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Find video protocols related to scientific articles indexed in Pubmed.
Testing the Developmental Origins of Health and Disease Hypothesis for Psychopathology Using Family-Based Quasi-Experimental Designs.
Child Dev Perspect
PUBLISHED: 11-04-2014
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The Developmental Origin of Health and Disease (DOHaD) hypothesis is a broad theoretical framework that emphasizes how early risk factors have a causal influence on psychopathology. Researchers have raised concerns about the causal interpretation of statistical associations between early risk factors and later psychopathology because most existing studies have been unable to rule out the possibility of environmental and genetic confounding. In this paper we illustrate how family-based quasi-experimental designs can test the DOHaD hypothesis by ruling out alternative hypotheses. We review the logic underlying sibling-comparison, co-twin control, offspring of siblings/twins, adoption, and in vitro fertilization designs. We then present results from studies using these designs focused on broad indices of fetal development (low birth weight and gestational age) and a particular teratogen, smoking during pregnancy. The results provide mixed support for the DOHaD hypothesis for psychopathology, illustrating the critical need to use design features that rule out unmeasured confounding.
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Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring.
J Child Psychol Psychiatry
PUBLISHED: 11-01-2014
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Maternal Smoking During Pregnancy (SDP) has consistently been associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring, but recent studies indicate that this association might be due to unmeasured familial confounding.
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Maternal age at childbirth and risk for ADHD in offspring: a population-based cohort study.
Int J Epidemiol
PUBLISHED: 10-31-2014
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Women who give birth at younger ages (e.g. teenage mothers) are more likely to have children who exhibit behaviour problems, such as attention-deficit/ hyperactivity disorder (ADHD). However, it is not clear whether young maternal age is causally associated with poor offspring outcomes or confounded by familial factors.
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Fetal growth and psychiatric and socioeconomic problems: population-based sibling comparison.
Br J Psychiatry
PUBLISHED: 09-25-2014
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Background It is unclear whether associations between fetal growth and psychiatric and socioeconomic problems are consistent with causal mechanisms. Aims To estimate the extent to which associations are a result of unmeasured confounding factors using a sibling-comparison approach. Method We predicted outcomes from continuously measured birth weight in a Swedish population cohort (n = 3 291 773), while controlling for measured and unmeasured confounding. Results In the population, lower birth weight (?2500 g) increased the risk of all outcomes. Sibling-comparison models indicated that lower birth weight independently predicted increased risk for autism spectrum disorder (hazard ratio for low birth weight = 2.44, 95% CI 1.99-2.97) and attention-deficit hyperactivity disorder. Although attenuated, associations remained for psychotic or bipolar disorder and educational problems. Associations with suicide attempt, substance use problems and social welfare receipt, however, were fully attenuated in sibling comparisons. Conclusions Results suggest that fetal growth, and factors that influence it, contribute to psychiatric and socioeconomic problems.
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Codevelopment of ADHD and externalizing behavior from childhood to adulthood.
J Child Psychol Psychiatry
PUBLISHED: 09-12-2014
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Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with externalizing disorders, but a clear understanding of the etiologic underpinnings is hampered by the limited understanding of the codevelopment of the traits from childhood into early adulthood.
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Stimulant ADHD medication and risk for substance abuse.
J Child Psychol Psychiatry
PUBLISHED: 08-28-2014
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There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse.
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Childhood family income, adolescent violent criminality and substance misuse: quasi-experimental total population study.
Br J Psychiatry
PUBLISHED: 08-21-2014
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Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviours but the causal mechanisms are questioned. Aims To investigate whether childhood family income predicts subsequent violent criminality and substance misuse and whether the associations are in turn explained by unobserved familial risk factors.
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Enhanced Neurocognitive Functioning and Positive Temperament in Twins Discordant for Bipolar Disorder.
Am J Psychiatry
PUBLISHED: 08-15-2014
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Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls.
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Bipolar disorder and its relation to major psychiatric disorders: a family-based study in the Swedish population.
Bipolar Disord
PUBLISHED: 08-13-2014
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Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders.
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Maternal smoking during pregnancy and adverse outcomes in offspring: genetic and environmental sources of covariance.
Behav. Genet.
PUBLISHED: 08-13-2014
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Maternal smoking during pregnancy (SDP) has been associated with several psychiatric outcomes in the offspring; studies have questioned whether the associations are causal, however. We analyzed all children born in Sweden between 1983 and 2009 to investigate the effect of SDP on multiple indicators of adverse outcomes in three areas: pregnancy outcomes (birth weight, preterm birth and being born small for gestational age), long-term cognitive abilities (low academic achievement and general cognitive ability) and externalizing behaviors (criminal conviction, violent criminal conviction and drug misuse). SDP was associated with all outcomes. Within-family analyses of the pregnancy outcomes were consistent with a causal interpretation as the associations persisted when siblings discordant for SDP were compared. For the cognitive and externalizing outcomes, the results were not consistent with causal effects; when comparing differentially exposed siblings none of the associations remained significant. In quantitative genetic models genetic factors explained the majority of the associations between SDP and cognitive and externalizing outcomes. The results suggest that the associations between SDP in mothers and cognition and externalizing behaviors in their offspring is primarily due to genetic effects that influence the behaviors in both generations.
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Association between ASMT and autistic-like traits in children from a Swedish nationwide cohort.
Psychiatr. Genet.
PUBLISHED: 08-02-2014
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Individuals with autism spectrum disorders often show low levels of melatonin, and it has been suggested that this decrease may be because of the low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin-synthesis pathway. Also, genetic variants in ASMT have been associated with autism, as well as with low ASMT activity and melatonin levels, suggesting that the low ASMT activity observed in autism may partly be because of variations within the ASMT gene. In this study, we present a symptom-based approach to investigate possible associations between ASMT and autistic-like traits in the general population. To this end, continuous measures of autistic-like traits were assessed in a nationally representative twin cohort (n=1771) from Sweden and six single nucleotide polymorphisms (SNPs), and a duplication of exons 2-8 in ASMT were genotyped. Our results show a nominally significant association, in girls, between one single nucleotide polymorphism (rs5949028) in the last intron of ASMT and social interaction impairments. No significant association, however, was observed with traits related to language impairment or restricted and repetitive behavior. In conclusion, our results support the possible involvement of the ASMT gene in autism spectrum disorders, and our finding that only one of the three traits shows association suggests that genetic research may benefit from adopting a symptom-specific approach to identify genes involved in autism psychopathology.
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Does Population Density and Neighborhood Deprivation Predict Schizophrenia? A Nationwide Swedish Family-Based Study of 2.4 Million Individuals.
Schizophr Bull
PUBLISHED: 07-24-2014
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People living in densely populated and socially disorganized areas have higher rates of psychiatric morbidity, but the potential causal status of such factors is uncertain. We used nationwide Swedish longitudinal registry data to identify all children born 1967-1989 (n = 2361585), including separate datasets for all cousins (n = 1715059) and siblings (n = 1667894). The nature of the associations between population density and neighborhood deprivation and individual risk for a schizophrenia diagnosis was investigated while adjusting for unobserved familial risk factors (through cousin and sibling comparisons) and then compared with similar associations for depression. We generated familial pedigree structures using the Multi-Generation Registry and identified study participants with schizophrenia and depression using the National Patient Registry. Fixed-effects logistic regression models were used to study within-family estimates. Population density, measured as ln(population size/km(2)), at age 15 predicted subsequent schizophrenia in the population (OR = 1.10; 95% CI: 1.09; 1.11). Unobserved familial risk factors shared by cousins within extended families attenuated the association (1.06; 1.03; 1.10), and the link disappeared entirely within nuclear families (1.02; 0.97; 1.08). Similar results were found for neighborhood deprivation as predictor and for depression as outcome. Sensitivity tests demonstrated that timing and accumulation effects of the exposures (mean scores across birth, ages 1-5, 6-10, and 11-15 years) did not alter the findings. Excess risks of psychiatric morbidity, particularly schizophrenia, in densely populated and socioeconomically deprived Swedish neighborhoods appear, therefore, to result primarily from unobserved familial selection factors. Previous studies may have overemphasized the etiological importance of these environmental factors.
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Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging: a histogram analysis approach.
Neuroradiology
PUBLISHED: 07-09-2014
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Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging that could best discriminate between grade II and III gliomas.
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Common etiological factors of attention-deficit/hyperactivity disorder and suicidal behavior: a population-based study in Sweden.
JAMA Psychiatry
PUBLISHED: 06-27-2014
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The prevention of suicidal behavior is one of the most important tasks for mental health clinicians. Although a few studies have indicated an increased risk of suicidal behavior among individuals with attention-deficit/hyperactivity disorder, the development of more effective ways of identifying and modifying the risk is hampered by our limited understanding of the underlying mechanisms for this association.
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Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study.
BMJ
PUBLISHED: 06-20-2014
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To investigate the association between drug treatment for attention-deficit/hyperactivity disorder (ADHD) and risk of concomitant suicidal behaviour among patients with ADHD.
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The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer.
Am J Psychiatry
PUBLISHED: 06-18-2014
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This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer.
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A Triarchic Model Analysis of the Youth Psychopathic Traits Inventory.
J. Pers. Disord.
PUBLISHED: 06-17-2014
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The Triarchic model of psychopathy characterizes this complex condition in terms of distinct phenotypic constructs of boldness, meanness, and disinhibition. The current study evaluated the coverage of these constructs provided by a well-established inventory for assessing psychopathy in adolescents, the Youth Psychopathic Traits Inventory (YPI). A consensus rating approach was used to identify YPI items relevant to each Triarchic model construct, and convergent and discriminant validity of the resulting YPI-Triarchic scales were examined in relation to criterion measures consisting of scores on other psychopathy measures and relevant personality trait variables (N = 618, M age = 18.8). The YPI-Triarchic scales showed good internal consistency and exhibited properties largely consistent with predictions based on the Triarchic model, aside from somewhat greater than expected covariance between boldness and other facet scales. Findings are discussed in terms of their implications for interpreting scores on the YPI and for investigating distinctive components of psychopathy in youth.
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Birth weight as an independent predictor of ADHD symptoms: a within-twin pair analysis.
J Child Psychol Psychiatry
PUBLISHED: 06-16-2014
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Studies have found an association between low birth weight and ADHD, but the nature of this relation is unclear. First, it is uncertain whether birth weight is associated with both of the ADHD dimensions, inattentiveness and hyperactivity-impulsivity. Second, it remains uncertain whether the association between birth weight and ADHD symptom severity is confounded by familial factors.
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The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study.
Bipolar Disord
PUBLISHED: 06-09-2014
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Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question.
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Structural gray matter abnormalities in migraine relate to headache lateralization, but not aura.
Cephalalgia
PUBLISHED: 05-10-2014
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The hallmark of migraine aura (MA) is transient cortical dysfunction but it is not known if MA is associated with structural cortical or subcortical changes. To determine the relation between MA and structural gray matter abnormalities, we studied a unique sample of 20 patients with frequent side-locked MA, i.e. visual aura consistently occurring in the same hemifield.
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Antipsychotics, mood stabilisers, and risk of violent crime.
Lancet
PUBLISHED: 05-08-2014
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Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden.
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The familial risk of autism.
JAMA
PUBLISHED: 05-06-2014
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Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental factors remains unresolved.
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Mediators of the association between parental severe mental illness and offspring neurodevelopmental problems.
Ann Epidemiol
PUBLISHED: 05-01-2014
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Parental severe mental illness (SMI) is associated with an increased risk of offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We conducted a study to examine the extent to which risk of preterm birth, low birth weight, and small for gestational age mediated this association.
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Determinants of iron accumulation in deep grey matter of multiple sclerosis patients.
Mult. Scler.
PUBLISHED: 04-30-2014
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Iron accumulation in deep grey matter (GM) structures is a consistent finding in multiple sclerosis (MS) patients. This study focused on the identification of independent determinants of iron accumulation using R2* mapping.
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Symptoms of autism and ADHD: a Swedish twin study examining their overlap.
J Abnorm Psychol
PUBLISHED: 04-14-2014
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Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) show high comorbidity. The following questions were addressed regarding their specific symptoms: What is the factor structure of ASD and ADHD symptoms, to what degree do different symptom domains cluster together, to what extent are these domains caused by the same genetic and environmental influences, and what is the best model of their co-occurrence? A population-based twin cohort of over 17,000 9- and 12-year-olds were assessed using the Autism-Tics, AD/HD, and other Comorbidities parental interview inventory. Principal component analyses were conducted, and symptom domain clustering was assessed. Four multivariate twin models were compared. Factors split into three ASD (social impairments, communication impairments, and restricted repetitive behaviors and interests), and three ADHD (inattention, hyperactivity, and impulsivity) symptom domains. Some ASD-ADHD symptom domain combinations clustered together often, although others not at all. A two-factor common pathway model fit the data, suggesting that ASD and ADHD symptom domains tap into separate "ASD" and "ADHD" latent factors that showed high genetic overlap. All subdomains also showed significant specific genetic and environmental influences, reflecting the etiological heterogeneity both within and between ASD and ADHD. These findings support the conceptual distinction of ASD and ADHD, and demonstrate the considerable natural co-occurrence of particular ASD/ADHD symptom domains. The results imply that more children with 1 condition show features of the other condition than show complete comorbidity. Emphasis on symptom co-occurrence, rather than complete comorbidity between disorders, may help focus clinical approaches and advance molecular genetic research.
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Migraine without aura is not associated with incomplete circle of Willis: a case-control study using high-resolution magnetic resonance angiography.
J Headache Pain
PUBLISHED: 03-23-2014
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The circle of Willis is an important source of collateral blood flow to maintain adequate cerebral perfusion, particularly in the posterior circulation. Some studies report a relationship between incomplete circle of Willis and migraine, whereas other studies show no difference between the prevalence of incomplete circle of Willis in migraineurs and controls. In the present study we compared the prevalence of incomplete circle of Willis in female migraine patients without aura to female healthy non-migraine controls.Using 3-Tesla magnetic resonance angiography we recorded three-dimensional time-of-flight angiograms in 85 female participants (48 migraine patients without aura [median age 28 years] and 37 healthy controls [median age 25 years]). The images were subsequently analysed blindly by a neuroradiologist to detect incomplete circle of Willis.
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Measurement precision and biological variation of cranial arteries using automated analysis of 3 T magnetic resonance angiography.
J Headache Pain
PUBLISHED: 03-23-2014
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Non-invasive magnetic resonance angiography (MRA) has facilitated repeated measurements of human cranial arteries in several headache and migraine studies. To ensure comparability across studies the same automated analysis software has been used, but the intra- and interobserver, day-to-day and side-to-side variations have not yet been published. We hypothesised that the observer related, side-to-side, and day-to-day variations would be less than 10%.
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Association of acetazolamide infusion with headache and cranial artery dilation in healthy volunteers.
Pain
PUBLISHED: 03-08-2014
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The carbonic anhydrase inhibitor acetazolamide causes extracellular acidosis and dilatation of cerebral arterioles. In this study, we tested the hypothesis that acetazolamide also may induce headache and dilatation of cranial arteries. In a randomized double-blind crossover study design, 12 young healthy women were allocated to injection of 1 g acetazolamide or placebo on 2 separate days. We recorded headache on a verbal rating scale from 0 to 10 during an immediate phase (0-90 minutes) and a delayed phase (2-12 hours). The circumference of cranial arteries was measured using 3T high-resolution magnetic resonance angiography 30 and 60 minutes after injection. Acetazolamide provoked immediate headache in 9 participants compared to 3 participants after placebo (P=.031). Eleven participants reported headache in the delayed phase after acetazolamide, compared with 4 after placebo (P=.016). The area under the curve for headache was increased after acetazolamide compared to placebo in the delayed phase (2-12 h) (P=.005). Compared to placebo, arterial circumference increased after acetazolamide in the basilar artery (P=.002) as well as the cerebral (P=.003), cavernous (P=.002), and cervical (P=.005) parts of the internal carotid artery, but no other extracranial arteries changed after acetazolamide. In conclusion, acetazolamide caused immediate and delayed headache as well as dilatation of intracranial arteries in healthy volunteers. It is possible that extracellular acidosis induced by acetazolamide causes sensitization of cephalic perivascular nociceptors, which, in combination with vasodilatation, leads to delayed headache.
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Suicide, hospital-presenting suicide attempts, and criminality in bipolar disorder: examination of risk for multiple adverse outcomes.
J Clin Psychiatry
PUBLISHED: 03-06-2014
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To compare risks for suicidality and criminality in a national cohort of people diagnosed with bipolar disorder, and to assess how risk factor profiles differ between these outcomes.
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Paternal age at childbearing and offspring psychiatric and academic morbidity.
JAMA Psychiatry
PUBLISHED: 03-01-2014
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Advancing paternal age is associated with increased genetic mutations during spermatogenesis, which research suggests may cause psychiatric morbidity in the offspring. The effects of advancing paternal age at childbearing on offspring morbidity remain unclear, however, because of inconsistent epidemiologic findings and the inability of previous studies to rigorously rule out confounding factors.
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Accurate determination of blood-brain barrier permeability using dynamic contrast-enhanced T1-weighted MRI: a simulation and in vivo study on healthy subjects and multiple sclerosis patients.
J. Cereb. Blood Flow Metab.
PUBLISHED: 02-07-2014
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Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used to estimate permeability in situations with subtle blood-brain barrier (BBB) leakage. However, the method's ability to differentiate such low values from zero is unknown, and no consensus exists on optimal selection of total measurement duration, temporal resolution, and modeling approach under varying physiologic circumstances. To estimate accuracy and precision of the DCE-MRI method we generated simulated data using a two-compartment model and progressively down-sampled and truncated the data to mimic low temporal resolution and short total measurement duration. Model fit was performed with the Patlak, the extended Tofts, and the Tikhonov two-compartment (Tik-2CM) models. Overall, 17 healthy controls were scanned to obtain in vivo data. Long total measurement duration (15 minutes) and high temporal resolution (1.25 seconds) greatly improved accuracy and precision for all three models, enabling us to differentiate values of permeability as low as 0.1?ml/100?g/min from zero. The Patlak model yielded highest accuracy and precision for permeability values <0.3?ml/100?g/min, but for higher values the Tik-2CM performed best. Our results emphasize the importance of optimal parameter setup and model selection when characterizing low BBB permeability.
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Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38.
Brain
PUBLISHED: 02-05-2014
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Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide are structurally and functionally closely related but show differences in migraine-inducing properties. Mechanisms responsible for the difference in migraine induction are unknown. Here, for the first time, we present a head-to-head comparison study of the immediate and long-lasting observations of the migraine-inducing, arterial, physiological and biochemical responses comparing PACAP38 and vasoactive intestinal polypeptide. In a double-blind crossover study 24 female migraine patients without aura were randomly allocated to intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We recorded incidence of migraine during and after infusion (0-24 h). Magnetic resonance angiography of selected extra- and intracranial arteries, blood samples (plasma PACAP38 and vasoactive intestinal polypeptide and serum tryptase), and vital signs (blood pressure, heart rate, respiratory frequency, and end-tidal pressure of CO2) was recorded before and up to 5 h after infusion. Twenty-two patients [mean age 24 years (range 19-36)] completed the study on both days. Sixteen patients (73%) reported migraine-like attacks after PACAP38 and four after vasoactive intestinal polypeptide (18%) infusion (P = 0.002). Three of four patients, who reported migraine-like attacks after vasoactive intestinal polypeptide, also reported attacks after PACAP38. Both peptides induced marked dilatation of the extracranial (P < 0.05), but not intracranial arteries (P > 0.05). PACAP38-induced vasodilatation was longer lasting (>2 h), whereas vasoactive intestinal polypeptide-induced dilatation was normalized after 2 h. We recorded elevated plasma PACAP38 at 1 h after the start of PACAP38 infusion only in those patients who later reported migraine attacks. Blood levels of vasoactive intestinal polypeptide and tryptase were unchanged after PACAP38 infusion. In conclusion, PACAP38-induced migraine was associated with sustained dilatation of extracranial arteries and elevated plasma PACAP38 before onset of migraine-like attacks. PACAP38 has a much higher affinity for the PAC1 receptor and we therefore suggest that migraine induction by PACAP38 may be because of activation of the PAC1 receptor, which may be a future anti-migraine drug target.
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Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: a population-based study.
JAMA Psychiatry
PUBLISHED: 01-31-2014
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Studies have shown that attention-deficit/hyperactivity disorder (ADHD) is associated with transport accidents, but the magnitude of the association remains unclear. Most important, it is also unclear whether ADHD medication reduces this risk.
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Genetic associations between the symptoms of attention-deficit/hyperactivity disorder and emotional lability in child and adolescent twins.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 01-30-2014
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Emotional lability is recognized as an associated feature of attention-deficit/hyperactivity disorder (ADHD). However, the degree of phenotypic and etiologic overlap between emotional lability and the ADHD dimensions of hyperactivity-impulsivity and inattention remains unclear. The present study examines these associations in a large, community twin sample.
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Quantification of myocardial perfusion using cardiac magnetic resonance imaging correlates significantly to rubidium-82 positron emission tomography in patients with severe coronary artery disease: a preliminary study.
Eur J Radiol
PUBLISHED: 01-25-2014
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Aim was to compare absolute myocardial perfusion using cardiac magnetic resonance imaging (CMRI) based on Tikhonov's procedure of deconvolution and rubidium-82 positron emission tomography (Rb-82 PET).
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Relative immaturity and ADHD: findings from nationwide registers, parent- and self-reports.
J Child Psychol Psychiatry
PUBLISHED: 01-21-2014
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We addressed if immaturity relative to peers reflected in birth month increases the likelihood of ADHD diagnosis and treatment.
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Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi.
Conrad L Schoch, Barbara Robbertse, Vincent Robert, Duong Vu, Gianluigi Cardinali, László Irinyi, Wieland Meyer, R Henrik Nilsson, Karen Hughes, Andrew N Miller, Paul M Kirk, Kessy Abarenkov, M Catherine Aime, Hiran A Ariyawansa, Martin Bidartondo, Teun Boekhout, Bart Buyck, Qing Cai, Jie Chen, Ana Crespo, Pedro W Crous, Ulrike Damm, Z Wilhelm De Beer, Bryn T M Dentinger, Pradeep K Divakar, Margarita Dueñas, Nicolas Feau, Katerina Fliegerová, Miguel A García, Zai-Wei Ge, Gareth W Griffith, Johannes Z Groenewald, Marizeth Groenewald, Martin Grube, Marieka Gryzenhout, Cécile Gueidan, Liangdong Guo, Sarah Hambleton, Richard Hamelin, Karen Hansen, Valérie Hofstetter, Seung-Beom Hong, Jos Houbraken, Kevin D Hyde, Patrik Inderbitzin, Peter R Johnston, Samantha C Karunarathna, Urmas Kõljalg, Gábor M Kovács, Ekaphan Kraichak, Krisztina Krizsán, Cletus P Kurtzman, Karl-Henrik Larsson, Steven Leavitt, Peter M Letcher, Kare Liimatainen, Jian-Kui Liu, D Jean Lodge, Janet Jennifer Luangsa-ard, H Thorsten Lumbsch, Sajeewa S N Maharachchikumbura, Dimuthu Manamgoda, María P Martín, Andrew M Minnis, Jean-Marc Moncalvo, Giuseppina Mulè, Karen K Nakasone, Tuula Niskanen, Ibai Olariaga, Tamás Papp, Tamás Petkovits, Raquel Pino-Bodas, Martha J Powell, Huzefa A Raja, Dirk Redecker, J M Sarmiento-Ramirez, Keith A Seifert, Bhushan Shrestha, Soili Stenroos, Benjamin Stielow, Sung-Oui Suh, Kazuaki Tanaka, Leho Tedersoo, M Teresa Telleria, Dhanushka Udayanga, Wendy A Untereiner, Javier Diéguez Uribeondo, Krishna V Subbarao, Csaba Vágvölgyi, Cobus Visagie, Kerstin Voigt, Donald M Walker, Bevan S Weir, Michael Weiss, Nalin N Wijayawardene, Michael J Wingfield, J P Xu, Zhu L Yang, Ning Zhang, Wen-Ying Zhuang, Scott Federhen.
Database (Oxford)
PUBLISHED: 01-01-2014
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DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi. Database URL: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353.
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Stereopsidales--a new order of mushroom-forming fungi.
PLoS ONE
PUBLISHED: 01-01-2014
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One new order, one new family, and one new combination are presented, as the result of molecular phylogenetic analyses. The new order Stereopsidales and the new family Stereopsidaceae are described incorporating Stereopsis radicans and S. globosa, formerly Clavulicium globosum. We show that not only do these species represent an old overlooked lineage, but both species harbor cryptic diversity. In addition, a third species, C. macounii, appears as a plausible sister to the new lineage, but there is conflict in the data. All specimens of S. radicans and S. globosa analysed here are from the South and Central Americas; several records of S. radicans have been made also from tropical Asia. We expect the true diversity in this group to be a lot higher than presented in this paper. Stereopsis radicans was formerly included in Polyporales, but a placement within that order is rejected by our data through SH tests. The dataset consisted of four nuclear markers: rpb2, tef1, LSU and SSU, each of which was analysed separately using maximum likelihood and Bayesian inference. Recombination detection tests indicate no plausible recombinations. The potential of S. radicans, S. globosa and C. macounii being amphitallic is briefly discussed.
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Glycopyrrolate does not influence the visual or motor-induced increase in regional cerebral perfusion.
Front Physiol
PUBLISHED: 01-01-2014
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Acetylcholine may contribute to the increase in regional cerebral blood flow (rCBF) during cerebral activation since glycopyrrolate, a potent inhibitor of acetylcholine, abolishes the exercise-induced increase in middle cerebral artery mean flow velocity. We tested the hypothesis that cholinergic vasodilatation is important for the increase in rCBF during cerebral activation. The subjects were 11 young healthy males at an age of 24 ± 3 years (mean ± SD). We used arterial spin labeling and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to evaluate rCBF with and without intravenous glycopyrrolate during a handgrip motor task and visual stimulation. Glycopyrrolate increased heart rate from 56 ± 9 to 114 ± 14 beats/min (mean ± SD; p < 0.001), mean arterial pressure from 86 ± 8 to 92 ± 12 mmHg, and cardiac output from 5.6 ± 1.4 to 8.0 ± 1.7 l/min. Glycopyrrolate had, however, no effect on the arterial spin labeling or BOLD responses to the handgrip motor task or to visual stimulation. This study indicates that during a handgrip motor task and visual stimulation, the increase in rCBF is unaffected by blockade of acetylcholine receptors by glycopyrrolate. Further studies on the effect of glycopyrrolate on middle cerebral artery diameter are needed to evaluate the influence of glycopyrrolate on mean flow velocity during intense exercise.
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Dynamic Permeability and Quantitative Susceptibility: Related Imaging Biomarkers in Cerebral Cavernous Malformations.
Stroke
PUBLISHED: 12-03-2013
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Hyperpermeability and iron deposition are 2 central pathophysiological phenomena in human cerebral cavernous malformation (CCM) disease. Here, we used 2 novel MRI techniques to establish a relationship between these phenomena.
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Preterm birth and mortality and morbidity: a population-based quasi-experimental study.
JAMA Psychiatry
PUBLISHED: 09-27-2013
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Preterm birth is associated with increased mortality and morbidity. However, previous studies have been unable to rigorously examine whether confounding factors cause these associations rather than the harmful effects of being born preterm.
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Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design.
Int J Epidemiol
PUBLISHED: 09-20-2013
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High maternal pre-pregnancy body mass index (BMI) is associated with increased risk of offspring attention deficit hyperactivity disorder (ADHD). However, the role of unmeasured familial confounding for this association remains unclear.
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Sex differences in jealousy: a population-based twin study in Sweden.
Twin Res Hum Genet
PUBLISHED: 08-21-2013
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According to the theory of evolved sex differences in jealousy, the challenge for women to ensure paternal investment increased their jealousy response to emotional infidelity, whereas paternal uncertainty exerted selective pressures that shaped men to become more distressed by sexual infidelity. Several studies have investigated whether the effect of these sexually dimorphic selection pressures can be detected in contemporary human populations, with conflicting results. To date, no genetically informed studies of sex differences in jealousy have been conducted. We used data from the Screening Across the Lifespan of Twins Younger (SALTY) sample, containing information concerning self-rated jealousy from 3,197 complete twin pairs collected by the Swedish Twin Registry. Intra-class correlations and structural equation models were used to assess the genetic influence on jealousy and to investigate sex differences at genetic level. We saw a highly significant sex effect on the relationship between infidelity types, indicating that men, relative to women, reported greater jealousy in response to sexual infidelity than in response to emotional infidelity. The twin models revealed significant heritabilities for both sexual (32%) and emotional (26%) jealousy. The heritabilities were of a similar magnitude in both sexes, and no qualitative sex differences could be detected. We show for the first time that variance in jealousy is to some extent explained by genetic factors. Even though our results from the mean value analyses are in line with the theory of evolved sex differences in jealousy, we could not identify any sex differences on a genetic level.
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Phylogenetic and phylogenomic overview of the Polyporales.
Mycologia
PUBLISHED: 08-11-2013
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We present a phylogenetic and phylogenomic overview of the Polyporales. The newly sequenced genomes of Bjerkandera adusta, Ganoderma sp., and Phlebia brevispora are introduced and an overview of 10 currently available Polyporales genomes is provided. The new genomes are 39 500 000-49 900 00 bp and encode for 12 910-16 170 genes. We searched available genomes for single-copy genes and performed phylogenetic informativeness analyses to evaluate their potential for phylogenetic systematics of the Polyporales. Phylogenomic datasets (25, 71, 356 genes) were assembled for the 10 Polyporales species with genome data and compared with the most comprehensive dataset of Polyporales to date (six-gene dataset for 373 taxa, including taxa with missing data). Maximum likelihood and Bayesian phylogenetic analyses of genomic datasets yielded identical topologies, and the corresponding clades also were recovered in the 373-taxa dataset although with different support values in some datasets. Three previously recognized lineages of Polyporales, antrodia, core polyporoid and phlebioid clades, are supported in most datasets, while the status of the residual polyporoid clade remains uncertain and certain taxa (e.g. Gelatoporia, Grifola, Tyromyces) apparently do not belong to any of the major lineages of Polyporales. The most promising candidate single-copy genes are presented, and nodes in the Polyporales phylogeny critical for the suprageneric taxonomy of the order are identified and discussed.
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Family income in early childhood and subsequent attention deficit/hyperactivity disorder: a quasi-experimental study.
J Child Psychol Psychiatry
PUBLISHED: 08-02-2013
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Studies have found negative associations between socioeconomic position and attention deficit/hyperactivity disorder (ADHD), but it remains unclear if this association is causal. The aim of this study was to determine the extent to which the association between family income in early childhood and subsequent ADHD depends on measured and unmeasured selection factors.
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Maternal diabetes in pregnancy and offspring cognitive ability: sibling study with 723,775 men from 579,857 families.
Diabetologia
PUBLISHED: 06-27-2013
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The aim of this study was to investigate the association between maternal diabetes in pregnancy and offspring cognitive ability and also to assess whether the association was due to intrauterine mechanisms or shared familial characteristics.
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Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.
Clin Physiol Funct Imaging
PUBLISHED: 05-30-2013
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Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43·6 ml per 100 g min(-1) , 5·5 l min(-1) and 2·7 l min(-1)  m(-2) , respectively, in males, and 53·4 ml per 100 g min(-1) , 4·3 l min(-1) and 2·4 l min(-1) m(-2) , respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2)  = 0·22, P = 0·008) and furthermore lower in males than in females (8·6% versus 12·5%, P = 0·003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease.
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Risk of bipolar disorder and schizophrenia in relatives of people with attention-deficit hyperactivity disorder.
Br J Psychiatry
PUBLISHED: 05-23-2013
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Attention-deficit hyperactivity disorder (ADHD) is associated with bipolar disorder and schizophrenia, and it has been suggested that combined bipolar disorder and ADHD is aetiologically distinct from the pure disorders.
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Towards a unified paradigm for sequence-based identification of fungi.
Mol. Ecol.
PUBLISHED: 05-10-2013
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The nuclear ribosomal internal transcribed spacer (ITS) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database (http://unite.ut.ee) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. Hymenoscyphus pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third-party annotation effort. We introduce the term species hypothesis (SH) for the taxa discovered in clustering on different similarity thresholds (97-99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released (http://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web-based sequence management system in UNITE.
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Periodicity in tumor vasculature targeting kinetics of ligand-functionalized nanoparticles studied by dynamic contrast enhanced magnetic resonance imaging and intravital microscopy.
Angiogenesis
PUBLISHED: 04-30-2013
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In the past two decades advances in the development of targeted nanoparticles have facilitated their application as molecular imaging agents and targeted drug delivery vehicles. Nanoparticle-enhanced molecular imaging of the angiogenic tumor vasculature has been of particular interest. Not only because angiogenesis plays an important role in various pathologies, but also since endothelial cell surface receptors are directly accessible for relatively large circulating nanoparticles. Typically, nanoparticle targeting towards these receptors is studied by analyzing the contrast distribution on tumor images acquired before and at set time points after administration. Although several exciting proof-of-concept studies demonstrated qualitative assessment of relative target concentration and distribution, these studies did not provide quantitative information on the nanoparticle targeting kinetics. These kinetics will not only depend on nanoparticle characteristics, but also on receptor binding and recycling. In this study, we monitored the in vivo targeting kinetics of ?v?3-integrin specific nanoparticles with intravital microscopy and dynamic contrast enhanced magnetic resonance imaging, and using compartment modeling we were able to quantify nanoparticle targeting rates. As such, this approach can facilitate optimization of targeted nanoparticle design and it holds promise for providing more quantitative information on in vivo receptor levels. Interestingly, we also observed a periodicity in the accumulation kinetics of ?v?3-integrin targeted nanoparticles and hypothesize that this periodicity is caused by receptor binding, internalization and recycling dynamics. Taken together, this demonstrates that our experimental approach provides new insights in in vivo nanoparticle targeting, which may proof useful for vascular targeting in general.
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Global optimization of parameters in the reactive force field ReaxFF for SiOH.
J Comput Chem
PUBLISHED: 04-16-2013
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We have used unbiased global optimization to fit a reactive force field to a given set of reference data. Specifically, we have employed genetic algorithms (GA) to fit ReaxFF to SiOH data, using an in-house GA code that is parallelized across reference data items via the message-passing interface (MPI). Details of GA tuning turn-ed out to be far less important for global optimization efficiency than using suitable ranges within which the parameters are varied. To establish these ranges, either prior knowledge can be used or successive stages of GA optimizations, each building upon the best parameter vectors and ranges found in the previous stage. We have finally arrive-ed at optimized force fields with smaller error measures than those published previously. Hence, this optimization approach will contribute to converting force-field fitting from a specialist task to an everyday commodity, even for the more difficult case of reactive force fields.
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The effect of sumatriptan on cephalic arteries: A 3T MR-angiography study in healthy volunteers.
Cephalalgia
PUBLISHED: 04-15-2013
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To explore a possible differential effect of sumatriptan on extracerebral versus cerebral arteries, we examined the superficial temporal (STA), middle meningeal (MMA), extracranial internal carotid (ICAextra), intracranial internal carotid (ICAintra), middle cerebral (MCA) and basilar arteries (BA).
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Klinefelter syndrome and risk of psychosis, autism and ADHD.
J Psychiatr Res
PUBLISHED: 04-12-2013
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Schizophrenia, bipolar disorder, autism spectrum disorders and ADHD might be overrepresented in Klinefelter syndrome, but previous investigations have yielded inconclusive results.
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Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study.
Lancet Neurol
PUBLISHED: 04-09-2013
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Extracranial arterial dilatation has been hypothesised to be the cause of pain in patients who have migraine without aura. To test that hypothesis, we aimed to measure extracranial and intracranial arteries during attacks of migraine without aura.
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Interhemispheric differences of fMRI responses to visual stimuli in patients with side-fixed migraine aura.
Hum Brain Mapp
PUBLISHED: 04-03-2013
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Migraine sufferers with aura often report photosensitivity and visual discomfort outside of attacks and many consider bright or flickering light an attack-precipitating factor. The nature of this visual hypersensitivity and its relation to the underlying pathophysiology of the migraine aura is unknown. Using fMRI measurements during visual stimulation we examined the visual cortical responsiveness of patients with migraine with aura. We applied a within-patient design by assessing functional interhemispheric differences in patients consistently experiencing visual aura in the same visual hemifield. We recruited 20 patients with frequent side-fixed visual aura attacks (?90% of auras occurring in the same visual hemifield) and 20 age and sex matched healthy controls and compared the fMRI blood oxygenation level dependent (BOLD) responses to visual stimulation between symptomatic and asymptomatic hemispheres during the interictal phase and between migraine patients and controls. BOLD responses were selectively increased in the symptomatic hemispheres. This was found in the inferior parietal lobule (P = 0.002), the inferior frontal gyrus (P = 0.003), and the superior parietal lobule (P = 0.017). The affected cortical areas comprise a visually driven functional network involved in oculomotor control, guidance of movement, motion perception, visual attention, and visual spatial memory. The patients also had significantly increased response in the same cortical areas when compared to controls (P < 0.05). We discovered a lateralized alteration of a visually driven functional network in patients with side-fixed aura. These findings suggest a hyperexcitability of the visual system in the interictal phase of migraine with visual aura. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
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A century of indicator dilution technique.
Clin Physiol Funct Imaging
PUBLISHED: 04-03-2013
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This review imparts the history and the present status of the indicator dilution technique with quantitative bolus injection. The first report on flow measurement with this technique appeared 100 years ago. In 1928, the use of intravascular dyes made possible a widespread application in animals and human during the next decades. Multiple indicators, radioactive tracers, inlet-outlet detection and residue detection were introduced in the 1950s and 1960s, and refined along with the development of indicator kinetics. From the 1970s, a wide clinical use in the study of heart, brain, lungs, liver and kidneys developed, and powerful computers in the 1980s and 1990s accorded the technique a new dimension. Today, the indicator dilution technique, on one hand, is applied in the same way as 100 years ago, on the other hand it forms the basis of quantitative SPECT, positron emission tomography, and dynamic MR scans. The technique still undergoes refinement and elaboration as a lasting concept with a high potential for further development.
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Measurement of brain oxygenation changes using dynamic T(1)-weighted imaging.
Neuroimage
PUBLISHED: 03-25-2013
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Magnetic resonance imaging (MRI) has proven useful in evaluating oxygenation in several types of tissue and blood. This study evaluates brain tissue oxygenation changes between normoxia and hyperoxia in healthy subjects using dynamic T1 and T2*-weighted imaging sequences. The change in FiO2 induced by hyperoxia caused a significant decrease in T1. A model to determine changes in tissue oxygen tension from the T1-weighted MRI signal is presented based on previous findings that T1 is sensitive to oxygen tension whereas T2* is sensitive to blood saturation. The two sequences produce results with different regional and temporal dynamics. These differences combined with results from simulations of the T1 signal intensities, indicate an increase in extravascular oxygen tension during hyperoxia. This study concludes that T1 and T2* responses to FiO2 serve as independent biomarkers of oxygen physiology in the brain with a potential to provide quantitative information on tissue oxygenation.
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Molecular analyses confirm Brevicellicium in Trechisporales.
IMA Fungus
PUBLISHED: 02-28-2013
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The genus Brevicellicium encompasses wood-inhabiting corticioid fungi characterized by isodiametric subhymenial hyphae, short basidia, and smooth, often subangular spores with a distinct apiculus. Eight new LSU nrDNA sequences and 13 new ITS nrDNA of this genus, including the type species, were aligned with 47 and 42 accessions respectively of species of Trechisporales obtained from GenBank, and phylogenetic analyses were performed. The order Trechisporales was confirmed as a monophyletic group; the genera Porpomyces, Sistotremastrum, Subulicystidium and Trechispora form a highly supported clade where all Brevicellicium sequences are included. Our analyses also support that this genus belongs to Hydnodontaceae. A new species, Brevicellicium atlanticum from the Azores Archipelago, is described.
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Sources of variability of resting cerebral blood flow in healthy subjects: a study using ¹³³Xe SPECT measurements.
J. Cereb. Blood Flow Metab.
PUBLISHED: 02-13-2013
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Measurements of cerebral blood flow (CBF) show large variability among healthy subjects. The aim of the present study was to investigate the relative effect of established factors influencing CBF on the variability of resting CBF. We retrospectively analyzed spontaneous variability in 430 CBF measurements acquired in 152 healthy, young subjects using (133)Xe single-photon emission computed tomography. Cerebral blood flow was correlated positively with both end-tidal expiratory PCO? (PETCO?) and female gender and inversely with hematocrit (Hct). Between- and within-subject CO? reactivity was not significantly different. Including PETCO?, Hct and gender in the model reduced between-subject and within-subject variance by 14% and 13.5%, respectively. Within-subject variability was mainly influenced by PETCO? and between-subject variability mostly by Hct, whereas gender appeared to be of little added value when Hct was also accounted for. The present study confirms large between-subject variability in CBF measurements and that gender, Hct, and PETCO? explain only a small part of this variability. This implies that a large fraction of CBF variability may be due to unknown factors such as differences in neuron density or metabolism that could be subject for further studies.
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Concurrent functional magnetic resonance imaging and electroencephalography assessment of sensory gating in schizophrenia.
Hum Brain Mapp
PUBLISHED: 01-23-2013
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Schizophrenia is frequently accompanied by deficits in basic information processing, such as sensory gating. The sources behind deficient sensory gating in schizophrenia patients are, however, still largely unclear. The aim of the current study was to identify the brain structures involved in deficient sensory gating in schizophrenia patients. Twenty healthy male volunteers and 23 male schizophrenia patients were initially assessed in a somatosensory P50 suppression paradigm using concurrent electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) methodology. The trials consisted of single stimuli or pairs of identical stimuli with either 500 ms or 1,000 ms interstimulus intervals. Not all subjects showed a P50 waveform as a result of the somatosensory stimuli: It was detected in 13 schizophrenia patients and 15 control subjects. Significant P50 suppression was found in the 500 ms trials in controls only. Region of interest analyses were performed for a priori chosen regions. Significant negative correlations between P50 ratios and the BOLD response were found bilaterally in the hippocampus, thalamus, anterior and posterior superior temporal gyrus (STG), and in the left inferior frontal gyrus pars opercularis. However, significant group differences were found in the hippocampus and the thalamus only. This is the first study in which P50 suppression was assessed in schizophrenia patients with concurrent fMRI/EEG methodology. The data support that the STG, thalamus, inferior frontal gyrus, and the hippocampus are involved in P50 suppression. However, of these structures only the hippocampus and thalamus appeared involved in the altered sensory processing found in schizophrenia. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
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Between-within models for survival analysis.
Stat Med
PUBLISHED: 01-21-2013
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A popular way to control for confounding in observational studies is to identify clusters of individuals (e.g., twin pairs), such that a large set of potential confounders are constant (shared) within each cluster. By studying the exposure-outcome association within clusters, we are in effect controlling for the whole set of shared confounders. An increasingly popular analysis tool is the between-within (BW) model, which decomposes the exposure-outcome association into a within-cluster effect and a between-cluster effect. BW models are relatively common for nonsurvival outcomes and have been studied in the theoretical literature. Although it is straightforward to use BW models for survival outcomes, this has rarely been carried out in practice, and such models have not been studied in the theoretical literature. In this paper, we propose a gamma BW model for survival outcomes. We compare the properties of this model with the more standard stratified Cox regression model and use the proposed model to analyze data from a twin study of obesity and mortality. We find the following: (i) the gamma BW model often produces a more powerful test of the within-cluster effect than stratified Cox regression; and (ii) the gamma BW model is robust against model misspecification, although there are situations where it could give biased estimates.
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Developmental twin study of attention problems: high heritabilities throughout development.
JAMA Psychiatry
PUBLISHED: 01-11-2013
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The genetic and environmental link between attention-deficit/hyperactivity disorder in childhood and the adult manifestation of the disorder is poorly understood because of a lack of longitudinal studies with cross-informant data.
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Relationship between cerebrospinal fluid biomarkers for inflammation, demyelination and neurodegeneration in acute optic neuritis.
PLoS ONE
PUBLISHED: 01-01-2013
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Various inflammatory biomarkers show prognostic potential for multiple sclerosis (MS)-risk after clinically isolated syndromes. However, biomarkers are often examined singly and their interrelation and precise aspects of their associated pathological processes remain unclear. Clarification of these relationships could aid the appropriate implementation of prognostic biomarkers in clinical practice.
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Headache and prolonged dilatation of the middle meningeal artery by PACAP38 in healthy volunteers.
Cephalalgia
PUBLISHED: 12-15-2011
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To explore a possible relationship between vasodilatation and delayed headache we examined the effect of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) on the middle meningeal artery (MMA) and middle cerebral artery (MCA) using high resolution magnetic resonance angiography (MRA).
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Negative BOLD signal changes in ipsilateral primary somatosensory cortex are associated with perfusion decreases and behavioral evidence for functional inhibition.
Neuroimage
PUBLISHED: 10-03-2011
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We used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the negative blood oxygenation level dependent (BOLD) signal and its underlying blood flow changes in healthy human subjects. This was combined with psychophysiological measurements to test that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7 Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI was accompanied by commensurate decreases in relative regional cerebral blood flow (rCBF). Conjunction analysis of the fMRI and PET data revealed a region in the ipsilateral postcentral gyrus showing overlap of negative BOLD signals and relative rCBF decreases. The current perception threshold (CPT) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition.
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Childhood attention-deficit hyperactivity disorder as an extreme of a continuous trait: a quantitative genetic study of 8,500 twin pairs.
J Child Psychol Psychiatry
PUBLISHED: 09-16-2011
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Although the clinical utility of categorically defined attention-deficit hyperactivity disorder (ADHD) is well established, there is also strong evidence supporting the notion of ADHD as an extreme of a continuous trait. Nevertheless, the question of whether the etiology is the same for different levels of DSM-IV ADHD symptoms remains to be investigated. The aim of this study was to assess genetic links between the extreme and the subthreshold range of ADHD symptoms.
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Simvastatin improves final visual outcome in acute optic neuritis: a randomized study.
Mult. Scler.
PUBLISHED: 09-15-2011
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In recent years, small-scale clinical trials have indicated that statins or 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors exert pleiotropic immunomodulatory effects, with potential therapeutic implications in multiple sclerosis (MS).
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Heritability of cortisol regulation in children.
Twin Res Hum Genet
PUBLISHED: 07-25-2011
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The normal development of cortisol regulation during childhood is thought to be influenced by a complex interplay between environmental and genetic factors.
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Tidying up international nucleotide sequence databases: ecological, geographical and sequence quality annotation of its sequences of mycorrhizal fungi.
PLoS ONE
PUBLISHED: 06-30-2011
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Sequence analysis of the ribosomal RNA operon, particularly the internal transcribed spacer (ITS) region, provides a powerful tool for identification of mycorrhizal fungi. The sequence data deposited in the International Nucleotide Sequence Databases (INSD) are, however, unfiltered for quality and are often poorly annotated with metadata. To detect chimeric and low-quality sequences and assign the ectomycorrhizal fungi to phylogenetic lineages, fungal ITS sequences were downloaded from INSD, aligned within family-level groups, and examined through phylogenetic analyses and BLAST searches. By combining the fungal sequence database UNITE and the annotation and search tool PlutoF, we also added metadata from the literature to these accessions. Altogether 35,632 sequences belonged to mycorrhizal fungi or originated from ericoid and orchid mycorrhizal roots. Of these sequences, 677 were considered chimeric and 2,174 of low read quality. Information detailing country of collection, geographical coordinates, interacting taxon and isolation source were supplemented to cover 78.0%, 33.0%, 41.7% and 96.4% of the sequences, respectively. These annotated sequences are publicly available via UNITE (http://unite.ut.ee/) for downstream biogeographic, ecological and taxonomic analyses. In European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena/), the annotated sequences have a special link-out to UNITE. We intend to expand the data annotation to additional genes and all taxonomic groups and functional guilds of fungi.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.