Search tips
Search criteria

Results 1-25 (364)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
1.  PET Tracers for Serotonin Receptors and Their Applications
Serotonin receptors (5-HTRs) are implicated in the pathophysiology of a variety of neuropsychiatric and neurodegenerative disorders and are also targets for drug therapy. In the CNS, most of these receptors are expressed in high abundance in specific brain regions reflecting their role in brain functions. Quantifying binding to 5-HTRs in vivo may permit assessment of physiologic and pathologic conditions, and monitoring disease progression, evaluating treatment response, and for investigating new treatment modalities. Positron emission tomography (PET) molecular imaging has the sensitivity to quantify binding of 5-HTRs in CNS disorders and to measure drug occupancy as part of a process of new drug development. Although research on PET imaging of 5-HTRs have been performed more than two decades, the successful radiotracers so far developed for human studies are limited to 5-HT1AR, 5-HT1BR, 5-HT2AR, 5-HT4R and 5-HT6R. Herein we review the development and application of radioligands for PET imaging of 5-HTRs in living brain.
PMCID: PMC4330993  PMID: 25360773
Molecular imaging; PET; 5-HTR; radioligands
2.  SSRI versus bupropion effects on symptom clusters in suicidal depression: post-hoc analysis of a randomized clinical trial
Identifying the depression symptoms most closely associated with suicidal thoughts and which medications provide the fastest relief may help suicide prevention.
Post hoc analysis of data from a randomized, double-blind, eight-week clinical trial of the serotonin reuptake inhibitor paroxetine (N=36) versus the norepinephrine-dopamine reuptake inhibitor bupropion (N=38) in patients with DSM-IV major depressive disorder and past suicide attempt or current suicidal thoughts. Treatment effects on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory symptom clusters were compared. We hypothesized a superior effect of paroxetine on non-suicide, affective/cognitive depression symptom clusters that our prior work found to be associated with suicidal thoughts and attempts. Data were collected from February 2005 to January 2010.
There was a treatment main effect on HDRS Psychic Depression (depressed mood, guilt, retardation, helpless, hopeless, worthless) (estimate = −2.2, 95% CI = −3.2 to −1.1, t = −4.01, df = 67.16, p < 0.001), one of the clusters most strongly correlated to suicidal ideation. The net drug effect was 2.2 points lower average Psychic Depression scores after one week of paroxetine, compared to bupropion, and was statistically significant until Week 4. Results for other depression scale factors were non-significant (p > 0.05).
The results require replication, but suggest a pathway by which SSRI treatment may exert a stronger effect compared with NDRI treatment on reduction of suicidal thoughts during initial weeks of pharmacotherapy in these higher risk patients.
PMCID: PMC4313534  PMID: 24107760
Suicide; depression; symptom cluster; antidepressant; clinical trial
3.  Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal, family study
To investigate relationships of depressed parents' attachment style to offspring suicidal behavior.
244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992–2008 during a longitudinal family study completed January 31, 2014.
Parent avoidant attachment predicted offspring suicide attempts at a trend level (p=0.083). Parent anxious attachment did not predict offspring attempts (p=0.961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (p=0.034), and in offspring suicide attempters, was associated with greater intent (p=0.045) and lethality of attempts (p=0.003). Avoidant attachment in parents was associated with offspring impulsivity (p=0.025) and major depressive disorder (p=0.012). Parent avoidant attachment predicted a greater number of suicide attempts (p=0.048) and greater intent in offspring attempters (p=0.003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder.
Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parent attachment traits were associated with impulsivity and major depressive disorder in all offspring, and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior.
PMCID: PMC4311521  PMID: 25098943
Attachment; Suicide attempt; Family study; Impulsivity; Depression
4.  Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice
Molecular psychiatry  2014;19(6):688-698.
Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypo-activity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21) but not during peri-adolescence (P22-41) increases anxiety- and depression-like behavior in adult (> P90) mice, mimicking the effect of P2-21 5-HTT inhibition. Moreover, MAOA blockade during peri-adolescence, but not P2-21 or P182-201, increases adult aggressive behavior, and 5-HTT blockade from P22-P41 reduced adult aggression. Blockade of the dopamine transporter, but not the norepinephrine transporter, during P22-41 also increases adult aggressive behavior. Thus, P2-21 is a sensitive period during which 5-HT modulates adult anxiety/depression-like behavior, and P22-41 is a sensitive period during which DA and 5-HT bi-directionally modulate adult aggression. Permanently altered DAergic function as a consequence of increased P22-P41 monoamine signaling might underlie altered aggression. In support of this hypothesis, we find altered aggression correlating positively with locomotor response to amphetamine challenge in adulthood. Proving that altered DA function and aggression are causally linked, we demonstrate that optogenetic activation of VTA DAergic neurons increases aggression. It therefore appears that genetic and pharmacologic factors impacting dopamine and serotonin signaling during sensitive developmental periods can modulate adult monoaminergic function and thereby alter risk for aggressive and emotional dysfunction.
PMCID: PMC4311886  PMID: 24589889
Serotonin; Dopamine; Development; Aggression; Anxiety; Depression; Mouse
5.  Suicidal Behavior: A Developmental Perspective
PMCID: PMC4302391  PMID: 18439441
6.  Past Suicide Attempts in Depressed Inpatients: Clinical versus Research Assessment
To compare structured clinical assessment versus research measurement of suicidal risk among inpatients with major depression.
50 depressed inpatients underwent a structured clinical and an independent research assessment of suicidal risk. Agreement between both assessments and its impact upon time to first readmission was tested.
A false negative rate of 25% in the clinical screening of past suicide attempts was associated with older age, concealment and reported lower frequency of suicidal thoughts. Mean times to first readmission (2.5-years follow-up) were 74 weeks (discordant responders) and 118 weeks (concordant responders).
A failure to detect 25% of patients with past suicide attempt history in the clinical assessment was associated with older age and concealment of suicidal thoughts.
PMCID: PMC3988802  PMID: 24350632
Suicide, Attempted; Depression; Inpatients; Diagnostic Errors; Assessment, Risk; Bipolar Disorder
7.  Hemispheric asymmetry of primary auditory cortex and Heschl’s gyrus in schizophrenia and nonpsychiatric brains
Psychiatry research  2013;214(3):10.1016/j.pscychresns.2013.08.009.
Heschl’s gyrus (HG) is reported to have a normal left>right hemispheric volume asymmetry, and reduced asymmetry in schizophrenia. Primary auditory cortex (A1) occupies the caudal-medial surface of HG, but it is unclear if A1 has normal asymmetry, or whether its asymmetry is altered in schizophrenia. To address these issues, we compared bilateral gray matter volumes of HG and A1, and neuron density and number in A1, in autopsy brains from male subjects with or without schizophrenia. Comparison of diagnostic groups did not reveal altered gray matter volumes, neuron density, neuron number or hemispheric asymmetries in schizophrenia. With respect to hemispheric differences, HG displayed a clear left>right asymmetry of gray matter volume. Area A1 occupied nearly half of HG, but had less consistent volume asymmetry, that was clearly present only in a subgroup of archival brains from elderly subjects. Neuron counts, in layers IIIb-c and V-VI, showed that the A1 volume asymmetry reflected differences in neuron number, and was not caused simply by changes in neuron density. Our findings confirm previous reports of striking hemispheric asymmetry of HG, and additionally show evidence that A1 has a corresponding asymmetry, although less consistent than that of HG.
PMCID: PMC3851973  PMID: 24148910
cerebral cortex; human; postmortem; stereology; neuron number
8.  fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study
Psychiatry research  2013;214(3):296-305.
Clinically useful predictors of treatment outcome in major depressive disorder (MDD) remain elusive. We examined associations between functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active negative word processing and subsequent selective serotonin reuptake inhibitor (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an emotional word processing fMRI task, and then received eight weeks of standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD responses to negative words in midbrain, dorsolateral prefrontal cortex, paracingulate, anterior cingulate, thalamus and caudate nuclei correlated significantly with greater improvement following escitalopram treatment. Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance. Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48% of the variance in response to treatment. This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli. Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design. Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy (CBT) in previous studies using the same task. Future studies may examine prediction of differential outcome across treatments in the context of a randomized controlled trial.
PMCID: PMC4083855  PMID: 24446548
fMRI; major depressive disorder; biomarker; SSRI; prediction; treatment outcome
9.  Varenicline, Smoking Cessation and Neuropsychiatric Adverse Events
The American journal of psychiatry  2013;170(12):1460-1467.
In 2009 FDA issued a black box warning for varenicline and neuropsychiatric events. We studied efficacy (smoking cessation) of varenicline, and safety (neuropsychiatric events) in both randomized clinical trials (RCTs) and a large observational study. The observational study was included to determine the generalizability of the RCT findings to the general population.
RCTs: Re-analysis of all 17 placebo controlled RCTs (n=8027) of varenicline conducted by Pfizer using complete intent-to-treat person-level longitudinal data.
Observational Study
Analysis of Department of Defense collected adverse neuropsychiatric adverse event data in inpatients and outpatients taking varenicline versus nicotine replacement therapy (NRT) (n=35,800). The primary endpoints for the RCTs were smoking abstinence and adverse event reports of suicidal thoughts and behavior, depression, aggression/agitation, and nausea. The effect of varenicline in patients with (n=1004) and without (n=7023) psychiatric disorders was examined. The primary endpoints for the observational study were anxiety, depression, drug induced mental disorder, episodic and mood disorder, other psychiatric disorder, post traumatic stress disorder, schizophrenia, suicide attempt, transient mental disorder.
RCTs: Varenicline did not increase rates of suicidal events, depression, or aggression/agitation. Varenicline increased risk of nausea (OR=3.69, 95% CI = (3.03, 4.48), p<0.0001). Varenicline increased rate of abstinence by 124% compared to placebo (p<0.0001), and 22% compared to bupropion (p<0.0001). While having a current psychiatric disorder or history of psychiatric illness increased the risk of neuropsychiatric events, it did so equally in treated and control patients.
Observational Study
Following propensity score matching, overall rate of neuropsychiatric disorders was lower for varenicline versus NRT (2.28% versus 3.16%, p<0.0001).
In the RCTs, varenicline revealed no increased risk of neuropsychiatric adverse events relative to placebo. Varenicline provided greater benefit in terms of smoking cessation relative to both placebo and bupropion. The same results were observed in patients with and without a current psychiatric disorder or history of psychiatric illness. In the observational study, the overall rate of neuropsychiatric disorders was lower in patients treated with varenicline relative to NRT, revealing that the finding of no increased risk of neuropsychiatric adverse events in RCTs generalizes to the population of patients engaging in treatment with varenicline.
PMCID: PMC4238282  PMID: 24030388
10.  If at first you don't succeed… Studies of ontogeny shed light on the cognitive demands of habitual tool use
Many species use tools, but the mechanisms underpinning the behaviour differ between species and even among individuals within species, depending on the variants performed. When considering tool use ‘as adaptation’, an important first step is to understand the contribution made by fixed phenotypes as compared to flexible mechanisms, for instance learning. Social learning of tool use is sometimes inferred based on variation between populations of the same species but this approach is questionable. Specifically, alternative explanations cannot be ruled out because population differences are also driven by genetic and/or environmental factors. To better understand the mechanisms underlying routine but non-universal (i.e. habitual) tool use, we suggest focusing on the ontogeny of tool use and individual variation within populations. For example, if tool-using competence emerges late during ontogeny and improves with practice or varies with exposure to social cues, then a role for learning can be inferred. Experimental studies help identify the cognitive and developmental mechanisms used when tools are used to solve problems. The mechanisms underlying the route to tool-use acquisition have important consequences for our understanding of the accumulation in technological skill complexity over the life course of an individual, across generations and over evolutionary time.
PMCID: PMC4027412  PMID: 24101632
habitual tool use; ontogeny; social learning; cognition; inhibition; phenotypic plasticity
11.  Brain Serotonin 1A Receptor Binding as a Predictor of Treatment Outcome in Major Depressive Disorder
Biological psychiatry  2013;74(10):760-767.
We previously reported higher serotonin 1A receptor (5-HT1A) binding in subjects with major depressive disorder (MDD) during a major depressive episode using positron emission tomography imaging with [11C]WAY-100635. 5-HT1A receptor binding is also associated with treatment outcome after nonstandardized antidepressant treatment. We examined whether pretreatment 5-HT1A binding is associated with treatment outcome following standardized escitalopram treatment in MDD. We also compared 5-HT1A binding between all MDD subjects in this cohort and a sample of healthy control subjects.
Twenty-four MDD subjects in a current major depressive episode and 51 previously studied healthy control subjects underwent positron emission tomography scanning with [11C]WAY-100635, acquiring a metabolite-corrected arterial input function and free-fraction measurement to estimate 5-HT1A binding potential (BPF = Bmax/KD, where Bmax = available receptors and KD = dissociation constant). Major depressive disorder subjects then received 8 weeks of treatment with escitalopram; remission was defined as a posttreatment 24-item Hamilton Depression Rating Scale <10 and ≥50% reduction in Hamilton Depression Rating Scale.
Remitters to escitalopram had 33% higher baseline 5-HT1A binding in the raphe nuclei than nonremitters (p = .047). Across 12 cortical and subcortical regions, 5-HT1A binding did not differ between remitters and nonremitters (p = .86). Serotonin 1A receptor binding was higher in MDD than control subjects across all regions (p = .0003). Remitters did not differ from nonremitters in several relevant clinical measures.
Elevated 5-HT1A binding in raphe nuclei is associated with subsequent remission with the selective serotonin reuptake inhibitor escitalopram; this is consistent with data from a separate cohort receiving naturalistic antidepressant treatment. We confirmed our previous findings of higher 5-HT1A binding in current MDD compared with control subjects.
PMCID: PMC4066966  PMID: 23664414
Antidepressant; depression; PET imaging; prediction; serotonin 1A receptor; treatment outcome
12.  Neuronal Tryptophan Hydroxylase Expression in BALB/cJ and C57Bl/6J Mice
Journal of neurochemistry  2011;118(6):1067-1074.
BALB/c is an inbred stress-sensitive mouse strain exhibiting low brain serotonin (5-HT) content and a 5-HT biosynthetic enzyme tryptophan hydroxylase (Tph2) variant reported to have lower catalytic activity compared to other inbred base strains. To evaluate other mechanisms that may explain low 5-HT, we compared BALB/cJ mice and a control inbred strain C57Bl/6J mice, for expression of Tph2 mRNA, TPH2 protein and regional levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). Tph2 mRNA and TPH2 protein in brainstem dorsal raphe nuclei (DRN) was assayed by in situ hybridization and immunocytochemistry respectively. 5-HT and 5-HIAA were determined by high pressure liquid chromatography (HPLC). BALB/cJ mice had 20% less Tph2 mRNA and 28% fewer TPH2 immunolabeled neurons than C57Bl/6J mice (t = -2.59, p = 0.02). The largest difference in Tph2 transcript expression was in rostral DRN (t = 2.731, p = 0.008). 5-HT was 15% lower in the midbrain of BALB/cJ compared to C57Bl/6J mice (p < 0.05). The behavioral differences in BALB/cJ mice relative to the C57Bl/6J strain may be due in part, to fewer 5-HT neurons and lower Tph2 gene expression resulting in less 5-HT neurotransmission. Future studies quantifying expression per neuron are needed to determine whether less expression is explained by fewer neurons or also less expression per neuron, or both.
PMCID: PMC4222035  PMID: 21740442
Tph2; 5-HT; dorsal raphe nucleus; depression; immunocytochemistry
13.  Higher Pre-treatment 5-HT1A Receptor Binding Potential in Bipolar Disorder Depression is Associated with Treatment Remission: A Naturalistic Treatment Pilot PET Study
Synapse (New York, N.Y.)  2013;67(11):10.1002/syn.21684.
Bipolar Disorder is a major cause of disability and a high risk for suicide. The pathophysiology of the disorder remains largely unknown. Medication choice for bipolar depression patients involves trial and error. Our group reported previously that brain serotonin 1A (5HT1A) receptor binding measured by positron emission tomography (PET) is higher in bipolar depression. We now investigated whether pretreatment 5HT1A levels correlates with antidepressant medication outcome. 41 medication-free DSM-IV diagnosed, bipolar patients in a major depressive episode (MDE) had brain PET scans performed using [11C]WAY-100635 and a metabolite corrected arterial input function. The patients then received naturalistic psychopharmacologic treatment as outpatients and a follow up Hamilton Depression Rating Scale (HDRS) after 3 months of treatment. Patients with 24 item HDRS scores less than 10 were considered to have remitted. A linear mixed effects model was used to compare BPF (binding potential, proportional to the total number of available receptors) in 13 brain regions of interest between remitters and non-remitters. 34 patients completed 3 months of treatment and ratings; 9 had remitted. Remitters and non-remitters did not differ in age, sex or recent medication history with serotonergic medications. Remitters had higher [11C]WAY-100635 BPF across all brain regions compared with non-remitters (p=0.02). Higher pre-treatment brain 5HT1A receptor binding was associated with remission after 3 months of pharmacological treatment in bipolar depression. Prospective treatment studies are warranted to determine whether this test predicts outcome of specific types of treatment.
PMCID: PMC3809836  PMID: 23720414
Bipolar Disorder; PET; [11C]WAY-100635; Antidepressant; Mood stabilizer
14.  IL-1alpha released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts
Mucosal immunology  2013;7(3):684-693.
Activation of the innate immune system plays a key role in exacerbations of chronic lung disease, yet the potential role of lung fibroblasts in innate immunity and the identity of epithelial danger signals (alarmins) that may contribute to this process are unclear. The objective of the study was to identify lung epithelial derived alarmins released during endoplasmic reticulum stress (ER stress) and oxidative stress and evaluate their potential to induce innate immune responses in lung fibroblasts. We found that treatment of primary human lung fibroblasts (PHLF) with conditioned media from damaged lung epithelial cells significantly upregulated IL-6, IL-8, MCP-1 and GM-CSF expression (p<0.05). This effect was reduced with anti-IL-1α or IL-1Ra but not anti-IL-1β antibody. Co-stimulation with a TLR3 ligand, Poly I:C, significantly accentuated the IL-1α induced inflammatory phenotype in PHLF, and this effect was blocked with IKK2 and TAKi inhibitors. Finally, Il1r1−/− and Il1a−/− mice exhibit reduced BAL neutrophilia and collagen deposition in response to bleomycin treatment. We conclude that IL-1α plays pivotal role in triggering proinflammatory responses in fibroblasts and this process is accentuated in the presence of dsRNA. This mechanism may be important in the repeated cycles of injury and exacerbation in chronic lung disease.
PMCID: PMC3931585  PMID: 24172847
15.  Familial transmission of parental mood disorders: unipolar and bipolar disorders in offspring
Bipolar disorders  2013;15(7):764-773.
Offspring of depressed parents are at increased risk for psychiatric disorders. Although bipolar disorder (BD) and major depressive disorder (MDD) are both found in the same families, it is not clear whether transmission to offspring of BD or MDD tends to occur from parents with the same mood disorder subtype. The primary hypothesis was that offspring of parents with BD would be at increased risk for BD and other comorbid disorders common to BD such as anxiety and substance use relative to offspring of parents with MDD. Offspring of parents with BD versus those with MDD were also hypothesized to be at greater risk for externalizing disorders, i.e., conduct disorder, attention-deficit hyperactivity disorder, or antisocial personality disorder.
Parents (n = 320) with mood disorders and their offspring (n = 679) were studied. Adult offspring were administered the Structured Clinical Interview for DSM-IV Axis I Disorders to establish the presence of psychopathology. Offspring aged 10 to 18-years-old were assessed with the School Aged Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and parents of children under age 10 completed the Child Behavioral Checklist. Data were examined using Cox Proportional Hazard regression.
There was no difference in hazard of mood disorders in the offspring of parents with BD as compared to offspring of parents with MDD. However, a number of other parent and offspring characteristics increased risk for mood, anxiety, externalizing, and substance use disorders in offspring, including self-reported childhood abuse in parent or offspring, offspring impulsive aggression, and age of onset of parental mood disorder.
Mood disorders are highly familial independent of whether the parent’s condition is unipolar or bipolar, and considerable overlap in the familial basis of MDD and BD was found. Although parental characteristics had limited influence on risk of offspring psychopathology, reported childhood adversity, be it in the parent or child, is a harbinger of negative outcomes. These risk factors extend previous findings, and are consistent with diathesis-stress conceptualizations.
PMCID: PMC3855182  PMID: 23909952
bipolar disorder; familial transmission; major depressive disorder
16.  Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: A randomized trial
Pain  2013;154(11):10.1016/j.pain.2013.07.028.
Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (−7.5 vs −2.1; P < 0.001) and the number of Headache Days per month (−8.8 vs −4.0; P = 0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (−4.6 vs −1.2; P = 0.01) and the n-6 in HUFA score (−21.0 vs −4.0%; P < 0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P < 0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P < 0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population.
PMCID: PMC3850757  PMID: 23886520
Omega-3; Omega-6; Headache; Migraine; Clinical trial
17.  Sex differences in clinical predictors of depression: a prospective study
Journal of affective disorders  2013;150(3):1179-1183.
Estimating the likelihood of future major depressive episodes (MDEs) would assist clinicians in decision-making regarding the optimal length of treatment for MDE. Unfortunately, little data are available to guide clinical practice.
We followed 200 females and 152 males who responded to treatment for a MDE for 2 years to determine risk factors for future MDE. Cox Proportional Hazard Regression modeled time to first relapse into MDE and mixed effect logistic regression modeled monthly depression status.
Females were more likely than males to experience a MDE in any month of the study, and marginally more likely to experience a relapse. By 12 months, 60% of females had relapsed compared to 51% of males (median time to relapse 8 vs 13 months, respectively). Several factors predicted worse outcome for both men and women: reported childhood abuse, earlier age of onset of first MDE, Bipolar Disorder, unemployment, and more years of education. For females, but not males, suicidal ideation predicted MDE relapse and both suicidal ideation and prior suicide attempts were associated with more time in a MDE.
The naturalistic treatment of participants, exclusion of individuals with current comorbid alcohol or substance use disorder, and a follow up period of two years are limitations.
Women are more vulnerable to relapse and spend more time depressed compared to men. Identification of general and sex-specific risk factors for future depression may provide clinicians with useful tools to estimate need for ongoing pharmacotherapy in MDE.
PMCID: PMC3759613  PMID: 23735213
depression; gender; predictors; relapse; risk; sex
18.  Metabolic abnormalities in fronto-striatal-thalamic white matter tracts in schizophrenia
Schizophrenia research  2009;109(0):159-166.
The anterior limb of the internal capsule (ALIC) is the major white matter tract providing reciprocal connections between the frontal cortex, striatum and thalamus. Mounting evidence suggests that this tract may be affected in schizophrenia, with brain imaging studies reporting reductions in white matter volume and density, changes in fractional anisotropy and reduced asymmetry. However, the molecular correlates of these deficits are currently unknown. The aim of this study was to identify alterations in protein and metabolite levels in the ALIC in schizophrenia. Samples were obtained post-mortem from individuals with schizophrenia (n=15) and non-psychiatric controls (n=13). Immunoreactivity for the myelin-associated protein myelin basic protein (MBP), and the axonal-associated proteins phosphorylated neurofilament and SNAP-25 was measured by enzyme-linked immunoadsorbant assay (ELISA). Metabolite concentrations were quantified by proton nuclear magnetic resonance (1H NMR) spectroscopy. Levels of myelin- or axonal-associated proteins did not differ between groups. Overall differences in metabolite concentrations were observed between the two groups (MANOVA F=2.685, p=0.036), with post-hoc tests revealing lower lactate (19%) and alanine (24%) levels in the schizophrenia group relative to controls. Observed changes in lactate and alanine levels indicate metabolic abnormalities within the ALIC in schizophrenia.
PMCID: PMC4169119  PMID: 19272755
myelin; axon; metabolite; internal capsule; lactate
Brain research  2013;1507:11-18.
[11C]CUMI-101 is the first selective serotonin receptor (5-HT1AR) partial agonist radiotracer for positron emission tomography (PET) tested in vivo in nonhuman primates and humans. We evaluated specific binding of [3H]CUMI-101 by quantitative autoradiography studies in postmortem baboon and human brain sections using the 5- HT1AR antagonist WAY100635 as a displacer. The regional and laminar distributions of [3H]CUMI-101 binding in baboon and human brain sections matched the known distribution of [3H]8-OH-DPAT and [3H]WAY100635. Prazosin did not measurably displace [3H]CUMI-101 binding in baboon or human brain sections, thereby ruling out [3H]CUMI-101 binding to α1-adrenergic receptors. This study demonstrates that [11C]CUMI-101 is a selective 5-HT1AR ligand for in vivo and in vitro studies in baboon and human brain.
PMCID: PMC4169296  PMID: 23454434
5-HT1AR; brain; serotonin agonist; autoradiography
20.  Biodistribution, toxicology and radiation dosimetry of 5-HT1A receptor agonist Positron Emission Tomography ligand [11C]CUMI-101
Sprague Dawley rats (10/sex/group) were given a single iv dose of CUMI-101 to determine acute toxicity of CUMI-101 and radiation dosimetry estimations were conducted in baboons with [11C]CUMI-101. Intravenous administration of CUMI-101 did not produce overt biologically or toxicologically significant adverse effects except transient hypoactivity immediately post dose in the mid and high dose groups, which is not considered to be a dose limiting toxic effect. No adverse effects were observed in the low dose group. The no observed adverse effect level (NOAEL) is considered to be 44.05 µg/kg for a single iv dose administration in rats. The maximum tolerated dose (MTD) was estimated to be 881 µg/kg for a single iv dose administration. The Medical Internal Radiation Dose (MIRDOSE) estimates indicate the maximum, permissible single study dosage of [11C]CUMI-101 in human is 52 mCi with testes and urinary bladder as the critical organ for male and female, respectively.
PMCID: PMC4169297  PMID: 21994241
PET; toxicity; dosimetry; radioligand
21.  Neuron Density and Serotonin Receptor Binding in Prefrontal Cortex in Suicide
Although serotonin receptor and cytoarchitectonic alterations are reported in prefrontal cortex (PFC) in suicide and depression, no study has considered binding relative to neuron density. Therefore, we measured neuron density and SERT, 5-HT1A and 5-HT2A binding in matched suicides and controls.
Suicides and normal controls (N=15 matched pairs) were psychiatrically characterized. Neuron density and binding were determined in dorsal (BA9) and ventral (BA47) PFC by stereology and quantitative autoradiography in near-adjacent sections. Binding index was defined as the ratio of receptor binding to neuron density.
Suicides had lower neuron density in the gyrus of both areas. The binding index was lower for the serotonin transporter in BA47 but not in BA9; the 5-HT1A binding index was higher in BA9 but not in BA47, while the 5-HT2A binding index was not different between groups. SERT binding was lower in suicides in BA47 but not BA9, while 5-HT1A binding was higher in BA9 but not BA47. SERT binding negatively correlated with 5-HT1A binding in BA47 in suicides. Neuron density decreased with age. 5-HT1A binding index was higher in females than males.
We found lower neuron density and lower SERT binding index in both PFC regions in suicides. More 5-HT1A binding with less SERT binding and the negative correlation in depressed suicides suggests post-synaptic receptor upregulation, and it is independent of the difference in neuron density. Thus, abnormalities in both cortical neurons and in their serotonergic innervation are present in suicides and future studies need to determine whether cortical changes reflect the trophic effect of altered serotonin innervation.
PMCID: PMC4167642  PMID: 21733245
serotonin; stereology; receptor binding; human; autoradiography
22.  Synthesis and in vivo evaluation of [18F]2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)-dione ([18F]FECUMI-101) as an imaging probe for 5-HT1A receptor agonist in nonhuman primates
Bioorganic & medicinal chemistry  2013;21(17):10.1016/j.bmc.2013.05.050.
The 5-HT1AR partial agonist PET radiotracer, [11C]CUMI-101, has advantages over an antagonist radiotracer as it binds preferentially to the high affinity state of the receptor and thereby provides more functionally meaningful information. The major drawback of C-11 tracers is the lack of cyclotron facility in many health care centers thereby limiting widespread clinical or research use. We identified the fluoroethyl derivative, 2-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione (FECUMI-101) (Ki = 0.1 nM; Emax = 77%; EC50 = 0.65 nM) as a partial agonist 5-HT1AR ligand of the parent ligand CUMI-101. FECUMI-101 is radiolabeled with F-18 by O-fluoroethylation of the corresponding desmethyl analogue (1) with [18F]fluoroethyltosylate in DMSO in the presence of 1.6 equiv. of K2CO3 in 45 ± 5% yield (EOS). PET shows [18F]FECUMI-101 binds specifically to 5-HT1AR enriched brain regions of baboon. The specificity of [18F]FECUMI-101 binding to 5-HT1AR was confirmed by challenge studies with the known 5-HT1AR ligand WAY100,635. These findings indicate that [18F]FECUMI-101 can be a viable agonist ligand for the in vivo quantification of high affinity 5-HT1AR with PET.
PMCID: PMC3858174  PMID: 23816046
PET; FECUMI-101; 5-HT1AR; agonist; brain; radiotracer
23.  Increased DNA methylation in the suicide brain
Clinical studies find that childhood adversity and stress-ful life events in adulthood increase the risk for major depression and for suicide. The predispositions to either major depression or suicide are thought to depend on genetic risk factors or epigenetic effects. We investigated DNA methylation signatures postmortem in brains of suicides with diagnosis of major depressive disorder. DNA methylation levels were determined at single C-phosphate-G (CpG) resolution sites within ventral prefrontal cortex of 53 suicides and nonpsychiatric controls, aged 16 to 89 years. We found that DNA methylation increases throughout the lifespan. Suicides showed an 8-fold greater number of methylated CpG sites relative to controls (P<2.2x10-16), with greater DNA methylation changes over and above the increased methylation observed in normal aging. This increased DNA methylation may be a significant contributor to the neuropathology and psychopathology underlying the risk of suicide in depression.
PMCID: PMC4214183  PMID: 25364291
aging; depression; DNA methylation; epigenetics; mood disorder; suicide
24.  PET quantification of serotonin transporter in suicide attempters with major depressive disorder
Biological psychiatry  2013;74(4):287-295.
Several lines of evidence implicate abnormal serotonergic function in suicidal behavior and completed suicide, including low serotonin transporter binding in postmortem studies of completed suicide. We have also reported low in vivo serotonin transporter binding in major depressive disorder (MDD) during a major depressive episode using positron emission tomography with [11C]McN5652. We quantified regional brain serotonin transporter binding in vivo in depressed suicide attempters, depressed non-attempters, and healthy controls using positron emission tomography and a superior radiotracer, [11C]DASB.
51 subjects with DSM-IV current MDD, 15 of whom were past suicide attempters, and 32 healthy controls underwent PET scanning with [11C]DASB to quantify in vivo regional brain serotonin transporter binding. Metabolite-corrected arterial input functions and plasma free-fraction were acquired to improve quantification.
Depressed suicide attempters had lower serotonin transporter binding in midbrain compared with depressed non-attempters (p=0.031) and controls (p=0.0093). There was no difference in serotonin transporter binding comparing all depressed subjects to healthy controls considering six a priori regions of interest simultaneously (p=0.41).
Low midbrain serotonin transporter binding appears to be related to the pathophysiology of suicidal behavior rather than of major depressive disorder. This is consistent with postmortem work showing low midbrain serotonin transporter binding capacity in depressed suicides, and may partially explain discrepant in vivo findings quantifying serotonin transporter in depression. Future studies should investigate midbrain serotonin transporter binding as a predictor of suicidal behavior in MDD, and determine the cause of low binding.
PMCID: PMC3725207  PMID: 23453288
serotonin transporter; depression; suicide; PET; midbrain; [11C]DASB; pathophysiology
25.  Foxo1 regulates Dbh expression and the activity of the sympathetic nervous system in vivo
Molecular Metabolism  2014;3(7):770-777.
The transcription factor FoxO1 regulates multiple physiological processes. Here, we show that FoxO1 is highly expressed in neurons of the locus coeruleus and of various sympathetic ganglions, but not in the adrenal medulla. Consistent with this pattern of expression, mice lacking FoxO1 only in sympathetic neurons (FoxO1Dbh−/−) display a low sympathetic tone without modification of the catecholamine content in the adrenal medulla. As a result, FoxO1Dbh−/− mice demonstrate an increased insulin secretion, improved glucose tolerance, low energy expenditure, and high bone mass. FoxO1 favors catecholamine synthesis because it is a potent regulator of the expression of Dbh that encodes the initial and rate-limiting enzyme in the synthesis of these neurotransmitters. By identifying FoxO1 as a transcriptional regulator of the sympathetic tone, these results advance our understanding of the control of some aspects of metabolism and of bone mass accrual.
PMCID: PMC4209360  PMID: 25353004
FoxO1; Locus coeruleus; Sympathetic tone

Results 1-25 (364)


killing season 3 mireille enos joel kinnanman linden holder 'The Killing' Season 3 premiere clip: Holder visits Linden to talk investigation“The Killing” returns for Season 3 this Sunday (June 2) night on AMC, which means Mireille Enos and Joel Kinnaman are back as Detectives Sarah Linden and Stephen Holder. Except, Linden isn’t actually a detective when the new season picks up.

After the prolonged investigation into Rosie Larsen’s murder left Linden battered and broken, she’s moved on to a quieter life. But Holder knows he needs his former partner’s help when he encounters a gruesome series of murders that echo a crucial case from Linden’s past, as seen in the following exclusive clip:

Any bets on how long it takes Linden to get back into the investigation game?

Enos and Kinnaman are the only returning cast members for the new season but they’re joined by an impressive line-up of newcomers including Elias Koteas, Amy Seimetz and Peter Sarsgaard as a mysterious inmate on death row.

The best news about the Season 3 mystery? Everyone involved has promised the season finale will offer a definitive solution to the case.


Syndicate content

Add new comment

Submitted by Ryan Li on

Thank you for raising such an important issue and for the excellent article. I agree with almost everything you have written. Some additional thoughts, with inspiration from the excellent speakers at yesterday’s Global Burden of Depression event at UCL (

- There is good reason to believe that the Global Burden of Disease estimates, based on DALYs, may *underestimate* the burden of mental health problems. Mental distress, as distinct from disability (which implies some functional or occupational impairment), is to my knowledge not well captured in the DALY (or QALY for that matter, although extensions to EQ-5D may be an improvement). In many LMICs where welfare support may be minimal or non-existent, people with mental health problems may have no choice but to keep working to earn wages, even if they feel subjectively terrible; and especially if this is compounded by a stigma against mental illness. Further, as has been emphasised by Richard Layard and others, we know that individuals on the whole can and do adapt to disability over time, but not to mental illness. So I would argue that in terms of disease burden, mental ill health is probably an even bigger problem than the current numbers suggest.

- You mention the role of UHC and ensuring medicines within an essential package. Evidence-based psychosocial interventions are equally important, and can be as clinically and cost-effective as drugs (and sometimes more so) for a range of mental health conditions, as established in UK's NICE guidelines ( With respect to their application in LMICs, there are however at least two challenges:

1) Defining the package of essential interventions
This is essentially an issue of priority-setting, i.e. within a given health budget, what mix of interventions can deliver the greatest health gains? Evidence-based clinical guidelines based on cost-effectiveness considerations would be very helpful here. Given that developing clinical guidelines de novo is time consuming and resource intensive, adapting existing guidelines could be a solution. For example, some success stories have been reported in sub-Saharan Africa: WHO mental health guidelines were adapted in Nigeria, contextualised to local cultural and health system context, and through a locally acceptable inclusive process ( We still yet to see any guideline adaptation processes that explicitly consider cost-effectiveness; this is a methodology we are currently developing as part of the International Decision Support Initiative (, led by NICE International with Gates Foundation and UK DFID funding support).

2) Downstream implementation issues
What could be realistically delivered in LMIC settings, where there are not enough specialist psychiatrists and psychologists? Then this might mean adapting evidence-based, manualised interventions for delivery in community and primary care settings, by non-specialists (e.g. nurses, graduates, even 'lay counsellors') with minimal training and ongoing supervision, and using group-based interventions. In the UK NHS, most psychological therapy delivered through a stepped-care model, with mild mental health problems treated by trained graduate mental health workers ( My personal experience was as a PhD student delivering effective CBT for dementia carers, following 2 weeks training alongside other graduate psychologists, and this proved to be extremely cost-effective intervention ( There are also many good and innovative examples in LMICs, for example Vikram Patel's work with lay counsellors in India.

- Finally, mental health is a particularly thorny issue for the clinician or policymaker, irrespective of any quantitative differences in burden, for various reasons:

1) Stigma across the broad spectrum of mental health problems has arguably been universal across different cultures in the world through time, in a way that has not dominated physical health problems as a whole (perhaps with the exception of some infectious diseases). Societal attitudes are improving in Western societies, but this has not happened overnight nor without changes in policy and legislation.

2) We simply know much less about the aetiology of mental health problems on the whole as compared with physical health problems; and we do know that they tend to be much more complex. Science tells us quite a lot about the multitude of biopsychosocial risk factors for depression, but no-one can say what “causes” depression. Primary prevention is relatively easy when statins can be prescribed to lower the population average cholesterol levels, but how do we do primary prevention for depression if we don’t even know the cause? Better identification through risk algorithms, as proposed by Michael King and colleagues, with targeted prevention/intervention might be one way forward.

In all, this is a timely article with timely action from the World Bank. Clearly the problem of mental illness is complex and needs to be tackled from multiple directions. If UHC is our goal, then mental health and physical health are inseparable. At NICE International and the International Decision Support Initiative, we believe that an evidence-based and inclusive approach should be an overarching principle to priority-setting, and is a necessary condition for achieving sustainable UHC (


There are a lot of questions that have been posted a lot, but if you haven't found what you need to know, there is no harm in asking again.
Contact printing is the most basic print making method, but, at the same time there are a lot of dimensions. For example, are you looking for making proofs, or making prints that are intended to stand on their own? Even though both are done by contact printing, the equipment approaches are different.
So, what is it you'd like to know?


Lip Reduction

5 of 48

Lip Reduction in a patient who had a permanent filler placed in the upper lip resulting in excessive upper lip size and projection.


What Does The Symbol Mean

This symbol is T’ai from the IChing a form of ancient wisdom used to identify what we need to learn about ourselves through the formation of hexagrams( words of wisdom occurring in random events) that we create by throwing three pennies twice. The first throw forms the bottom of the hexagram which is the male or Heaven symbol and the three top broken lines are the female or Earth. These placed together form T’ai which represents peace and balance. Together they are in perfect balance.


]> 20.3 Always Integrable Functions

20.3 Always Integrable Functions

There are two circumstances in which we know that f will be Riemann integrable over the interval between a and b .

If f is continuous everywhere in the interval including its endpoints which are finite, then f will be integrable.

A function is continuous at x if its values sufficiently near x are as close as you choose to one another and to its value at x .

Continuity of f throughout [ a , b ] implies that the variation in estimates in any strip can be made as small a multiple of the width of the strip as you choose by you making the width small enough.

Thus you can make the total possible variation in Riemann sums as small a multiple of b a as you like, by requiring that the maximum strip width is sufficiently small.

We can (and soon will) also prove that a bounded increasing or decreasing function on a finite interval is integrable even if it is not continuous.

We can define the total variation of a function to be the total of its increase over intervals in which it is increasing, plus total of its decrease over intervals in which it is decreasing.

We will deduce that a function having bounded (total) variation between a and b will be Riemann integrable in that interval.


Servings:Makes 4 servings.
Preparation Time:15 minutes
Cook Time:15 minutes
These elegant but easy loin lamb chops are marinated then quickly cooked in a skillet. Crushed rosemary complements the other savory flavors in the lamb marinade.

Rosemary Marinated Lamb Chops
McCormick Gourmet

Mix first 8 ingredients and 2 tablespoons of the oil in small bowl. Reserve 1/2 cup marinade. Place lamb chops in large resealable plastic bag or glass dish. Add remaining marinade; turn to coat well.

Refrigerate 30 minutes or longer for extra flavor. Remove lamb chops from marinade. Discard any remaining marinade.

Heat remaining 1 tablespoon oil in large skillet on medium-high heat. Add lamb chops; cook 8 minutes or until desired doneness, turning once. Add reserved marinade; simmer 2 minutes.


External Web sites

Britannica Web sites

Articles from Britannica encyclopedias for elementary and high school students.

coast - Children's Encyclopedia (Ages 8-11)

The area where the sea and land meet is called a coast. The coasts of the world measure about 193,000 miles (312,000 kilometers) in total. Coastal areas are also known as shores and seasides. They form unique habitats where a range of animals and plants survive in a challenging environment.

coast - Student Encyclopedia (Ages 11 and up)

Land bordering an ocean, sea, or lake is called a coast or shore. Coasts feature a great variety of landforms ranging from gently sloping beaches to steep cliffs. This variety is the result of the different natural processes that formed the coasts as well as the type and structure of the rock that underlies them.

Or click Continue to submit anonymously:


Shape photography: how to balance your composition (and when to break the rules)

Managing shapes in silhouette photography

On a few occasions here at Digital Camera World we’ve mentioned the importance of balancing shapes and tones in your photo composition. This is a rather vague-sounding notion, in comparison to more scientific discussions about the Rule of Thirds and the impact of leading lines. This is something we’ll attempt to put right, because shape photography, though we shoot them so often, doesn’t seem to be mentioned very much in textbooks. But does have a real significance on the impact of your photographs.

Shape photography: how to balance your compositions (and when to break the rules)

Many pictures rely on balance – or at least they fall down through a lack of it. They may have an object near the edge of the frame on one side with nothing of interest on the other side to act as a counterweight.

It’s like a set of kitchen scales with a bag of sugar in the bowl and no weights on the other side. But it’s not as scientific as our example makes it sound.

You don’t necessarily need an object of the same size, tone or colour, and it doesn’t always have to be on the diametrically opposite side of the frame.

Shape photography: how to balance your compositions

You may find the tiny silhouette of a park bench provides just the counterweight you need for the silhouette of a tree, for example, or that one figure you framed for foreground interest in your shot is perfectly balanced by a distant figure further away.

That doesn’t mean you have to go around looking for counterweights for your subjects, though this can be an effective compositional technique.

But what can often happen is that the scene you’re photographing contains more than one element and that you can’t (or don’t want to) exclude these additional elements.

That’s when you have to develop your sense of balance. Maybe looking at a couple of examples will help.

PAGE 1: Achieving balance in your shape photography
PAGE 2: Choose your own rules of shape photography
PAGE 3: How to manage silhouettes

49 awesome photography tips and time savers
Download free photography cheat sheets
Creative landscape photography: master the dark art of shadows and shade


The Best Raisin Bread for Bread Maker / Machine

Total Time
2hrs 40mins
Prep 10 mins
Cook 2 hrs 30 mins

I have tried no less than 5 different recipes and several variations of Raisin Bread recipes before finding what I think is the best tasting recipe. It is a culmination of trail and error using various recipes found on the internet and in Bread Machine Cookbooks. This recipe makes approximately a 1.5lb (750gm) loaf.

Ingredients Nutrition

  1. Firstly, mix the flour, milk powder, sugar, salt and cinnamon together thoroughly in a mixing bowl making sure there are no lumps.
  2. Now add the luke warm water and butter into the bread machine. (I divide the butter into four pieces and put one in each corner of the pan for easier mixing).
  3. Then add the dry mixed ingredients into the pan. Make a small well in the centre of the dry mixture and add the yeast.
  4. Set the Bread Maker / Machine to 'Sweet Bread' setting and wait for it to 'BEEP' (approx 15 minutes) before adding the raisins.
  5. Wait until cooked and enjoy fresh or toasted with butter -- YUM !
  6. ** If the mixture is too dry while mixing you can add a tablespoon of water. Alternatively if its too moist, a tablespoon of flour should sort it out nicely. **.
Most Helpful

5 5

A ! I've already made this TWICE in the last 24 hours! Took the first loaf to my parents and it got gobbled up. It is wonderfully moist on the inside, but has a firm enough crust that slices hold their shape when sliced. I added 3/4 cup walnuts to one loaf and it was even better IMO. Delicious toasted, with peanut butter, and just plain! Flavor is incredible. Thank you so much tinytrev!

This is the best recipe for raisin bread for the bread machine. My machine is very large and does 2 loafs so I converted the recipe to make 1.5 loafs, turned out perfect for two loafs of raisin bread. I do my bread on the dough cycle in the machine and then shape the loaves for the two pans and raise in warm place approximately 1.5 hrs. and then bake.


Tuesday, April 9, 2013

EX0-117 ITIL Foundation Dumps Updated 2013

Exam Number ---- EX0-117

PDF Download Link Given Below

Important Questions For EX0-117 Exams

A. Process owner
B. Change manager
C. Service manager
D. Process practitioner

Correct Answer: D

A. Service level management
B. IT operations management
C. Capacity management
D. Incident management

Correct Answer: B

A. Wisdom - Information - Data - Knowledge
B. Data - Information - Knowledge - Wisdom
C. Knowledge - Wisdom - Information - Data
D. Information - Data - Knowledge - Wisdom

Correct Answer: B

A. Service design: Design the processes
B. Service strategy: Develop the offerings
C. Service transition: Plan and prepare for deployment
D. Service operation: IT operations management

Correct Answer: A

B. Public frameworks are always cheaper to adopt

Correct Answer: A

Which of the following is an objective of business relationship management?

A. To identify patterns of business activity
B. To ensure high levels of customer satisfaction
C. To secure funding to manage the provision of services
D. To ensure strategic plans for IT services exist

Correct Answer: B

The design of IT services requires the effective and efficient use of "the four Ps". What are these four Ps?

A. People, process, partners, performance
B. Performance, process, products, plans
C. People, process, products, partners
D. People, products, plans, partners

Correct Answer: C

A. Allows higher volumes of successful change
B. Reduction in unplanned costs through optimized handling of service outages
C. Reduction in the duration and frequency of service outages

Correct Answer: D

Which two processes will contribute MOST to enabling effective problem detection?

A. Incident and financial management
B. Change and release and deployment management
C. Incident and event management
D. Knowledge and service level management

Correct Answer: C

involved significant cost and risk to the organization?

A. Change proposal
B. Change policy
C. Service request
D. Risk register

Correct Answer: A

Which of the following should be documented in an incident model?
2. Chronological order of steps to resolve the incident

A. 1 only
B. 2 only
C. Both of the above
D. Neither of the above

Correct Answer: B

A. PBA are based on organizational roles and responsibilities
B. IT service providers CANNOT schedule changes until they understand PBA

Correct Answer: C

  2. For ITIL certification dumps in PDF format kindly contact completeexamcollection@gmail.com

  3. Latest dumps for this exam in PDF format are available with completedump@gmail.com . Those who are in need of dumps for EXIN certification exams can send me an email or can ping me in gtalk directly.

    1. hi, my name is Segun from Nigeria. I would like to request for the latest dump for Exo 117 exam. My email is emitomosegun@gmail.com. Thanks.

  4. Best and quality ITIL Foundation Exam questions are available in PDf format at - Trainings24x7. Enrol and get quality ITIL dumps questions + 2 Days training + Certificate.

    Must visit at once if you are really serious about ITIL Foundation Certification

  5. For ITIL certification dumps in PDF format kindly contact completeexamcollection@gmail.com

  6. For latest and updated ITIL certification in PDF format contact us at completeexamcollection@gmail.com.
    Refer our blog for more details http://completeexamcollection.blogspot.in/2015/06/itilexin-certification-dumps.html

  7. ITIL Foundation Study materials and dumps are available for free at itil4all.com


Best Known Translations
Other Translations

Jeremiah 7:34

Overview - Jeremiah 7
He rejects their vain confidence,
12 by the example of Shiloh.
17 He threatens them for their idolatry.
21 He rejects the sacrifices of the disobedient.
29 He exhorts to mourn for their abominations in Tophet;
32 and the judgments for the same.
Treasury of Scripture Knowledge

Jeremiah 7:34  (King James Version)

to cease
16:9 25:10 33:10 Isaiah 24:7 Isaiah 24:8 ; Ezekiel 26:13 ; Hosea 2:11 ; Revelation 18:23

4:27 Leviticus 26:33 ; Isaiah 1:7 ; 3:26 6:11 Micah 7:13


Statistics for occurrence #1 of “Culpepper” in chapter 20 of Heros von Borcke, Memoirs of the Confederate War for Independence:

...for the stratagem, he continued to inflate himself with a sense of his own importance at having been honoured with a visit from such distinguished guests. We reached Hampton's headquarters, near Culpepper Court-house, before noon, where we met Stuart; and in the evening we all went by invitation to the village, where Fitz Lee's men had got up a negro-minstrel entertainment, and, with the assistance of...

Max. Freq. Min. Freq.
Entity Corpus Doc Corpus Doc
Culpepper (Arkansas, United States) 65 36 1 0 0 user votes
Culpepper (Tennessee, United States) 25 10 5 0 0 user votes
Culpepper (Alabama, United States) 5 0 1 0 0 user votes


Notifications You have no notifications

    2. Revolution

    Something about an Italian-American taking on the cause during the American revolution already seems off. You should have known to let this go to someone else, but you took it anyway. We stared at this for months on the video store shelf when we were younger before finally succumbing and renting it. That was not a fun memory for us. But today, we start our own revolution and we move past this tragic point in, not just our American history, but in the history of Al.


Request for information

I second Gary Collier's recommendation of Mounce.  Mounce has a complete
package, including Grammar, Workbook, vocabulary and parsing software,
quizzes, and exams.  Also answers to Workbook exercises, which are taken from
the NT.

I also second Carl Conrad's query re why scholars prefer the UBS 2nd ed.?