areas of which some are probably more specifically associated with performance, whereas others may serve a more general function within the task constraints.
The Neural Substrate for Concrete, Abstract, and Emotional Word Lexica A Positron Emission Tomography Study
Authors: Beauregard Mario , Chertkow H. , Bub D. , Murtha S. , Dixon R. , Evans A.
Published: February 2008

Viewing of single words produces a cognitively complex mental state in which anticipation, emotional responses, visual perceptual analysis, and activation of orthographic representations are all occurring. Previous PET studies have produced conflicting results, perhaps due to the conflation of these separate processes or the presence of subtle differences in stimulus material and methodology. A PET study of 10 normal individuals was carried out using the bolus H2 15O intravenous injection technique to examine components of processing of passively viewed words. Subjects viewed blocks of random-letter strings or abstract, concrete, or emotional words (words with positive or negative emotional salience). Baseline conditions were either passive viewing of plus signs or an anticipatory state (viewing plus signs after being warned to expect words or random letters to appear imminently). All words (and to a lesser extent the random letters) produced robust activation of cerebral blood flow in the left posterior temporal lobe, in addition to bilateral occipital activation. Furthermore, emotional words produced activation in orbital and midline frontal structures. Further activation in the left orbital frontal gyrus, the left inferior temporal gyrus, the left caudate nucleus, the anterior cingulate, and the cerebellum could be ascribed to the anticipatory state. This pattern of activity suggests that the occipital regions are recruited for visual-perceptual analysis of words, and the left temporal lobe represents the neural substrate for the orthographic lexicon. In addition, emotionally relevant material produces further processing in limbic brain structures of the frontal lobes. Detailed analysis of the task therefore substantially clarifies the neuroanatomic basis of single-word processing.
What Is Special about Face Recognition? Nineteen Experiments on a Person with Visual Object Agnosia and Dyslexia but Normal Face Recognition
Authors: Moscovitch Morris , Winocur Gordon , Behrmann Marlene
Published: February 2008

In order to study face recognition in relative isolation from visual processes that may also contribute to object recognition and reading, we investigated CK, a man with normal face recognition but with object agnosia and dyslexia caused by a closed-head injury. We administered recognition tests of up right faces, of family resemblance, of age-transformed faces, of caricatures, of cartoons, of inverted faces, and of face features, of disguised faces, of perceptually degraded faces, of fractured faces, of faces parts, and of faces whose parts were made of objects. We compared CK's performance with that of at least 12 control participants. We found that CK performed as well as controls as long as the face was upright and retained the configurational integrity among the internal facial features, the eyes, nose, and mouth. This held regardless of whether the face was disguised or degraded and whether the face was represented as a photo, a caricature, a cartoon, or a face composed of objects. In the last case, CK perceived the face but, unlike controls, was rarely aware that it was composed of objects. When the face, or just the internal features, were inverted or when the configurational gestalt was broken by fracturing the face or misaligning the top and bottom halves, CK's performance suffered far more than that of controls. We conclude that face recognition normally depends on two systems: (1) a holistic, face-specific system that is dependent on orientationspecific coding of second-order relational features (internal), which is intact in CK and (2) a part-based object-recognition system, which is damaged in CK and which contributes to face recognition when the face stimulus does not satisfy the domain-specific conditions needed to activate the face system.
On the Different Processing of Wholes and Parts: A Psychophysiological Analysis
Authors: Han Shihui , Fan Silu , Chen Lin , Zhuo Yan
Published: February 2008

The global precedence hypothesis (Navon, 1977) assumes that the processing of the global level of a hierarchical pattern precedes that of the local level. To explore further the nature of global and local processing of compound stimuli, we recorded the event-related brain potentials (ERPs) associated with ident@ing the global and local levels of nonlinguistic compound stimuli in a selective attention task. Wile subjects' behavioral responses were similar to those observed by Navon (1977), the analyses of ERP data showed that identification of the local level elicited longer N2 and P3 peak latencies with enhanced N2 and decreased P3 amplitudes relative to the identification of the global level. The inconsistency between the global and local levels made N2 and P3 amplitudes more negative with longer peak latencies. This interference effect on N2 and P3 amplitude and P3 latency was stronger on the local level than on the global level. The modulation of N2 by the consistency of the global and local levels observed in this and the previous (Heinze, Muente, et al., 1994) study suggests that the interference effect may be mediated by the early perceptual processing. Moreover, we found that the amplitude of an early posterior P1 component was modulated by attention to the global and local levels, being larger to the local target than to the global one. This PI effect gives no support to the notion that the variation of attentional spotlight determines the global precedence effect.
Semantic Repetition Priming for Verbal and Pictorial Knowledge: A Functional MRI Study of Left Inferior Prefrontal Cortex
Authors: Wagner Anthony D. , Desmond John E. , Demb Jonathan B. , Glover Gary H. , Gabrieli John D. E.
Published: February 2008

Functional neuroimaging studies of single-word processing have demonstrated decreased activation in left inferior prefrontal cortex (LIPC) during repeated semantic processing relative to initial semantic processing. This item-specific memory effect occurs under implicit test instructions and represents word-toword semantic repetition priming. The present study examined the stimulus generality of LIPC function by measuring prefrontal cortical activation during repeated relative to initial semantic processing of words (word-to-word semantic repetition priming) and of pictures (picture-to-picture semantic repetition priming). For both words and pictures, LIPC activation decreased with repetition, suggesting that this area subserves semantic analysis of stimuli regardless of perceptual form. Decreased activation was greater in extent for words than for pictures. The LIPC area may act as a semantic executive system that mediates on-line retrieval of long-term conceptual knowledge necessary for guiding task performance.
Localization of Auditory Evoked Potentials Related to Selective Intermodal Attention
Authors: Dien Joseph , Tucker Don M. , Potts Geoff , Hartry-Speiser Ann
Published: February 2008

A long-standing question in attention research is the extent to which selection involves gates in the sensory stream and the extent to which they involve added secondary processes. Intermodal attention paradigms are useful for examining this issue since different modalities involve readily distinguished cortical regions. Evoked potential studies have identified an attention-related frontal negativity labeled the Nd in auditory attention studies. It has been suggested that it arises from modulation of the auditory cortex (compatible with gating mechanisms) or of the frontal cortex (compatible with secondary processes such as short-term memory buffers). Efforts to localize the Nd have been impaired by the finding that the Nd comprises multiple components. Some novel procedures utilizing principal components analysis, in conjunction with high-density 64-channel recordings, were used to address this issue. Results suggest that the major source of the early Nd (the portion of most interest) resides in the frontal cortex, supporting the secondary process view for this particular mechanism.
Coordinate Frame for Pattern Recognition in Unilateral Spatial Neglect
Authors: Pavlovskaya Marina , Glass Itzhak , Soroker Nachum , Blum Baruch , Groswasser Zeev
Published: February 2008

The present research examines the effect of spatial (object-centered) attentional constraints on pattern recognition. Four normal subjects and two right-hemisphere-damaged patients with left visual neglect participated in the study. Small, letterlike, prelearned patterns served as stimuli. Short exposure time prevented overt scanpaths during stimulus presentation. Attention was attracted to a central (midsagittal) hation point by precuing this location prior to each stimulus presentation. Minute (up to 1.5° of visual angle) rightward and leftward stimulus shifts caused attention to be allocated each time to a different location on the object space, while remaining in a fixed central position in viewercentered coordinates. The task was to decide which of several prelearned patterns was presented in each trial. In the normal subjects, best performance was achieved when the luminance centroid (LC; derived from the analysis of low-spatial frequencies in the object space) of each pattern coincided with the spatial position of the precue. In contrast, the patients with neglect showed optimal recognition performance when precuing attracted attention to locations within the object space, to the left of the LC. The normal performance suggests that the LC may serve as a center of gravity for attention allocation during pattern recognition. This point seems to be the target location where focal attention is normally directed, following a primary global analysis based on the low spatial frequencies. Thus, the LC of a simple pattern may serve as the origin point for an object-centered-coordiate-frame (OCCF), dividing it into right and left. This, in turn, serves to create a prototype description of the pattern, in its own coordinates, in memory, to be addressed during subsequent recognition tasks. The best match of the percept with the stored description may explain the observed advantage of allocating attention to the LC. The performance of the brain- damaged patients can be explained in terms of neglect operating in the OCCE
Glacier Changes and Regional Climate: A Mass and Energy Balance Approach*
Authors: Rupper Summer , Roe Gerard
Published: February 2008

The mass balance of a glacier is a complex consequence of the combination of atmospheric variables that control it. However, the understanding of past, present, and future glacier states is often predicated on very simplified representations of the mass balance–climate relationship. Here, a full surface energy and mass balance (SEMB) model is developed to explore the relationship between glacier equilibrium-line altitudes (ELAs) and climate at a regional scale. This model is applied to central Asia because of the diverse climate regimes and glacier history. The model captures the pattern in ELAs well; the seasonal cycle in energy balance terms are comparable to studies on individual glaciers in central Asia, and the proportionality factor relating melt to temperature is within the range of those reported for individual glaciers within the area. In regions where precipitation is low, ablation at the ELA is dominated by sublimation. Conversely, where precipitation is high, ablation at the ELA is dominated by melt and surface runoff. In turn, the sensitivity of the ELA to changes in climate is strongly tied to the dominant ablation process. In particular, ELAs in melt-dominated regions are most sensitive to interannual variability in air temperature, while ELAs in sublimation-dominated regions are most sensitive to interannual variability in precipitation. Glaciers in sublimation-dominated regions are acutely sensitive to even small changes in atmospheric variables. Finally, changes in clouds are shown to be important in all regions through their influence on the shortwave and longwave radiative fluxes, which dominate the surface energy balance at the ELA.
A Technique for Eliminating Water Returns from Lidar Beach Elevation Surveys
Authors: Yates Marissa L. , Guza R. T. , Gutierrez Roberto , Seymour Richard
Published: February 2008

Airborne light detecting and ranging (lidar) systems can survey hundreds of kilometers of shoreline with high spatial resolution (several elevation estimates per square meter). Sequential surveys yield spatial change maps of beach and dune sand levels. However, lidar data include elevations of the exposed, subaerial beach and, seaward of the waterline, the ocean surface. Here, a simple method is developed to find the waterline and eliminate returns from the ocean surface. A vertical elevation cutoff is used, with the waterline elevation (W) above the known tide level because of the superelevation from wave setup and runup. During each lidar pass, the elevation cutoff (W) is assumed proportional (C) to the offshore significant wave height Hs. Comparison of in situ and lidar surveys on a moderately sloped, dissipative California beach yields C ≈ 0.4, which is qualitatively consistent with existing observations of runup and setup. The calibrated method rejects ocean surface data, while retaining subaerial beach points more than 70 m seaward of the mean high waterline, which is often used as a conservative default waterline.
A Surface Wave Model for Coupling with Numerical Ocean Circulation Models
Authors: Mellor George L. , Donelan Mark A. , Oey Lie-Yauw
Published: February 2008

A surface wave model is developed with the intention of coupling it to three-dimensional ocean circulation models. The model is based on a paper by Mellor wherein depth-dependent coupling terms were derived. To be compatible with circulation models and to be numerically economical, this model is simplified compared to popular third-generation models. However, the model does support depth and current refraction, deep and shallow water, and proper coupling with depth-variable currents.

The model is demonstrated for several simple scenarios culminating in comparisons of model calculations with buoy data during Hurricane Katrina and with calculations from the model Simulating Waves Nearshore (SWAN); for these calculations, coupling with the ocean was not activated.
Thermodynamic Properties of Mesoscale Convective Systems Observed during BAMEX
Authors: Correia James , Arritt Raymond W.
Published: February 2008

Dropsonde observations from the Bow Echo and Mesoscale Convective Vortex Experiment (BAMEX) are used to document the spatiotemporal variability of temperature, moisture, and wind within mesoscale convective systems (MCSs). Onion-type sounding structures are found throughout the stratiform region of MCSs, but the temperature and moisture variability is large. Composite soundings were constructed and statistics of thermodynamic variability were generated within each subregion of the MCS. The calculated air vertical velocity helped identify subsaturated downdrafts. It was found that lapse rates within the cold pool varied markedly throughout the MCS. Layered wet-bulb potential temperature profiles seem to indicate that air within the lowest several kilometers comes from a variety of source regions. It was also found that lapse-rate transitions across the 0°C level were more common than isothermal, melting layers. The authors discuss the implications these findings have and how they can be used to validate future high-resolution numerical simulations of MCSs.
Shape based indexing for faster search of RNA family databases
Authors: Janssen Stefan , Reeder Jens , Giegerich Robert
Published: February 2008

Background

Most non-coding RNA families exert their function by means of a conserved, common secondary structure. The Rfam data base contains more than five hundred structurally annotated RNA families. Unfortunately, searching for new family members using covariance models (CMs) is very time consuming. Filtering approaches that use the sequence conservation to reduce the number of CM searches, are fast, but it is unknown to which sacrifice.

Results

We present a new filtering approach, which exploits the family specific secondary structure and significantly reduces the number of CM searches. The filter eliminates approximately 85% of the queries and discards only 2.6% true positives when evaluating Rfam against itself. First results also capture previously undetected non-coding RNAs in a recent human RNAz screen.

Conclusion

The RNA s hape i ndex f ilter (RNAsifter) is based on the following rationale: An RNA family is characterised by structure, much more succinctly than by sequence content. Structures of individual family members, which naturally have different length and sequence composition, may exhibit structural variation in detail, but overall, they have a common shape in a more abstract sense. Given a fixed release of the Rfam data base, we can compute these abstract shapes for all families. This is called a shape index. If a query sequence belongs to a certain family, it must be able to fold into the family shape with reasonable free energy. Therefore, rather than matching the query against all families in the data base, we can first (and quickly) compute its feasible shape(s), and use the shape index to access only those families where a good match is possible due to a common shape with the query.
PITX2 gain-of-function induced defects in mouse forelimb development
Authors: Holmberg Johan , Ingner Gorel , Johansson Curt , Leander Peter , Hjalt Tord A
Published: February 2008

Background

Limb development and patterning originate from a complex interplay between the skeletal elements, tendons, and muscles of the limb. One of the genes involved in patterning of limb muscles is the homeobox transcription factor Pitx2 but its role in forelimb development is uncharacterized. Pitx2 is expressed in the majority of premature presumptive forelimb musculature at embryonic day 12.5 and then maintained throughout embryogenesis to adult skeletal muscle.

Results

To further study the role of Pitx2 in forelimb development we have generated transgenic mice that exhibit a pulse of PITX2 over-expression at embryonic day 13.5 and 14.5 in the developing forelimb mesenchyme. These mice exhibit a distal misplacement of the biceps brachii insertion during embryogenesis, which twists the forelimb musculature resulting in severe skeletal malformations. The skeletal malformations have some similarities to the forearm deformities present in Leri-Weill dyschondrosteosis.

Conclusion

Taken together, the tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development and may also shed light on the interaction between the skeletal elements and muscles of the limb during embryogenesis.
Unusual accelerated rate of deletions and insertions in toxin genes in the venom glands of the pygmy copperhead (Austrelaps labialis) from kangaroo island
Authors: Doley Robin , Tram Nguyen Ngoc Bao , Reza Md Abu , Kini R Manjunatha
Published: February 2008

Background

Toxin profiling helps in cataloguing the toxin present in the venom as well as in searching for novel toxins. The former helps in understanding potential pharmacological profile of the venom and evolution of toxins, while the latter contributes to understanding of novel mechanisms of toxicity and provide new research tools or prototypes of therapeutic agents.

Results

The pygmy copperhead (Austrelaps labialis) is one of the less studied species. In this present study, an attempt has been made to describe the toxin profile of A. labialis from Kangaroo Island using the cDNA library of its venom glands. We sequenced 658 clones which represent the common families of toxin genes present in snake venom. They include (a) putative long-chain and short-chain neurotoxins, (b) phospholipase A2, (c) Kunitz-type protease inhibitor, (d) CRISPs, (e) C-type lectins and (f) Metalloproteases. In addition, we have also identified a novel protein with two Kunitz-type domains in tandem similar to bikunin.

Conclusion

Interestingly, the cDNA library reveals that most of the toxin families (17 out of 43 toxin genes; ~40%) have truncated transcripts due to insertion or deletion of nucleotides. These truncated products might not be functionally active proteins. However, cellular trancripts from the same venom glands are not affected. This unusual higher rate of deletion and insertion of nucleotide in toxin genes may be responsible for the lower toxicity of A. labialis venom of Kangroo Island and have significant effect on evolution of toxin genes.
Molecular evolution and functional divergence of the bestrophin protein family
Authors: Milenkovic Vladimir M , Langmann Thomas , Schreiber Rainer , Kunzelmann Karl , Weber Bernhard HF
Published: February 2008

Background

Mutations in human bestrophin 1 are associated with at least three autosomal-dominant macular dystrophies including Best disease, adult onset vitelliform macular dystrophy and autosomal dominant vitreo-retinochoroidopathy. The protein is integral to the membrane and is likely involved in Ca2+-dependent transport of chloride ions across cellular membranes. Bestrophin 1 together with its three homologues forms a phylogenetically highly conserved family of proteins.

Results

A bioinformatics study was performed to investigate the phylogenetic relationship among the bestrophin family members and to statistically evaluate sequence conservation and functional divergence. Phylogenetic tree assembly with all available eukaryotic bestrophin sequences suggests gene duplication events in the lineage leading to the vertebrates. A common N-terminal topology which includes four highly conserved transmembrane domains is shared by the members of the four paralogous groups of vertebrate bestrophins and has been constrained by purifying selection. Pairwise comparison shows that altered functional constraints have occurred at specific amino acid positions after phylogenetic diversification of the paralogues. Most notably, significant functional divergence was found between bestrophin 4 and the other family members, as well as between bestrophin 2 and bestrophin 3. Site-specific profiles were established by posterior probability analysis revealing significantly divergent clusters mainly in two hydrophilic loops and a region immediately adjacent to the last predicted transmembrane domain. Strikingly, codons 279 and 347 of human bestrophin 4 reveal high divergence when compared to the paralogous positions strongly indicating the functional importance of these residues for the bestrophin 4 protein. None of the functionally divergent amino acids were found to reside within obvious sequences patterns or motifs.

Conclusion

Our study highlights the molecular evolution of the bestrophin family of transmembrane proteins and indicates amino acid residues likely relevant for distinct functional properties of the paralogues. These findings may provide a starting point for further experimental verifications.
Annotation and analysis of a large cuticular protein family with the R&R Consensus in Anopheles gambiae
Authors: Cornman R Scott , Togawa Toru , Dunn W Augustine , He Ningjia , Emmons Aaron C , Willis Judith H
Published: February 2008

Background

The most abundant family of insect cuticular proteins, the CPR family, is recognized by the R&R Consensus, a domain of about 64 amino acids that binds to chitin and is present throughout arthropods. Several species have now been shown to have more than 100 CPR genes, inviting speculation as to the functional importance of this large number and diversity.

Results

We have identified 156 genes in Anopheles gambiae that code for putative cuticular proteins in this CPR family, over 1% of the total number of predicted genes in this species. Annotation was verified using several criteria including identification of TATA boxes, INRs, and DPEs plus support from proteomic and gene expression analyses. Two previously recognized CPR classes, RR-1 and RR-2, form separate, well-supported clades with the exception of a small set of genes with long branches whose relationships are poorly resolved. Several of these outliers have clear orthologs in other species. Although both clades are under purifying selection, the RR-1 variant of the R&R Consensus is evolving at twice the rate of the RR-2 variant and is structurally more labile. In contrast, the regions flanking the R&R Consensus have diversified in amino-acid composition to a much greater extent in RR-2 genes compared with RR-1 genes. Many genes are found in compact tandem arrays that may include similar or dissimilar genes but always include just one of the two classes. Tandem arrays of RR-2 genes frequently contain subsets of genes coding for highly similar proteins (sequence clusters). Properties of the proteins indicated that each cluster may serve a distinct function in the cuticle.

Conclusion

The complete annotation of this large gene family provides insight on the mechanisms of gene family evolution and clues about the need for so many CPR genes. These data also should assist annotation of other Anopheles genes.
The United States and Canada as a coupled epidemiological system: An example from hepatitis A
Authors: Amariei Raluca , Willms Allan R , Bauch Chris T
Published: February 2008

Background

Hepatitis A (HA) is a low-incidence, non-endemic disease in Canada and the United States (US). However, a large difference in HA incidence between Canada and HA-endemic countries has made travel an important contributor to hepatitis A prevalence in Canada. There is also a (smaller) incidence differential between Canada and the US. Although the US has only moderately higher HA incidence, the volume of travel by Canadians to the US is many times higher than travel volume to endemic countries. Hence, travel to the US may constitute a source of low to moderate risk for Canadian travelers. To our knowledge, travel to the US has never been included as a potential risk factor for HA infection in Canadian epidemiologic analyses. The objective of this study was to use dynamic models to investigate the possible effects on hepatitis A incidence in Canada due to (1) implementing vaccination in the US, and (2) varying the volume of travel by Canadians to the US.

Methods

We developed and analyzed age-structured compartmental models for the transmission and vaccination of hepatitis A, for both Canada and the US. Models were parameterized using data on seroprevalence, case reporting, and travel patterns. The potential effect of hepatitis A prevalence in the US on hepatitis A prevalence in Canada was captured through a term representing infection of Canadians due to travel in the US.

Results

The model suggests that approximately 22% of HA cases in Canada in the mid 1990s may have been attributable to travel to the US. A universal vaccination programme that attained 70% coverage in young children in the US in the mid 1990s could have reduced Canadian incidence by 21% within 5 years.

Conclusion

Since not all necessary data were available to parameterize the model, the results should be considered exploratory. However, the analysis shows that, under plausible assumptions, the US may be more important for determining HA prevalence in Canada than is currently supposed. As international travel continues to grow, making vaccination policies ever more relevant to populations beyond a country's borders, such multi-country models will most likely come into wider use as predictive aids for policy development.
A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models
Authors: Sniekers Yvonne H , Intema Femke , Lafeber Floris PJG , van Osch Gerjo JVM , van Leeuwen Johannes PTM , Weinans Harrie , Mastbergen Simon C
Published: February 2008

Background

This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model.

Methods

Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT.

Results

At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15–20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25–40%) and plate porosity was strongly increased (25–85%) at all time points studied.

Conclusion

These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process.
Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
Authors: Lucchi Naomi W , Peterson David S , Moore Julie M
Published: February 2008

Background

Malaria during pregnancy is characterized by the sequestration of malaria-infected red blood cells (iRBC) in the intervillous spaces of the placenta, often accompanied by the infiltration of maternal mononuclear cells, causing substantial maternal and foetal/infant morbidity. The iRBC bind to receptors expressed by the syncytiotrophoblast (ST). How ST responds to this interaction remains poorly understood. Because it is known that ST is immunoactive and can respond to infectious agents, the consequences of this ST-iRBC interaction should be investigated.

Methods

An in vitro system was used to assess the biochemical and immunological changes induced in ST by ST-adherent iRBCs. Changes in ST mitogen-activated protein kinase (MAPK) activation were assessed by immunoblotting and mRNA expression levels of selected cytokine and chemokines in primary ST bound by iRBC were determined using real-time, reverse transcription PCR. In addition, secreted cytokine and chemokine proteins were assayed by standard ELISA, and chemotaxis of PBMC was assessed using a two-chamber assay system.

Results

Following iRBC/ST interaction, ST C-Jun N-terminal kinase 1 (JNK1) was activated and modest increases in the mRNA expression of TGF-β and IL-8/CXCL8 were observed. In addition, this interaction increased secretion of MIF and MIP-1α/CCL3 by ST and induced migration of PBMC towards iRBC-stimulated ST.

Conclusion

Results from this study provide the first evidence that ST participates in shaping the local immunological milieu and in the recruitment of maternal immune cells to the maternal blood space during placental malaria infection.
Post-traumatic soft tissue tumors: Case report and review of the literature a propos a Post-traumatic paraspinal desmoid tumor
Authors: Cohen Sarit , Ad-El Dean , Benjaminov Ofer , Gutman Haim
Published: February 2008

Background

Antecedent trauma has been implicated in the causation of soft tissue tumors. Several criteria have been established to define a cause-and-effect relationship. We postulate possible mechanisms in the genesis of soft tissue tumors following antecedent traumatic injury.

Case presentation

We present a 27-year-old woman with a paraspinal desmoid tumor, diagnosed 3-years following a motor vehicle accident. Literature is reviewed.

Conclusion

Soft tissue tumors arising at the site of previous trauma may be desmoids, pseudolipomas or rarely, other soft tissue growths. The cause-and-effect issue of desmoid or other soft tissue tumors goes beyond their diagnosis and treatment. Surgeons should be acquainted with this diagnostic entity as it may also involve questions of longer follow-up and compensation and disability privileges.
A study to assess changes in myocardial perfusion after treatment with spinal cord stimulation and percutaneous myocardial laser revascularisation; data from a randomised trial
Authors: Khan Sadia N , McNab Duncan C , Sharples Linda D , Freeman Carol J , Hardy Ian , Stone David L , Schofield Peter M
Published: February 2008

Background

Spinal cord stimulation (SCS) and percutaneous myocardial laser revascularisation (PMR) are treatment modalities used to treat refractory angina pectoris, with the major aim of such treatment being the relief of disabling symptoms. This study compared the change in myocardial perfusion following SCS and PMR treatment.

Methods

Subjects with Canadian Cardiovascular Society class 3/4 angina and reversible perfusion defects as assessed by single-photon emission computed tomographic myocardial perfusion scintigraphy were randomised to SCS (34) or PMR (34). 28 subjects in each group underwent repeat myocardial perfusion imaging 12 months post intervention. Visual scoring of perfusion images was performed using a 20-segment model and a scale of 0 to 4.

Results

The mean (standard deviation) baseline summed rest score (SRS) and stress scores (SSS) were 4.6 (5.7) and 13.6 (9.0) in the PMR group and 6.1 (7.4) and 16.8 (11.6) in the SCS group. At 12 months, SRS was 5.5 (6.0) and SSS 15.3 (11.3) in the PMR group and 6.9 (8.2) and 15.1 (10.9) in the SCS group. There was no significant difference between the two treatment groups adjusted for baseline (p = 1.0 for SRS, p = 0.29 for SSS).

Conclusion

There was no significant difference in myocardial perfusion one year post treatment with SCS or PMR.
Intensive insulin therapy and mortality in critically ill patients
Authors: Treggiari Miriam M , Karir Veena , Yanez N David , Weiss Noel S , Daniel Stephen , Deem Steven A
Published: February 2008

Introduction

Intensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.

Methods

We conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I.

Results

Insulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III.

Conclusion

A policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed prior to widespread implementation of IIT in critically ill patients.
Working together
Authors: Gask Linda , Lester Helen
Published: February 2008

From the standpoint of primary care, mental health services in the UK now appear very fragmented. We have to address the problems of working across interfaces as they continue to multiply. There is now a considerable evidence base relating to what works at the interface between psychiatry and primary care. Psychiatrists should consider the challenge of adopting new ways of working in the management of anxiety and depression in partnership with primary care.
Predictors of employment for people with severe mental illness: results of an international six-centre randomised controlled trial
Authors: Catty Jocelyn , Lissouba Pascale , White Sarah , Becker Thomas , Drake Robert E. , Fioritti Angelo , Knapp Martin , Lauber Christoph , Rössler Wulf , Tomov Toma , van Busschbach Jooske , Wiersma Durk , Burns Tom ,   EQOLISE Group
Published: February 2008

Background

An international six-centre randomised controlled trial comparing individual placement and support (IPS) with usual vocational rehabilitation for people with serious mental illness found IPS to be more effective for all vocational outcomes.

Aims

To determine which patients with severe mental illness do well in vocational services and which process and service factors are associated with better outcomes.

Method

Patient characteristics and early process variables were tested as predictors of employment outcomes. Service characteristics were explored as predictors of the effectiveness of IPS.

Results

Patients with previous work history, fewer met social needs and better relationships with their vocational workers were more likely to obtain employment and work for longer. Remission and swifter service uptake were associated with working more. Having an IPS service closer to the original IPS model was the only service characteristic associated with greater effectiveness.

Conclusions

The IPS service was found to be more effective for all vocational outcomes. In addition, maintaining high IPS fidelity and targeting relational skills would be a valuable focus for all vocational interventions, leading to improved employment outcomes. Motivation to find work may be decreased by satisfaction with current life circumstances.
Audit of advice on driving following hospitalisation for an acute psychotic episode
Authors: Orr Eilidh M. , Elworthy Timothy S. E.
Published: February 2008

Aims and Method

Psychiatrists are expected to follow guidelines in relation to patients' responsibilities regarding driving. In this study we reviewed advice on driving recorded for patients discharged from hospital following an acute psychotic episode. Guidelines on appropriate advice were then sent to all medical staff looking after in-patients.

Results

The first cycle of the audit included 48 patients. No advice was recorded. The second cycle included 70 patients. Advice was recorded for 8 patients. Six of these patients received a standard discharge letter with a prompt for ‘driving advice’.

Clinical Implications

In contrast to current guidelines, advice regarding driving is not routinely given to patients with an acute psychotic episode. A standard discharge letter with prompts on driving may improve adherence to guidelines.
Preparing for the MMC interviews: a practical guide for trainees
Authors: Sholinghur Hari Kumar
Published: February 2008

When the Modernising Medical Careers (MMC) programme was proposed in 2003, it was designed to ensure that ‘the end product of the training process, whether a Hospital Doctor or a General Practitioner, should be a high-quality, well-trained and accredited doctor who can deliver the care and treatment to patients in the modern NHS’ (Department of Health, 2003). Currently we are at the stage where interviews and recruitment for August 2007 have been completed, and recruitment for 2008 has commenced. It is vital for candidates to have an insight into the interview mechanism. In this article, the structure, types of questions, competencies tested and the methods used for selection such as Objective Structured Clinical Examinations, clinical vignettes, audit and research, teaching and presentation skills are discussed, so that candidates are able to better prepare themselves.
Shared care for treatment of opioid dependence and the new General Medical Services contract
Authors: Felice Anna Marie , Kouimtsidis Christos
Published: February 2008

Aims and Methods

An audit of clients in specialist and shared care services was undertaken in 2003 and in 2005 to investigate the capacity, quality of prescribed medication and profile of clients, and to assess the impact of the new General Medical Services contract on drug misuse treatment.

Results

Capacity in specialist services increased by 55% from 2003 to 2005, but not in shared care, and type and dosage of prescribed medication improved for shared care. Profile of clients suggests that stable clients are treated within shared care.

Clinical Implications

Attention should be given in training general practitioners to provide shared care treatment, increasing the number of clients accepted in shared care, and considering new treatment models.
Patient characteristics and clinical activities at a British military department of community mental health
Authors: Gould Matthew , Sharpley John , Greenberg Neil
Published: February 2008

Aims and Method

To describe patient characteristics and clinical activities at a British military department of community mental health (DCMH). Data were drawn from a clinical database over a 1-year period (n=409).

Results

Mean age was 29 years, 50% were single and 76% were from the junior ranks. Women were over-represented compared with the wider military population. Mean length of service prior to presentation was 5 years. The main presenting problem was alcohol misuse (33%) followed by depression (19%). Twenty-five per cent were referred for psychotherapy and 68% returned to full employment after treatment.

Clinical Implications

Patient characteristics of those treated at a DCMH differ from those in the wider military. An out-patient occupational mental health service returns a substantial number of patients to occupational fitness within the Armed Forces.
What is the role of the MRCPsych course for the new specialist training grade in psychiatry?
Authors: Vassilas Christopher , Haeney Owen , Brown Nick
Published: February 2008

This paper outlines the changes in specialist training that are occurring and also how postgraduate teaching is currently delivered in psychiatry. There is a review of the different ways that teaching can be delivered. Suggestions are then made as to how teaching can be organised in the specialist training programme in psychiatry.