bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial Learning of Timing in Combined Serial Movements and a No-Movement Situation
Authors: LaRue Jacques
Published: February 2005

We investigate differences in timing errors in a task that imitated the movement sequence of a cello player. We trained a group of 17 young adults to perform a sequence of linear reversal movements of different lengths but with a constant movement time. Thus, each segment required the movement speed to be changed. The sequence had to be performed with fluidity, except for a �no-movement� segment that was embedded in the movement series. Feedback on timing was given for each segment. Results from this experiment show that the no-movement segment is more variable than any of the movement segments. There was no significant correlation between the timing errors of the successive movements and the timing error of the pause. These results provide further evidence in favor of two distinct timing processes: one used for continuous movements and one used for no-movement and discontinuous movements.
Differential Brain Response to Metrical Accents in Isochronous Auditory Sequences
Authors: Abecasis Donna , Brochard Renaud , Granot Roni , Drake Carolyn
Published: February 2005

Even within equitonal isochronous sequences, listeners report perceiving differences among the tones, reflecting some grouping and accenting of the sound events. In a previous study, we explored this phenomenon of �subjective rhythmization� physiologically through brain event-related potentials (ERPs). We found differences in the ERP responses to small intensity deviations introduced in different positions of isochronous sequences, even though all sound events were physically identical. These differences seemed to follow a binary pattern, with larger amplitudes in the response elicited by deviants in odd-numbered than in even-numbered positions. The experiments reported here were designed to test whether the differences observed corresponded to a metrical pattern, by using a similar design in sequences of a binary (long-short) or a ternary (long-short-short) meter. We found a similar pattern of results in the binary condition, but a significantly different pattern in the ternary one. Importantly, the amplitude of the ERP response was largest in positions corresponding to strong beats in all conditions. These results support the notion of a binary default metrical pattern spontaneously imposed by listeners, and a better processing of the first (accented) event in each perceptual group. The differences were mainly observed in a late, attention-dependent component of the ERPs, corresponding to rather high-level processing.
The Neural Locus of Temporal Structure and Expectancies in Music: Evidence From Functional Neuroimaging At 3 Tesla
Authors: Levitin Daniel J. , Menon Vinod
Published: February 2005

The neuroanatomical correlates of temporal structure and expectancies in music were investigated using a unique stimulus manipulation involving scrambled music. The experiment compared brain responses (using functional magnetic resonance imaging) while participants listened to classical music and scrambled versions of that same music. The scrambled versions disrupted musical structure while holding low-level musical attributes constant, including such psychoacoustic parameters as pitch, loudness, and timbre. Comparing music to its scrambled counterpart, we found focal activation in the pars orbitalis region (Brodmann Area 47) of the left inferior frontal cortex, a region that has been previously closely associated with the processing of linguistic structure in spoken and signed language, and additional activation in the right hemisphere homologue of that area. We speculate that this particular region of inferior frontal cortex may be more generally responsible for processing fine-structured stimuli that evolve over time, not merely those that are linguistic.
Vitamin A Supplementation for Extremely Low Birth Weight Infants: Outcome at 18 to 22 Months
Authors: Ambalavanan Namasivayam , Tyson Jon E. , Kennedy Kathleen A. , Hansen Nellie I. , Vohr Betty R. , Wright Linda L. , Carlo Waldemar A. ,   and National Institute of Child Health and Human Development Neonatal Research Network
Published: February 2005

Background. A National Institute of Child Health and Human Development Neonatal Research Network randomized trial showed that vitamin A supplementation reduced bronchopulmonary dysplasia (O2 at 36 weeks' postmenstrual age) or death in extremely low birth weight (ELBW) neonates (relative risk [RR]: 0.89). As with postnatal steroids or other interventions, it is important to ensure that there are no longer-term adverse effects that outweigh neonatal benefits.

Primary Objective. To determine if vitamin A supplementation in ELBW infants during the first month after birth affects survival without neurodevelopmental impairment at a corrected age of 18 to 22 months.

Design/Methods. Infants enrolled in the National Institute of Child Health and Human Development vitamin A trial were evaluated at 18 to 22 months by carefully standardized assessments: Bayley Mental Index (MDI) and Psychomotor Index (PDI), visual and hearing screens, and physical examination for cerebral palsy (CP). The medical history was also obtained. Neurodevelopmental impairment (NDI) was predefined as ≥1 of MDI <70, PDI <70, CP, blind in both eyes, or hearing aids in both ears.

Results. Of 807 enrolled infants, 133 died before and 16 died after discharge. Five hundred seventy-nine (88%) of the 658 remaining infants were followed up. The primary outcome of NDI or death could be determined for 687 of 807 randomized infants (85%). Baseline characteristics and predischarge and postdischarge mortality were comparable in both study groups. NDI or death by 18 to 22 months occurred in 190 of 345 (55%) infants in the vitamin A group and in 204 of 342 (60%) of the control group (RR: 0.94; 95% confidence interval: 0.80-1.07). RRs for low MDI, low PDI, and CP were also <1.0. We found no evidence that neonatal vitamin A supplementation reduces hospitalizations or pulmonary problems after discharge.

Conclusion. Vitamin A supplementation for ELBW infants reduces bronchopulmonary dysplasia without increasing mortality or neurodevelopmental impairment at 18 to 22 months. However, this study was not powered to evaluate small magnitudes of change in long-term outcomes.
Flocculation mechanism induced by phenolic resin/PEO and floc properties
Authors: Negro C. , Fuente E. , Blanco A. , Tijero J.
Published: February 2005

The flocculation of an industrial furnish of TCF Kraft bleached pulp and ground calcium carbonate, induced by polyethylene oxide, and by the dual system formed by polyethylene oxide (PEO) and formaldehyde‐phenol resin (PFR), was investigated and compared in order to study the flocculation kinetics, the flocculation mechanism and the properties of the formed flocs. A technique based on the measurement of the particle chord size distribution, called focused beam reflectance measurement, was used to carry out the research. The ability of the polyacrylate contained in the commercial ground calcium carbonate as a PEO cofactor was observed. Results confirmed the formation and the coacervation of the complex PFR‐PEO, which loses its flocculant properties over time, confirming the complex bridging flocculation model. The shearing forces effect on the flocculation kinetics and on the properties of the formed flocs was also studied. © 2005 American Institute of Chemical Engineers AIChE J, 51: 1022–1031, 2005
Continuous RAFT miniemulsion polymerization of styrene in a train of CSTRs
Authors: Smulders Wilfred W. , Jones Christopher W. , Schork F. Joseph
Published: February 2005

Reversible addition fragmentation transfer (RAFT) miniemulsion polymerization of styrene in a train of continuous stirred tank reactors (CSTRs) is described. It is observed that the polydispersity of the polymer decreases as the number of CSTRs in the train increases, as has been derived theoretically. Furthermore, the CSTRs do not reach steady state, which has been attributed to, at least in part, slow oligomerization of monomer and capping by RAFT agent in the feed. Particle nucleation in a CSTR is found to be less effective than in a batch reactor. This is attributed to a “dry‐out” mechanism, which is observed to be more significant in a CSTR than in batch, leading to a “nongrowing” population of dormant chains. Experimental evidence for the presence of this “nongrowing” population is also provided. © 2005 American Institute of Chemical Engineers AIChE J, 51: 1009–1021, 2005
Association analysis of transcripts from the bipolar susceptibility locus on chromosome 4q35, exclusion of a pathogenic role for eight positional candidate genes
Authors: Blair Ian P. , Badenhop Renee F. , Scimone Anna , Moses Melissa J. , Kerr Nicholas P. , Donald Jennifer A. , Mitchell Philip B. , Schofield Peter R.
Published: February 2005

Bipolar affective disorder is a major psychiatric illness with a population prevalence of up to 1.6%. The disorder is genetically complex. To date, no specific gene or DNA sequence variation that predisposes to the disorder has been described, however several susceptibility loci have been proposed through genetic linkage analysis. We previously identified one such susceptibility locus on chromosome 4q35, and refined the interval harboring this susceptibility gene to a size that is amenable to positional cloning. Several independent studies have now been described that support the presence of a susceptibility gene at this locus. In order to identify candidate genes for testing association with bipolar disorder, we previously established a comprehensive transcript map that encompasses the chromosome 4q35 susceptibility locus implicated in our linkage analysis. In this study, we have selected full‐length genes from the transcript map and determined the genomic structure of each gene. We identified informative, intragenic single nucleotide polymorphisms (SNPs) by screening all exons and flanking intron sequences in affected individuals from seven bipolar pedigrees that we previously reported as showing evidence for linkage to chromosome 4q35. Analysis of these SNPs was then extended to our unrelated bipolar case‐control cohort to test for association with the disorder. Our data suggests that all genes analyzed can be excluded from direct involvement in the disorder. We have therefore, excluded approximately half the genes within the chromosome 4q35 candidate interval from playing a direct pathogenic role in bipolar disorder. © 2005 Wiley‐Liss, Inc.
Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report
Authors: Abdolmaleky Hamid Mostafavi , Cheng Kuang‐hung , Russo Andrea , Smith Cassandra L. , Faraone Stephen V. , Wilcox Marsha , Shafa Rahim , Glatt Stephen J. , Nguyen Giang , Ponte Joe F. , Thiagalingam Sam , Tsuang Ming T.
Published: February 2005

DNA methylation changes could provide a mechanism for DNA plasticity and dynamism for short‐term adaptation, enabling a type of cell memory to register cellular history under different environmental conditions. Some environmental insults may also result in pathological methylation with corresponding alteration of gene expression patterns. Evidence from several studies has suggested that in schizophrenia and bipolar disorder, mRNA of the reelin gene (RELN), which encodes a protein necessary for neuronal migration, axonal branching, synaptogenesis, and cell signaling, is severely reduced in post‐mortem brains. Therefore, we investigated the methylation status of the RELN promoter region in schizophrenic patients and normal controls as a potential mechanism for down regulation of its expression. Ten post‐mortem frontal lobe brain samples from male schizophrenic patients and normal controls were obtained from the Harvard Brain Tissue Resources Center. DNA was extracted using a standard phenol–chloroform DNA extraction protocol. To evaluate differences between patients and controls, we applied methylation specific PCR (MSP) using primers localized to CpG islands flanking a potential cyclic AMP response element (CRE) and a stimulating protein‐1 (SP1) binding site located in the promoter region. For each sample, DNA extraction, bisulfite treatment, and MSP were independently repeated at least four times to accurately determine the methylation status of the target region. Forty‐three PCR trials were performed on the test and control samples. MSP analysis of the RELN promoter revealed an unmethylated signal in all reactions (43 of 43) using DNA from the frontal brain tissue, derived from either the schizophrenic patients or normal controls indicating that this region of the RELN promoter is predominantly unmethylated. However, we observed a distinct methylated signal in 73% of the trials (16 of 22) in schizophrenic patients compared with 24% (5 of 21) of controls. Thus, the hypermethylation of the CpG islands flanking a CRE and SP1 binding site observed at a significantly higher level (t = −5.07, P = 0.001) may provide a mechanism for the decreased RELN expression, frequently observed in post‐mortem brains of schizophrenic patients. We also found an inverse relationship between the level of DNA methylation using MSP analysis and the expression of the RELN gene using semi‐quantitative RT‐PCR. Despite the small sample size, these studies indicate that promoter hypermethylation of the RELN gene could be a significant contributor in effecting epigenetic alterations and provides a molecular basis for the RELN gene hypoactivity in schizophrenia. Further studies with a larger sample set would be required to validate these preliminary observations. © 2005 Wiley‐Liss, Inc.
Serotonin receptor 2C (HTR2C) and schizophrenia: Examination of possible medication and genetic influences on expression levels
Authors: Castensson Anja , Åberg Karolina , McCarthy Shane , Saetre Peter , Andersson Björn , Jazin Elena
Published: February 2005

The serotonin receptor 2C (HTR2C) gene is of interest in schizophrenia due to its involvement in regulation of dopamine activity in the prefrontal cortex. We have previously reported a decreased expression of HTR2C mRNA levels in the prefrontal cortex of schizophrenia patients. The variability in mRNA expression levels is evaluated here more closely in relation to promoter haplotypes and neuroleptic treatment received by the patients. The decrease in HTR2C mRNA was present in neuroleptic treated individuals and in patients untreated at death, indicating that the lower expression is not a short‐term medication effect. Three promoter polymorphisms were used to construct haplotypes. No SNP displayed genotypic or haplotypic association with the disease. Gene expression of HTR2C was not affected by haplotype and the expression decrease in schizophrenia patients was similar in all haplotype combinations (diplotypes). We conclude that the decrease in HTR2C expression in schizophrenia may be related to the disease mechanism rather than to drug treatment. The disease related changes in HTR2C expression are not related to the promoter variants typed in our sample, but could be due to other regulatory variants or trans‐acting factors. © 2005 Wiley‐Liss, Inc.
Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs
Authors: Eissa Sanaa , Kassim Samar K. , Labib Randa Ali , El‐Khouly Inas M. , Ghaffer Taghreed M. , Sadek Mohamed , Razek Omar Abdel , El‐Ahmady Omar
Published: February 2005

BACKGROUND

A new, sensitive, noninvasive method for the detection of urothelial carcinomas of the urinary bladder would open new possibilities in both the diagnosis and followup of patients.

METHODS

This study included 228 patients diagnosed with bladder carcinoma, 68 patients with benign bladder lesions, and 44 healthy persons served as the control group. All were subjected to: serologic schistosomiasis antibody assay in serum, urine cytology, estimation of urine hyaluronic acid (HA) by enzyme‐linked immunosorbent assay, and detection of CK‐20 and hyaluronidase (HAase) by reverse transcription polymerase chain reaction (RT‐PCR) in urothelial cells from voided urine.

RESULTS

HA mean rank was higher in benign and malignant groups than in the healthy group (P < 0.0001) and was significantly related to tumor grade (P = 0.021). HA best‐cutoff, determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups, was 58.5 units/mg protein at 85.8% sensitivity and 60.7% specificity. HAase RNA showed superior sensitivity (90.8%) over cytology (68.9%) and CK‐20 (78.1%) with specificity of 93.4%, 98.1% and 80.2%, respectively. The sensitivity reached 94.7% at a specificity of 91.5% when combined with CK‐20. All 4 of the investigated markers were related to grade at P <0.05. Whereas only HAase and CK‐20 were significantly related to stage (P < 0.05). As to schistosomiasis, only HAase RNA positivity was significantly associated (P = 0.038).

CONCLUSIONS

HAase RNA is a promising noninvasive test with high sensitivity and specificity in bladder carcinoma detection. Cancer 2005. © 2005 American Cancer Society.
Transitin, a nestin‐related intermediate filament, is expressed by neural progenitors and can be induced in Müller glia in the chicken retina
Authors: Fischer Andy J. , Omar Ghezal
Published: February 2005

The purpose of this study was to test whether transitin, the avian homologue of nestin, is expressed by retinal progenitors in the developing and postnatal chicken. Because nestin has been widely used as a cell‐distinguishing marker of neural progenitors in the mammalian nervous system, we expected to find transitin expressed specifically by the neural progenitors of the retina. In early stages of development, transitin is expressed by neural progenitors in the retina and by cells in the developing ciliary body. During later stages of development, transitin expression persists in differentiating Müller glia but is down‐regulated by these cells as maturation proceeds. In the postnatal chick, transitin expression is restricted to neural progenitors at the peripheral edge of the retina. We found that the expression of transitin in mature Müller glia was induced by intraocular injections of insulin and fibroblast growth factor‐2 (FGF2) but not by ciliary neurotrophic factor. In response to insulin and FGF2, the expression of transitin was induced in the nonpigmented epithelium (NPE) of the ciliary body. In the postnatal retina, acute retinal damage transiently induces transitin expression in Müller glia. We propose that the expression of transitin by retinal Müller glia and NPE cells in the postnatal animal represents a state of de‐differentiation and a step toward becoming neurogenic progenitor cells. Taken together, our findings indicate that transitin is expressed by neural progenitors in the embryonic and postnatal chicken retina. However, transitin is not exclusively expressed by neural progenitors and is also expressed by non‐neurogenic cells. J. Comp. Neurol. 484:1–14, 2005. © 2005 Wiley‐Liss, Inc.
Heterogeneity of γ‐aminobutyric acid type A receptors in mitral and tufted cells of the rat main olfactory bulb
Authors: Panzanelli Patrizia , Perazzini Alice‐Zaira , Fritschy Jean‐Marc , Sassoè‐Pognetto Marco
Published: February 2005

Mitral and tufted cells of the olfactory bulb receive strong γ‐aminobutyric acid (GABA)‐ergic input and express GABAA receptors containing the α1 or α3 subunit. The distribution of these subunits was investigated in rats via multiple immunofluorescence and confocal microscopy, by using gephyrin as a marker of GABAergic synapses. A prominent immunoreactivity was detected throughout the external plexiform layer (EPL) and glomerular layer (GL). However, although staining for the α1 subunit was uniform throughout the EPL, that of the α3 subunit was most intense in the outer one‐third of this layer. All mitral cells were positive for the α1 subunit. In contrast, the α3 subunit was restricted to a subpopulation of mitral cells, many of which also expressed calretinin. Likewise, external tufted cells could be subdivided into distinct groups, either singly labeled for the α1 or α3 subunit or doubly labeled. At the subcellular level, staining for the α1 and α3 subunits was punctate, forming clusters partially colocalized with gephyrin. However, many α1‐ and α3‐positive clusters lacked gephyrin, suggesting the existence of either nonsynaptic GABAA receptor clusters or synaptic receptors not associated with gephyrin. Quantitative analysis of colocalization among the three markers in the inner EPL, outer EPL, and GL revealed considerable heterogeneity, suggestive of a differential organization of GABAA receptor subtypes in the apical and basal dendrites of mitral and tufted cells. Together these results reveal a complex subunit organization of GABAA receptors in the olfactory bulb and suggest that mitral and tufted cells participate in different synaptic circuits controlled by distinct GABAA receptor subtypes. J. Comp. Neurol. 484:121–131, 2005. © 2005 Wiley‐Liss, Inc.
Organization and regulation of paraventricular nucleus glutamate signaling systems: N‐methyl‐D‐aspartate receptors
Authors: Ziegler Dana R. , Cullinan William E. , Herman James P.
Published: February 2005

Stress activation of the hypothalamo–pituitary–adrenocortical (HPA) axis is mediated in part by glutamatergic neurotransmission. The precise nature of glutamate effects on stress‐integrative hypothalamic paraventricular nucleus (PVN) neurons remains to be determined. Therefore, the current study was designed to delineate the organization of glutamate/NMDA receptor systems in the PVN and to assess regulation of PVN glutamate receptor subunit expression by chronic intermittent stress and glucocorticoids. Immunohistochemical studies verified that N‐methyl‐D‐aspartate (NMDA) receptor subunit proteins NR1 and NR2A/2B are expressed in the medial parvocellular PVN, indicating the potential for NMDA receptor regulation of corticotropin‐releasing hormone (CRH) release. Dual‐label confocal analysis revealed that CRH neurons are apposed by vesicular glutamate transporter 2 (VGLUT2)‐containing terminals, consistent with glutamatergic innervation from hypothalamus and/or brainstem. In situ hybridization analysis revealed a significant and selective stress‐induced decrease (37%) in NR2B subunit mRNA expression in the CRH‐containing region of the PVN. No changes were observed for NR1 or NR2A mRNAs. In contrast, none of the subunits investigated showed altered expression following adrenalectomy with or without low/high‐dose corticosterone replacement. Thus, the observed stress regulation is likely mediated by neurogenic mechanisms in the PVN and upstream stress‐transducing neurocircuitry. Because a loss of NR2B subunit inclusion in NR receptors would likely confer increased Ca++ conductance and faster deactivation kinetics, the stress‐induced decrease in NR2B mRNA is consistent with enhanced glutamate signaling in the PVN following chronic stress and, perhaps, increased basal HPA activity and more rapid and/or more robust HPA responses to stress. J. Comp. Neurol. 484:43–56, 2005. © 2005 Wiley‐Liss, Inc.
Semantic and phonological skills in predicting reading development: from 3–16 years of age
Authors: Frost Jørgen , Madsbjerg Sigrid , Niedersøe Jan , Olofsson Åke , Sørensen Peer Møller
Published: February 2005

The present longitudinal study investigated the relationship between pre‐school semantic skills (vocabulary, comprehension and sentence construction), phonological awareness and later word decoding and reading comprehension skills. More than 200 Danish children were followed from a speech therapist screening at the age of three, through a phonological group screening at six, word decoding tests in Grade 2, sentence reading tests in Grades 3, 4, and 6, and to a text reading test in Grade 9 (age 16). The predictor variables consisted of both standardized test results, professional ratings, and a factor of interest in books.

The results showed that both the semantic variables and interest in books at the age of three and the phonological variables at the age of six predicted reading development significantly at the age of 16. In addition the results demonstrated changing main effect from semantic and phonological variables on reading development. Phonological awareness at the age of 6 seemed to have the greatest influence on reading at the beginning of Grade 2 compared to the semantic variables at the age of three. On all other measures in time, the semantic variables had the greatest influence. Copyright © 2005 John Wiley & Sons, Ltd.
The Use of Tosylhydrazone Salts as a Safe Alternative for Handling Diazo Compounds and Their Applications in Organic Synthesis
Authors: Fulton J. Robin , Aggarwal Varinder K. , de Vicente Javier
Published: February 2005

Diazo compounds are useful synthetic intermediates in organic synthesis but, due to their toxicity and unpredictable explosive behaviour, their unique reactivity has not been fully exploited and their use on large scale has been avoided. We have developed a reliable method that generates diazo compounds in situ. Our approach is based on the Bamford–Stevens reaction, which utilizes tosylhydrazone salts as diazo precursors. In the presence of phase‐transfer‐catalysts (PTC), we found that tosylhydrazone salts can be cleanly converted to diazo compounds under mild reaction conditions and in a wide range of solvents. These diazo compounds can then be induced to react directly with alkenes or alkynes to synthesize pyrazoles or with aldehydes to generate ketones. Alternatively, diazo compounds can react with transition metals capable of carbene transfer reactions. We have shown the usefulness of this chemistry in a number of different transformations, such as Wittig olefination reactions and the sulfur ylide mediated epoxidation, as well as aziridination and cyclopropanation chemistry as applied toward the synthesis of more complicated molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Cognitive and functional neuroimaging correlate for anosognosia in Mild Cognitive Impairment and Alzheimer's disease
Authors: Vogel Asmus , Hasselbalch Steen G. , Gade Anders , Ziebell Morten , Waldemar Gunhild
Published: February 2005

Objectives

To investigate the correlation between anosognosia and behavioural symptoms, performance on executive tests, and frontal cortex regional cerebral blood flow (rCBF) in patients with ‘amnestic mild cognitive impairment’ (MCI) and mild Alzheimer's disease (AD).

Methods

From a prospective Memory Clinic cohort including consecutively referred patients, age 60 years or above, and with MMSE score 20 or above, 36 patients with AD and 30 with MCI were included in this study. Anosognosia was assessed using a categorical scale and discrepancy scores between patients' and relatives' reports on a 20‐item Memory Questionnaire (MQ). Behavioural symptoms were assessed with Frontal Behavioural Inventory (FBI). Executive functions were examined with a range of neuropsychological tests. Tc99m‐HMPAO SPECT was obtained in an unselected sample of 55 of the 66 patients, and rCBF was analysed in six cortical frontal regions.

Results

Insight was equally impaired in the two patient groups. A significant correlation was found between impaired awareness and dementia severity (MMSE). Discrepancy‐scores on the MQ were significantly correlated to scores on FBI and to rCBF in the right inferior frontal gyrus, but not to executive tests. The groups classified by the categorical ratings ‘full’, ‘shallow’ and ‘no’ awareness were not characterized by differences in behavioural symptoms, executive performance or frontal rCBF.

Conclusions

Impaired awareness is associated with behavioural symptoms and may reflect functional impairment in the right inferior frontal cortex. Copyright © 2005 John Wiley & Sons, Ltd.
Clinical trials of potential antidepressants: to what extent are the elderly represented: a review
Authors: Giron Maria Stella T. , Fastbom Johan , Winblad Bengt
Published: February 2005

Background

There is widespread use of antidepressants in the elderly population. The principle of treatment of depression, however, is derived mostly from studies employing young adults and healthy elderly. This article reviews the literature on the extent to which the elderly are represented in clinical trials of potential antidepressants.

Method

Medline search of relevant articles of clinical trials of potential antidepressants.

Results

The maximum age of inclusion for most clinical trials was 65 years. The highest age reported for depressed subjects was 90 years. There was no clear consensus on who were considered to be elderly; clinical trials conducted on the elderly included subjects who were 50, 55, or 60 years and over. Pharmacological studies on healthy subjects were most often done on young adults, age range 18 to 65 years. The period of study was relatively shorter for clinical trials done on elderly subjects. There was however, no difference in the exclusion or inclusion criteria between studies done in young and elderly subjects.

Conclusions

Elderly subjects aged 75 years and over were clearly underrepresented in the clinical trials of potential antidepressants. For drugs that are used by the elderly, in its pivotal studies for registration, the inclusion of at least 25% of subjects aged 75 years and over is recommended. Copyright © 2005 John Wiley & Sons, Ltd.
Beyond the global score of the Zarit Burden Interview: useful dimensions for clinicians
Authors: Ankri Joël , Andrieu Sandrine , Beaufils Béatrice , Grand Alain , Henrard Jean Claude
Published: February 2005

Objectives

The purpose of this study was to explore the structure of the Zarit Burden Interview (ZBI) for informal caregivers of patients suffering from AD or related disorders, and to examine the relations of the dimensions found with functional disabilities and other patient health indicators.

Design

152 dyads of community‐dwelling older adults with dementia and their primary caregivers were analysed.

Methods

Caregiver burden was measured by the 22‐item ZBI. Caregivers' and care recipients' characteristics were collected with the MDS (Minimum Data Set) of the RAI (Resident Assessment Instrument) Home Care instrument. Data on dementia (diagnosis, severity, MMSE) were also obtained. Burden data were analysed by principal component analysis (PCA) with varimax rotation. Relationships between scores on PCA factors and care recipients' health indicators were studied with inferential statisti cal tests.

Results

Three dimensions of burden were found: effect on the social and personal life of caregivers, psychological burden and feelings of guilt. Some health variables were linked to these dimensions. Spouses and children perceived burden differently. Spouse caregivers emphasized the deterioration of their personal and social life. Children, less involved in daily care, were more prone to feel guilt that they were not doing enough for their parent. Copyright © 2005 John Wiley & Sons, Ltd.
Seasonal mood variation in the elderly: the Leiden 85‐plus Study
Authors: de Craen Anton J. M. , Gussekloo Jacobijn , van der Mast Roos C. , Cessie Saskia le , Lemkes Johanna W. , Westendorp Rudi G. J.
Published: February 2005

Background

The influence of seasonal changes on mood and behaviour is called seasonality. The prevalence of seasonality in elderly subjects is unknown.

Aim

To investigate the seasonality pattern in mood and behaviour at old age.

Methods

All subjects from the Leiden 85‐plus Study with an MMSE score of 19 or more were assessed for depressive feelings at age 85 and yearly thereafter. The influence of time of the year, duration of sunlight, daylight, and rain on the prevalence of depressive symptoms was assessed using linear mixed models for repeated measurements.

Results

There was no significant seasonal pattern in the data (p = 0.44). Within each of the four years of observation (85, 86, 87 and 88 years) and all years combined, there was also no significant association between the one‐month cumulation of duration of sunlight, daylight, or rain and the score on the GDS (all p‐values >0.05). The results of either the one week or three‐month accumulation of sunlight, daylight, or rain were comparable to the one‐month results.

Conclusions

Estimates of prevalence of seasonality reported in the literature might be overestimated or a remarkable difference between young and old subjects exists. Copyright © 2005 John Wiley & Sons, Ltd.
Relationship of exercise and other risk factors to depression of Alzheimer's disease: the LASER‐AD study
Authors: Regan Ciaran , Katona Cornelius , Walker Zuzana , Livingston Gill
Published: February 2005

Background

Depression is common in Alzheimer's disease (AD; 5–35%). It is associated with increased disability, cost of care and carer burden. Exercise is known to be associated with a lower prevalence of depression across the age range but little is known about its relationship to depression in AD.

Aims

To investigate exercise and putative risk factors for depression in a community based sample of people with AD representative of the range of cognitive impairment found in the population with dementia.

Methods

Information was collected from 224 people with AD and their caregiver using standardised cognitive, psychological and behavioural instruments. Exercise levelswere classified into three categories: absent, moderate, and vigorous, using the previous two weeks exercise levels to confirm regularity and recency.

Results

9/51 (17.6%) depressed participants took exercise compared with 76/173 (43.9%) non‐depressed [odds ratio (OR) = 2.9, confidence interval (CI) = 1.5–5.6, p = 0.001]. Not taking part in other activities (hobbies and interests) was associated with depression but less so than lack of exercise. Independent predictors of depression were: lack of exercise (p < 0.001, OR = 3.4, CI = 1.7–7.2), taking cholinesterase inhibitors (p < 0.05, OR = 2.4, CI = 1.2–4.9) and having less involvement in hobbies or interests (p < 0.05, OR = 1.2, CI = 1.0–1.5).

Conclusion

None of the traditional risk factors for depression in older people were associated with depression in AD. Taking regular exercise may protect against depression in AD. Copyright © 2005 John Wiley & Sons, Ltd.
Cognitive intervention for community‐dwelling older persons with memory problems: telemedicine versus face‐to‐face treatment
Authors: Poon Patricia , Hui Elsie , Dai David , Kwok Timothy , Woo Jean
Published: February 2005

Background

Memory complaints and decline in cognitive function are common in the elederly. Cognitive intervention has been shown to be beneficial in Alzheimer's disease (AD). However, few community‐based cognitive intervention programs are available in Hong Kong. The aim of this project is to examine and compare the feasibility, acceptability, and clinical outcome of a cognitive intervention program for older patients with mild cognitive impairment and mild dementia using telemedicine versus a conventional face‐to‐face method.

Methods

Community‐dwelling older subjects with mild dementia or mild cognitive impairments were recruited from a community center. A total of 12 sessions of assessment and cognitive intervention were conducted via videoconferencing or by face‐to‐face method. Assessment included: Cantonese version of Mini Mental State Examination (C‐MMSE), Cantonese version of Rivermead Behavioural Memory test (C‐RBMT) and Hierarchic Dementia Scale (HDS).

Results

Twenty‐two clients were recruited. There was significant and comparable cognitive improvement in clients in both treatment arms. The videoconference arm was highly accepted by the clients and the community center. Overall compliance rate of participants was above 95%.

Conclusions

Telemedicine was a feasible, effective and acceptable means in providing cognitive assessment and intervention to older persons with mild cognitive deficits. Promoting such a program to other community settings would further enhance the accessibility of dementia service to the community. Copyright © 2005 John Wiley & Sons, Ltd.
A computational approach to predicting cell growth on polymeric biomaterials
Authors: Abramson Sascha D. , Alexe Gabriela , Hammer Peter L. , Kohn Joachim
Published: February 2005

A predictive model that can correlate the chemical composition of a biomaterial with the biological response of cells that are in contact with that biomaterial would represent a major advance and would facilitate the rational design of new biomaterials. As a first step toward this goal, we report here on the use of Logical Analysis of Data (LAD) to model the effect of selected polymer properties on the growth of two different cell types, rat lung fibroblasts (RLF, a transformed cell line), and normal foreskin fibroblasts (NFF, nontransformed human cells), on 112 surfaces obtained from a combinatorially designed library of polymers. LAD is a knowledge extraction methodology, based on using combinatorics, optimization, and Boolean logic. LAD was trained on a subset of 62 polymers and was then used to predict cell growth on 50 previously untested polymers. Experimental validation indicated that LAD correctly predicted the high and low cell growth polymers and found optimal ranges for polymer chemical composition, surface chemistry, and bulk properties. Particularly noteworthy is that LAD correctly identified high‐performing polymer surfaces, which surpassed commercial tissue culture polystyrene as growth substratum for normal foreskin fibroblasts. Our results establish the feasibility of using computational modeling of cell growth on flat polymeric surfaces to identify promising “lead” polymers for applications that require either high or low cell growth. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res 73A: 116–124, 2005
Intracellular domain of the IFNaR2 interferon receptor subunit mediates transcription via Stat2
Authors: El Fiky Ashraf , Arch Allison E. , Krolewski John J.
Published: February 2005

We recently demonstrated that IFNaR2, a subunit of the interferon receptor, can be proteolytically cleaved in response to interferon‐alpha and other activators of protein kinase C. Cleavage occurs at multiple sites, via a mechanism similar to that employed by Notch and the Alzheimer's precursor protein, and releases the intracellular domain (ICD). In this study, we demonstrate that the IFNaR2 ICD, when fused to the yeast Gal4 DNA binding domain (Gal4DBD) selectively modulates transcription of four different promoters under the control of Gal4 upstream activating sequences. We previously showed that Stat2 binds constitutively to the ICD of IFNaR2, in a manner that is independent of tyrosine phosphorylation. Here, we show that ICD transcriptional modulation is dependent upon the carboxyl‐terminal transactivation domain of Stat2. Specifically, complementing Stat2 deficient cells with wild‐type Stat2 restored the ICD‐mediated transcriptional effects while complementation with a mutant form of Stat2 lacking the transcriptional activation domain (TAD) did not. In addition, mutation of the Stat2 binding site on the ICD reduced the transcriptional activity of the Gal4DBD–ICD. Finally, we demonstrate that the activity of Jak1, a tyrosine kinase also known to bind to IFNaR2, is required for ICD‐mediated transcriptional effects. © 2005 Wiley‐Liss, Inc.
Comparison of mass transfer efficiency in horizontal rotating packed beds and rotating biological contactors
Authors: Mathure Pankaj , Patwardhan Ashwin
Published: February 2005

In this study, the mass transfer efficiencies of a novel horizontal rotating packed (h‐RPB) bed and the conventional disc‐type rotating biological contactor (RBC) were studied at four speeds and seven submergences. Pall rings of two different sizes (25, 38 mm), superintalox saddles and a wiremesh spiral bundle were used as packings in the h‐RPB. Volumetric gas–liquid mass transfer coefficients were determined by unsteady state absorption of atmospheric oxygen in de‐aerated water. Power consumption per unit liquid volume has been found for all geometries tested. The oxygen transfer efficiency values for the h‐RPB were found to be 2–5 kg kWh−1 and for the disc RBC were found to be 1–2 kg kWh−1. The performance of the h‐RPB was also compared with other gas–liquid contactors such as surface aerators. The study proves that the h‐RPB is a energy efficient alternative to conventional contactors. Copyright © 2005 Society of Chemical Industry
Application of residence time distribution technique to the study of the hydrodynamic behaviour of a full‐scale wastewater treatment plant plug‐flow bioreactor
Authors: Olivet David , Valls Joan , Gordillo M Àngels , Freixó Àngel , Sánchez Antoni
Published: February 2005

The hydrodynamic behaviour of a full‐scale wastewater treatment plant (WWTP) bioreactor treating municipal wastewater, situated in Granollers (Barcelona, Spain), has been studied by means of a residence time distribution (RTD) technique using lithium (chloride) as tracer. The bioreactor studied is designed to work as a plug‐flow reactor and it is divided into two independent lanes (1 and 2), each one composed of four compartments in series resulting in a total volume of 3970 m3 per lane. During the RTD experiments, working flow was 1000 m3 h−1 per lane, which implied an ideal mean residence time of 3.97 h. When a lithium chloride tracer was injected in the bioreactor, both lanes showed a similar highly non‐ideal hydrodynamic behaviour, which had an important effect on the reactor's performance. This global RTD was complemented by means of local RTDs in different locations of the bioreactor in order to determine qualitatively the reactor's mixing regime. Different non‐ideal models (namely axial dispersion, tanks‐in‐series and some simple compartment models) have been tested for the modelling of the experimental RTD. The best model fitting RTD data for Lanes 1 and 2 was a configuration consisting of four mixed tanks in series. The RTD study proposed in this work will permit improvement of the reactor's mixing performance, which is of special interest in future projects including simultaneous removal of carbon, nitrogen and phosphorus. Copyright © 2005 Society of Chemical Industry
The use of hybrid anaerobic solid–liquid (HASL) system for the treatment of lipid‐containing food waste
Authors: Stabnikova Olena , Ang Suay‐Siong , Liu Xue‐Yan , Ivanov Volodymyr , Tay Joo‐Hwa , Wang Jing‐Yuan
Published: February 2005

The hybrid anaerobic solid–liquid (HASL) system was a modified two‐phase anaerobic digester developed for bioconversion of food waste. The aim of this study was to estimate the feasibility of the HASL system for the treatment of food waste with a high content of lipids. The presence of lipids in food waste increased the energy value of nutrients but could inhibit growth of methanogens. The positive effect of lipids on the performance of anaerobic digestion dominated when the contents of lipids were in the range from 20 to 30% of total solids of food waste. Lipid contents of 40% diminished the production of volatile fatty acids in the acidogenic reactor as well as biogas production and the concentration of total bacteria and methanogens in the methanogenic reactor. Therefore, the HASL system can be used for the treatment of lipid‐containing food wastes if the lipid content is below 40% of total solids. Copyright © 2005 Society of Chemical Industry
Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: Virological features of IFN‐resistant cases with hepatocyte steatosis
Authors: Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Sezaki Hitomi , Hosaka Tetsuya , Someya Takashi , Kobayashi Masahiro , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kobayashi Mariko , Kumada Hiromitsu
Published: February 2005

The role of hepatocyte steatosis in interferon (IFN) resistance is still unclear, especially in patients infected with hepatitis C virus (HCV) genotype 2a. The present study was conducted in 364 consecutive non‐cirrhotic naive patients infected with genotype 2a, who were evaluated for the severity of steatosis and response to IFN monotherapy after a 24‐week median duration of therapy. The patients were examined for factors associated with steatosis and treatment efficacy according to the grade of steatosis. Early viral kinetics was also evaluated in 64 patients for predictors of response to therapy. Nine IFN‐resistant patients were assessed for the relationship between amino acid sequence of HCV core region/NS5A and severity of steatosis. Multivariate analysis identified two independent factors associated with steatosis; serum ferritin ≥200 μg/l and body mass index ≥25.0 kg/m2. The sustained virological response rate in patients with high‐grade steatosis was significantly lower than in the low‐grade group. Study of early viral kinetics showed a significantly lower cumulative HCV‐RNA negative rate for the high‐grade than low‐grade steatosis group. Sequence analysis of HCV core region/NS5A in IFN‐resistant patients with or without steatosis failed to identify steatosis‐specific amino acid substitutions associated with resistance. This study of HCV genotype 2a suggested that steatosis is associated with excess iron storage, and that it is an important predictor of efficacy of IFN monotherapy. Further large‐scale studies are warranted to examine the role of amino acid substitutions on IFN resistance specific for steatosis. J. Med. Virol. 75:550–558, 2005. © 2005 Wiley‐Liss, Inc.
Phenotypic and genetic changes in coxsackievirus B5 following repeated passage in mouse pancreas in vivo
Authors: Al‐Hello Haider , Davydova Berta , Smura Teemu , Kaialainen Svetlana , Ylipaasto Petri , Saario Elise , Hovi Tapani , Rieder Elizabeth , Roivainen Merja
Published: February 2005

Common enterovirus infections appear to initiate or facilitate the pathogenetic processes leading to type 1 diabetes, and also sometimes precipitate the clinical disease. In experimental infection of mice, coxsackieviruses have shown to have a strong affinity for the exocrine tissue, while even in lethal cases, the islets remain unaffected. The virus strain most intensively studied in this respect is the diabetogenic variant E2 of coxsackievirus B4. In addition, it is known that all six serotypes of coxsackie B viruses can be made diabetogenic by repeated passages in either mouse pancreas in vivo or in cultured mouse beta‐cells in vitro. However, the genetic determinants of the phenomenon have not been determined. In the present study, a laboratory strain of coxsackievirus B5 was passaged repeatedly in mouse pancreas in vivo. After 15 passages, the virus phenotype was clearly changed and infection of the variant resulted in a diabetes‐like syndrome in mice characterized by chronic pancreatic inflammation together with dysregulation in glucose metabolism, loss of pancreatic acinar tissue, and mild insulitis. In order to characterize the genetic determinants involved in mouse pancreas adaptation, the passaged virus variant together with the parental virus strain was cloned for molecular characterization. The whole genome sequencing of both virus strains revealed only limited differences. Altogether, eight nucleotides were changed resulting in five amino acid substitutions, of which three were located in the capsid proteins. J. Med. Virol. 75:566–574, 2005. © 2005 Wiley‐Liss, Inc.