[Individual Motivational Interventions after Alcohol-Related Event Treated in Hospital - Effective Option for Secondary Prevention in Adolescence?] / Motivierende Kurzinterventionen nach Krankenhausaufenthalt bei Alkoholintoxikation bei Jugendlichen ­ Effektive Option sekundärer Prävention?

Individual Motivational Interventions after alcohol-related event treated in Hospital - Effective Option for Secondary Prevention in Adolescence? In a prospective, randomized, single-blind study 48 adolescents between 13 and 17 years answered a standardized questionnaire about their behavior of alcohol-consumption after an alcohol-related event with hospitalization. They were divided in 2 groups by randomization: Group A (n=28) took part in an individual motivational intervention (HaLT-Präventionsprojekt), Group B (n=20) did not get any intervention. Six and 12 weeks after the hospitalization the same questionnaire was answered again by telephone-based interviews. The interviewer did not know to which group the interview-partner belonged. 58% (n=28) of all adolescents drank less alcohol or in a lower frequency than before the alcohol-related event. 17% (n=8) did not drink any alcohol in that period of 12 weeks. 54% (n=26) explained, that they had no events of drunkenness in that period. 38% (n=18) did not change their behavior in consumption of alcohol. 6% (n=3) drank more or in higher frequency than before. We could not find any significant difference in the behavior of alcohol-consumption of both groups: 58% (A) resp. 65% (B) drank less than the time before the alcohol-related event (χ²=0,6269; p=0,4285). An influence of the individual motivational intervention could not be shown. Further studies should include interventions for parents and peers.

Effect of alarm therapy on conditioning of central reflex control in nocturnal enuresis: pilot study on changes in prepulse inhibition (PPI).

BACKGROUND: Alarm therapy is a long-established first-line therapy for nocturnal enuresis (NE). Desamino-arginine vasopressin (dDAVP) as alternative first-line therapy was shown to increase the prepulse inhibition (PPI) of startle reflexes, thus supporting the hypothesis of a maturational delay of reflex inhibition in NE. Effects of alarm therapy on PPI have not yet been investigated. METHODS: The PPI of startle reflexes was measured in 20 children with NE (13 boys, 7 girls, median age 8.5 years, range 5-13) before and after at least 6 weeks of alarm treatment and compared with repeated PPI measurements in 11 healthy controls (7 boys, 4 girls, median age 8 years, range 6-13). RESULTS: In the NE patients, PPI increased from a median baseline of 20-46% under alarm therapy (p = 0.005), with a reduction from a median of 7 to 2 wet nights per week (p = 0.002). The controls showed no difference in PPI (52% median at first, 40% at second measurement, p = 0.966). CONCLUSIONS: The increase of PPI trough alarm therapy was comparable with that under dDAVP, suggesting an analogous method of action and explaining the alternative or synergistic effect of both therapies. In addition, it further substantiates the hypothesis of a maturational delay of reflex control in NE.

Simultaneous EMG-fMRI during startle inhibition in monosymptomatic enuresis--an exploratory study.

Evidence is growing that monosymptomatic enuresis (ME) is a maturational disorder of the central nervous system with a lack of arousal and lacking inhibition of the micturition reflex. Previous studies have shown a significant reduction of prepulse inhibition (PPI) of startle in children with enuresis. However, it is still unclear whether the abnormal PPI in enuresis is based on an inhibitory deficit at brainstem or cortical level. Nine children with ME and ten healthy children were investigated using simultaneous recording of EMG from the M. orbicularis oculi and functional MRI. The experimental paradigm consisted of acoustic startle stimulation, with startle-alone stimuli and prepulse-startle combinations. Functional MRI data were processed using multiple regression and parametric modulation with startle amplitudes as a parameter. Neither patients with enuresis nor healthy children revealed measurable PPI in the MRI scanner. Startle stimuli caused equal hemodynamic changes in the acoustic cortex, medial prefrontal and orbitofrontal cortex in both groups. The amplitude of startle correlated with more prominent BOLD signal changes in the anterior cingulate cortex in healthy subjects than in patients with ME. This pronounced frontal activation in healthy controls was related to the PPI condition, indicating that the prefrontal cortex of healthy children was activated more strongly to inhibit startle than in patients with ME. In conclusion, apart from the possibility that recordings of PPI inside the MRI scanner may be compromised by methodological problems, the results of this study suggest that high cortical control mechanisms at the prefrontal level are relevant for the pathogenesis of ME.

Practical consensus guidelines for the management of enuresis.

UNLABELLED: Despite the high prevalence of enuresis, the professional training of doctors in the evaluation and management of this condition is often minimal and/or inconsistent. Therefore, patient care is neither optimal nor efficient, which can have a profound impact on affected children and their families. Once comprehensive history taking and evaluation has eliminated daytime symptoms or comorbidities, monosymptomatic enuresis can be managed efficaciously in the majority of patients. Non-monosymptomatic enuresis is often a more complex condition; these patients may benefit from referral to specialty care centers. We outline two alternative strategies to determine the most appropriate course of care. The first is a basic assessment covering only the essential components of diagnostic investigation which can be carried out in one office visit. The second strategy includes several additional evaluations including completion of a voiding diary, which requires extra time during the initial consultation and two office visits before treatment or specialty referral is provided. This should yield greater success than first-line treatment. CONCLUSION: This guideline, endorsed by major international pediatric urology and nephrology societies, aims to equip a general pediatric practice in both primary and secondary care with simple yet comprehensive guidelines and practical tools (i.e., checklists, diary templates, and quick-reference flowcharts) for complete evaluation and successful treatment of enuresis.

Differentiation of subgroups of monosymptomatic enuresis according to prepulse inhibition of the startle reflex.

AIM: Monosymptomatic enuresis (ME) is a common disorder in children with serious social and psychological consequences. Treatment is usually initiated with desamino-arginine vasopressin (dDAVP) and/or alarm therapy as first-line treatment and imipramine as second-line. All treatments have proven efficacy, but are not successful with all patients. Therefore, a differentiation into subgroups according to treatment efficacy would be beneficial. METHODS: A group of patients resistant to first-line treatment was treated with imipramine and compared with matched controls successfully treated with dDAVP and/or alarm therapy. Prepulse inhibition (PPI) to acoustic startle reflexes was measured in all patients. RESULTS: In a group of 23 nonresponders, the median PPI was 72% (range 43-94%) compared with the matched dDAVP/alarm - responders with a median PPI of 26% (range 0-61%) (p < 0.0001). The response rate to imipramine was 87%. CONCLUSION: The presented data provide evidence that PPI allows to identify two subgroups of ME. The results offer further insight into (at least) two different pathomechanisms involved in ME: (i) a maturational delay of reflex inhibition with reduced PPI and (ii) a normal PPI, possibly with abnormal sleep patterns, that can be influenced by imipramine.

Applications of the pipeline environment for visual informatics and genomics computations.

BACKGROUND: Contemporary informatics and genomics research require efficient, flexible and robust management of large heterogeneous data, advanced computational tools, powerful visualization, reliable hardware infrastructure, interoperability of computational resources, and detailed data and analysis-protocol provenance. The Pipeline is a client-server distributed computational environment that facilitates the visual graphical construction, execution, monitoring, validation and dissemination of advanced data analysis protocols. RESULTS: This paper reports on the applications of the LONI Pipeline environment to address two informatics challenges - graphical management of diverse genomics tools, and the interoperability of informatics software. Specifically, this manuscript presents the concrete details of deploying general informatics suites and individual software tools to new hardware infrastructures, the design, validation and execution of new visual analysis protocols via the Pipeline graphical interface, and integration of diverse informatics tools via the Pipeline eXtensible Markup Language syntax. We demonstrate each of these processes using several established informatics packages (e.g., miBLAST, EMBOSS, mrFAST, GWASS, MAQ, SAMtools, Bowtie) for basic local sequence alignment and search, molecular biology data analysis, and genome-wide association studies. These examples demonstrate the power of the Pipeline graphical workflow environment to enable integration of bioinformatics resources which provide a well-defined syntax for dynamic specification of the input/output parameters and the run-time execution controls. CONCLUSIONS: The LONI Pipeline environment http://pipeline.loni.ucla.edu provides a flexible graphical infrastructure for efficient biomedical computing and distributed informatics research. The interactive Pipeline resource manager enables the utilization and interoperability of diverse types of informatics resources. The Pipeline client-server model provides computational power to a broad spectrum of informatics investigators--experienced developers and novice users, user with or without access to advanced computational-resources (e.g., Grid, data), as well as basic and translational scientists. The open development, validation and dissemination of computational networks (pipeline workflows) facilitates the sharing of knowledge, tools, protocols and best practices, and enables the unbiased validation and replication of scientific findings by the entire community.

Prepulse inhibition of the startle reflex for differentiation of enuresis in children.

Children with enuresis can be classified into those who wet their beds only at night (monosymptomatic enuresis, mE), and those who additionally suffer from daytime symptoms, such as urgency or incontinence (non-monosymptomatic enuresis, nmE). Evidence is growing that enuresis may have a central origin: bedwetting children have lower brainstem reflex control (impaired prepulse inhibition) than normal controls. However, findings on this subject are inconsistent. To date, there has been no study in pediatric patients according to the type of enuresis. With the aim of determining whether mE and nmE children differ in terms of central reflex control, we divided 30 enuretic children into two groups (mE and nmE) based on data recorded in a bladder diary and clinical history (19 with history of diurnal urge, 11 without; age 5-14 years). Prepulse inhibition (PPI) of the startle reflex of the children was measured and compared between groups. A significant difference in PPI was observed between the groups, with the nmE group having a lower median PPI level than the mE group (10 vs. 73%, respectively; p = 0.0002). These findings lead to the assumption that a loss of central control plays a role only in the etiology of nmE. Moreover, they may throw a new light on the classification of enuresis.

Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children's Continence Society.

PURPOSE: We provide updated, clinically useful recommendations for treating children with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: Evidence was gathered from the literature and experience was gathered from the authors with priority given to evidence when present. The draft document was circulated among all members of the International Children's Continence Society as well as other relevant expert associations before completion. RESULTS: Available evidence suggests that children with monosymptomatic nocturnal enuresis could primarily be treated by a primary care physician or an adequately educated nurse. The mainstays of primary evaluation are a proper history and a voiding chart. The mainstays of primary therapy are bladder advice, the enuresis alarm and/or desmopressin. Therapy resistant cases should be handled by a specialist doctor. Among the recommended second line therapies are anticholinergics and in select cases imipramine. CONCLUSIONS: Enuresis in a child older than 5 years is not a trivial condition, and needs proper evaluation and treatment. This requires time but usually does not demand costly or invasive procedures.

Poor compliance with primary nocturnal enuresis therapy may contribute to insufficient desmopressin response.

PURPOSE: Studies of desmopressin in children with primary nocturnal enuresis show a greater than 90% decrease in wet nights in 20% to 30%, a 50% to less than 90% decrease in 20% to 40% and less than a 50% decrease in up to 60%. Insufficient response to desmopressin is attributable to various factors, including differences in the primary nocturnal enuresis definition, underlying bladder dysfunction and/or desmopressin pharmacokinetic characteristics. However, little attention has been given to poor compliance with therapy as a possible explanatory factor. For a drug with an effect duration limited to the night after administration a high degree of compliance is essential to ensure consistent therapeutic effects. MATERIALS AND METHODS: This was a substudy of an international investigation of treatment for 6 months or less with desmopressin tablets in children with primary nocturnal enuresis. Medication was dispensed at each visit as required and collected at each subsequent visit. Compliance was determined by pill counts by study staff. RESULTS: Compliance data were available on 723 patients. Of the patients 81% to 91% ingested all medication as instructed during the initial run-in phases. However, this decreased to 77% and 71% during the first and second 3-month treatment periods, respectively. CONCLUSIONS: Patient motivation and compliance are generally stronger in clinical trials than in clinical practice. However, this study shows that some patients were poorly compliant with medication even at study initiation and only 71% were fully compliant with long-term treatment. Decreased compliance was associated with a lower response rate. Patients should be encouraged to comply fully with treatment to achieve an optimal outcome.

Comparing the German Emergency Department Medical Record with the US HL7 Data Elements for Emergency Department Systems.

Interoperability between emergency department (ED) information systems requires a shared data specification. In 2013 Health Level Seven International, an international standards body, approved a specification for Data Elements for Emergency Department Systems (DEEDS) for use in the United States. A similar specification was created in Germany for national employment, defining data elements and forms. This study presents the first step in the efforts to harmonize the two data definitions for International approval by comparing the meaning of the German Emergency Department Medical Record (GEDMR) data element definitions with the US DEEDS using a methodology for terminology mapping from ISO/TR 12300. The comparison between GEDMR and DEEDS did show significant differences in certain domains. The results support development of an international standard for ED data elements.

Effect of 1-desamino-8-D-arginine vasopressin on prepulse inhibition of startle supports a central etiology of primary monosymptomatic enuresis.

OBJECTIVE: To test the hypothesis that 1-desamino-8-D-arginine vasopressin (dDAVP) has an effect on prepulse inhibition (PPI) of startle in patients with primary monosymptomatic enuresis (PME), thus indicating a central effect. STUDY DESIGN: Patients with PME (n = 21, age 6 to 12 years) were enrolled in a prospective, randomized, double-blinded, cross-over study. Startle reflexes and PPI were measured under dDAVP treatment versus placebo. RESULTS: The data show that dDAVP has a significant effect on PPI, raising it from 38.88% under placebo to the age-related normal level of 62.6% with dDAVP treatment (P = .0127). CONCLUSIONS: Our findings revive the concept of a central pathophysiology of PME and offer a different explanation for the effects of dDAVP, which not only acts on the kidney, but also is (as is AVP) a central neurotransmitter with a signal cascade on relevant reflex mechanisms.

Predictive parameters of response to desmopressin in primary nocturnal enuresis.

INTRODUCTION/BACKGROUND: Many recent treatment guidelines have advocated the importance of a full noninvasive medical evaluation. To individualize treatment, special emphasis must be put on recording of the maximum voided volume (MVV) and nocturnal diuresis in a diary or frequency/volume chart. OBJECTIVE: The aim of this study was to identify any possible predictive factors to desmopressin response. STUDY DESIGN: This study is a re-analysis of a prospective, open-label, multinational, phase-IV study evaluating ≤6 months of treatment with desmopressin tablets for children with primary nocturnal enuresis. The children were enrolled between April 2002 and December 2004 from 86 centers in four countries: UK, Canada, Germany and France. A total of 936 children were screened; 744 children aged 5-15 years participated in the study. Of these, 471 children completed the study with 6 months follow-up and recording in a frequency/volume chart. All children experienced six or more wet nights during the 14-day screening period. Exclusion criteria were: organic pathology, treatment for enuresis within the past year, previous treatment for enuresis for >4 weeks, diurnal symptoms, renal or central diabetes insipidus and the use of systemic antibiotics or other drugs known to affect desmopressin activity. The predictive value of number of wet nights a week, fluid intake, daytime voiding frequency and diuresis was investigated by performing a multinomial logistic regression. RESULTS: Of the demographic variables, age was the only significant predictor for response to desmopressin. Controlling for age, the significant predictive variables were: number of wet nights a week, average voided volume daytime, maximum voided volume daytime, total daytime diuresis, nocturnal diuresis (see Figure), maximum voided volume 24 h and total 24 h diuresis. More than 80% of the children had no nocturnal polyuria and a low maximum voided volume. DISCUSSION: Performing a secondary analysis is a limitation because the original study was not designed for that. A new prospective study is ethically hardly defendable for children if data are available from previous literature [1]; therefore, a re-analysis was the appropriate choice. The study confirms the predictive value of age, number of wet nights a week and nocturnal diuresis [1,2]. CONCLUSIONS: The study demonstrates that desmopressin response rates are higher in children with greater age, limited number of wet nights a week and nocturnal polyuria. Only a minority of a primary nocturnal enuresis population, based on history alone, had nocturnal polyuria. The majority had a low maximum voided volume. The results clearly stress the importance of a frequency/volume chart for individualizing therapy to the characteristics, thereby resulting in elevated success rates. Registration number of clinical trial: Clinical Trials.gov NCT00245479.

Comparative tolerability of drug treatment for nocturnal enuresis in children.

Primary nocturnal enuresis is one of the most frequent complaints in paediatric and urologic practice. Physicians face the dilemma of whether or not to treat primary nocturnal enuresis since the trend towards spontaneous remission is countered by social disadvantages and reduced self esteem of the children affected and their families. We reviewed randomised, controlled trials investigating efficacy and adverse effects of current medical treatment for primary nocturnal enuresis. Only desmopressin and imipramine displayed significant effects in reducing wet nights: when compared with baseline bedwetting or placebo controls, 30-70% of the studied children achieved therapeutic success. For drugs such as indometacin or oxybutynin, convincing studies displaying a significant positive effect are still needed. However, considering the adverse effects profiles of desmopressin and imipramine it can be seen that imipramine is associated with about twice as many unwanted reactions. More importantly, a serious adverse effect of imipramine is sudden cardiac arrest. In general, adverse effects with desmopressin are rare and mild, but there have been a number of case reports of hyponatraemic hypervolaemia associated with coma and seizures. Of these, many cases were attributed to excess water intake before taking the drug and all children recovered fully. In summary, if medical treatment is considered, preference should be given to desmopressin.

What's new in enuresis?

UNLABELLED: Treatment of primary nocturnal enuresis (PNE) using desmopressin (dDAVP) is based upon the hypothesis that antidiuretic hormone (arginine vasopressin (AVP) secretion is insufficient during the night. Persisting doubts about the theoretical background of this treatment gave reason to different studies: In a first study, AVP regulation in children with PNE was investigated. AVP levels after fluid restriction were compared to those of healthy controls. In order to maintain osmolality, the plasma AVP concentrations of the enuretic children rose to significant higher levels than in the controls. In a second study, the short-time memory of children treated with dDAVP because of PNE was measured. Children under dDAVP showed a significantly better short- time memory. CONCLUSION: The results are consistent with the established fact that AVP secretion is a function of plasma osmolality. They contradict the hypothesis that enuretic children have a AVP deficiency which has to be supplemented. Rather, the results point to central action of dDAVP, a defect at the central AVP receptor level or the signal transduction pathway.

Prepulse inhibition of acoustic startle and the influence of methylphenidate in children with ADHD.

OBJECTIVE: ADHD is common among children with comorbidity of enuresis. Findings concerning prepulse inhibition (PPI) of startle reflexes are controversial. Although PPI is improved through desamino-arginine vasopressin (dDAVP) in enuresis, some patients also improve concomitant ADHD through dDAVP. This study aims to evaluate whether methylphenidate (MPH) also improves PPI in ADHD. METHOD: Nineteen ADHD patients were investigated in a prospective, double-blind, crossover study with MPH versus placebo. PPI was measured as a reduction of acoustic startle reflexes. Subgroups of gender, ADHD subtype, and baseline PPI were analyzed. RESULTS: Median baseline PPI of ADHD patients (51.7%) was below the value of age-matched normal controls (73%, p = .090). MPH showed no improvement in the whole group, or the subgroups gender or subtype. Reduced baseline PPI was significantly improved (22.5%-39.3%, p = .039). CONCLUSION: Heterogeneity of ADHD is confirmed with a wide range of baseline PPI. The improvement of reduced baseline PPI through MPH suggests impaired sensorimotor gating in this subgroup.

Safety profile of desmopressin tablet for enuresis in a prospective study.

INTRODUCTION: This pre-specified sub-study of the desmopressin response in primary nocturnal enuresis study (DRIP study) evaluates the safety profile of the oral desmopressin tablet in children with primary nocturnal enuresis. Endpoints are adverse events and change in body mass index. METHODS: The DRIP study was an open-label, intention-to-treat, phase IV, multi-national study. Overall, 936 patients were screened and 744 children aged 5-15 years with previously untreated primary nocturnal enuresis were eligible to receive the study medication desmopressin once daily as an oral tablet formulation. At each visit, adverse events were questioned and observed signs or symptoms were recorded. RESULTS: Overall, 222 (30%) patients experienced 404 treatment-emergent adverse events. The proportion of patients experiencing treatment-emergent adverse events was similar regardless of patient gender or age. Most treatment-emergent adverse events were experienced in three system organ classes: gastrointestinal disorders; infections and infestations; and respiratory, thoracic and mediastinal disorders and were considered unrelated to the study drug. There was a slight increase in body mass index from screening levels during the study, however, clinically not significant. CONCLUSION: Desmopressin tablet treatment is well tolerated in children with primary nocturnal enuresis, regardless of patient gender or age. FUNDING: The desmopressin response in primary nocturnal enuresis study (DRIP- study) was funded by Ferring.

High-throughput neuroimaging-genetics computational infrastructure.

Many contemporary neuroscientific investigations face significant challenges in terms of data management, computational processing, data mining, and results interpretation. These four pillars define the core infrastructure necessary to plan, organize, orchestrate, validate, and disseminate novel scientific methods, computational resources, and translational healthcare findings. Data management includes protocols for data acquisition, archival, query, transfer, retrieval, and aggregation. Computational processing involves the necessary software, hardware, and networking infrastructure required to handle large amounts of heterogeneous neuroimaging, genetics, clinical, and phenotypic data and meta-data. Data mining refers to the process of automatically extracting data features, characteristics and associations, which are not readily visible by human exploration of the raw dataset. Result interpretation includes scientific visualization, community validation of findings and reproducible findings. In this manuscript we describe the novel high-throughput neuroimaging-genetics computational infrastructure available at the Institute for Neuroimaging and Informatics (INI) and the Laboratory of Neuro Imaging (LONI) at University of Southern California (USC). INI and LONI include ultra-high-field and standard-field MRI brain scanners along with an imaging-genetics database for storing the complete provenance of the raw and derived data and meta-data. In addition, the institute provides a large number of software tools for image and shape analysis, mathematical modeling, genomic sequence processing, and scientific visualization. A unique feature of this architecture is the Pipeline environment, which integrates the data management, processing, transfer, and visualization. Through its client-server architecture, the Pipeline environment provides a graphical user interface for designing, executing, monitoring validating, and disseminating of complex protocols that utilize diverse suites of software tools and web-services. These pipeline workflows are represented as portable XML objects which transfer the execution instructions and user specifications from the client user machine to remote pipeline servers for distributed computing. Using Alzheimer's and Parkinson's data, we provide several examples of translational applications using this infrastructure.

The perfect neuroimaging-genetics-computation storm: collision of petabytes of data, millions of hardware devices and thousands of software tools.

The volume, diversity and velocity of biomedical data are exponentially increasing providing petabytes of new neuroimaging and genetics data every year. At the same time, tens-of-thousands of computational algorithms are developed and reported in the literature along with thousands of software tools and services. Users demand intuitive, quick and platform-agnostic access to data, software tools, and infrastructure from millions of hardware devices. This explosion of information, scientific techniques, computational models, and technological advances leads to enormous challenges in data analysis, evidence-based biomedical inference and reproducibility of findings. The Pipeline workflow environment provides a crowd-based distributed solution for consistent management of these heterogeneous resources. The Pipeline allows multiple (local) clients and (remote) servers to connect, exchange protocols, control the execution, monitor the states of different tools or hardware, and share complete protocols as portable XML workflows. In this paper, we demonstrate several advanced computational neuroimaging and genetics case-studies, and end-to-end pipeline solutions. These are implemented as graphical workflow protocols in the context of analyzing imaging (sMRI, fMRI, DTI), phenotypic (demographic, clinical), and genetic (SNP) data.

Next generation sequence analysis and computational genomics using graphical pipeline workflows.

Whole-genome and exome sequencing have already proven to be essential and powerful methods to identify genes responsible for simple Mendelian inherited disorders. These methods can be applied to complex disorders as well, and have been adopted as one of the current mainstream approaches in population genetics. These achievements have been made possible by next generation sequencing (NGS) technologies, which require substantial bioinformatics resources to analyze the dense and complex sequence data. The huge analytical burden of data from genome sequencing might be seen as a bottleneck slowing the publication of NGS papers at this time, especially in psychiatric genetics. We review the existing methods for processing NGS data, to place into context the rationale for the design of a computational resource. We describe our method, the Graphical Pipeline for Computational Genomics (GPCG), to perform the computational steps required to analyze NGS data. The GPCG implements flexible workflows for basic sequence alignment, sequence data quality control, single nucleotide polymorphism analysis, copy number variant identification, annotation, and visualization of results. These workflows cover all the analytical steps required for NGS data, from processing the raw reads to variant calling and annotation. The current version of the pipeline is freely available at http://pipeline.loni.ucla.edu. These applications of NGS analysis may gain clinical utility in the near future (e.g., identifying miRNA signatures in diseases) when the bioinformatics approach is made feasible. Taken together, the annotation tools and strategies that have been developed to retrieve information and test hypotheses about the functional role of variants present in the human genome will help to pinpoint the genetic risk factors for psychiatric disorders.

Neuroimaging study designs, computational analyses and data provenance using the LONI pipeline.

Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges--management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu.