bluuebunny/crossref_metadata_2025 huggingface dataset:
Where Memory Meets Attention: Neural Substrates of Negative Priming
Authors: Egner Tobias , Hirsch Joy
Published: October 2005

The negative priming (NP) effect refers to the observed increase in identification time for a current target stimulus or stimulus feature (the “probe”) that has been employed as a distractor stimulus or stimulus feature on the previous trial (the “prime”), representing strong evidence that ignored information is actively processed to a high level by selective attention systems. However, theoretical accounts of NP differ in whether they attribute the effect to processes of selective inhibition or episodic memory retrieval. Here we derived neurophysiological predictions from the rival “selective inhibition” and “episodic retrieval” models of NP, and employed event-related fMRI in a color-naming Stroop task to assess neural responses to probe trials that were subject to either no priming or negative priming. Compared to no-priming probe trials, NP resulted in increased activation of the right dorsolateral prefrontal cortex, in a region which has been closely linked with episodic memory retrieval functions. NP was also accompanied by activation of the right thalamus, particularly the mediodorsal nucleus, which has been implicated in the pathophysiology of schizophrenia, a condition associated with diminished NP effects. Our results support the proposal that ignored stimulus information is fully encoded in memory, and that episodic retrieval, not selective inhibition, of such information affects selective attention performance on subsequent trials.
Correlates of Capture of Attention and Inhibition of Return across Stages of Visual Processing
Authors: Fecteau Jillian H. , Munoz Douglas P.
Published: October 2005

How do visual signals evolve from early to late stages in sensory processing? We explored this question by examining two neural correlates of spatial attention. The capture of attention and inhibition of return refer to the initial advantage and subsequent disadvantage to respond to a visual target that follows an irrelevant visual cue at the same location. In the intermediate layers of the superior colliculus (a region that receives input from late stages in visual processing), both behavioral effects link to changes in the neural representation of the target: strong target-related activity correlates with the capture of attention and weak target-related activity correlates with inhibition of return. Contrasting these correlates with those obtained in the superficial layers (a functionally distinct region that receives input from early stages in visual processing), we show that the target-related activity of neurons in the intermediate layers was the best predictor of orienting behavior, although dramatic changes in the target-related response were observed in both subregions. We describe the important consequences of these findings for understanding the neural basis of the capture of attention and inhibition of return and interpreting changes in neural activity more generally.
Dynamics of a Temporo-Fronto-Parietal Network during Sustained Spatial or Spectral Auditory Processing
Authors: Bidet-Caulet Aurélie , Bertrand Olivier
Published: October 2005

Animal and human studies have suggested that posterior temporal, parietal, and frontal regions are specifically involved in auditory spatial (location and motion) processing, forming a putative dorsal “where” pathway. We used scalp EEG and current density mapping to investigate the dynamics of this network in human subjects presented with a varying acoustic stream in a two-factor paradigm: spatial versus pitch variations, focused versus diverted attention. The main findings were: (i) a temporo-parieto-frontal network was activated during the whole duration of the stream in all conditions and modulated by attention; (ii) the left superior temporal cortex was the only region showing different activations for pitch and spatial variations. Therefore, parietal and frontal regions would be involved in task-related processes (attention and motor preparation), whereas the differential processing of acoustic spatial and object-related features seems to take place at the temporal level.
Regional Brain Activation Evoked When Approaching a Virtual Human on a Virtual Walk
Authors: Morris James P. , Pelphrey Kevin A. , McCarthy Gregory
Published: October 2005

We investigated the necessity of biological motion for activation of the posterior superior temporal sulcus (pSTS) in circumstances in which the rapid approach of the observer to a virtual human induced the observer to make inferences about the characters intentions. Using a virtual reality environment, subjects experienced themselves walking towards a complex scene composed of animate and/or inanimate objects. During “person” trials, the scene contained a virtual human either making a simple gesture such as scratching his face (Study 1) or standing completely still (Study 2). During “object” trials, the scenes contained items such as furniture, a face portrait, and a clock, but not the virtual human. Using functional MRI to measure brain activity, we demonstrated strong activity in the pSTS while the observer approached the social scene, but only when the virtual human was making gestures. This result emphasizes the importance of biological motion in inferring the intentions of others.
Familiarity Affects the Processing of Task-irrelevant Auditory Deviance
Authors: Jacobsen Thomas , Schröger Erich , Winkler István , Horváth János
Published: October 2005

The effects of familiarity on auditory change detection on the basis of auditory sensory memory representations were investigated by presenting oddball sequences of sounds while participants ignored the auditory stimuli. Stimulus sequences were composed of sounds that were familiar and sounds that were made unfamiliar by playing the same sounds backward. The roles of frequently presented stimuli (standards) and infrequently presented ones (deviants) were fully crossed. Deviants elicited the mismatch negativity component of the event-related brain potential. We found an enhancement in detecting changes when deviant sounds appeared among familiar standard sounds compared when they were delivered among unfamiliar standards. Familiarity with the deviant sounds also enhanced the change-detection process. We suggest that tuning to familiar items sets up preparatory processes that affect change detection in familiar sound sequences.
FROST: A Distributed Neurocomputational Model of Working Memory Maintenance
Authors: Ashby F. Gregory , Ell Shawn W. , Valentin Vivian V. , Casale Michael B.
Published: October 2005

Many studies suggest that the sustained activation underlying working memory (WM) maintenance is mediated by a distributed network that includes the prefrontal cortex and other structures (e.g., posterior parietal cortex, thalamus, globus pallidus, and the caudate nucleus). A computational model of WM, called FROST (short for FROntal-Striatal-Thalamic), is proposed in which the representation of items and spatial positions is encoded in the lateral prefrontal cortex. During delay intervals, activation in these prefrontal cells is sustained via parallel, prefrontal cortical-thalamic loops. Activation reverberates in these loops because prefrontal cortical excitation of the head of the caudate nucleus leads to disinhibition of the thalamus (via the globus pallidus). FROST successfully accounts for a wide variety of WM data, including single-cell recording data and human behavioral data.
Comparing the Effects of Auditory Deprivation and Sign Language within the Auditory and Visual Cortex
Authors: Fine Ione , Finney Eva M. , Boynton Geoffrey M. , Dobkins Karen R.
Published: October 2005

To investigate neural plasticity resulting from early auditory deprivation and use of American Sign Language, we measured responses to visual stimuli in deaf signers, hearing signers, and hearing nonsigners using functional magnetic resonance imaging. We examined “compensatory hypertrophy” (changes in the responsivity/size of visual cortical areas) and “cross-modal plasticity” (changes in auditory cortex responses to visual stimuli). We measured the volume of early visual areas (V1, V2, V3, V4, and MT+). We also measured the amplitude of responses within these areas, and within the auditory cortex, to a peripheral visual motion stimulus that was attended or ignored. We found no major differences between deaf and hearing subjects in the size or responsivity of early visual areas. In contrast, within the auditory cortex, motion stimuli evoked significant responses in deaf subjects, but not in hearing subjects, in a region of the right auditory cortex corresponding to Brodmann's areas 41, 42, and 22. This hemispheric selectivity may be due to a predisposition for the right auditory cortex to process motion; earlier studies report a right hemisphere bias for auditory motion in hearing subjects. Visual responses within the auditory cortex of deaf subjects were stronger for attended than ignored stimuli, suggesting top-down processes. Hearing signers did not show visual responses in the auditory cortex, indicating that cross-modal plasticity can be attributed to auditory deprivation rather than sign language experience. The largest effects of auditory deprivation occurred within the auditory cortex rather than the visual cortex, suggesting that the absence of normal input is necessary for large-scale cortical reorganization to occur.
Using Psilocybin to Investigate the Relationship between Attention, Working Memory, and the Serotonin 1A and 2A Receptors
Authors: Carter Olivia L. , Burr David C. , Pettigrew John D. , Wallis Guy M. , Hasler Felix , Vollenweider Franz X.
Published: October 2005

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were tested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 Ag/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggesting a primary involvement of the 5-HT1A receptor in the observed deficit. Based on physiological and pharmacological data, we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.
Emerging Neurophysiological Specialization for Letter Strings
Authors: Maurer Urs , Brem Silvia , Bucher Kerstin , Brandeis Daniel
Published: October 2005

In adult readers, printed words and other letter strings activate specialized visual functions within 200 msec, as evident from neurophysiological recordings of brain activity. These fast, specialized responses to letter strings are thought to develop through plastic changes in the visual system. However, it is unknown whether this specialization emerges only with the onset of word reading, or represents a precursor of literacy. We compared 6-year-old kindergarten children who could not yet read words to adult readers. Both age groups detected immediate repetitions of visually presented words, pseudo-words, symbol strings, and pictures during event-related potential (ERP) mapping. Maps from seven corresponding ERP segments in children and adults were analyzed regarding fast (<250 msec) and slow (>300 msec) specialization for letter strings. Adults reliably differentiated words through increased fast (<150 msec) occipito-temporal N1 activity from symbols. Children showed a later, more mid-occipital N1 with marginal word-symbol differences, which were absent in those children with low letter knowledge. Children with high letter knowledge showed some fast sensitivity to letter strings, which was confined to right occipito-temporal sites, unlike the stronger adult N1 specialization. This suggests that a critical degree of early literacy induces some immature, but fast, specialization for letter strings before word reading becomes possible. Children also differentiated words from symbols in later segments through increased right occipito-temporal negativity for words. This slow specialization for letter strings was not modulated by letter knowledge and was absent in adults, possibly reflecting a visual precursor of literacy due to visual familiarity with letter strings.
Left Auditory Cortex and Amygdala, but Right Insula Dominance for Human Laughing and Crying
Authors: Sander Kerstin , Scheich Henning
Published: October 2005

Evidence suggests that in animals their own species-specific communication sounds are processed predominantly in the left hemisphere. In contrast, processing linguistic aspects of human speech involves the left hemisphere, whereas processing some prosodic aspects of speech as well as other not yet well-defined attributes of human voices predominantly involves the right hemisphere. This leaves open the question of hemispheric processing of universal (species-specific) human vocalizations that are more directly comparable to animal vocalizations. The present functional magnetic resonance imaging study addresses this question. Twenty subjects listened to human laughing and crying presented either in an original or time-reversed version while performing a pitch-shift detection task to control attention. Time-reversed presentation of these sounds is a suitable auditory control because it does not change the overall spectral content. The auditory cortex, amygdala, and insula in the left hemisphere were more strongly activated by original than by time-reversed laughing and crying. Thus, similar to speech, these nonspeech vocalizations involve predominantly left-hemisphere auditory processing. Functional data suggest that this lateralization effect is more likely based on acoustical similarities between speech and laughing or crying than on similarities with respect to communicative functions. Both the original and time-reversed laughing and crying activated more strongly the right insula, which may be compatible with its assumed function in emotional self-awareness.
Neural Correlates of Syntactic Processing in Two-Year-Olds
Authors: Oberecker Regine , Friedrich Manuela , Friederici Angela D.
Published: October 2005

Event-related brain potential (ERP) studies of sentence processing in adults have shown that phrase-structure violations are associated with two ERP components: an early left anterior negativity (ELAN) and a late, centro-parietal positivity (P600). Although the ELAN reflects highly automatic first-pass sentence parsing, the P600 has been interpreted to reflect later, more controlled processes. The present ERP study investigates the processing of phrase-structure violations in children below three years of age. Both children (mean age of 2.8 years) and adults passively listened to short active sentences that were either correct or syntactically incorrect. Adults displayed an ELAN that was followed by a P600 to the syntactic violation. Children also demonstrated a biphasic ERP pattern consisting of an early left hemispheric negativity and a late positivity. Both components, however, started later and persisted longer than those observed in adults. The left lateralization of the children's negativity suggests that this component can be interpreted as a child-specific precursor to the ELAN observed in adults. The appearance of the early negativity indicates that the neural mechanisms of syntactic parsing are present, in principle, during early language development.
Who's in Control? Proficiency and L1 Influence on L2 Processing
Authors: Elston-Güttler Kerrie E. , Paulmann Silke , Kotz Sonja A.
Published: October 2005

We report three reaction time (RT)/event-related brain potential (ERP) semantic priming lexical decision experiments that explore the following in relation to L1 activation during L2 processing: (1) the role of L2 proficiency, (2) the role of sentence context, and (3) the locus of L1 activations (ortho-graphic vs. semantic). All experiments used German (L1) homonyms translated into English (L2) to form prime-target pairs (pine-jaw for Kiefer) to test whether the L1 caused interference in an all-L2 experiment. Both RTs and ERPs were measured on targets. Experiment 1 revealed reversed priming in the N200 component and RTs for low-proficiency learners, but only RT interference for high-proficiency participants. Experiment 2 showed that once the words were processed in sentence context, the low-proficiency participants still showed reversed N200 and RT priming, whereas the high-proficiency group showed no effects. Experiment 3 tested native English speakers with the words in sentence context and showed a null result comparable to the high-proficiency group. Based on these results, we argue that cognitive control relating to translational activation is modulated by (1) L2 proficiency, as the early interference in the N200 was observed only for low-proficiency learners, and (2) sentence context, as it helps high-proficiency learners control L1 activation. As reversed priming was observed in the N200 and not the N400 component, we argue that (3) the locus of the L1 activations was orthographic. Implications in terms of bilingual word recognition and the functional role of the N200 ERP component are discussed.
Does Prosopagnosia Take the Eyes Out of Face Representations? Evidence for a Defect in Representing Diagnostic Facial Information following Brain Damage
Authors: Caldara Roberto , Schyns Philippe , Mayer Eugéne , Smith Marie L. , Gosselin Frédéric , Rossion Bruno
Published: October 2005

One of the most impressive disorders following brain damage to the ventral occipitotemporal cortex is prosopagnosia, or the inability to recognize faces. Although acquired prosopagnosia with preserved general visual and memory functions is rare, several cases have been described in the neuropsychological literature and studied at the functional and neural level over the last decades. Here we tested a brain-damaged patient (PS) presenting a deficit restricted to the category of faces to clarify the nature of the missing and preserved components of the face processing system when it is selectively damaged. Following learning to identify 10 neutral and happy faces through extensive training, we investigated patient PS's recognition of faces using Bubbles, a response classification technique that sampled facial information across the faces in different bandwidths of spatial frequencies [Gosselin, F., & Schyns, P. E., Bubbles: A technique to reveal the use of information in recognition tasks. Vision Research, 41, 2261-2271, 2001]. Although PS gradually used less information (i.e., the number of bubbles) to identify faces over testing, the total information required was much larger than for normal controls and decreased less steeply with practice. Most importantly, the facial information used to identify individual faces differed between PS and controls. Specifically, in marked contrast to controls, PS did not use the optimal eye information to identify familiar faces, but instead the lower part of the face, including the mouth and the external contours, as normal observers typically do when processing unfamiliar faces. Together, the findings reported here suggest that damage to the face processing system is characterized by an inability to use the information that is optimal to judge identity, focusing instead on suboptimal information.
Automatic Encoding of Polyphonic Melodies in Musicians and Nonmusicians
Authors: Fujioka Takako , Trainor Laurel J. , Ross Bernhard , Kakigi Ryusuke , Pantev Christo
Published: October 2005

In music, multiple musical objects often overlap in time. Western polyphonic music contains multiple simultaneous melodic lines (referred to as “voices”) of equal importance. Previous electrophysiological studies have shown that pitch changes in a single melody are automatically encoded in memory traces, as indexed by mismatch negativity (MMN) and its magnetic counterpart (MMNm), and that this encoding process is enhanced by musical experience. In the present study, we examined whether two simultaneous melodies in polyphonic music are represented as separate entities in the auditory memory trace. Musicians and untrained controls were tested in both magnetoencephalogram and behavioral sessions. Polyphonic stimuli were created by combining two melodies (A and B), each consisting of the same five notes but in a different order. Melody A was in the high voice and Melody B in the low voice in one condition, and this was reversed in the other condition. On 50% of trials, a deviant final (5th) note was played either in the high or in the low voice, and it either went outside the key of the melody or remained within the key. These four deviations occurred with equal probability of 12.5% each. Clear MMNm was obtained for most changes in both groups, despite the 50% deviance level, with a larger amplitude in musicians than in controls. The response pattern was consistent across groups, with larger MMNm for deviants in the high voice than in the low voice, and larger MMNm for in-key than out-of-key changes, despite better behavioral performance for out-of-key changes. The results suggest that melodic information in each voice in polyphonic music is encoded in the sensory memory trace, that the higher voice is more salient than the lower, and that tonality may be processed primarily at cognitive stages subsequent to MMN generation.
Effects of Vestibular Rotatory Accelerations on Covert Attentional Orienting in Vision and Touch
Authors: Figliozzi Francesca , Guariglia Paola , Silvetti Massimo , Siegler Isabelle , Doricchi Fabrizio
Published: October 2005

Peripheral vestibular organs feed the central nervous system with inputs favoring the correct perception of space during head and body motion. Applying temporal order judgments (TOJs) to pairs of simultaneous or asynchronous stimuli presented in the left and right egocentric space, we evaluated the influence of leftward and rightward vestibular rotatory accelerations given around the vertical head-body axis on covert attentional orienting. In a first experiment, we presented visual stimuli in the left and right hemifield. In a second experiment, tactile stimuli were presented to hands lying on their anatomical side or in a crossed position across the sagittal body midline. In both experiments, stimuli were presented while normal subjects suppressed or did not suppress the vestibulo-ocular response (VOR) evoked by head-body rotation. Independently of VOR suppression, visual and tactile stimuli presented on the side of rotation were judged to precede simultaneous stimuli presented on the side opposite the rotation. When limbs were crossed, attentional facilitatory effects were only observed for stimuli presented to the right hand lying in the left hemispace during leftward rotatory trials with VOR suppression. This result points to spatiotopic rather than somatotopic influences of vestibular inputs, suggesting that cross-modal effects of these inputs on tactile ones operate on a representation of space that is updated following arm crossing. In a third control experiment, we demonstrated that temporal prioritization of stimuli presented on the side of rotation was not determined by response bias linked to spatial compatibility between the directions of rotation and the directional labels used in TOJs (i.e., “left” or “right” first). These findings suggest that during passive rotatory head-body accelerations, covert attention is shifted toward the direction of rotation and the direction of the fast phases of the VOR.
Specificity of the Effect of a Nicotinic Receptor Polymorphism on Individual Differences in Visuospatial Attention
Authors: Greenwood Pamela M. , Fossella John A. , Parasuraman Raja
Published: October 2005

Cortical neurotransmitter availability is known to exert domain-specific effects on cognitive performance. Hence, normal variation in genes with a role in neurotransmission may also have specific effects on cognition. We tested this hypothesis by examining associations between polymorphisms in genes affecting cholinergic and noradrenergic neurotransmission and individual differences in visuospatial attention. Healthy individuals were administered a cued visual search task which varied the size of precues to the location of a target letter embedded in a 15-letter array. Cues encompassed 1, 3, 9, or 15 letters. Search speed increased linearly with precue size, indicative of a spatial attentional scaling mechanism. The strength of attentional scaling increased progressively with the number of C alleles (0, 1, or 2) of the alpha-4 nicotinic receptor gene C1545T polymorphism (n = 104). No association was found for the dopamine beta hydroxylase gene G444A polymorphism (n = 135). These findings point to the specificity of genetic neuromodulation. Whereas variation in a gene linked to cholinergic transmission systematically modulated the ability to scale the focus of visuospatial attention, variation in a gene governing dopamine availability did not. The results show that normal variation in a gene controlling a nicotinic receptor makes a selective contribution to individual differences in visuospatial attention.
Interaction between Syntax Processing in Language and in Music: An ERP Study
Authors: Koelsch Stefan , Gunter Thomas C. , Wittfoth Matthias , Sammler Daniela
Published: October 2005

The present study investigated simultaneous processing of language and music using visually presented sentences and auditorily presented chord sequences. Music-syntactically regular and irregular chord functions were presented synchronously with syntactically correct or incorrect words, or with words that had either a high or a low semantic cloze probability. Music-syntactically irregular chords elicited an early right anterior negativity (ERAN). Syntactically incorrect words elicited a left anterior negativity (LAN). The LAN was clearly reduced when words were presented simultaneously with music-syntactically irregular chord functions. Processing of high and low cloze-probability words as indexed by the N400 was not affected by the presentation of irregular chord functions. In a control experiment, the LAN was not affected by physically deviant tones that elicited a mismatch negativity (MMN). Results demonstrate that processing of musical syntax (as reflected in the ERAN) interacts with the processing of linguistic syntax (as reflected in the LAN), and that this interaction is not due to a general effect of deviance-related negativities that precede an LAN. Findings thus indicate a strong overlap of neural resources involved in the processing of syntax in language and music.
Selling Compromise
Authors: Pugh Allison J.
Published: October 2005

The turbulent social conflict over what counts as good-enough mothering and the greedy institution of work leaves many women trapped in what Joan Williams called the gender system of domesticity. Like self-help books, advertisements can lead mothers toward a culturally sanctioned compromise. This article looks at the “cultural deals” being offered for mothers by toy catalogs. The author examined the marketing of more than 3,500 toys in 11 catalogs fromthe 2000-2001holiday season. She found that the catalogs presented toys as solutions that would allow mothers to be good mothers without having to physically be there, even as the advertising copy evoked images of companionship and togetherness. Catalogs also emphasized skill building over fun, defined only certain skills as skills in the first place, and dismissed nurturing as feelings at best worth of expression and not of practice. The author argues that the toys promise to perpetuate for the children the same contradictions the catalogs purport to solve for their mothers.
KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival
Authors: Schnittger Susanne , Kohl Tobias M. , Haferlach Torsten , Kern Wolfgang , Hiddemann Wolfgang , Spiekermann Karsten , Schoch Claudia
Published: October 2005

Mutations in codon D816 of the KIT gene represent a recurrent genetic alteration in acute myeloid leukemia (AML). To clarify the biologic implication of activation loop mutations of the KIT gene, 1940 randomly selected AML patients were analyzed. In total, 33 (1.7%) of 1940 patients were positive for D816 mutations. Of these 33 patients, 8 (24.2%) had a t(8;21), which was significantly higher compared with the subgroup without D816 mutations. Analyses of genetic subgroups showed that KIT-D816 mutations were associated with t(8;21)/AML1-ETO and other rare AML1 translocations. In contrast, other activating mutations like FLT3 and NRAS mutations were very rarely detected in AML1-rearranged leukemia. KIT mutations had an independent negative impact on overall (median 304 vs 1836 days; P = .006) and event-free survival (median 244 vs 744 days; P = .003) in patients with t(8;21) but not in patients with a normal karyotype. The KIT-D816V receptor expressed in Ba/F3 cells was resistant to growth inhibition by the selective PTK inhibitors imatinib and SU5614 but fully sensitive to PKC412. Our findings clearly indicate that activating mutations of receptor tyrosine kinases are associated with distinct genetic subtypes in AML. The KIT-D816 mutations confer a poor prognosis to AML1-ETO-positive AML and should therefore be included in the diagnostic workup. Patients with KIT-D816-positive/AML1-ETO-positive AML might benefit from early intensification of treatment or combination of conventional chemotherapy with KIT PTK inhibitors.
131I–anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission
Authors: Pagel John M. , Appelbaum Frederick R. , Eary Janet F. , Rajendran Joseph , Fisher Darrell R. , Gooley Ted , Ruffner Katherine , Nemecek Eneida , Sickle Eileen , Durack Larry , Carreras Jeanette , Horowitz Mary M. , Press Oliver W. , Gopal Ajay K. , Martin Paul J. , Bernstein Irwin D. , Matthews Dana C.
Published: October 2005

In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a phase 1/2 study in which targeted irradiation delivered by 131I–anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/mL) and cyclophosphamide (CY; 120 mg/kg). Fifty-two (88%) of 59 patients receiving a trace 131I-labeled dose of 0.5 mg/kg anti-CD45 murine antibody had higher estimated absorbed radiation in bone marrow and spleen than in any other organ. Forty-six patients were treated with 102 to 298 mCi (3774-11 026 MBq) 131I, delivering an estimated 5.3 to 19 (mean, 11.3) Gy to marrow, 17-72 (mean, 29.7) Gy to spleen, and 3.5 Gy (n = 4) to 5.25 Gy (n = 42) to the liver. The estimated 3-year nonrelapse mortality and disease-free survival (DFS) were 21% and 61%, respectively. These results were compared with those from 509 similar International Bone Marrow Transplant Registry patients who underwent transplantation using BU/CY alone. After adjusting for differences in age and cytogenetics risk, the hazard of mortality among all antibody-treated patients was 0.65 times that of the Registry patients (95% CI 0.39-1.08; P = .09). The addition of targeted hematopoietic irradiation to conventional BU/CY is feasible and well tolerated, and phase 2 results are sufficiently encouraging to warrant further study.
Designer blood: creating hematopoietic lineages from embryonic stem cells
Authors: Olsen Abby L. , Stachura David L. , Weiss Mitchell J.
Published: October 2005

Embryonic stem (ES) cells exhibit the remarkable capacity to become virtually any differentiated tissue upon appropriate manipulation in culture, a property that has been beneficial for studies of hematopoiesis. Until recently, the majority of this work used murine ES cells for basic research to elucidate fundamental properties of blood-cell development and establish methods to derive specific mature lineages. Now, the advent of human ES cells sets the stage for more applied pursuits to generate transplantable cells for treating blood disorders. Current efforts are directed toward adapting in vitro hematopoietic differentiation methods developed for murine ES cells to human lines, identifying the key interspecies differences in biologic properties of ES cells, and generating ES cell-derived hematopoietic stem cells that are competent to repopulate adult hosts. The ultimate medical goal is to create patient-specific and generic ES cell lines that can be expanded in vitro, genetically altered, and differentiated into cell types that can be used to treat hematopoietic diseases.
Clinical presentation and prognostic factors of Streptococcus pneumoniae meningitis according to the focus of infection
Authors: Østergaard Christian , Konradsen Helle Bossen , Samuelsson Susanne
Published: October 2005

Background

We conducted a nationwide study in Denmark to identify clinical features and prognostic factors in patients with Streptococcus pneumoniae according to the focus of infection.

Methods

Based on a nationwide registration, clinical information's was prospectively collected from all reported cases of pneumococcal meningitis during a 2-year period (1999–2000). Clinical and laboratory findings at admission, clinical course and outcome of the disease including follow-up audiological examinations were collected retrospectively. The focus of infection was determined according to the clinical diagnosis made by the physicians and after review of the medical records.

Results

187 consecutive cases with S. pneumoniae meningitis were included in the study. The most common focus was ear (30%), followed by lung (18%), sinus (8%), and other (2%). In 42% of cases a primary infection focus could not be determined. On admission, fever and an altered mental status were the most frequent findings (in 93% and 94% of cases, respectively), whereas back rigidity, headache and convulsion were found in 57%, 41% and 11% of cases, respectively. 21% of patients died during hospitalisation (adults: 27% vs. children: 2%, Fisher Exact Test, P < 0.001), and the causes of death were due to neurological – and systemic complications or the combination of both in 8%, 5% and 6% of cases, respectively. Other causes (e.g. gastrointestinal bleeding, incurable cancer) accounted for 2% of cases. 41% of survivors had neurological sequelae (hearing loss: 24%, focal neurological deficits: 16%, and the combination of both: 1%). The mortality varied with the focus of the infection (otogenic: 7%, sinusitic: 33%, pneumonic: 26%, other kind of focus: 50%, no primary infection focus: 21%, Log rank test: P = 0.0005). Prognostic factors associated with fatal outcome in univariate logistic regression analysis were advanced age, presence of an underlying disease, history of headache, presence of a lung focus, absence of an otogenic focus, having a CT-scan prior to lumbar puncture, convulsions, requirement of assisted ventilation, and alterations in various CSF parameters (WBC <500 cells/μL, high protein levels, glucose levels<1 mmol/L, low CSF/blood glucose levels), P < 0.05. Independent prognostic factor associated with fatal outcome in multivariate logistic regression analysis was convulsions (OR: 4.53, 95%CI: (1.74–11.8), p = 0.002), whereas presence of an otogenic focus was independently associated with a better survival (OR: 6.09, 95%CI: (1.75–21.2), P = 0.005).

Conclusion

These results emphasize the prognostic importance of an early recognition of a predisposing focus to pneumococcal meningitis.
The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase
Authors: Cappello Francesco , David Sabrina , Rappa Francesca , Bucchieri Fabio , Marasà Lorenzo , Bartolotta Tommaso E , Farina Felicia , Zummo Giovanni
Published: October 2005

Background

The involvement of Heat Shock Proteins (HSP) in cancer development and progression is a widely debated topic. The objective of the present study was to evaluate the presence and expression of HSP60 and HSP10 in a series of large bowel carcinomas and locoregional lymph nodes with and without metastases.

Methods

82 Astler and Coller's stage C2 colorectal cancers, of which 48 well-differentiated and 34 poorly-differentiated, were selected along with 661 lymph nodes, including 372 with metastases and 289 with reactive hyperplasia only, from the same tumours. Primitive tumours and both metastatic and reactive lymph nodes were studied; specifically, three different compartments of the lymph nodes, secondary follicle, paracortex and medullary sinus, were also analysed. An immunohistochemical research for HSP60 and HSP10 was performed and the semiquantitative results were analysed by statistical analysis to determine the correlation between HSPs expression and 1) tumour grading; 2) degree of inflammation; 3) number of lymph nodes involved; 4) lymph node compartment hyperplasia. Moreover, western blotting was performed on a smaller group of samples to confirm the immunohistochemical results.

Results

Our data show that the expression of HSP60, in both primary tumour and lymph node metastasis, is correlated with the tumoral grade, while the HSP10 expression is not. Nevertheless, the levels of HSP10 are commonly higher than the levels of HSP60. In addition, statistical analyses do not show any correlation between the degree of inflammation and the immunopositivity for both HSP60 and HSP10. Moreover, we find a significant correlation between the presence of lymph node metastases and the positivity for both HSP60 and HSP10. In particular, metastatic lymph nodes show a higher percentage of cells positive for both HSP60 and HSP10 in the secondary follicles, and for HSP10 in the medullary sinuses, when compared with hyperplastic lymph nodes.

Conclusion

HSP60 and HSP10 may have diagnostic and prognostic significance in the management of this tumour and their overexpression in tumoral cells may be functionally related to tumoral progression. We hypothesise that their expression in follicular and medullary cells of lymph nodes may be induced by formation of metastases. Further studies based on these observations could lead to a better understanding of the HSPs involvement in colorectal cancer progression, as well as other neoplasms.
Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial
Authors: Roudsari Arezoo Haghighian , Tahbaz Farideh , Hossein-Nezhad Arash , Arjmandi Bahram , Larijani Bagher , Kimiagar Seyed Masoud
Published: October 2005

Background

Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility.

Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens.

This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women.

Materials and methods

This clinical trial of before-after type was carried out on 15 women 45–64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed.

Results

Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p < 0.05), although the alterations in osteocalcin, c-telopeptide, IGFBP3 and type I collagen telopeptide were not significant.

Conclusion

In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis.
Employment status in chronic fatigue syndrome. A cross-sectional study examining the value of exercise testing and self-reported measures for the assessment of employment status
Authors: Nijs Jo , Van de Putte Karen , Louckx Fred , De Meirleir Kenny
Published: October 2005

Objective: To examine the value of exercise testing and self-reported disability for the assessment of employment status in patients with chronic fatigue syndrome.

Design: Cross-sectional observational study.

Setting: A university-based chronic fatigue clinic.

Subjects: Fifty-four consecutive, Flemish, employed (not self-employed) chronic fatigue syndrome patients (49/54 female).

Interventions: Not applicable.

Main outcome measures: Participants were questioned about their current and premorbid employment status, filled in the Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ), the Medical Outcomes Short Form 36 Health Status Survey (SF-36), and performed a maximal exercise test on a bicycle ergometer with continuous monitoring of cardiorespiratory variables.

Results: A significant association was observed between the current employment rate and two SF-36 subscales (i.e., role limitations due to physical functioning and social functioning; rho=0.39 and 0.35 respectively) ( n = 54). Analysing only the female chronic fatigue syndrome patients ( n = 49), the current employment rate correlated significantly with the peak workload (rho=0.38).

Conclusions: The associations between either exercise testing or self-reported disability and employment status are too weak to predict employment status.
The reproducibility of the Canadian Occupational Performance Measure
Authors: Eyssen I C J M , Beelen A , Dedding C , Cardol M , Dekker J
Published: October 2005

Objective: To assess the reproducibility (reliability and inter-rater agreement) of the client-centred Canadian Occupational Performance Measure (COPM).

Design: The COPM was administered twice, with a mean interval of seven days (SD 1.6, range 4-14), by two different occupational therapists. Data analysis was based on intraclass correlation coefficients, the Bland and Altman method and Cohen's weighted kappas.

Setting: Occupational therapy departments of two university medical centres.

Subjects: Consecutive clients, with various diagnoses, newly referred to the outpatient clinic of two occupational therapy departments, were included. They were all over 18 years of age and perceived limitations in more than one activity of daily life. Complete data on 95 clients were obtained: 31 men and 64 women.

Results: Sixty-six per cent of the activities prioritized at the first assessment were also prioritized at the second assessment. The intraclass correlation coefficients were 0.67 (95% confidence interval (CI) 0.54-0.78) for the mean performance score and 0.69 (95% CI 0.56-0.79) for the mean satisfaction score. The limits of agreement were-2.5 to 2.4 for the mean performance score and-2.3 to 2.7 for the mean satisfaction score. For the separate prioritized problems, the weighted kappas ranged from 0.37 to 0.49.

Conclusions: Inter-rater agreement of the prioritized problems was moderate. The reproducibility of the mean performance and satisfaction scores was moderate, but it was poor for the scores of the separate problems. Therefore, the mean scores should be used for individual assessment.
Construct validity and reliability of the Rivermead Post-Concussion Symptoms Questionnaire
Authors: Eyres Sophie , Carey Amy , Gilworth Gill , Neumann Vera , Tennant Alan
Published: October 2005

Objectives: To provide further evidence of reliability and internal and external construct validity of the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), which measures severity of postconcussion symptoms following head injury.

Design and setting: A cross-sectional study of consecutive patients presenting with a head injury in two urban teaching hospitals and a community trust.

Patients: Three hundred and sixty-nine patients returned a questionnaire from 1689 consecutive adult patients (18 years and above) referred to radiology for a skull X-ray following a head injury, and those who were currently under the care of a community-based multidisciplinary head injury team.

Method: Internal construct validity tested by fit to the Rasch Measurement model; external construct validity tested by correlations with Rivermead Head Injury Follow-up Questionnaire (RHFUQ); test-retest reliability tested by correlations at two-week intervals.

Outcome measures: Rivermead Post-Concussion Symptoms Questionnaire and Rivermead Head Injury Follow-up Questionnaire.

Main results: RPQ scores ranged from 0 to 64 (17.3% floor, 0.3% ceiling). Overall fit to the Rasch model was poor (item fit mean-0.416, SD=1.989, chi-squared=172.486, p < 0.01) suggesting a lack of unidimensionality. The items headaches, dizziness and forgetful displayed misfitting residuals and the first two items also displayed significant item trait fit statistics (p < 0.0006). After removing the items headaches, dizziness and subsequently nausea the RPQ demonstrated good fit at overall and individual item levels, both for the remaining 13 items (RPQ-13) and the three items (RPQ-3) which now formed a subsidiary scale. All items functioned consistently across age and gender. The RPQ-13 and RPQ-3 scales showed test-retest reliability coefficients of 0.89 and 0.72 (both p-values < 0.01) and positive correlations with RHFUQ scores (0.83 for RPQ-13, 0.62 for RPQ-3, both p-values< 0.01).

Conclusions: As currently used, the RPQ does not meet modern psychometric standards. Its 16 items do not tap into the same underlying construct and should not be summated in a single score. When the RPQ is split into two separate scales, the RPQ-13 and the RPQ-3, each set of items forms a unidimensional construct for people with head injury at three months post injury. These scales show good test-retest reliability and adequate external construct validity.