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Showing papers by "University of Bergen published in 2007"


Journal ArticleDOI
TL;DR: Clinical diagnostic criteria for probable and possible PD‐D are proposed, characterized by impairment in attention, memory, executive and visuo‐spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent.
Abstract: Dementia has been increasingly more recognized to be a common feature in patients with Parkinson's disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD-D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD-D. The Task Force members were assigned to sub-committees and performed a systematic review of the literature, based on pre-defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point-prevelance is close to 30%, older age and akinetic-rigid form are associated with higher risk. PD-D is characterized by impairment in attention, memory, executive and visuo-spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body-type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD-D are proposed.

2,454 citations


Journal ArticleDOI
TL;DR: This work proposes a population-based, youth focused model, explicitly integrating mental health with other youth health and welfare expertise, and challenges to addressing mental- health needs include the shortage of mental-health professionals, the fairly low capacity and motivation of non-specialist health workers, and the stigma associated with mental disorder.

2,249 citations


Journal ArticleDOI
TL;DR: This worldwide study showed higher levels and more advanced staging of spirometrically confirmed COPD than have typically been reported and variations in disease prevalence-other factors also seem to be important.

2,038 citations


Book ChapterDOI
26 Nov 2007
TL;DR: The effects of gear selectivity and ontogenetic behavioural changes of fl atfi shes on the accurate estimation of age structure and growth rates were recognised, especially with the offshore movement of larger juvenile plaice from the nursery grounds and a general offshore movement with size and age.
Abstract: Flatfi shes are very accessible in the wild and hardy in the laboratory, thus many of the early studies of fi sh growth used fl atfi shes, especially plaice (Pleuronectes platessa) in the Atlantic and a number of species in the Pacifi c. As the science of fi sheries developed, so did the need to quantify the population structure and growth characteristics of the different fl atfi sh species. In fact, the importance of ageing fi shes and determining their growth rate was realised early in the last century (Allen 1916). Much of the early information on the aging and growth of fl atfi shes (primarily plaice) is referenced in Wimpenny (1953), Graham (1956) and Beverton & Holt (1957). Prior to the 1950s researchers had gained a fairly good understanding of the methods. A clear pattern of summer and winter growth was recognised in the otoliths, which were fi rst used in the late 1800s. Other bony structures such as opercular bones, the pectoral girdle and the concave faces of the vertebrae exhibited seasonal growth patterns (Cunningham 1905) but these were not as distinctive as those on the otoliths. The observation that a pair of rings may not delimit 1 year’s growth led to early verifi cation studies based on marginal increment analyses. Experimental work on plaice and fl ounder (Platichthys fl esus) showed that the seasonal pattern on both otoliths and scales was primarily driven by seasonal changes in water temperature rather than by variations in food availability. The use of otoliths for age estimation of fl atfi shes was not universal. Species differences slowly became apparent and methodological refi nements followed. Direct measurements of the growth of fl atfi shes were afforded by series of tagging and transplantation experiments, and laboratory or enclosure experiments (Johnstone et al. 1921). In all cases it was apparent that there was considerable variability in individual growth rates and that growth rates varied between areas. The widespread sexual dimorphism in growth with females growing faster and reaching larger sizes than males was also recognised (e.g. Johnstone et al. 1921; Bigelow & Schroeder 1953; Bagenal, 1955). The effects of gear selectivity and ontogenetic behavioural changes of fl atfi shes on the accurate estimation of age structure and growth rates were recognised, especially with the offshore movement of larger juvenile plaice from the nursery grounds and a general offshore movement with size and age. The possibility that fi shing pressure could make major changes to the age structure and growth of commercially exploited fl atfi sh populations was mentioned by Jones (1958), citing the prevalence of Rosa Lee’s phenomenon in plaice.

1,851 citations


Journal ArticleDOI
06 Jul 2007-Science
TL;DR: A comparative analysis of the draft genome of an emerging cnidarian model, the starlet sea anemone Nematostella vectensis, suggests that gene “inventions” along the lineage leading to animals were likely already well integrated with preexisting eukaryotic genes in the eumetazoan progenitor.
Abstract: Sea anemones are seemingly primitive animals that, along with corals, jellyfish, and hydras, constitute the oldest eumetazoan phylum, the Cnidaria. Here, we report a comparative analysis of the draft genome of an emerging cnidarian model, the starlet sea anemone Nematostella vectensis. The sea anemone genome is complex, with a gene repertoire, exon-intron structure, and large-scale gene linkage more similar to vertebrates than to flies or nematodes, implying that the genome of the eumetazoan ancestor was similarly complex. Nearly one-fifth of the inferred genes of the ancestor are eumetazoan novelties, which are enriched for animal functions like cell signaling, adhesion, and synaptic transmission. Analysis of diverse pathways suggests that these gene "inventions" along the lineage leading to animals were likely already well integrated with preexisting eukaryotic genes in the eumetazoan progenitor.

1,485 citations


Journal ArticleDOI
23 Feb 2007-Cell
TL;DR: Polycomb group (PcG) and trithorax group (trxG) proteins are critical regulators of numerous developmental genes and recent work suggests that PcG-mediated gene silencing involves noncoding RNAs and the RNAi machinery.

1,448 citations


Journal ArticleDOI
TL;DR: This work analyzes functional and structural MRI data from healthy elderly and patients with amnestic mild cognitive impairment and concludes that in individuals at risk for AD, a specific subset of RSNs is altered, likely representing effects of ongoing early neurodegeneration.
Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that prominently affects cerebral connectivity. Assessing the functional connectivity at rest, recent functional MRI (fMRI) studies reported on the existence of resting-state networks (RSNs). RSNs are characterized by spatially coherent, spontaneous fluctuations in the blood oxygen level-dependent signal and are made up of regional patterns commonly involved in functions such as sensory, attention, or default mode processing. In AD, the default mode network (DMN) is affected by reduced functional connectivity and atrophy. In this work, we analyzed functional and structural MRI data from healthy elderly (n = 16) and patients with amnestic mild cognitive impairment (aMCI) (n = 24), a syndrome of high risk for developing AD. Two questions were addressed: (i) Are any RSNs altered in aMCI? (ii) Do changes in functional connectivity relate to possible structural changes? Independent component analysis of resting-state fMRI data identified eight spatially consistent RSNs. Only selected areas of the DMN and the executive attention network demonstrated reduced network-related activity in the patient group. Voxel-based morphometry revealed atrophy in both medial temporal lobes (MTL) of the patients. The functional connectivity between both hippocampi in the MTLs and the posterior cingulate of the DMN was present in healthy controls but absent in patients. We conclude that in individuals at risk for AD, a specific subset of RSNs is altered, likely representing effects of ongoing early neurodegeneration. We interpret our finding as a proof of principle, demonstrating that functional brain disorders can be characterized by functional-disconnectivity profiles of RSNs.

984 citations


Journal ArticleDOI
TL;DR: The main focus of this article is to operationalize the diagnosis of PD‐D and to propose pratical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment.
Abstract: A preceding article described the clinical features of Parkinson's disease dementia (PD-D) and proposed clinical diagnostic criteria for "probable" and "possible" PD-D. The main focus of this article is to operationalize the diagnosis of PD-D and to propose practical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment. Level I is aimed primarily at the clinician with no particular expertise in neuropsychological methods, but who requires a simple, pragmatic set of tests that are not excessively time-consuming. Level I can be used alone or in concert with Level II, which is more suitable when there is the need to specify the pattern and the severity on the dementia of PD-D for clinical monitoring, research studies or pharmacological trials. Level II tests can also be proposed when the diagnosis of PD-D remains uncertain or equivocal at the end of a Level I evaluation. Given the lack of evidence-based standards for some tests when applied in this clinical context, we have tried to make practical and unambiguous recommendations, based upon the available literature and the collective experience of the Task Force. We accept, however, that further validation of certain tests and modifications in the recommended cut off values will be required through future studies.

907 citations


Journal ArticleDOI
06 Jun 2007-JAMA
TL;DR: In this paper, the safety and efficacy of folic acid supplements for preventing colorectal adenomas were evaluated in a randomized clinical trial. But, the results showed that folic acids at 1 mg/d did not reduce coloreCTal adnoma risk.
Abstract: ContextLaboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine.ObjectiveTo assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas.Design, Setting, and ParticipantsA double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma.InterventionParticipants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later).Main Outcome MeasuresThe primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (≥25% villous features, high-grade dysplasia, size ≥1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or ≥3 adenomas).Results During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. ConclusionsFolic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.Trial Registration clinicaltrials.gov Identifier: NCT00272324

879 citations


Journal ArticleDOI
TL;DR: In this paper, the authors discuss the whole-of-government movement as a reaction to the negative effects of New Public Management reforms such as structural devolution, single-purpose organizations, and performance management.
Abstract: In this article, the authors discuss “whole-of-government” initiatives as a reaction to the negative effects of New Public Management reforms such as structural devolution, “single-purpose organizations,” and performance management but also as a reaction to a more insecure world. The authors examine what is meant by a “whole-of-government” approach and explore how this concept might be interpreted in analytical terms. The structural approach is contrasted with a cultural perspective and a myth-based perspective. Finally, results, experiences, and lessons from the whole-of-government movement are discussed.

853 citations


Journal ArticleDOI
TL;DR: In this paper, the authors propose a definition and a descriptive model of destructive leadership behavior, defined as the systematic and repeated behaviour by a leader, supervisor or manager that violates the legitimate interest of the organisation by undermining and/or sabotaging the organisation's goals, tasks, resources, and effectiveness and/ or the motivation, well-being or job satisfaction of his/her subordinates.
Abstract: This paper proposes a definition and a descriptive model of destructive leadership behaviour. Destructive leadership behaviour is defined as the systematic and repeated behaviour by a leader, supervisor or manager that violates the legitimate interest of the organisation by undermining and/or sabotaging the organisation's goals, tasks, resources, and effectiveness and/or the motivation, well-being or job satisfaction of his/her subordinates. Three categories of such destructive leadership are identified in the proposed model: tyrannical, derailed, and supportive–disloyal leadership behaviour. The model may provide a useful link between the field of leadership and research on bullying, counterproductive behaviour, and aggression at work. The model contributes to a more nuanced concept of destructive leadership showing how destructive leadership behaviours also may have constructive elements.

Journal ArticleDOI
TL;DR: The assumption that laissez-faire leadership behavior is a destructive leadership behavior that shows systematic relationships with workplace stressors, bullying at work, and psychological distress is supported.
Abstract: The aim of the study is to test the assumption that laissez-faire leadership behavior is not a type of zero-leadership, but a type of destructive leadership behavior that shows systematic relationships with workplace stressors, bullying at work, and psychological distress. A survey of 2,273 Norwegian employees was conducted and analyzed. Laissez-faire leadership was positively correlated with role conflict, role ambiguity, and conflicts with coworkers. Path modeling showed that these stressors mediated the effects of laissez-faire leadership on bullying at work and that the effects of laissez-faire leadership on distress were mediated through the workplace stressors, especially through exposure to bullying. The results support the assumption that laissez-faire leadership behavior is a destructive leadership behavior.

Journal ArticleDOI
TL;DR: Recent advances in the understanding of the biosynthesis and signalling functions of NAD(P) are summarized and new insights into the molecular mechanisms of NADPH generation and their roles in cell physiology are highlighted.
Abstract: The pyridine nucleotides NAD and NADP play vital roles in metabolic conversions as signal transducers and in cellular defence systems. Both coenzymes participate as electron carriers in energy transduction and biosynthetic processes. Their oxidized forms, NAD + and NADP + , have been identified as important elements of regulatory pathways. In particular, NAD + serves as a substrate for ADP-ribosylation reactions and for the Sir2 family of NAD + -dependent protein deacetylases as well as a precursor of the calcium mobilizing molecule cADPr (cyclic ADP-ribose). The conversions of NADP + into the 2′-phosphorylated form of cADPr or to its nicotinic acid derivative, NAADP, also result in the formation of potent intracellular calcium-signalling agents. Perhaps, the most critical function of NADP is in the maintenance of a pool of reducing equivalents which is essential to counteract oxidative damage and for other detoxifying reactions. It is well known that the NADPH/NADP + ratio is usually kept high, in favour of the reduced form. Research within the past few years has revealed important insights into how the NADPH pool is generated and maintained in different subcellular compartments. Moreover, tremendous progress in the molecular characterization of NAD kinases has established these enzymes as vital factors for cell survival. In the present review, we summarize recent advances in the understanding of the biosynthesis and signalling functions of NAD(P) and highlight the new insights into the molecular mechanisms of NADPH generation and their roles in cell physiology.

Journal ArticleDOI
TL;DR: This Review attempts to integrate current knowledge of dendritic mRNA transport, storage and translation, placing particular emphasis on the coordination of regulation and function during activity-dependent synaptic plasticity in the adult mammalian brain.
Abstract: Many cellular functions require the synthesis of a specific protein or functional cohort of proteins at a specific time and place in the cell. Local protein synthesis in neuronal dendrites is essential for understanding how neural activity patterns are transduced into persistent changes in synaptic connectivity during cortical development, memory storage and other long-term adaptive brain responses. Regional and temporal changes in protein levels are commonly coordinated by an asymmetric distribution of mRNAs. This Review attempts to integrate current knowledge of dendritic mRNA transport, storage and translation, placing particular emphasis on the coordination of regulation and function during activity-dependent synaptic plasticity in the adult mammalian brain.

Journal ArticleDOI
TL;DR: Deformation bands are the most common strain localization feature found in deformed porous sandstones and sediments, including Quaternary deposits, soft gravity slides and tectonically affected sandstones in hydrocarbon reservoirs and aquifers as discussed by the authors.
Abstract: Deformation bands are the most common strain localization feature found in deformed porous sandstones and sediments, including Quaternary deposits, soft gravity slides and tectonically affected sandstones in hydrocarbon reservoirs and aquifers. They occur as various types of tabular deformation zones where grain reorganization occurs by grain sliding, rotation and/or fracture during overall dilation, shearing, and/or compaction. Deformation bands with a component of shear are most common and typically accommodate shear offsets of millimetres to centimetres. They can occur as single structures or cluster zones, and are the main deformation element of fault damage zones in porous rocks. Factors such as porosity, mineralogy, grain size and shape, lithification, state of stress and burial depth control the type of deformation band formed. Of the different types, phyllosilicate bands and most notably cataclastic deformation bands show the largest reduction in permeability, and thus have the greatest potential to influence fluid flow. Disaggregation bands, where non-cataclastic, granular flow is the dominant mechanism, show little influence on fluid flow unless assisted by chemical compaction or cementation.

Journal ArticleDOI
23 Nov 2007-Science
TL;DR: Evolutionary impact assessment is a framework for quantifying the effects of harvest-induced evolution on the utility generated by fish stocks.
Abstract: Evolutionary impact assessment is a framework for quantifying the effects of harvest-induced evolution on the utility generated by fish stocks

Journal ArticleDOI
01 Jul 2007-Sleep
TL;DR: Results are consistent with insomnia being a risk factor for the development of anxiety disorders, and a state-like association between insomnia and depression was found.
Abstract: Study Objective: To study prospectively the relations of insomnia to the development of anxiety disorders and depression in a population-based sample.

Journal ArticleDOI
TL;DR: This work has shown that most mammalian genes do not conform to the simple model in which a TATA box directs transcription from a single defined nucleotide position, and alternative promoter usage generates diversity and complexity in the mammalian transcriptome and proteome.
Abstract: The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealing that most mammalian genes do not conform to the simple model in which a TATA box directs transcription from a single defined nucleotide position. In fact, most genes have multiple promoters, within which there are multiple start sites, and alternative promoter usage generates diversity and complexity in the mammalian transcriptome and proteome. Promoters can be described by their start site usage distribution, which is coupled to the occurrence of cis-regulatory elements, gene function and evolutionary constraints. A comprehensive survey of mammalian promoters is a major step towards describing and understanding transcriptional control networks.

Journal ArticleDOI
TL;DR: In sub-Saharan Africa, male children under five years of age are more likely to become stunted than females, which might suggest that boys are more vulnerable to health inequalities than their female counterparts in the same age groups.
Abstract: Many studies in sub-Saharan Africa have occasionally reported a higher prevalence of stunting in male children compared to female children. This study examined whether there are systematic sex differences in stunting rates in children under-five years of age, and how the sex differences in stunting rates vary with household socio-economic status. Data from the most recent 16 demographic and health surveys (DHS) in 10 sub-Saharan countries were analysed. Two separate variables for household socio-economic status (SES) were created for each country based on asset ownership and mothers' education. Quintiles of SES were constructed using principal component analysis. Sex differentials with stunting were assessed using Student's t-test, chi square test and binary logistic regressions. The prevalence and the mean z-scores of stunting were consistently lower amongst females than amongst males in all studies, with differences statistically significant in 11 and 12, respectively, out of the 16 studies. The pooled estimates for mean z-scores were -1.59 for boys and -1.46 for girls with the difference statistically significant (p < 0.001). The stunting prevalence was also higher in boys (40%) than in girls (36%) in pooled data analysis; crude odds ratio 1.16 (95% CI 1.12–1.20); child age and individual survey adjusted odds ratio 1.18 (95% CI 1.14–1.22). Male children in households of the poorest 40% were more likely to be stunted compared to females in the same group, but the pattern was not consistent in all studies, and evaluation of the SES/sex interaction term in relation to stunting was not significant for the surveys. In sub-Saharan Africa, male children under five years of age are more likely to become stunted than females, which might suggest that boys are more vulnerable to health inequalities than their female counterparts in the same age groups. In several of the surveys, sex differences in stunting were more pronounced in the lowest SES groups.

Journal ArticleDOI
TL;DR: The structural diversity of dihydroflavonols characterized from onions is restricted compared with the wide structural assortment of flavonols and anthocyanins identified, and they may occur at high concentrations in some cultivars.
Abstract: Onion bulbs (Allium cepa L) are among the richest sources of dietary flavonoids and contribute to a large extent to the overall intake of flavonoids This review includes a compilation of the existing qualitative and quantitative information about flavonoids reported to occur in onion bulbs, including NMR spectroscopic evidence used for structural characterization In addition, a summary is given to index onion cultivars according to their content of flavonoids measured as quercetin Only compounds belonging to the flavonols, the anthocyanins, and the dihydroflavonols have been reported to occur in onion bulbs Yellow onions contain 270–1187 mg of flavonols per kilogram of fresh weight (FW), whereas red onions contain 415–1917 mg of flavonols per kilogram of FW Flavonols are the predominant pigments of onions At least 25 different flavonols have been characterized, and quercetin derivatives are the most important ones in all onion cultivars Their glycosyl moieties are almost exclusively glucose, which

Journal ArticleDOI
TL;DR: The authors agreed to endorse “Lewy body disorders” as the umbrella term for PD, PDD, and DLB to promote the continued practical use of these three clinical terms, and to encourage efforts at drug discovery that target the mechanisms of neurodegeneration shared by these disorders of α-synuclein metabolism.
Abstract: For more than a decade, researchers have refined criteria for the diagnosis of dementia with Lewy bodies (DLB) and at the same time have recognized that cognitive impairment and dementia occur commonly in patients with Parkinson disease (PD). This article addresses the relationship between DLB, PD, and PD with dementia (PDD). The authors agreed to endorse "Lewy body disorders" as the umbrella term for PD, PDD, and DLB, to promote the continued practical use of these three clinical terms, and to encourage efforts at drug discovery that target the mechanisms of neurodegeneration shared by these disorders of alpha-synuclein metabolism. We concluded that the differing temporal sequence of symptoms and clinical features of PDD and DLB justify distinguishing these disorders. However, a single Lewy body disorder model was deemed more useful for studying disease pathogenesis because abnormal neuronal alpha-synuclein inclusions are the defining pathologic process common to both PDD and DLB. There was consensus that improved understanding of the pathobiology of alpha-synuclein should be a major focus of efforts to develop new disease-modifying therapies for these disorders. The group agreed on four important priorities: 1) continued communication between experts who specialize in PDD or DLB; 2) initiation of prospective validation studies with autopsy confirmation of DLB and PDD; 3) development of practical biomarkers for alpha-synuclein pathologies; 4) accelerated efforts to find more effective treatments for these diseases.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the relationship between job stressors and leadership behaviour as possible predictors of bullying at work on the basis of the work environment hypothesis, which states that stressful and poorly organized work environments may give rise to conditions resulting in bullying.
Abstract: This paper contributes to the relatively sparse knowledge about relationships between stressful work environments and bullying. Relationships between job stressors and leadership behaviour were analysed as possible predictors of bullying at work on the basis of the work environment hypothesis, which states that stressful and poorly organized work environments may give rise to conditions resulting in bullying. Analyses of a representative sample (n=2539) of the Norwegian workforce showed role conflict, interpersonal conflicts, and tyrannical and laissez-faire leadership behaviour to be strongly related to bullying, and that the strength of associations to a high degree differed for various measures of bullying. Support was found for an interactive relationship between decision authority and role conflict at different levels of laissez-faire leadership. Not only targets and bully/targets but also bystanders assessed their work environment more negatively than did non-involved employees, while perpe...

Journal ArticleDOI
TL;DR: Results couple activity-induced expression of Arc to expansion of the actin cytoskeleton underlying enduring LTP, identifying Arc as a key molecular effector of BDNF in synaptic plasticity.
Abstract: New gene expression is necessary for long-term potentiation (LTP) consolidation, yet roles for specific activity-induced mRNAs have not been defined. Here we probed the dynamic function of activity-induced Arc (activity-regulated cytoskeletal-associated protein)/Arg3.1 (activity-regulated gene 3.1 protein homolog) mRNA using brief, local infusions of antisense (AS) oligodeoxynucleotides at multiple time points during dentate gyrus LTP in vivo. Surprisingly, early Arc synthesis is necessary for early expression of LTP, whereas sustained synthesis is required to generate stably modified synapses. AS application 2 h after LTP induction results in a rapid and permanent reversal of LTP. This reversal is associated with rapid knockdown of upregulated Arc, dephosphorylation of actin depolymerization factor/cofilin, and loss of nascent filamentous actin (F-actin) at synaptic sites. Infusion of the F-actin stabilizing drug jasplakinolide during LTP maintenance blocks the ability of AS to reverse LTP. These results couple activity-induced expression of Arc to expansion of the actin cytoskeleton underlying enduring LTP. Furthermore, Arc synthesis is required for both the induction and consolidation of LTP elicited by local BDNF infusion, thus identifying Arc as a key molecular effector of BDNF in synaptic plasticity.

Journal ArticleDOI
TL;DR: It is suggested that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxication, and are a potential indication for therapy development.
Abstract: There are no standardized diagnostic criteria for psychosis associated with Parkinson's disease (PDPsy). As part of an NIH sponsored workshop, we reviewed the existing literature on PDPsy to provide criteria that distinguish PDPsy from other causes of psychosis. Based on these data, we pro- pose provisional criteria for PDPsy in the style of the Diagnos- tic and Statistical Manual of Mental Disorders IV-TR. PDPsy has a well-characterized temporal and clinical profile of hallu- cinations and delusions, which is different than the pattern seen in other psychotic disorders such as substance induced psycho- sis or schizophrenia. PDPsy is associated with a poor prognosis of chronic psychosis, nursing home placement, and death. Medications used to treat Parkinson's disease (PD) contribute to PDPsy but may not be sufficient or necessary contributors to PDPsy. PDPsy is associated with Lewy bodies pathology, imbalances of monoaminergic neurotransmitters, and visuospa- tial processing deficits. These findings suggest that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxica- tion. PDPsy is not adequately described by existing criteria for psychotic disorders. We established provisional diagnostic cri- teria that define a constellation of clinical features not shared by other psychotic syndromes. The criteria are inclusive and con- This article is part of the journal's CME program. The CME form can be found on page 1214 and is available online at http://www.

Journal ArticleDOI
TL;DR: Results from new scientific drill cores from Lake Malawi are presented, the first long and continuous, high-fidelity records of tropical climate change from the continent itself, providing evidence for dramatically wetter conditions after 70 kyr ago.
Abstract: The environmental backdrop to the evolution and spread of early Homo sapiens in East Africa is known mainly from isolated outcrops and distant marine sediment cores. Here we present results from new scientific drill cores from Lake Malawi, the first long and continuous, high-fidelity records of tropical climate change from the continent itself. Our record shows periods of severe aridity between 135 and 75 thousand years (kyr) ago, when the lake's water volume was reduced by at least 95%. Surprisingly, these intervals of pronounced tropical African aridity in the early late-Pleistocene were much more severe than the Last Glacial Maximum (LGM), the period previously recognized as one of the most arid of the Quaternary. From these cores and from records from Lakes Tanganyika (East Africa) and Bosumtwi (West Africa), we document a major rise in water levels and a shift to more humid conditions over much of tropical Africa after ≈70 kyr ago. This transition to wetter, more stable conditions coincides with diminished orbital eccentricity, and a reduction in precession-dominated climatic extremes. The observed climate mode switch to decreased environmental variability is consistent with terrestrial and marine records from in and around tropical Africa, but our records provide evidence for dramatically wetter conditions after 70 kyr ago. Such climate change may have stimulated the expansion and migrations of early modern human populations.

Journal ArticleDOI
TL;DR: The overall prevalence of psychiatric disorders in children is relatively low in this Norwegian sample, when assessed with the Development and Well-Being Assessment.
Abstract: Objective: The Bergen Child Study is a longitudinal study of child mental health from the city of Bergen, Norway. We present methods and results from the first wave of the study, focusing on prevalence of disorders, associations with risk factors, and the use of services. Method: The target population included all 9,430 children attending grades 2 to 4 in Bergen schools during the academic year 2002/2003. The main screening instrument was the Strengths and Difficulties Questionnaire, whereas diagnoses were based on the Development and Well-Being Assessment. Information about child and family risk factors and service use was also obtained in this second stage. Results: In the first phase, the teacher Strengths and Difficulties Questionnaire was obtained for 9,155 (97%) of the target children and the matching parent Strengths and Difficulties Questionnaire for 6,297 (67%); 1,011 children (11%) were assessed with the Development and Well-Being Assessment in the second phase. The weighted prevalence for any DSM-IV psychiatric disorder was 7.0% (95% confidence interval 5.6%-8.5%). Disorders were associated with age, gender, learning difficulties, family type, and poverty. Although 75% of children with attention-deficit/hyperactivity disorder had been in contact with specialist mental health services, this was true for only 13% of those with pure emotional disorders. Conclusions: The overall prevalence of psychiatric disorders in children is relatively low in this Norwegian sample, when assessed with the Development and Well-Being Assessment. Children with emotional disorders have limited access to specialist services.

Journal ArticleDOI
TL;DR: The aim of the present intergenerational study was to estimate and compare fetal and maternal genetic effects and shared sibling environmental effects on birth weight and gestational age and also on crown-heel length and head circumference and found that fetal genes were most important for birth length andHead circumference.
Abstract: Familial correlations in birth weight and gestational age have been explained by fetal and maternal genetic factors, mainly in studies on offspring of twins. The aim of the present intergenerational study was to estimate and compare fetal and maternal genetic effects and shared sibling environmental effects on birth weight and gestational age and also on crown-heel length and head circumference. The authors used path analysis and maximum likelihood principles to estimate these effects and, at the same time, to adjust for covariates. Parent-offspring data were obtained from the Medical Birth Registry of Norway from 1967 to 2004. For the analysis of birth weight and crown-heel length, 101,748 families were included; for gestational age, 91,617 families; and for head circumference, 77,044 families. Assuming no cultural transmission and random mating, the authors found that fetal genetic factors explained 31% of the normal variation in birth weight and birth length, 27% of the variation in head circumference, and 11% of the variation in gestational age. Maternal genetic factors explained 22% of the variation in birth weight, 19% of the variation in birth length and head circumference, and 14% of the variation in gestational age. Relative to the proportion of explained variation, fetal genes were most important for birth length and head circumference.

Journal ArticleDOI
TL;DR: It is shown that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment, which explains the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs.
Abstract: We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated "bystander" genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes. Reporter insertions distal to zebrafish developmental regulatory genes pax6.1/2, rx3, id1, and fgf8 and miRNA genes mirn9-1 and mirn9-5 recapitulate the expression patterns of these genes even if located inside or beyond bystander genes, suggesting that the regulatory domain of a developmental regulatory gene can extend into and beyond adjacent transcriptional units. We termed these chromosomal segments genomic regulatory blocks (GRBs). After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment. These findings explain the absence of evolutionary breakpoints from large vertebrate chromosomal segments and will aid in the recognition of position effect mutations within human GRBs.

01 Dec 2007
TL;DR: Life-history theory predicts that increased mortality generally favors evolution toward earlier sexual maturation at smaller size and elevated reproductive effort, and these evolutionary changes are unfolding on decadal time scales—much faster than previously thought.
Abstract: Darwinian evolution is the driving process of innovation and adaptation across the world’s biota. Acting on top of natural selection, human-induced selection pressures can also cause rapid evolution. Sometimes such evolution has undesirable consequences, one example being the spreading resistance to antibiotics and pesticides, which causes suffering and billion-dollar losses annually (1). A comparable anthropogenic selection pressure originates from fishing, which has become the main source of mortality in many fish stocks, and may exceed natural mortality by more than 400% (2). This has, however, been largely ignored, even though studies based on fisheries data and controlled experiments have provided strong empirical evidence for fisheries-induced evolution over a range of species and regions (see table, page 1248). These evolutionary changes are unfolding on decadal time scales—much faster than previously thought. Life-history theory predicts that increased mortality generally favors evolution toward earlier sexual maturation at smaller size and elevated reproductive effort. Fishing that is selective with respect to size, maturity status, behavior, or morphology causes further evolutionary pressures (3). Evidence that harvesting can bring about genetic changes comes from breeding programs in aquaculture, which have shown heritable genetic variation in numerous traits (4), and from experiments

Book
20 Dec 2007
TL;DR: The public sector organizations are fundamentally different from their private-sector counterparts as mentioned in this paper, they are multifunctional, follow a political leadership and the majority do not operate in an external market.
Abstract: Public-sector organizations are fundamentally different from their private-sector counterparts. They are part of the society’s political organizations and are major political actors. They are multifunctional, follow a political leadership and the majority do not operate in an external market. In an era of rapid reform, reorganization and modernization of the public sector, this book offers a timely and illuminating introduction to the public-sector organization that recognizes its unique values, interests, knowledge and power base. Drawing on both instrumental and institutional perspectives within organization theory, as well as democratic theory and empirical studies of decision-making, the book addresses five central aspects of the public-sector organization: ■ goals, values and motivation ■ leadership and steering ■ reform and change ■ effects, learning and implications ■ understanding and design The book challenges conventional economic analysis of the public sector, arguing instead for a political-democratic approach and a new prescriptive organization theory. A rich resource of both theory and practice, Organization Theory and the Public Sector: Instrument, Culture and Myth is essential reading for anybody studying the public sector. This second edition of the book contains a range of new and updated themes, examples and references.