Showing papers by "University of Bergen published in 2009"

IntCal13 and Marine13 radiocarbon age calibration curves 0-50,000 years cal BP

Abstract: Additional co-authors: TJ Heaton, AG Hogg, KA Hughen, KF Kaiser, B Kromer, SW Manning, RW Reimer, DA Richards, JR Southon, S Talamo, CSM Turney, J van der Plicht, CE Weyhenmeyer

Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency.

Abstract: BACKGROUND Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia. METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 μg per liter or between 100 and 299 μg per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio, to receive 200 mg of intravenous iron (ferric carboxymaltose) or saline (placebo). The primary end points were the self-reported Patient Global Assessment and NYHA functional class, both at week 24. Secondary end points included the distance walked in 6 minutes and the health-related quality of life. RESULTS Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups. CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable. (ClinicalTrials.gov number, NCT00520780.)

Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health.

Abstract: In the present paper, we describe a model of neurovisceral integration in which a set of neural structures involved in cognitive, affective, and autonomic regulation are related to heart rate variability (HRV) and cognitive performance. We detail the pathways involved in the neural regulation of the cardiovascular system and provide pharmacological and neuroimaging data in support of the neural structures linking the central nervous system to HRV in humans. We review a number of studies from our group showing that individual differences in HRV are related to performance on tasks associated with executive function and prefrontal cortical activity. These studies include comparisons of executive- and nonexecutive-function tasks in healthy participants, in both threatening and nonthreatening conditions. In addition, we show that manipulating resting HRV levels is associated with changes in performance on executive-function tasks. We also examine the relationship between HRV and cognitive performance in ecologically valid situations using a police shooting simulation and a naval navigation simulation. Finally, we review our studies in anxiety patients, as well as studies examining psychopathy. These findings in total suggest an important relationship among cognitive performance, HRV, and prefrontal neural function that has important implications for both physical and mental health. Future studies are needed to determine exactly which executive functions are associated with individual differences in HRV in a wider range of situations and populations.

Measuring exposure to bullying and harassment at work: Validity, factor structure and psychometric properties of the Negative Acts Questionnaire-Revised

Abstract: This study investigates the psychometric properties, factor structure and validity of the revised Negative Acts Questionnaire-Revised (NAQ-R), an instrument designed to measure exposure to bullying in the workplace. By reanalyzing data based on a heterogeneous sample of 5288 UK employees, the results show that the 22-item instrument has a high internal stability, with three underlying factors: personal bullying, work-related bullying and physically intimidating forms of bullying, although the instrument may also be used as a single factor measure. Criterion validity was explored by relating the scores on the NAQ-R to a single-item measure of perceived victimization from bullying, showing high correlations with both the total NAQ-R and scores on the three factors. Targets of bullying scored significantly higher on all 22 items compared to non-targets. The NAQ-R correlated as expected with measures of mental health, psychosocial work environment and leadership, indicating a good construct validity ...

Accurate determination of microbial diversity from 454 pyrosequencing data

Abstract: We present an algorithm, PyroNoise, that clusters the flowgrams of 454 pyrosequencing reads using a distance measure that models sequencing noise. This infers the true sequences in a collection of amplicons. We pyrosequenced a known mixture of microbial 16S rDNA sequences extracted from a lake and found that without noise reduction the number of operational taxonomic units is overestimated but using PyroNoise it can be accurately calculated.

A cross-national profile of bullying and victimization among adolescents in 40 countries

Abstract: Objectives: (1) To compare the prevalence of bullying and victimization among boys and girls and by age in 40 countries. (2) In 6 countries, to compare rates of direct physical, direct verbal, and indirect bullying by gender, age, and country.

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Abstract: Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.

Self-selection and bias in a large prospective pregnancy cohort in Norway.

Abstract: Self-selection in epidemiological studies may introduce selection bias and influence the validity of study results. To evaluate potential bias due to self-selection in a large prospective pregnancy cohort in Norway, the authors studied differences in prevalence estimates and association measures between study participants and all women giving birth in Norway. Women who agreed to participate in the Norwegian Mother and Child Cohort Study (43.5% of invited; n = 73 579) were compared with all women giving birth in Norway (n = 398 849) using data from the population-based Medical Birth Registry of Norway in 2000-2006. Bias in the prevalence of 23 exposure and outcome variables was measured as the ratio of relative frequencies, whereas bias in exposure-outcome associations of eight relationships was measured as the ratio of odds ratios. Statistically significant relative differences in prevalence estimates between the cohort participants and the total population were found for all variables, except for maternal epilepsy, chronic hypertension and pre-eclampsia. There was a strong under-representation of the youngest women (<25 years), those living alone, mothers with more than two previous births and with previous stillbirths (relative deviation 30-45%). In addition, smokers, women with stillbirths and neonatal death were markedly under-represented in the cohort (relative deviation 22-43%), while multivitamin and folic acid supplement users were over-represented (relative deviation 31-43%). Despite this, no statistically relative differences in association measures were found between participants and the total population regarding the eight exposure-outcome associations. Using data from the Medical Birth Registry of Norway, this study suggests that prevalence estimates of exposures and outcomes, but not estimates of exposure-outcome associations are biased due to self-selection in the Norwegian Mother and Child Cohort Study.

A Genome-Wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci

Abstract: There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of alpha(1)-antitrypsin, which is present in 1-2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the alpha-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48 x 10(-10), (rs8034191) and 5.74 x 10(-10) (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429). The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer.

High-resolution palaeoclimatology of the last millennium: a review of current status and future prospects:

Abstract: This review of late-Holocene palaeoclimatology represents the results from a PAGES/CLIVAR Intersection Panel meeting that took place in June 2006. The review is in three parts: the principal high-resolution proxy disciplines (trees, corals, ice cores and documentary evidence), emphasizing current issues in their use for climate reconstruction; the various approaches that have been adopted to combine multiple climate proxy records to provide estimates of past annual-to-decadal timescale Northern Hemisphere surface temperatures and other climate variables, such as large-scale circulation indices; and the forcing histories used in climate model simulations of the past millennium. We discuss the need to develop a framework through which current and new approaches to interpreting these proxy data may be rigorously assessed using pseudo-proxies derived from climate model runs, where the `answer' is known. The article concludes with a list of recommendations. First, more raw proxy data are required from the diverse disciplines and from more locations, as well as replication, for all proxy sources, of the basic raw measurements to improve absolute dating, and to better distinguish the proxy climate signal from noise. Second, more effort is required to improve the understanding of what individual proxies respond to, supported by more site measurements and process studies. These activities should also be mindful of the correlation structure of instrumental data, indicating which adjacent proxy records ought to be in agreement and which not. Third, large-scale climate reconstructions should be attempted using a wide variety of techniques, emphasizing those for which quantified errors can be estimated at specified timescales. Fourth, a greater use of climate model simulations is needed to guide the choice of reconstruction techniques (the pseudo-proxy concept) and possibly help determine where, given limited resources, future sampling should be concentrated.

A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking

Abstract: There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.

The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV-Naive Women Aged 16–26 Years

Abstract: Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of >= 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for similar to 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type. (Less)

Explaining microbial population genomics through phage predation

Abstract: Not all isolates of a species contain the same set of genes. In this Opinion article, Rodriguez-Valera and colleagues propose the constant-diversity model to account for these differences. In this model, predation by phages promotes bacterial diversity and allows more efficient use of the nutrients in the environment. The remarkable differences that have been detected by metagenomics in the genomes of strains of the same bacterial species are difficult to reconcile with the widely accepted paradigm that periodic selection within bacterial populations will regularly purge genomic diversity by clonal replacement. We have found that many of the genes that differ between strains affect regions that are potential phage recognition targets. We therefore propose the constant-diversity dynamics model, in which the diversity of prokaryotic populations is preserved by phage predation. We provide supporting evidence for this model from metagenomics, mathematical analysis and computer simulations. Periodic selection and phage predation dynamics are not mutually exclusive; we compare their predictions to shed light on the ecological circumstances under which each type of dynamics could predominate.

The Health Behaviour in School-aged Children (HBSC) study: methodological developments and current tensions

Abstract: Objectives: To describe the methodological development of the HBSC survey since its inception and explore methodological tensions that need to be addressed in the ongoing work on this and other large-scale cross-national surveys

Long-term Cultures of Bone Marrow–Derived Human Mesenchymal Stem Cells Frequently Undergo Spontaneous Malignant Transformation

Abstract: Human mesenchymal stem cells (hMSC) aid in tissue maintenance and repair by differentiating into specialized cell types. Due to this ability, hMSC are currently being evaluated for cell-based therapies of tissue injury and degenerative diseases. However, extensive expansion ex vivo is a prerequisite to obtain the cell numbers required for human cell-based therapy protocols. Recent studies indicate that hMSC may contribute to cancer development and progression either by acting as cancer-initiating cells or through interactions with stromal elements. If spontaneous transformation ex vivo occurs, this may jeopardize the use of hMSC as therapeutic tools. Whereas murine MSC readily undergo spontaneous transformation, there are conflicting reports about spontaneous transformation of hMSC. We have addressed this controversy in a two-center study by growing bone marrow-derived hMSC in long-term cultures (5-106 weeks). We report for the first time spontaneous malignant transformation to occur in 45.8% (11 of 24) of these cultures. In comparison with hMSC, the transformed mesenchymal cells (TMC) showed a significantly increased proliferation rate and altered morphology and phenotype. In contrast to hMSC, TMC grew well in soft agar assays and were unable to undergo complete differentiation. Importantly, TMC were highly tumorigenic, causing multiple fast-growing lung deposits when injected into immunodeficient mice. We conclude that spontaneous malignant transformation may represent a biohazard in long-term ex vivo expansion of hMSC. On the other hand, this spontaneous transformation process may represent a unique model for studying molecular pathways initiating malignant transformation of hMSC.

Constraints on the magnitude and patterns of ocean cooling at the Last Glacial Maximum

Abstract: Observation-based reconstructions of sea surface temperature from relatively stable periods in the past, such as the Last Glacial Maximum, represent an important means of constraining climate sensitivity and evaluating model simulations1. The first quantitative global reconstruction of sea surface temperatures during the Last Glacial Maximum was developed by the Climate Long-Range Investigation, Mapping and Prediction (CLIMAP) project in the 1970s and 1980s (refs 2, 3). Since that time, several shortcomings of that earlier effort have become apparent4. Here we present an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project5. We integrate microfossil and geochemical reconstructions of surface temperatures and include assessments of the reliability of individual records. Our reconstruction reveals the presence of large longitudinal gradients in sea surface temperature in all of the ocean basins, in contrast to the simulations of the Last Glacial Maximum climate available at present6, 7.

The HELLP syndrome: Clinical issues and management. A Review

Abstract: The HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10–20% of cases with severe preeclampsia. The present review highlights occurrence, diagnosis, complications, surveillance, corticosteroid treatment, mode of delivery and risk of recurrence. Clinical reports and reviews published between 2000 and 2008 were screened using Pub Med and Cochrane databases. About 70% of the cases develop before delivery, the majority between the 27th and 37th gestational weeks; the remainder within 48 hours after delivery. The HELLP syndrome may be complete or incomplete. In the Tennessee Classification System diagnostic criteria for HELLP are haemolysis with increased LDH (> 600 U/L), AST (≥ 70 U/L), and platelets < 100·109/L. The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts. The syndrome is a progressive condition and serious complications are frequent. Conservative treatment (≥ 48 hours) is controversial but may be considered in selected cases < 34 weeks' gestation. Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. If the cervix is unfavourable, it is reasonable to induce cervical ripening and then labour. In gestational ages between 24 and 34 weeks most authors prefer a single course of corticosteroid therapy for foetal lung maturation, either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg or dexamethasone 12 hours apart before delivery. Standard corticosteroid treatment is, however, of uncertain clinical value in the maternal HELLP syndrome. High-dose treatment and repeated doses should be avoided for fear of long-term adverse effects on the foetal brain. Before 34 weeks' gestation, delivery should be performed if the maternal condition worsens or signs of intrauterine foetal distress occur. Blood pressure should be kept below 155/105 mmHg. Close surveillance of the mother should be continued for at least 48 hours after delivery.

Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans

Abstract: Nα-terminal acetylation is one of the most common protein modifications in eukaryotes. The COmbined FRActional DIagonal Chromatography (COFRADIC) proteomics technology that can be specifically used to isolate N-terminal peptides was used to determine the N-terminal acetylation status of 742 human and 379 yeast protein N termini, representing the largest eukaryotic dataset of N-terminal acetylation. The major N-terminal acetyltransferase (NAT), NatA, acts on subclasses of proteins with Ser-, Ala-, Thr-, Gly-, Cys- and Val- N termini. NatA is composed of subunits encoded by yARD1 and yNAT1 in yeast and hARD1 and hNAT1 in humans. A yeast ard1-Δ nat1-Δ strain was phenotypically complemented by hARD1 hNAT1, suggesting that yNatA and hNatA are similar. However, heterologous combinations, hARD1 yNAT1 and yARD1 hNAT1, were not functional in yeast, suggesting significant structural subunit differences between the species. Proteomics of a yeast ard1-Δ nat1-Δ strain expressing hNatA demonstrated that hNatA acts on nearly the same set of yeast proteins as yNatA, further revealing that NatA from humans and yeast have identical or nearly identical specificities. Nevertheless, all NatA substrates in yeast were only partially N-acetylated, whereas the corresponding NatA substrates in HeLa cells were mainly completely N-acetylated. Overall, we observed a higher proportion of N-terminally acetylated proteins in humans (84%) as compared with yeast (57%). N-acetylation occurred on approximately one-half of the human proteins with Met-Lys- termini, but did not occur on yeast proteins with such termini. Thus, although we revealed different N-acetylation patterns in yeast and humans, the major NAT, NatA, acetylates the same substrates in both species.

The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

Abstract: Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.

Environmental, genomic and taxonomic perspectives on methanotrophic Verrucomicrobia.

Abstract: Aerobic methanotrophic bacteria are capable of utilizing methane as their sole energy source. They are commonly found at the oxic/anoxic interfaces of environments such as wetlands, aquatic sediments, and landfills, where they feed on methane produced in anoxic zones of these environments. Until recently, all known species of aerobic methanotrophs belonged to the phylum Proteobacteria, in the classes Gammaproteobacteria and Alphaproteobacteria. However, in 2007-2008 three research groups independently described the isolation of thermoacidophilic methanotrophs that represented a distinct lineage within the bacterial phylum Verrucomicrobia. Isolates were obtained from geothermal areas in Italy, New Zealand and Russia. They are by far the most acidophilic methanotrophs known, with a lower growth limit below pH 1. Here we summarize the properties of these novel methanotrophic Verrucomicrobia, compare them with the proteobacterial methanotrophs, propose a unified taxonomic framework for them and speculate on their potential environmental significance. New genomic and physiological data are combined with existing information to allow detailed comparison of the three strains. We propose the new genus Methylacidiphilum to encompass all three newly discovered bacteria.

Cognitive Functioning in Major Depression – A Summary

Abstract: The aim of the present paper is to summarize the research during the past decade regarding cognitive functioning in Major Depressive Disorder (MDD). Cognitive impairment in the acute phase of illness has been frequently reported. The findings are shown in different cognitive domains, such as executive functions (EF), attention, memory and psychomotor speed. Fewer reports have investigated cognitive functioning in MDD in longitudinal studies. Some longitudinal reports show that the impairment observed in the acute phase of illness may be long lasting despite symptom reduction and recovery. However, findings regarding cognitive functioning in depression are divergent. Factors that might contribute to the divergent findings, such as depression subtype, severity and comorbidity are discussed. Clinical implications and focus of future research directions is highlighted. .In conclusion, depression is associated with cognitive impairment in the acute phase of illness, and some reports indicate that this impairment might be long lasting despite symptom reduction and recovery.

Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial

Abstract: Summary Background Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are common forms of dementia that substantially affect quality of life. Currently, the only treatment licensed for PDD is rivastigmine, and there are no licensed treatments for DLB. We aimed to test the safety and efficacy of the N-methyl D-aspartate (NMDA) receptor antagonist memantine in patients with PDD or DLB. Methods We did a parallel-group, 24-week, randomised controlled study of memantine (20 mg per day) versus placebo at four psychiatric and neurological outpatient clinics in Norway, Sweden, and the UK during 2005–08. Patients were included if they fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease (PD) and developed dementia according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM IV) criteria at least 1 year after the onset of motor symptoms (PDD) or met the revised consensus operationalised criteria for DLB. Patients were assigned to a computer-generated randomisation list. All physicians who had contact with patients were masked to treatment allocation. The primary outcome measure was clinical global impression of change (CGIC), which ranged from 1 to 7 points, and a low score means a better outcome. Analysis was by intention to treat based on the last observation carried forward. This trial is registered, number ISRCTN89624516. Findings 72 patients with PDD or DLB were randomly assigned and started treatment: 34 with memantine and 38 with placebo. 56 (78%) completed the study. All withdrawals were owing to adverse events, but the proportion of withdrawals was similar in both groups. At week 24 the patients in the memantine group had better CGIC scores than those taking placebo (mean difference 0·7, 95% CI 0·04–1·39; p=0·03). With the exception of improved speed on attentional tasks in the memantine group (a quick test of cognition [AQT] form: difference 12·4, 95% CI 6·0–30·9; p=0·004), there were no significant differences between the groups in secondary outcome measures. Interpretation Patients with DLB or PDD might benefit from treatment with memantine, which was well tolerated. Large-scale studies are now required to confirm our preliminary findings. Funding The Western Norway Regional Health Authority; H Lundbeck A/S.

Rolandic alpha and beta EEG rhythms' strengths are inversely related to fMRI-BOLD signal in primary somatosensory and motor cortex

Abstract: Similar to the posterior alpha rhythm, pericentral (Rolandic) EEG rhythms in the alpha and beta frequency range are referred to as "idle rhythms" indicating a "resting state" of the respective system. The precise function of these rhythms is not clear. We used simultaneous EEG-fMRI during a bimanual motor task to localize brain areas involved in Rolandic alpha and beta EEG rhythms. The identification of these rhythms in the MR environment was achieved by a blind source separation algorithm. Rhythm "strength", i.e. spectral power determined by wavelet analysis, inversely correlated most strongly with the fMRI-BOLD signal in the postcentral cortex for the Rolandic alpha (mu) rhythm and in the precentral cortex for the Rolandic beta rhythm. FMRI correlates of Rolandic alpha and beta rhythms were distinct from those associated with the posterior "classical" alpha rhythm, which correlated inversely with the BOLD signal in the occipital cortex. An inverse correlation with the BOLD signal in the respective sensory area seems to be a general feature of "idle rhythms".

Sex Differences and the Impact of Steroid Hormones on the Developing Human Brain

Abstract: Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

The sagittal growth of the eye. IV. Ultrasonic measurement of the axial length of the eye from birth to puberty.

Abstract: The length of the optic axis is measured ultrasonically by adding the values for the depth of the anterior chamber, the length of the axial diameter of the lens, and the length of the posterior segment (the vitreous). T h e object of this s tudy is t o investigate t h e axial l eng th of t he eye in bo th sexes f r o m bir th t o puberty a n d t o th row l ight o n t h e relationship be tween i ts components ( t h e d e p t h of t h e anterior chamber, t h e axial diameter of t h e lens and t h e l eng th of t h e v i treous) during t h e same period. A considerable number of measurements of the sagittal diameter of the eye have been made in enucleated eyes from newborns. Most authors give mean values for the outer diameter of the bulb of between 1 7 and 18 mm (von Jaeger 1861, Merkel & Orr 1892, Halben 1900, Sorsby & Sheridan 1960) but mean values as low as 16.4 mm (Weiss 1897) have also been given. Ultrasonic measurements of the axial length in living newborns were made by Gernet (1964), Luyckx (1966) and Grignolo & Rivara (1968), who all give mean values in the neighbourhood of 17 mm. Our knowledge of the longitudinal growth of the axis after birth is based mainly on studies made by Weiss (1897), Halben (1900) and Favoloro (1934) in