“
“Genetic variation may influence initial sensitivity to nicotine (i.e. during early tobacco exposure), perhaps helping to

explain differential vulnerability to nicotine dependence. This study explored associations of functional candidate gene polymorphisms with initial sensitivity to nicotine in 101 young adult nonsmokers of European ancestry. Nicotine (0, 5, 10 mu g/kg) was administered through nasal spray followed by mood, nicotine reward (e.g.’liking’) and perception (e.g.’feel effects’) measures, physiological responses, sensory processing (prepulse inhibition of startle), and performance tasks. Nicotine reinforcement was assessed in a separate session using a nicotine versus placebo spray choice Emricasan procedure. For the dopamine D4 receptor [DRD4 variable number of tandem repeats (VNTR)], presence of the 7-repeat allele was associated with greater aversive responses to nicotine (decreases in ‘vigor’, positive affect, and rapid information processing; increased cortisol) and reduced nicotine choice. Individuals with at least one DRD4 7-repeat allele also reported increased ‘feel effects’ and greater startle response, but in men only. Other genetic associations were also observed in men but not women, such as greater ‘feel effects’ and anger, and reduced fatigue,

in the dopamine D2 receptor (DRD2 C957T single nucleotide polymorphism) TT versus CT or CC genotypes. Very few or no significant associations were seen for the DRD2/ANKK1 TaqIA polymorphism, the serotonin transporter

promoter Acalabrutinib supplier VNTR or 5HTTLPR (SLC6A4), the dopamine transporter 3 ‘ VNTR (SLC6A3), and the mu opioid receptor A1 18G single nucleotide polymorphism (mu opioid receptor polymorphism 1). Although these Nepicastat solubility dmso results are preliminary, this study is the first to suggest that genetic polymorphisms related to function in the dopamine D4, and perhaps D2, receptor may modulate initial sensitivity to nicotine before the onset of dependence and may do so differentially between men and women.”
“Trophic deprivation-mediated neuronal death is important during development, after acute brain or nerve trauma, and in neurodegeneration. Serum deprivation (SD) approximates trophic deprivation in vitro, and an in vivo model is provided by neuronal death in the mouse dorsal lateral geniculate nucleus (LGNd) after ablation of the visual cortex (VCA). Oxidant-induced intracellular Zn2+ release ([Zn2+](i)) from metallothionein-3 (MT-III), mitochondria or ‘protein Zn2+’, was implicated in trophic deprivation neurotoxicity. We have previously shown that neurotoxicity of extracellular Zn2+ required entry, increased [Zn2+](i), and reduction of NAD+ and ATP levels causing inhibition of glycolysis and cellular metabolism. Exogenous NAD+ and sirtuin inhibition attenuated Zn2+ neurotoxicity.

The recurrence of the tumour after previous initial surgical resection GSI-IX order is common and occurs in more than half of the patients. Surgical resection of a local recurrence is poorly described in the literature and the available data are restricted to a small number of cases. We report the case of a 62 year old woman, who was referred to our vascular surgical unit for recurrence of a leiomyosarcoma of the inferior vena cava, 35 months

after diagnosis and initial surgical treatment. We performed an extensive local resection and circumferencial replacement of the IVC. 18 months after the second operation and adjuvant radiotherapy, the patient is in a very good physical condition and CT-scans show no evidence of tumour recurrence.”
“Painful peripheral neuropathy is a common complication of diabetes mellitus. The symptom of pain can become a major factor that decreases the quality of life of patients with diabetes, while effective treatment is lacking. In the present study, we aimed to investigate the changes of pain threshold in the

early stage of diabetes in db/db mice, an animal model of type 2 diabetes mellitus, and the underlying molecular mechanisms. We found that (1) db/db mice (with a leptin receptor-null mutation and characterized by PF-04929113 in vivo obesity and hyperglycemia) showed hypersensitivity to mechanical and thermal stimuli at the early stage of diabetes; (2) phosphorylated extracellular signalregulated kinase (pERK), but not total ERK in the spinal cord and dorsal root ganglia in db/db mice significantly increased compared with wild-type mice. The increased pERK immunoreactivity occurred in both NeuN-expressing neurons and GFAPexpressing astrocytes, but not in Iba-1-expressing microglia; (3) both single and consecutive (for 5 days) intrathecal injections

of U0126 (2 nmol per day), a selective MEK (an ERK kinase) inhibitor beginning at 8 weeks of age, attenuated the bilateral mechanical allodynia in the von-Frey test and heat hyperalgesia in Hargreave’s test; and (4) db/db mice also displayed increased nocifensive behavior during the formalin test, and this was blocked by intrathecal injection of U0126. Also, the Epigenetic inhibitors library expression of pERK1 and pERK2 was upregulated following the formalin injection. Our results suggested that the activation of ERK in spinal neurons and astrocytes is correlated with pain hypersensitivity of the type 2 diabetes animal model. Inhibiting the ERK pathway may provide a new therapy for pain control in type 2 diabetes.”
“Pseudomonas aeruginosa, a human opportunistic pathogen, is capable of provoking acute and chronic infections that are associated with defined sets of virulence factors. During chronic infections, the bacterium accumulates mutations that silence some and activate other genes.

A 55-year-old woman presented to our outpatient department for routine eye examination. Clinical examination revealed bilateral corneal gray-white bands appearing as intraepithelial microcysts. Her past medical history included breast cancer, for which she underwent chemotherapy and subsequent treatment with exemestane. She was followed up for 1 year, during which the clinical picture of the cornea remained

unchanged in both eyes and visual acuity remained unaffected. A causal connection seems to be possible between systemic treatment with exemestane and persisting corneal intraepithelial cysts.”
“Increasing exposure to extremely low frequency electromagnetic fields (ELF-EMF), generated by power lines and electric appliances, raises concern about potential adverse health effects of ELF-EMF. The central nervous system is expected to be particularly vulnerable

to ELF-EMF AZD6738 cell line as its function strongly depends on electrical excitability. We therefore investigated effects Bucladesine molecular weight of acute (30 min) and sub-chronic (48 h) exposure to 50 Hz ELF-EMF on na ve and chemically stressed pheochromocytoma (PC12) cells. The latter have higher levels of iron and/or reactive oxygen species (ROS) and display increased vulnerability to environmental insults. Effects of ELF-EMF on Ca2+-homeostasis, ROS production and membrane integrity were assessed using Fura-2 single cell fluorescence microscopy, H-2-DCFDA and CFDA assays, respectively. Our data demonstrate that acute exposure of na ve PC12 cells to 50 Hz ELF-EMF up to 1000 mu T fails to affect basal or depolarization-evoked [Ca2+](i). Moreover, sub-chronic ELF-EMF exposure up to 1000 mu T has no consistent effects on Ca2+-homeostasis in na ve PC12 cells and does not affect ROS production and membrane integrity. Notably, in chemically stressed PC12 cells both acute and sub-chronic ELF-EMF exposure also failed to exert consistent effects on Ca2+-homeostasis, ROS production and membrane integrity. Our combined findings thus indicate that exposure to 50 Hz ELF-EMF up to 1000 mu T, i.e. 10,000 times above background exposure,

does not induce neurotoxic effects in vitro, neither in na ve nor in chemically stressed PC12 cells. Though our data require confirmation, e.g. in developing neuronal cells in vitro or (developing) animals, GW-572016 molecular weight it appears that the neurotoxic risk of ELF-EMF exposure is limited. (C) 2014 Elsevier Inc. All rights reserved.”
“Background: Because of the difficulties involved in learning and using 3D modeling and rendering software, many scientists hire programmers or animators to create models and animations. This both slows the discovery process and provides opportunities for miscommunication. Working with multiple collaborators, a tool was developed (based on a set of design goals) to enable them to directly construct models and animations.

Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non-use was 0.57 [95% confidence interval (CI): 0.440.74] among PPI buy CP-868596 users and 0.47 (95% CI: 0.420.53) among PPI non-users, yielding an interaction effect (i.e. relative rate

increase) of 1.20 (95% CI: 0.911.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non-users, independent of clopidogrel use [adjusted HR = 1.24 (95% CI: 0.971.58) for clopidogrel users and 1.26 (95% CI: 0.971.63) for clopidogrel non-users]. Conclusions The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention.”
“A case study and whole-farm modelling approach was used to examine the potential impacts of negative associative effects on milk production and economic performance of two dairy farms in northern Victoria. The two case studies differed in herd and farm size, calving pattern, forages grown and use of labour, but both had production systems based on grazed pasture, grain fed in the dairy at milking and conserved hay fed out in the paddock. The

feeding system of each farm was altered by implementing a partial mixed ration (PMR), where cows grazed once a day and received find more supplements in a well formulated mix once a day. Negative associative effects between feeds were included in the biophysical modelling by deriving a relationship from published studies between declining neutral detergent fibre digestibility and increasing grain intake. Before applying a PMR system, both farms were profitable and earning competitive rates of return after tax, with mean real internal rate

of return higher than 5%, and positive mean annual operating profit and mean net present value, at a discount rate of 5%. Feeding a PMR enabled both farms to increase profitability and internal rate of return, particularly if milk production was Vactosertib price increased as well, but only when associative effects were less than those in the feeding system based on grain fed in the dairy and hay in the paddock. Increased profitability was also associated with higher standard deviation in annual operating profit, internal rate of return and net present value, in other words risk increased under the PMR feeding system, as the businesses would be more vulnerable to fluctuating supplementary feed prices.”
“Tyrosine kinase inhibitors such as imatinib can effectively target the BCR-ABL oncoprotein in a majority of patients with chronic myeloid leukemia (CML). Unfortunately, some patients are resistant primarily to imatinib and others develop drug resistance, prompting interest in the discovery of new drug targets.

(C) 2013 Elsevier Ltd. All rights reserved.”
“The see more in vitro activity of iclaprim, a novel diaminopyrimidine derivative, was evaluated against 5,937 recent gram-positive clinical isolates collected in the United States and Europe. Iclaprim demonstrated potent activity against Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]), beta-hemolytic Streptococcus

spp., and Enterococcus faecalis strains tested. In addition, iclaprim exhibited bactericidal activity against all S. aureus strains tested, including MRSA.”
“Systemic acquired resistance (SAR) to Uromyces pisi in pea was studied by using a proteomic approach. Two-dimensional electrophoresis (2-DE) was used in order to compare the leaf proteome of

two pea genotypes displaying different phenotypes (susceptible and partial resistance to the fungus), and in response to parasite infection under the effect of two inducers of SAR, BTH and BABA. Multivariate statistical analysis identified 126 differential protein spots under the experimental conditions (genotypes/treatments). All of these 126 protein spots were subjected to MALDI-TOF/TOF mass spectrometry to deduce their possible functions. A total of 50 proteins were identified using a combination of peptide mass fingerprinting (PMF) and MSMS fragmentation. Most of the identified proteins corresponded to enzymes belonging to photosynthesis, metabolism, biosynthesis, binding and defense Fosbretabulin nmr response, whose behavior pattern was different in relation to susceptibility/resistance of the genotypes studied

and to the BTH/BABA induction to pathogen response. Results obtained in this work suggested that plants could reduce their photosynthesis and other energy metabolism and enhance the production of defense-related proteins to cope the stress. On the other side, we postulated that resistance induced by the chemicals operates via different mechanisms: BABA inducer could act via phenolic biosynthesis pathway, whereas resistance provided by BTH inducer seems to be mediated by defense and stress-related proteins. The results are discussed in terms of response to rust under PD0332991 the effect of inducers. (c) 2012 Elsevier B.V. All rights reserved.”
“A homeostatic concentration of glutamate in the synaptic cleft ensures a correct signal transduction along the neuronal network. An unbalance in this concentration can lead to neuronal death and to severe neurodegenerative diseases such as Alzheimer’s or Parkinson’s. Glutamate transporters play a crucial role in this respect because they are responsible for the reuptake of the neurotransmitter from the synaptic cleft, thus controlling the glutamate concentration. Understanding the molecular mechanism of this transporter can provide the possibility of an exogenous control. Structural studies have shown that this transporter can assume at least three conformations, thus suggesting a pronounced dynamical behavior.

“
“This study was carried out on volunteers to evaluate a newly developed interactive software package aimed at informing prospective Le Fort I osteotomy patients regarding the surgical technique and possible complications. The aim of the study was to compare two methods of information delivery: a multi-media tablet

device delivering both graphic and verbal information, and an audio device delivering essentially the same information in verbal form only. The null hypothesis was that there would be no difference between the efficiencies of the two methods. The subjects’ ability to recall the information delivered by both devices was assessed using a questionnaire. The tablet device participants scored an average of 15.48 points, while the audio device participants scored an average of 268 selleck products points. The difference was statistically significant (p smaller than 0.001), suggesting that the multi-media tablet device was https://www.selleckchem.com/products/nct-501.html more effective method. (c) 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.”
“In this study, a group of 11 Holstein-Friesian bulls used for semen production

has been monitored. Due to inadequate living space, some of bulls (experimental group, n = 5) with higher body measures developed ulcera and blisters on claws and distal extremities. At the beginning of the trial these animals were treated Sonidegib purchase by surgical removal of ulcera, claw correction and supportive therapy. The other bulls (control group, n = 6) only had claw correction.

All 11 bulls were monitored daily for next 90 days following surgery. Blood samples were collected weekly for haemogram and clinical biochemistry. After short interval of recovery, bulls were returned in semen collection and spermiograms were performed regularly. According to laboratory data, bulls after surgery and during supportive therapy (n = 5) had shown changes specific for reversible renal damage and endotoxaemia (altered total proteins, creatinin, urea, lymphopenia) for more than 30 days, although they appeared clinically healthy. All bulls that were cured for ulcera and blisters, were returned back to semen collection and gave ejaculat of acceptable quality. There was no noticeable difference in spermiograms of two investigated groups of bulls.”
“Whereas some aspects of olfactory hedonism in humans are present from birth, others form during development and throughout adulthood. Although it is generally agreed that such hedonic representations emerge by associative learning, it is not yet clear which learning parameters are prominent. The present study investigated the influence of number of trials on odor preference acquisition in human adults. Forty-eight subjects randomly assigned to three groups were tested in three sessions. In the first session, subjects ranked eight food odors from most pleasant to most unpleasant.

In experiment 3, rats were injected with palonosetron (0.1 mg/kg) 2 h before each of three sucrose-fluoxetine (20 mg/kg) or sucrose-lithium chloride (LiCl, 25 mg/kg) pairings. In experiment 4, rats were pretreated with the 5-HT1A

autoreceptor Selleck eFT-508 agonist, 8-OH-DPAT (DPAT, 0.1 mg/kg) 30 min before each of three sucrose-fluoxetine (20 mg/kg) pairings.\n\nAfter two sucrose-fluoxetine pairings, the highest dose of fluoxetine tested (20 mg/kg) produced conditioned gaping reactions. These conditioned gaping reactions were prevented by pretreatment with DPAT, but not with the 5-HT3 antagonists. On the other hand, palonosetron administered 2 h prior to sucrose-LiCl pairings attenuated conditioned gaping reactions.\n\nThese results suggest that the conditioned nausea produced by SSRIs, but not LiCl, may be resistant to treatment with 5-HT3 antagonists, but not 5-HT1A autoreceptor agonists.”
“A high-fat (HF) diet, the serotonergic system and stromal elements have all been implicated in colon carcinogenesis. We investigated whether the colonic serotonergic system could play a main role in the development of colonic dysplasia and stromal reactivity in carcinogen-treated rats under HF diet. For this, dimethylhydrazine-treated rats were fed with standard diet and a HF diet. Fat distribution was quantified by computerized tomography exam, serotonergic activity was analyzed by high-performance liquid

chromatography, gene expression, and immunohistochemistry, which along with histopathological technique enabled us to enumerate dysplasia, microvessels

density, cell proliferation and COX-2 expression. We found that the HF diet induced an increase GKT137831 supplier in the amount of viscera! adipose tissue, even without expressive changes in the average body weight. This was correlated with a loss of serotonergic balance in colon tissue. Moreover, the HF diet promoted dysplasia and microvessel density in association with increased proliferation and COX-2 expression within pericryptal colonic stroma. Our current findings suggest that a HF diet promotes the enlargement of adipose tissue via loss of control in colon serotonergic activity, which enhances colonic dysplasia by supporting microvessel development. (C) 2012 Duvelisib Elsevier Ireland Ltd. All rights reserved.”
“Tumor cytology has proven to be inadequate for precise diagnosis of thyroid follicular adenoma. This suggests the need for a molecular approach for its diagnosis. Expression of CD26/DPPIV (dipeptidyl peptidas IV), p53, and PTEN was analyzed in smears or sections obtained from 19 patients with histologically proven thyroid follicular adenoma. Papanicolaou staining, CD26/DPPIV activity staining, and HE staining were performed and the specimens were observed morphologically. Immunohistochemical analysis using antibodies against p53 and PTEN was performed. Genetic mutation of PTEN exons was performed using the laser capture microdissection method.

According to the tumor histological type, differentiation, location

and TNM staging of colorectal carcinoma, we divided the clinicopathological characteristics into different subgroups. Fixed and random effects models were applied for estimation of the summarized risk ratios (RRs) and 95% confidence intervals (CIs) in different subgroups. Finally, forest plots and funnel plots were created to allow for visual comparison of the results or the effect of publication bias.\n\nResults: According with the inclusive criteria, fourteen studies (n=1,558) were eligible for the meta-analysis. We observed a trend towards a correlation of MUC2 higher positivity in mucinous than non-mucinous carcinoma (RR, 2.10; 95% CI, 1.30-3.40; P=0.002) and less positivity in distal than proximal colon (RR, 0.74; 95% CI, 0.64-0.85; P=0.000). There was no statistically significance for the association between MUC2 expression and selleck products differentiation or TNM staging of colorectal cancer, but MUC2 overexpression tended to be associated BAY 80-6946 molecular weight with the presence of T stage tumor (RR, 1.17; P=0.052).\n\nConclusion: MUC2 overexpression was associated with the mucinous and proximal colorectal cancer.”
“Background: The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese

A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model.\n\nMethods: Cancers with over 100 deaths in the 0 – 20 mSv subcohort of

the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the ASP2215 datasheet Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model.\n\nResults: The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 – 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 – 20 mSv and 5 – 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 – 500 mSv range.\n\nConclusion: Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response.

Castrates were more aggressive or in panic than ewes. Castrates had longer (72.6 see more +/- 0.53 s) BT than the ewes (63.6 +/- 2.82 s). Ewes had higher CL

(39.8 +/- 1.04%) values than castrates (35.1 +/- 0.95%). Meat from castrates was Tougher (32.6 +/- 1.95 N) than the meat from ewes (24.3 +/- 1.16 N). There were no significant correlations obtained between BT and meat quality variables. It can therefore be concluded that abattoir conditions, breed, age and gender had an effect on AB at slaughter. Gender had an effect on BT and mutton quality.”
“The aim of this study was to investigate the effect of 12 weeks of aerobic training on the serum levels of adiponectin and leptin and on inflammatory markers of coronary heart disease in obese men. Sixteen non-athlete obese men were randomly assigned to one of two experimental groups. The experimental group underwent aerobic training consisting of three

sessions per week for 12 weeks, while the control group did not participate in the training programme during the study period. Five millilitres of CH5424802 in vivo venous blood was taken from each participant at the beginning of the study, during week six and at the end of week 12 to measure the levels of leptin, adiponectin, C-reactive protein, interleukin-6 and tumour necrosis factor-a. The findings showed that aerobic training led to decreases in the levels of CRP (P=0.002), IL-6 (P = 0.001) and leptin (P = 0.003) and an increase in the level of adiponectin (P = 0.002) in the experimental group relative to the control group. In addition, the level of TNF-alpha decreased in the experimental group after the

12-week aerobic training period, although this change was not statistically significant. According to the results of this study, regular aerobic exercise decreases the potential risk of coronary heart disease by improving the plasma levels of IL-6, adiponectin, leptin and CRP Additionally, aerobic exercise can be used as effective non-pharmacological treatment to prevent diseases.”
“In the past few decades, the use of silibinin, a plant this website flavonoid extracted from the milk thistle, as a hepato-protective and chemopreventive agent has gained much attention. In this study, we investigated the effects of silibinin on adipogenesis. Treatment with silibinin suppressed terminal differentiation of 3T3-L1 cells into adipocytes as evidenced by Oil red O staining and TG assay results. Real-time RTPCR analysis revealed that silibinin decreased the expression of adipogenesis-related genes such as CAAT/enhancer binding protein-alpha, fatty acid synthase, sterol response element binding protein 1c, adipocyte-specific lipid binding protein, peroxisome proliferator-activated receptor gamma and lipoprotein lipase, and increased the expression of preadipocyte factor-1, a preadipocyte marker gene. The anti-adipogenic effect of silibinin was associated with the up-regulation of insig-1 and insig-2.

\n\nMethodsA prospective, multicenter, selleckchem cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations

at 1 and 2weeks, followed by standardized telephone interviews at 30 and 90days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis.\n\nResultsIn this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population PD98059 solubility dmso experiencing clinically significant pain (>3 of 10) at 90days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients.\n\nConclusionsTo the authors’ knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort.”
“Genetic markers at the GRM7 gene have shown allelic association with bipolar disorder (BP) in several case-control samples including

our own sample. In this report, we present results of resequencing the GRM7 gene in 32 bipolar samples and 32 random controls selected

from 553 bipolar cases and 547 control samples (UCL1). Novel and potential etiological base pair changes discovered by resequencing were genotyped in BI 6727 purchase the entire UCL case-control sample. We also report on the association between GRM7 and BP in a second sample of 593 patients and 642 controls (UCL2). The three most significantly associated SNPs in the original UCL1 BP GWAS sample were genotyped in the UCL2 sample, of which none were associated. After combining the genotype data for the two samples only two (rs1508724 and rs6769814) of the original three SNP markers remained significantly associated with BP. DNA sequencing revealed mutations in three cases which were absent in control subjects. A 3′-UTR SNP rs56173829 was found to be significantly associated with BP in the whole UCL sample (P = 0.035; OR = 0.482), the rare allele being less common in cases compared to controls. Bioinformatic analyses predicted a change in the centroid secondary structure of RNA and alterations in the miRNA binding sites for the mutated base of rs56173829. We also validated two deletions and a duplication within GRM7 using quantitative-PCR which provides further support for the pre-existing evidence that copy number variants at GRM7 may have a role in the etiology of BP. (C) 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Published by Wiley Periodicals, Inc.