Probing the Time Structure of the Quark-Gluon Plasma with Top Quarks.

The tiny droplets of quark gluon plasma (QGP) created in high-energy nuclear collisions experience fast expansion and cooling with a lifetime of a few fm/c. Despite the information provided by probes such as jet quenching and quarkonium suppression, and the excellent description by hydrodynamical models, direct access to the time evolution of the system remains elusive. We point out that the study of hadronically decaying W bosons, notably in events with a top-antitop quark pair, can provide key novel insight into the time structure of the QGP. This is because of a unique feature, namely a time delay between the moment of the collision and that when the W-boson decay products start interacting with the medium. Furthermore, the length of the time delay can be constrained by selecting specific reconstructed top-quark momenta. We carry out a Monte Carlo feasibility study and find that the LHC has the potential to bring first limited information on the time structure of the QGP. Substantially increased LHC heavy-ion luminosities or future higher-energy colliders would open opportunities for more extensive studies.

A phase II trial of enzastaurin (LY317615) in combination with bevacizumab in adults with recurrent malignant gliomas.

We evaluated the efficacy of combination enzastaurin (LY317615) and bevacizumab for recurrent malignant gliomas and explored serologic correlates. We enrolled 81 patients with glioblastomas (GBM, n = 40) and anaplastic gliomas (AG, n = 41). Patients received enzastaurin as a loading dose of 1125 mg, followed by 500 or 875 mg daily for patients on non-enzyme-inducing or enzyme-inducing antiepileptics, respectively. Patients received bevacizumab 10 mg/kg intravenously biweekly. Clinical evaluations were repeated every 4 weeks. Magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset. Phosphorylated glycogen synthase kinase (GSK)-3 levels from peripheral blood mononuclear cells (PBMCs) were checked with each MRI. Median overall survival was 7.5 and 12.4 months for glioblastomas and anaplastic glioma cohorts, with median progression-free survivals of 2.0 and 4.4 months, respectively. Of GBM patients, 3/40 (7.5 %) were not evaluable, while 8/37 (22 %) had partial or complete response and 20/37 (54 %) had stable disease for 2+ months. Of the 39 evaluable AG patients, 18 (46 %) had an objective response, and 16 (41 %) had stable disease for 2+ months. The most common grade 3+ toxicities were lymphopenia (15 %), hypophosphatemia (8.8 %) and thrombotic events (7.5 %). Two (2.5 %) GBM patients died suddenly; another death (1.3 %) occurred from intractable seizures. Phosphorylated GSK-3 levels from PBMCs did not correlate with treatment response. A minimally important improvement in health-related quality of life was self-reported in 7-9/24 (29.2-37.5 %). Early response based on Levin criteria was significantly associated with significantly longer progression free survival for glioblastomas. Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy.

NCAM1-TTC12-ANKK1-DRD2 gene cluster and the clinical and genetic heterogeneity of adults with ADHD.

Dysfunctions of the dopaminergic system have been implicated on the etiology of Attention Deficit/Hyperactivity Disorder (ADHD). Meta-analyses addressing the association of the dopamine receptor D2 (DRD2) gene and ADHD were inconclusive due to excessive heterogeneity across studies. Both the great phenotypic heterogeneity of ADHD and the complexity of the genomic region where DRD2 is located could contribute to the inconsistent findings. Most previous DRD2 studies focused on the well-known Taq1A (rs1800497) SNP, which is actually placed in a neighbor gene (ANKK1). These two genes, together with NCAM1 and TTC12, form the NTAD gene cluster on Chr11q22-23. In order to address the reasons for the high heterogeneity previously reported on DRD2 effects on ADHD, this study investigates the role of NTAD variants on ADHD susceptibility in adults and on the modulation of comorbidity and personality profiles in these patients. Functional polymorphisms from NTAD were analyzed, both individually and in haplotypes, on a sample of 520 adults with ADHD and 630 non-ADHD controls. No direct association of NTAD variants with ADHD susceptibility itself was observed. However, different NTAD polymorphisms and haplotypes were associated to various phenotypes relevant to the clinical heterogeneity of ADHD, including Major Depressive Disorder, Generalized Anxiety Disorder, and Harm Avoidance and Persistence temperament scores. Therefore, these findings represent a possible explanation for the multiple conflicting findings regarding polymorphisms in this genomic region in psychiatry. The NTAD cluster may comprise a variety of independent molecular influences on various brain and behavior characteristics eventually associated with ADHD comorbidities and personality traits. © 2015 Wiley Periodicals, Inc.

Severity but not comorbidities predicts response to methylphenidate in adults with attention-deficit/hyperactivity disorder: results from a naturalistic study.

Although the identification of reliable predictors of methylphenidate response in adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide treatment decisions, very few data exist on this issue. Here, we assessed the predictors of clinical response to immediate-release methylphenidate hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of demographic factors, severity, and a wide range of comorbid psychiatric disorders. Two hundred fifty adult patients with ADHD were evaluated and completed a short-term treatment with IR-MPH. Mental health diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria through the use of standard structured interviews. The Swanson, Nolan, and Pelham Rating Scale, version 4, adapted to adults was used to assess the severity of ADHD. In the linear regression model, only higher severity of ADHD was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of comorbidities in a subsample (n = 62) did not modify this pattern. Our findings suggest that in clinical settings, patients with more severe ADHD symptoms have a good response to treatment independently from the presence of mild or stabilized comorbidities and their treatments. For adults with ADHD, differently from other common psychiatric disorders such as depression and anxiety, higher severity is associated with better treatment response.

Could comorbid bipolar disorder account for a significant share of executive function deficits in adults with attention-deficit hyperactivity disorder?

OBJECTIVE: The frequent comorbidity between attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BD) represents a challenge for disentangling specific impairments of each disorder in adulthood. Their functional impairments seem to be mediated by executive function deficits. However, little is known about the extent to which each executive function deficit might be disorder specific or explained by the comorbidity. The aim of the present study was to determine if comorbid BD could account for a significant share of executive function deficits when measured by the Wisconsin Card Sorting Test (WCST) in adults with ADHD. METHODS: Adult patients with ADHD and healthy subjects were evaluated in the ADHD outpatient Program at the Hospital de Clínicas de Porto Alegre. Psychiatric diagnoses were based on DSM-IV criteria. WCST scores were compared by multivariate analysis of covariance among three groups: ADHD with BD (n = 51), ADHD without BD (n = 278), and healthy subjects (n = 91). RESULTS: When compared to patients without BD and healthy subjects, patients with ADHD and comorbid BD showed lower scores in total correct answers (p = 0.003); higher scores in total errors (p = 0.004) and non-perseverative errors (p = 0.002); and completed fewer categories (p = 0.009). Patients with ADHD without BD did not differ from healthy subjects. CONCLUSIONS: WCST impairments among patients with ADHD seem to be to a large extent attributable to comorbid BD. Although other executive function deficits (e.g., in the inhibitory control domain) have been demonstrated to accompany ADHD, the present findings suggest that set-shifting deficits are strongly related to comorbid BD.

Agreement of neutrino deep inelastic scattering data with global fits of parton distributions.

The compatibility of neutrino-nucleus deep inelastic scattering data within the universal, factorizable nuclear parton distribution functions has been studied independently by several groups in the past few years. The conclusions are contradictory, ranging from a violation of the universality up to a good agreement, most of the controversy originating from the use of the neutrino-nucleus data from the NuTeV Collaboration. Here, we pay attention to non-negligible differences in the absolute normalization between different neutrino data sets. We find that such variations are large enough to prevent a tensionless fit to all data simultaneously and could therefore misleadingly point towards nonuniversal nuclear effects. We propose a concrete method to deal with the absolute normalization and show that an agreement between independent neutrino data sets is established.

Video-teleconferencing with medical students to improve exposure to child and adolescent psychiatry.

OBJECTIVE: The chronic workforce shortage in child and adolescent psychiatry (CAP) remains a germane issue that has been difficult to deal with effectively. Collaboration between medical schools without sufficient CAP resources and those with enough to share may help improve interest in the field. METHOD: This lecture series piloted a collaborative effort between CAP residents from a Midwest academic center and student-led interest groups from two osteopathic medical schools. CAP residents led nine interactive lectures with medical students on relevant topics, using video-teleconferencing. Baseline and follow-up surveys were used to assess attitudes and responses to the lecture series. RESULTS A group of 175 students completed the baseline survey; 43 students completed the follow-up survey; 21 of 43 (48%) reported that the lectures would positively influence their career choice toward CAP. CONCLUSION: Interactive lectures via video teleconferencing demonstrated potential to improve medical students' exposure to CAP, and they were well received in this initial pilot study.

No significant association between genetic variants in 7 candidate genes and response to methylphenidate treatment in adult patients with ADHD.

Results from pharmacogenetic investigations of methylphenidate (MPH) response in patients with ADHD are still inconsistent, especially among adults. This study investigates the role of genetic variants (SLC6A4, HTR1B, TPH2, DBH, DRD4, COMT, and SNAP25) in the response to MPH in a sample of 164 adults. Genes were chosen owing to previous evidence for an influence in ADHD susceptibility. No significant differences in allele or genotype frequencies between MPH responders and nonresponders were detected. In conclusion, our findings do not support an effect of these genes in the pharmacogenetics of MPH among adults with ADHD.

The role of a lifetime history of oppositional defiant and conduct disorders in adults with ADHD: implications for clinical practice.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are frequently co-occurring disorders in children and adolescents. However, their clinical status among adults is still under discussion. This study analyzes how the current clinical presentation of adult ADHD might be influenced by a lifetime history of CD and ODD. METHODS: We compared three groups of patients: ADHD without history of CD/ODD (n = 178), ADHD + history of ODD (n = 184), and ADHD + history of CD (n = 96). RESULTS: A history of CD (and to a lower extent ODD) is associated with a more severe and externalizing profile. CONCLUSION: Past CD and ODD entail a significant negative mental health impact on persistent ADHD, reinforcing the importance of actively assessing the developmental history of adult ADHD patients.

Antiangular ordering of gluon radiation in QCD media.

We investigate angular and energy distributions of medium-induced gluon emission off a quark-antiquark antenna in the framework of perturbative QCD as an attempt toward understanding, from first principles, jet evolution inside the quark-gluon plasma. In-medium color coherence between emitters, neglected in all previous calculations, leads to a novel mechanism of soft-gluon radiation. The structure of the corresponding spectrum, in contrast with known medium-induced radiation, i.e., off a single emitter, retains some properties of the vacuum case; in particular, it exhibits a soft divergence. However, as opposed to the vacuum, the collinear singularity is regulated by the pair opening angle, leading to a strict angular separation between vacuum and medium-induced radiation, denoted as antiangular ordering. We comment on the possible consequences of this new contribution for jet observables in heavy-ion collisions.

Adrenergic α2A receptor gene is not associated with methylphenidate response in adults with ADHD.

Adrenergic α2A receptor gene (ADRA2A) is one of the most promising candidate genes for ADHD pharmacogenetics. Thus far, three studies have investigated the association between the ADRA2A -1291 C>G polymorphism and the therapeutic response to methylphenidate (MPH) in children with ADHD, all of them with positive results. The aim of this study is to investigate, for the first time, the association between three ADRA2A polymorphisms (-1291 C>G, -262 G>A, and 1780 C>T) and the response to MPH in adults with ADHD. The sample comprises 165 Brazilians of European descent evaluated in the adult ADHD outpatient clinic of the Hospital de Clínicas de Porto Alegre. The diagnostic procedures followed the DSM-IV criteria. Drug response was assessed by both categorical and dimensional approaches, through the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. We found no evidence of association between the three ADRA2A polymorphisms and the therapeutic response to MPH treatment. Our findings do not support a significant role for the ADRA2A gene in ADHD pharmacogenetics, at least among adult patients.

BMP8 and activated brown adipose tissue in human newborns.

The classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature in neonates. However, although BAT has been studied in infants for more than a century, the knowledge about its physiological features at this stage of life is rather limited. This has been mainly due to the lack of appropriate investigation methods, ethically suitable for neonates. Here, we have applied non-invasive infrared thermography (IRT) to investigate neonatal BAT activity. Our data show that BAT temperature correlates with body temperature and that mild cold stimulus promotes BAT activation in newborns. Notably, a single short-term cold stimulus during the first day of life improves the body temperature adaption to a subsequent cold event. Finally, we identify that bone morphogenic protein 8B (BMP8B) is associated with the BAT thermogenic response in neonates. Overall, our data uncover key features of the setup of BAT thermogenesis in newborns.

Response to methylphenidate is not influenced by DAT1 polymorphisms in a sample of Brazilian adult patients with ADHD.

Several lines of evidence suggest a relevant role for the dopamine transporter (DAT1) gene not only as a susceptibility factor for attention-deficit hyperactivity disorder (ADHD), but also as a predictor of individual methylphenidate (MPH) response. Pharmacogenetic studies of MPH response in ADHD have mainly focused on the 40-bp variable number of tandem repeats (VNTR) in the 3' untranslated region (3'-UTR) of DAT1. Most studies were performed in samples of children and conflicting findings were obtained. Only two studies have assessed 3'-VNTR in samples of adults-one with positive and the other with negative findings. In the present study, we investigate three potentially relevant polymorphisms in DAT1 gene (-839 C > T; Int8 VNTR and 3'-VNTR), and their possible role in therapeutic response to MPH treatment in a sample of 171 Brazilian adults with ADHD. The diagnostic procedures followed the DSM-IV criteria and the outcome measures were the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. Drug response was assessed by both categorical and dimensional approaches. There was no effect of any DAT1 polymorphisms or haplotypes on MPH response. This is the second report demonstrating absence of differences in MPH response according to DAT1 genotypes in adults with ADHD. Although DAT protein is crucial for the effect of MPH, genetic variations in DAT1 gene probably do not have a significant clinical role in this sample of adults with ADHD.

Inattention and hyperactivity dimensions of ADHD are associated with different personality profiles.

BACKGROUND: Previous studies have suggested that individuals with ADHD have high scores in novelty seeking and harm avoidance. However, it is not known whether personality is associated with specific subtypes and dimensions of the disorder. The aim of this study is to test for associations between scores in the temperament and character inventory of C.R. Cloninger with adult ADHD subtypes and severity. SAMPLING AND METHODS: The diagnostic interviews of 296 adult ADHD patients followed the DSM-IV criteria. ADHD dimensions were evaluated with the SNAP-IV scores, and personality dimensions were assessed using the Temperament and Character Inventory. RESULTS: The combined subtype (n=168) was associated with higher scores in novelty seeking (p<0.001) and lower scores in cooperativeness (p=0.006) than the inattentive subtype (n=128). Higher inattention scores were associated with decreased self-directedness (p<0.001) and increased harm avoidance (p=0.02), whereas higher hyperactivity/impulsivity scores correlated positively with novelty seeking (p<0.001) and persistence (p=0.03). CONCLUSIONS: These findings suggest that personality dimensions are strongly correlated with ADHD subtypes and severity dimensions, pointing to the need for studies evaluating the mechanisms behind this association.

The role of comorbid major depressive disorder in the clinical presentation of adult ADHD.

Most adults with attention-deficit/hyperactivity disorder (ADHD) are not recognized and remain untreated, although a large fraction of these individuals are diagnosed and treated for other comorbid mental disorders, such as major depressive disorder (MDD). The fact that MDD is one of the most commonly occurring mental disorders with high comorbidity with adult ADHD raises the question whether such comorbidity is associated with differences in the clinical picture of ADHD. Three hundred and twenty adult ADHD outpatients were evaluated. Diagnoses followed DSM-IV criteria. Interviews to evaluate ADHD and oppositional defiant disorder (ODD) were performed based on the Portuguese version of K-SADS-E. Psychiatric comorbidities were investigated using SCID-IV and MINI. Regression models were applied to test MDD association with clinical and demographic outcomes. Subjects presenting ADHD and MDD had a higher frequency of generalized anxiety disorder and social phobia and a lower frequency of substance dependence, grade repetition and school suspensions, when compared to subjects with ADHD without MDD. Furthermore, adults presenting ADHD and MDD reported higher demand for psychotherapy and pharmacological treatment prior to enrollment in the study when compared to ADHD subjects free of MDD. However, contrary to what could be expected based on these data, the presence of MDD was not associated with an earlier ADHD diagnosis. These results point to the need for research and medical education into an earlier and more efficient ADHD diagnosis in patients who search for mental health care.

EPPS16: nuclear parton distributions with LHC data.

We introduce a global analysis of collinearly factorized nuclear parton distribution functions (PDFs) including, for the first time, data constraints from LHC proton-lead collisions. In comparison to our previous analysis, EPS09, where data only from charged-lepton-nucleus deep inelastic scattering (DIS), Drell-Yan (DY) dilepton production in proton-nucleus collisions and inclusive pion production in deuteron-nucleus collisions were the input, we now increase the variety of data constraints to cover also neutrino-nucleus DIS and low-mass DY production in pion-nucleus collisions. The new LHC data significantly extend the kinematic reach of the data constraints. We now allow much more freedom for the flavor dependence of nuclear effects than in other currently available analyses. As a result, especially the uncertainty estimates are more objective flavor by flavor. The neutrino DIS plays a pivotal role in obtaining a mutually consistent behavior for both up and down valence quarks, and the LHC dijet data clearly constrain gluons at large momentum fraction. Mainly for insufficient statistics, the pion-nucleus DY and heavy-gauge-boson production in proton-lead collisions impose less visible constraints. The outcome - a new set of next-to-leading order nuclear PDFs called EPPS16 - is made available for applications in high-energy nuclear collisions.

An analysis of the impact of LHC Run I proton-lead data on nuclear parton densities.

We report on an analysis of the impact of available experimental data on hard processes in proton-lead collisions during Run I at the large hadron collider on nuclear modifications of parton distribution functions. Our analysis is restricted to the EPS09 and DSSZ global fits. The measurements that we consider comprise production of massive gauge bosons, jets, charged hadrons and pions. This is the first time a study of nuclear PDFs includes this number of different observables. The goal of the paper is twofold: (i) checking the description of the data by nPDFs, as well as the relevance of these nuclear effects, in a quantitative manner; (ii) testing the constraining power of these data in eventual global fits, for which we use the Bayesian reweighting technique. We find an overall good, even too good, description of the data, indicating that more constraining power would require a better control over the systematic uncertainties and/or the proper proton-proton reference from LHC Run II. Some of the observables, however, show sizeable tension with specific choices of proton and nuclear PDFs. We also comment on the corresponding improvements as regards the theoretical treatment.

Energy versus centrality dependence of the jet quenching parameter [Formula: see text] at RHIC and LHC: a new puzzle?

The central goal of jet quenching studies in high-energy nuclear collisions is the characterization of those QCD medium properties that are accessible by these probes. Most of the discussion in the last years has been focused on the determination of the jet quenching parameter, [Formula: see text]. We present here an extraction of this parameter using data of inclusive particle suppression at RHIC and LHC energies for different centralities. Our approach consists in fitting a K factor that quantifies the departure of this parameter from an ideal estimate, [Formula: see text], where [Formula: see text] is determined by the local medium quantities as provided by hydrodynamical calculations. We find that this K factor is larger at RHIC than at the LHC, as obtained already in previous analyses, but, surprisingly, it is almost independent of the centrality of the collision. Taken at face value, the K factor would not depend on the local properties of the medium as energy density or temperature, but on global collision quantities such as the center of mass energy. This is a very intriguing, unexpected possibility for which we cannot yet provide a clear interpretation. We also comment on the limitations of the formalism that may affect this conclusion.

Pleiotropic effects of Chr15q25 nicotinic gene cluster and the relationship between smoking, cognition and ADHD.

Polymorphisms in the CHRNA5-CHRNA3-CHRNB4 gene cluster (Chr15q25) have been robustly associated with nicotine dependence, including genome-wide studies, as well as with cognitive and neuropsychological measures. In addition, cognitive processes can be influenced by nicotine use through nicotinic acetylcholine receptors (nAChRs). Here, we evaluated the effect of polymorphisms in CHRNA5-CHRNA3-CHRNB4 gene cluster and their interaction with tobacco smoking status on cognition in patients with Attention Deficit/Hyperactivity Disorder (ADHD). Eight SNPs from the CHRNA5-CHRNA3-CHRNB4 gene cluster were evaluated on a clinical sample of 403 adults with ADHD. Cognitive performance was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Analyses of covariance were used to assess the influence of single markers and their interaction with smoking status in the Vocabulary and Block Design subtests of WAIS-R. Correction for multiple comparisons was applied. Lifetime smoking was associated to Vocabulary subtest. The TT genotypes of CHRNA5 SNPs rs588765 and rs514743 showed a trend towards association with, respectively, higher and lower scores on the Vocabulary subtest. There was a significant interaction between intergenic SNP rs8023462 and smoking on Vocabulary scores. Our results are consistent with an influence of variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster on cognitive measures. The overall scenario suggests a pleiotropic role of Chr15q25 nicotinic gene cluster with complex influences in ADHD, tobacco smoking and cognitive performance, characteristics that can be partially interdependent and may share underlying genetic factors.