Murray Stein - US grants

Determine self-reported rates of childhood and adult traumatic events in patients with depressive and anxiety disorders in comparison to non ill subjects and medical outpatients, determine if the self-reported occurrence of traumatic events is preferentially associated with specific disorders, and determine if the self-reported occurrence of particular traumatic events is associated with a more malignant course of psychiatric illness and or increased service utilization.

To determine whether idazoxan, a selective adreoceptor antagonist, can induce flashbacks and panic attacks in combat veterans with posttraumatic stress disorder during a controlled laboratory challenge procedure.

depression; anxiety; genetic polymorphism; human population genetics; alleles; genotype; clinical research; human subject;

Determine if female domestic violence victims show evidence of disturbed attention and memory shortly after the cessation of the battering and to what extent this persists into the following 4 months, determine if brain regions thought to be involved in cognitive processes show evidence of structural abnormalities determined by MRI and MRS, determine whether altered hypothalamo-pituitary-adrenal axis functioning is abnormal in these subjects and to what extent this is associated with cognitive or neuroanatomical abnormalities.

Investigate differences in central serotonergic functioning in patients with social phobia, persons with extreme shyness, and non-shy control subjects through the use of pharmacological probes. The study will use the strategy employed to understand the psychobiology of other mood and anxiety disorders, the administration of a 5HT-selective pharmacologic probe, to examine the functioning of central 5HT systems in social phobia.

Determine the efficacy and safety of Pregabalin in the treatment of generalized type of social phobia.

Assessment of prevalence of panic and other anxiety disorders in primary care settings.

Investigate differences in central noradrenergic functioning in patients with social phobia, persons with extreme shyness, and non-shy control subjects through the use of pharmacological probes.

With the rise of managed care, the primary care setting is assuming increasing importance as a site for the detection and treatment of all mental health problems. In this setting, panic disorder is prevalent, poorly recognized, and inadequately treated. Because it is both disabling and often masquerades as a variety of other medical conditions, it increases both direct (physician visits and unnecessary testing) and indirect (disability days) costs. This is a multi-institutional collaborative research project designed to implement an intervention to identify and treat panic disorder in the primary care setting and to study the clinical and cost effectiveness of this intervention over a one-year period. Three sites (UCSD, UCLA, UW) will screen and identify patients in a university primary care clinic who suffer from panic disorder and test an innovative model of service delivery for panic disorder in this setting. Patients will be randomized to receive either care as usual from their primary care physician or collaborative care (CC). CC employs a combination of cognitive-behavioral psychotherapy (delivered in six sessions over eight weeks by a behavioral health specialist [BHS]), expert pharmacotherapy (guided by a psychiatrist's recommendations relayed by the BHS to the prescribing primary care physician), and disease management elements (education and activation of patient and provider and more careful monitoring and sustained follow-up over the next year via phone contact). It is hypothesized that CC will have superior clinical effectiveness (measured in terms of symptom reduction, quality of life, and functioning). It is also hypothesized that although direct health care costs will be higher for CC than for usual care, indirect costs will be lower and cost-effectiveness analysis will support the adoption of CC as a preferred model of care.

Posttraumatic stress disorder (PTSD) is a frequent consequence of severe physical trauma, occurring in approximately 30% of traumatized individuals. It is associated with substantial functional impairment and reduced quality of life, and is often complicated by major depression- which further adds to the burden of illness. Brief psychological therapies administered in the acute post-trauma period have not demonstrated utility to prevent the occurrence of PTSD. Furthermore, the provision of specialized psychological therapies in an acute surgical setting is impractical- even if efficacy of two different medications (propranolol or gabapentin) for the secondary prevention of PTSD following severe physical trauma. Each of these agents has a separate antagonist, is predicted to prevent PTSD on the basis of its ability in preclinical studies to block the augmentation of recall typically seen in relation to highly emotional valent or stressful events. Gabapentin, an anticonvulsant, is predicted to prevent PTSD on the basis of its neuroprotective, anti- kindling, and anxiolytic properties. We propose to pilot our pharmacological interventions in sequential phases. This planned development path will have us, if necessary, test two different dose and duration regimens. Treatment will be administered in the immediate post-trauma period. A broadly representative sample for intervention than others. Patients will be assessed at 1- and 4 months following injury. Outcomes assessed will include measures of psychiatric status, functional disability of life. The study is powered at each stage of development to detect a clinically meaningful difference between either of the interventions (i.e., propranolol or gabapentin)- or two different dose/duration regimes- and placebo on two primary measures of PTSD and depressive symptom severity. Safety and tolerability are additional outcomes of major interest. Findings will provide justification for and information about optimal parameters (e.g., subject selection; sample size; dose and duration) for a future randomized controlled trial (RCT).

DESCRIPTION (provided by applicant): This is a request for an NIMH Midcareer Patient-Oriented Investigator Award (K24). The purpose of the award is to enable Dr. Stein, an experienced and productive researcher in adult anxiety disorders clinical trials and epidemiology, to 1) enhance his knowledge of health services research theory and methods, and 2) to enhance his experience in developing and testing interventions for children and adolescents. The purpose of acquiring this additional expertise is to enable the candidate and his trainees to move more rapidly and successfully into effectiveness research, and to include children and adolescents in their studies. The research program builds upon an R01 held by the applicant as well as other ongoing studies aimed at improving care for patients with anxiety disorders in medical systems. Anxiety disorders, among the most common of all mental disorders, are associated with tremendous functional disability and reduced health-related quality of life. The working model for the applicant's research is that the primary care setting is the venue where anxiety disorders can and should be most successfully treated. Treatment, however, must be provided in a form that suits the context of the primary care healthcare delivery system. At the present time, this means that interventions must be relatively brief, they must be fairly easy to administer (i.e., extensive training of specialized mental health therapists is rarely feasible), and they must be generalizable to a wide array of patients and practice settings. Because anxiety disorders so often begin early in life, strategies to detect and treat anxiety disorders in pediatric healthcare settings are needed. The applicants work is geared toward the development, implementation, and testing of methods for detecting and treating anxiety and related disorders in medical (adult and pediatric) settings. The primary career goals that will be met by this award are: 1) To provide the applicant with protected time to continue his extensive mentorship of junior investigators in the conduct of outcome studies in anxiety disorders; 2) To provide the applicant with the opportunity to upgrade his research skills in several specific areas requisite to his transition into effectiveness research in adults and youth. These goals will be met through continued and expanded research activities, collaboration and individual consultation with senior scientists (in effectiveness research, and in treatment of behavioral disorders in children and adolescents) both locally and nationally, and graduate level course work in epidemiology, health services, biostatistics, and health economics at the San Diego State University School of Public Health. A K24 Award at this stage of the applicant's career will provide the time and resources needed to achieve these goals.

DESCRIPTION (provided by applicant): Anxiety affects how people process stimuli and select actions. High Trait Anxious (HTA) subjects are more sensitive than Normatively Trait Anxious (NTA) subjects to detect threat-related material. The consequences of this perceptual bias for the selection of action have been little studied and the neural basis underlying the selection of action in anxious subjects is poorly understood. Behavioral studies of patients with panic disorder and studies with HTA subjects support the hypothesis that increased anxiety is associated with increased error sensitivity, i.e., an undesired or incorrect outcome is more likely to change ongoing response strategies. In addition, HTA subjects show increased risk aversion in a simple decision-making task. Neuroimaging studies have implicated rostral and dorsal anterior cingulate (ACC), which receive input from limbic and non-limbic structures including the amygdala, as critical neural substrates for conflict detection and cognitive or affective evaluative processing. Preliminary studies show that HTA subjects relative to NTA subjects show increased activation of rostral and dorsal ACC during decision-making. This proposal aims to elucidate the behavioral characteristics and neural substrates in HTA subjects during decision-making. Experiments will be conducted with age-, gender-, education-, ethnicity-, comorbidity- matched college students that are > 85 percentile on the Spielberger Trait Anxiety Inventory (HTA) and a normative group that are within the 40th- 60th percentile on this inventory (NTA) to examine a behavioral and a neural substrate hypothesis as well as the relationship between these hypotheses: (1) In comparison to NTA subjects: HTA subjects show increased sensitivity to errors in a decision-making task; HTA subjects show decreased risk-taking in a simple decision-making task. (2) In comparison to NTA subjects: HTA subjects show increased activation in dorsal ACC during a simple decision-making task; HTA subjects show increased rostral ACC activation during anticipation of a potential adverse outcome during the risk-taking decision-making task. Results from these experiments will provide important data toward a neurocognitive and neural substrate model of anxiety and anxiety disorders. In addition, identifying dysfunctional neurocognitive processes and underlying neural substrates will enable us to better specify anxiety-based intermediate phenotypes.

paroxetine; human therapy evaluation; social psychology; phobias; mental disorder chemotherapy; anxiety disorders; drug screening /evaluation; fear; neuroimaging; functional magnetic resonance imaging; positron emission tomography; human subject; deoxyglucose; behavioral /social science research tag; clinical research;

DESCRIPTION (provided by applicant): Social anxiety disorder (also referred to as social phobia) is among the most common psychiatric conditions in the community, and is associated with significant distress and dysfunction in affected individuals. This combination of high prevalence (conservatively 4-5%) and substantial attendant morbidity in generalized social anxiety disorder (GSAD) positions it as a serious public health problem. Although currently available treatments for GSAD are efficacious, most patients remain residually symptomatic after initial psychosocial or psychopharmacological intervention. Clinicians regularly face the question of what to do next for these patients, but there are no empirically derived data available to guide clinical practice regarding the relative benefits of "next step" strategies to improve outcome. The absence of such data is a substantial barrier to advancing knowledge and patient care in this area. Given the extensive use of medication treatment in psychiatric and primary care settings and the relative dearth of availability of empirically based psychosocial therapies outside of rarified research settings, we are proposing a 5-year study to systematically assess the relative efficacy of alternate pharmacologic treatment strategies in patients with GSAD remaining symptomatic despite initial SSRI pharmacotherapy. In addition, we will examine predictors of response (e.g., age at onset, duration of illness, comorbidity) to initial SSRI therapy and predictors of differential response to the strategies under study. We will also examine whether polymorphisms in well-studied genes that influence serotonin and/or catecholamine metabolism influence response to treatment in GSAD. The study comprises a double-blind, placebo controlled, randomized trial to compare the relative benefits of the addition of a benzodiazepine (clonazepam), or a switch to an alternative antidepressant (venlafaxine extended-release), for patients with GSAD who remain symptomatic after a 10-week trial of sertraline alone. One hundred sixty-three patients will be entered at each of the three sites (total N = 490): the Center for Anxiety and Traumatic Stress Related Disorders at the Massachusetts General Hospital, the Anxiety Disorders Program at the University of California San Diego, and the Anxiety Disorders Clinic at McMaster University. The CMSD mechanism is being employed to take advantage of each of the sites' previous experience with the systematic evaluation and treatment of individuals with GSAD and to ensure timely recruitment of an adequate number of subjects. This study will provide systematic, prospectively derived data in an understudied area - that of improving outcomes in patients with anxiety disorders. It thus directly addresses a critical public health issue that adversely affects a substantial proportion of the population.

[unreadable] DESCRIPTION (provided by applicant): Although it is now well established that collaborative, chronic disease management approaches are clinically and cost effective for treating depression in primary care, we know very little about how such models perform for anxiety disorders, which occur more commonly than depression in primary care and are particularly difficult to manage. To address this gap, we propose the first large-scale effectiveness study to test a collaborative care approach to treating primary care anxiety. This work builds directly on our Collaborative Care for Panic study, key informant interviews of clinicians, patients and clinic administrators, and more recent studies in primary care depression. Based on these considerations, we have developed a single, specially designed intervention called CALM (Coordinated Anxiety Learning and Management), that can deliver evidence-based treatment to patients with any of four anxiety disorders prevalent in primary care (Panic Disorder [PD], Generalized Anxiety Disorder [GAD], Social Anxiety Disorder [SAD], and Posttraumatic Stress Disorder [PTSD]), including those patients with comorbid depression and/or moderate substance abuse. This intervention allows patients treatment choice (CBT and/or medication), uses techniques to maximize patient engagement, and includes stepped care algorithms - approaches successfully employed in large-scale studies of primary care depression. We have also included an ethnically diverse study population, as well as Spanish-speaking patients, and propose qualitative studies to better understand how CALM should be tailored to individual clinics and to examine the acceptability of CALM for disadvantaged patients. These qualitative studies will provide valuable information needed for future dissemination of this approach. The primary aims are: (1) to use experimental, quantitative methods to determine the clinical effectiveness of CALM compared to treatment as usual (TAD) for the above four anxiety disorders (as a group and individually) and to compare CALM and TAU in terms of intermediate outcomes such as quality of care, self-efficacy, and social stigma; and (2) to use qualitative methods to assess acceptability and barriers to sustainability of CALM in participating clinics, providers, and patients. The secondary aims are: (1) to use quasi-experimental methods (e.g. instrumental variables) to examine the effects of appropriate treatment, independent of intervention assignment, on functioning and other clinical outcomes; and (2) to estimate health care costs and cost effectiveness of CALM. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): The long-term objective of this application is to validate and optimize a human, in vivo bioassay for dentifying pharmaceutical compounds that are highly likely to have anti-anxiety properties. No new classes of anxiolytic medications have entered the marketplace in the past two decades, and the current drug development pathway suffers from many costly, time-consuming failures of compounds that enter Phase studies. The FDA has pointed to this "pipeline problem" as a significant challenge to drug development in the 21st century. Among their recommendations is the need to invent new drug development tools to enhance the movement along the "critical path" from Phase I to Phase III. This proposal outlines a series of studies aimed at determining whether functional magnetic resonance imaging (fMRI) in conjunction with the administration of pharmacological agents can be used as a human, in vivo bioassay at the juncture between Phase I and Phase II drug development for anxiety disorders. This predictive tool would be used to guide selection of lead compound(s) and optimal dosing, and would increase the prior probability of success in Phase II. In this application, we propose to examine the sensitivity, specificity, and reliability of a two emotion-processing tasks during blood oxygen dependent (BOLD) and arterial spin labeling (ASL) fMRI to probe the activation in amygdala, insula, and medial prefrontal cortex with standard anxiolytic and other psychopharmacological agents. A goal of this line of research is to be able to relate the degree of attenuation of the BOLD-fMRI signal in the target areas to the anxiolytic potential of a novel drug. The studies proposed here over 3 years are intended to establish the utility of these techniques for this purpose. Studies in healthy volunteers will optimize the procedures and paradigms and document their sensitivity and reliability (Aim #1). Dose-response studies in anxious subjects will examine sensitivity and specificity of the procedures to known anxiolytic agents in the contexts of acute dose-response (alprazolam and pregabalin) and subchronic (4 weeks of escitalopram) administration (Aim #2). Anxiety disorders are the most prevalent form of mental disorder in the United States, and are disabling to individuals and costly to society. Current pharmacotherapies fail to provide complete relief to 50% of patients. Enhancing the development of new treatments for anxiety is a public health priority. The projects proposed in this application have the potential to achieve this important aim. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): This proposal is the competing renewal of our ongoing work into the neural substrates of anxiety. In a natural progression of this work, we now propose to test key aspects of a neural circuit model for anxiety disorders. We will use BOLD fMRI in conjunction with emotion processing tasks to compare healthy controls subjects (HC) to patients with panic disorder (PD) and generalized anxiety disorder (GAD), who will be studied before and after cognitive behavioral treatment (CBT). This proposal brings together methods and approaches from behavioral and cognitive neuroscience, functional neuroimaging imaging, and psychological clinical therapeutics to outline a series of studies with the long-term objective of delineating the neural substrates of anxiety disorders. The principal objective of this competitive renewal is to build on the applicants'previously accomplished work in non-clinical individuals with anxiety proneness and apply this to patients with anxiety disorders with the following specific aims: (1) To develop a basic systems neuroscience endophenotype for anxiety disorders. Based on our prior work, we hypothesize that, compared to healthy controls (HC), patients with GAD or PD will show increased activation of the anterior insula during various types of emotion processing that engage interoceptive systems. Moreover, we hypothesize that there is less functional coupling between the insular cortex and both the amygdala and the medial prefrontal cortex (mPFC) in patients with anxiety disorders. (2) To evaluate effects of CBT on the neural systems hypothesized to be dysfunctional in patients with anxiety disorders. We expect that successful treatment will be associated with attenuation of insular cortex activity and increased coupling between insula and both amygdala and mPFC, respectively. In the case of GAD, we also expect to see a reduction in task-related dorsolateral prefrontal cortex (DLPFC) activity. Anxiety disorders are early onset, prevalent, serious conditions that impact adversely on individual and societal functioning. Improved understanding of the neural circuitry of anxiety disorders will inform diagnostic conceptualizations and enable the more directed development and testing of novel therapies that are based on a more thorough understanding of pathophysiology, thereby conveying new therapeutic options to the many patients with anxiety disorders for whom existing treatments are inadequate.

[unreadable] DESCRIPTION (provided by applicant): The long-term objective of this application is to validate and optimize a human, in vivo bioassay for dentifying pharmaceutical compounds that are highly likely to have anti-anxiety properties. No new classes of anxiolytic medications have entered the marketplace in the past two decades, and the current drug development pathway suffers from many costly, time-consuming failures of compounds that enter Phase studies. The FDA has pointed to this "pipeline problem" as a significant challenge to drug development in the 21st century. Among their recommendations is the need to invent new drug development tools to enhance the movement along the "critical path" from Phase I to Phase III. This proposal outlines a series of studies aimed at determining whether functional magnetic resonance imaging (fMRI) in conjunction with the administration of pharmacological agents can be used as a human, in vivo bioassay at the juncture between Phase I and Phase II drug development for anxiety disorders. This predictive tool would be used to guide selection of lead compound(s) and optimal dosing, and would increase the prior probability of success in Phase II. In this application, we propose to examine the sensitivity, specificity, and reliability of a two emotion-processing tasks during blood oxygen dependent (BOLD) and arterial spin labeling (ASL) fMRI to probe the activation in amygdala, insula, and medial prefrontal cortex with standard anxiolytic and other psychopharmacological agents. A goal of this line of research is to be able to relate the degree of attenuation of the BOLD-fMRI signal in the target areas to the anxiolytic potential of a novel drug. The studies proposed here over 3 years are intended to establish the utility of these techniques for this purpose. Studies in healthy volunteers will optimize the procedures and paradigms and document their sensitivity and reliability (Aim #1). Dose-response studies in anxious subjects will examine sensitivity and specificity of the procedures to known anxiolytic agents in the contexts of acute dose-response (alprazolam and pregabalin) and subchronic (4 weeks of escitalopram) administration (Aim #2). Anxiety disorders are the most prevalent form of mental disorder in the United States, and are disabling to individuals and costly to society. Current pharmacotherapies fail to provide complete relief to 50% of patients. Enhancing the development of new treatments for anxiety is a public health priority. The projects proposed in this application have the potential to achieve this important aim. [unreadable] [unreadable] [unreadable]

This is a Major Research Equipment and Facilities Construction project for the construction of a 236 foot research vessel to work in the waters off the coast of Alaska including the Chukchi and Beaufort Seas. The University of Alaska, Fairbanks (UAF) proposal is in response to the National Science Foundation Program Solicitation NSF 07-515 for the management, acquisition and operation of an Alaska Region Research Vessel (ARRV). The construction of an ARRV was given the highest priority in the report ?National Academic Research Fleet ? a Long Range Plan for Renewal?. The proposed design was developed with input from the oceanographic science community and the academic fleet operators. The design was completed in December 2004 and is well suited for oceanographic and fisheries research in the harsh, ice-infested Alaska seas during all seasons.

UAF proposes to assemble a management team for the acquisition of the ship that draws on extensive experience for public agency ship procurements. They propose to use experienced personnel and vessel acquisition procedures that have proven successful in Alaska Marine Highways (AMS) recent vessel acquisitions. UAF will be using the Earned Value Management (EVM) and Project Execution Plan (PEP) systems used by AMS during these acquisitions. The University is contracting with two experience marine science technical engineers to insure the ship science capabilities are not compromised.

The proposal was reviewed by 10 mail reviewers and 10 panelists. A major recommendation from the panel was a phased acquisition strategy to mitigate risk. A four phase approach is proposed with given milestones to be completed prior to funding of the next phase. This CSA provides the funds for Phase I and completion of related milestones including the design refresh and cost update, project execution plan, development of an oversight committee, draft shipyard contract and completing the formation of the project management team.

DESCRIPTION (provided by applicant): This proposal requests continued NIMH funding for the Midcareer Investigator Award in Patient-Oriented Research (K24) to Murray B. Stein, MD, MPH. During the first 5 years of support provided by the K24 award, Dr. Stein has upgraded his own skill set as a research mentor by completing an MPH degree with an emphasis on epidemiology, and has obtained three new patient-oriented research grants from NIMH. He has also, during this period, served as primary or co-mentor to approximately fifteen clinician-scientists-in training. Several of these trainees have gone on to receive independent research support from NIH (two K awards), NARSAD (a Young Investigator Award), and private foundations. Furthermore, all of these mentees have published one or, in most cases multiple, first-authored peer-reviewed research papers reporting their work, and many continue to work in full-time academic patient-oriented research positions. The need for training of patient-oriented researchers is profound. UCSD is fortunate to have several formal training programs (including an institutional K30 award and departmental T32 and R25 training grants) to support the structured didactic training of clinician-scientists. Each of these programs requires the availability of skilled mentors. The K24 award permits Dr. Stein, an established, highly productive clinician scientist whose work in anxiety disorders ranges from epidemiology to neurobiology to outcomes research, to devote substantial time to mentoring beginning patient-oriented researchers. It also provides him with time to enhance his own research skills in order to mentor new clinical investigators and to conduct meritorious patient-oriented research. The proposed 5 years of continued support will focus on facilitating the convergence of his research group's expertise in anxiety disorder clinical trials with their growing skill and interest in genomics. With the help of several identified "resource" experts in clinical trials biostatistics, public health aspects of genomics, and genetic epidemiology and analysis, Dr. Stein proposes to enrich and deepen his research expertise in these areas with the dual aims of (1) keeping his research group at the vanguard of anxiety disorder research teams, and simultaneously, (2) transmitting these skills to the many clinician scientists he mentors in an effort to advance their own careers in patient-oriented research.

A request is made to fund additional and back-up instrumentation on the R/V Point Sur, a 135? general purpose Regional research vessel. The vessel is operated by Moss Landing Marine Labs as part of the University-National Oceanographic Laboratory System research fleet. The request includes two items listed by priority:

1) Network Upgrade
2) Precision Spectral Pyranometer

Broader Impacts: The acquisition, maintenance and operation of shared-use instrumentation allows NSF-funded researchers from any US university or lab access to working, calibrated instruments for their research, reducing the cost of that research, and expanding the base of potential researchers.

San Jose State University proposes to support technical services on R/V Point Sur, a 135? general purpose UNOLS research vessel operated by the Moss Landing Marine Laboratories as part of the University-National Oceanographic Laboratory System research fleet. They request support for basic services and maintenance of a towed, undulating vehicle as specialized services. They will provide one technician on each seagoing research project of R/V Point Sur to support seagoing research projects and to maintain, calibrate and provide for qualified users items from their pool of shared-use research instrumentation. The budget in this proposal is for the first year of a 5-year continuing grant.

Broader Impacts
The principal impact of the present proposal is under criterion two, providing infrastructure support for scientists to use the vessel and its shared-use instrumentation in support of their NSF-funded oceanographic research projects (which individually undergo separate review by the relevant research program of NSF). The support of maintenance and operation of shared-use instrumentation allows NSF-funded researchers from any US university or lab access to working, calibrated instruments for their research, reducing the cost of that research, and expanding the base of potential researchers.

ABSTRACT

31 July 2012
Proposal Number: 1219431
Institution: San Jose State University, Moss Landing Marine Labs
PI: S. Lamerdin
Co-PI: J. Harvey

The proposal requests four Shipboard Scientific Support Equipment (SSSE) items for the San Jose State University, Moss Landing Marine Labs (MLML) for use aboard the R/V POINT SUR; namely a new global distress communication suite (GMDSS), a forward-looking sonar, an oily water separator, and a night vision thermal imaging camera. These items will either allow the vessel to meet regulatory requirements or enhance operational safety; particularly for the planned Antarctic deployment.


Broader Impacts: The R/V POINT SUR supports federally-funded scientific research in the Pacific Northwest in order to expand human knowledge of the ocean environment. During operations, the vessel routinely exposes graduate and undergraduate students to seagoing oceanography. Pubic outreach is also achieved through the State?s Center for Integrative Coastal Observation, Research and Education program (CI-CORE) and the Alliance for Coastal Technologies program (ACT), real-time satellite connectivity from ship to shore, and open house events. The POINT SUR is scheduled to complete over 60 NSF sponsored days in 2012.

This award will fund the first of five years of operation under a renewal of the NSF Cooperative Agreement, OCE- 0505385. Ship awards will be renegotiated each year and is based on the number of days of ship time in support of NSF funded research programs. R/V Pt. Sur, a NSF-owned research vessel, is operated as part of the University-National Oceanographic Laboratory System (UNOLS) research fleet by Moss Landing Marine Laboratories. In 2012, Pt. Sur anticipates operating 102 days, of which 72 days will be in direct support of NSF peer-reviewed sea-going work.


R/V Point Sur has been successfully operated by Moss Landing Marine Laboratories (MLML) since 1986. MLML is located in Central California on the Monterey Bay at the head of the deep undersea Monterey canyon and has unique proximity to a wide variety of coastal, canyon and offshore study sites along the Central CA coast The R/V Point Sur continues to serve scientists from institutions around the world as well as institutions associated with the Monterey Bay Crescent Ocean Research Consortium (MBCORC).

During 2012 the R/V Point Sur will provide ship time for several research and marine science educational programs funded by the National Science Foundation (NSF), the Office of Naval Research (ONR), the Monterey Bay Aquarium Research Institute (MBARI), the Army Corps of Engineers, MLML and consortium campuses of the California State University system. This proposal requests the funding necessary to support the NSF portion of our operation that amounts to 63 days out of a total schedule of 95 days at sea. These NSF days encompass 4 discrete cruises. Two of these cruises are repeat users of the vessel (Bishop and McPhee-Shaw) while the remaining cruises will be new. The first of these cruises will take the ship off the coast of Oregon for CTD and mid-water trawling operations. The second cruise represents a transit from the vessels homeport to Punta Arenas, Chile. This transit is part of a larger project that involves science support at Palmer Station, Antarctica. This represents one of the longest and most logistically challenging cruises the vessel has ever undertaken. Funds have been included in the current proposal to help prepare the vessel for this work.

Broader Impacts:
The Moss Landing Marine Laboratories continues to be successful in advancing the California State University's Center for Integrative Coastal Observation, Research and Education program (CI-CORE, http://www.mlml.calstate.edu/cicore/) and the Alliance for Coastal Technologies program (ACT, http://www.actonline.ws/). As a key partner in both these efforts MLML has been funded (at no cost to NSF) to provide instrumentation for the underway measurement of surface water parameters (temperature, salinity, fluorescence, oxygen, and turbidity) from a number of our vessels. As part of the CI-CORE program these data will be formatted and made available on our web site for educators, scientists, policy makers and the public.
Various other Federal, State and private supported work is also included in the schedule. The MBARI maintains several moored arrays near the mouth of the Monterey Bay and offshore that will be serviced using the R/V Point Sur. MLML will use approximately 10 days of ship time in support of class cruises and thesis work for the California State Universities (CSU) providing graduate and undergraduate students valuable field time to gather data for class projects. These classes include physical, chemical and biological oceanography, geology, ichthyology, benthic ecology and marine mammal behavior. Several CSU instructors have taken advantage of these class cruises by using them to help educate junior college and high school students as well. In the past weve also opened the R/V Point Sur to local middle school students and their parents for dockside tours and informal talks about the local ocean environment.

This award is for operations of R/V Sikuliaq in calendar 2014, and is year-one of a three-year cooperative agreement to the University of Alaska Fairbanks for operations of the research vessel to support peer-reviewed sea-going science. In calendar year 2014, R/V Sikuliaq will transition from construction to operations after a series of sea-trials. Approximately 90 science/operational days will be carried out in the latter half of 2014. R/V Sikuliaq will be operating in the Western Pacific off Hawaii and Guam, with one cruise utilizing an autonomous underwater vehicle (AUV) SENTRY within the Emperor Seamounts, specifically Papahanaumokuakea Marine National Monument, and a second cruise operating a high resolution AUV to conduct a magnetic survey of the Hawaiian Jurassic Basin. One of R/V Sikuliaq's missions will include provision of educational opportunities both for students of the marine sciences and the general public. Periodically, the University plans to hold open houses and outreach events to provide early exposure to oceanography that target Alaskan tribal nations. Additionally, community events will include tours through the ship facility, hands-on demonstrations of on board marine science research guided by faculty, students and ships' crewmembers, or at sea real-time internet connection to classrooms with the ship's telepresence capabilities.


R/V Sikuliaq - pronounced see-koo-leee-auk, and translated from Inupiaq as "young sea ice" - is a 261-foot ice capable research vessel designed to weather harsh conditions to help advance polar and sub-polar scientific research. Owned by the National Science Foundation and operated by the University of Alaska Fairbanks, R/V Sikuliaq was launched in October 2012 and is outfitted with state-of-the-art equipment to bring scientists to ice-choked polar regions, able to cut through ice up to 2.5 feet thick. In this calendar year, one of the cruises will utilize SENTRY, an AUV operated by Woods Hole Oceanographic Institution, which is equipped with a standard suite of scientific and engineering sensors. SENTRY is a flexible platform where scientists, according to their specific interests and scientific needs, can interface additional sensors. R/V Sikuliaq is well suited to support these research programs in terms of equipment and ship capabilities for AUV operations.

University of Alaska, Fairbanks (UAF) proposes to support technical services on R/V Sikuliaq, a new, 261-foot, general purpose research vessel operated as part of the US Academic Research Fleet. The vessel is owned by NSF and operated by the University of Alaska, Fairbanks. For basic technical services, UAF will provide three shipboard technicians on each cruise on R/V Sikuliaq to support seagoing research projects and to maintain, calibrate and provide for qualified users items from their pool of shared-use research instrumentation. This is the first proposal written for technical services for this vessel. Ordinarily, the various institutions that support vessels in the Academic Fleet operate under 5-year continuing grants. In order to maintain the same proposal cycle among the various institutions, this award will be the first of a two-year continuing grant.

Broader Impacts
The principal impact of the present report is under Merit Review Criterion 2 of the Proposal Guidelines (NSF 13-589). It provides infrastructure support for scientists to use the vessel and its shared-use instrumentation in support of their NSF-funded oceanographic research projects (which individually undergo separate review by the relevant research program of NSF). The acquisition, maintenance and operation of shared-use instrumentation allows NSF-funded researchers from any US university or lab access to working, calibrated instruments for their research, reducing the cost of that research, and expanding the base of potential researchers,

Project Summary Psychiatric Genomics Consortium for PTSD Posttraumatic stress disorder (PTSD) occurs only in vulnerable individuals after exposure to severe traumatic events. This risk is due, in part, to 40-50% heritability of differential vulnerability. Due to increasing collaborations across the field of PTSD genomics and the advent of new analytical tools, it is a very exciting time for PTSD genetic risk discovery. The purpose of this application is to facilitate meta-analyses of genome- wide association study (GWAS) data for symptoms and diagnosis of PTSD. We propose to conduct large-scale meta-analyses through the PTSD group of the Psychiatric Genomics Consortium (PGC). The PGC was created in 2007 to conduct field-wide mega-analyses of individual data for 5 major psychiatric disorders. With its current 11 working groups, it is the largest consortium (>800 scientists from 40 countries) in the history of psychiatry. The PGC has produced major findings with regard to the genetic architecture of psychiatric disorders. Meta-analyses of GWAS have produced over 100 loci at the genome- wide significance threshold, at sample sizes ranging from 36,000 cases for schizophrenia to 246K cases for depression. The polygenic architecture inferred from family studies was confirmed with molecular evidence. Corroborating findings from twin studies, shared genetic contributions among psychiatric disorders has been found. The PGC-PTSD group was launched in 2013 and has been enormously successful. Currently our multi- ethnic data collection includes genotypes from 60 studies with a total N of over 200K combined cases and trauma-exposed controls. We recently identified 6 genome-wide significant loci and generated a polygenic risk score to identify individuals at highest risk for PTSD after trauma exposure. We hypothesize that with an increased sample size and deeper phenotype characterization, the PGC- PTSD will accelerate our current understanding of the genetic architecture of PTSD. Our progress thus far demonstrates feasibility and initial successes of the proposed work. Aim 1 will increase sample size (with commitments for 50K additional cases and 300K controls from banked samples) to reach the PGC goal of 100K cases for psychiatric disorders, create psychometrically optimized PTSD subphenotypes, conduct GWAS meta-analyses to detect novel common variants, and identify copy-number variants (CNVs) hypothesized to contribute to PTSD heritability through rare and low-frequency CNVs. This aim will be supplemented by the contribution of diverse ancestry groups to ensure that advances in our genetic understanding of PTSD extend across ancestral backgrounds in Aim 2. Aim 3 is centered around the characterization of functional consequences of identified variants. Lastly, we will use polygenic risk scores (PRS) to provide insights into relationships to other traits and advance causal inference in Aim 4. Identifying the genetic pathways underlying PTSD will lead to improved neurobiological understanding, enhanced prevention, and improved treatment of this debilitating and prevalent syndrome.