ABSTRACT
The recent COVID-19 crisis, as well as the resulting international response, have demonstrated the importance of medical innovation in meeting current and future health challenges. Yet capacity for innovation differs from country to country, and policymakers are wise to find ways to increase each nation's ability to generate new solutions. This study examines medical innovation, measured as patents per capita, for 27 EU countries from 2004 to 2018. Modelling innovation as a function of international and domestic macroeconomic variables, government and private-sector R&D, the rate of return to physical and human capital, and a measure of risk, a dynamic panel analysis finds that real-exchange-rate volatility reduces patent applications for some countries, particularly in Central and Eastern Europe. The response to the explanatory variables differs by countries' overall innovation levels, with innovation in weaker innovators reduced by risk and increased by higher education levels. In stronger innovators, the internal rate of return most strongly drives innovation, suggesting that this process more closely resembles "traditional” investments.
ABSTRACT
[...]the agency has created a wide variety of innovative programs and free or low-cost services aimed at spurring innovation and technology development at the grassroots level. For independent inventors and small businesses that choose to file patent applications "pro se"- that is, without the assistance of a registered patent attorney-the USPTO provides special resources to explain and demystify the patent application process. Here is where you can find a PTRC in your state. Because the cost of securing IP protection should not prohibit inventors from filing for a patent and trademark, the USPTO offers substantially reduced fees for its services.
ABSTRACT
This report covers Year 2 of the project. This project examines the impact of disturbances in normal sleep and circadian regulation on mechanisms underlying vulnerability to, and maintenance of, posttraumatic stress disorder (PTSD). The goal of Year 2 was data collection and initial validation of data collection procedures and harmonization with Monash. We proposed to complete 30 participants (45 in total with year 1). Progress was slowed due to COVID19, which prompted our VA facility to shut down all human research the fall. Our study, which requires a hospital stay, was finally approved for collection in October with mitigation procedures in place. We have completed 18 subjects (30 of target). However we do have 6 weeks now booked for collection and a large list of applicants for the study. During the COVID period we examined data for errors and trained and harmonized sleep scoring across the study. We have seen exceptional interest in the study since recruitment opened and hope to make up for lost time this year.
ABSTRACT
The combination of alcohol use and negative emotional states has been identified as a particularly toxic combination for suicide risk. The current study proposes to examine changes in (a) alcohol use/misuse and (b) depression (as the primary suicide-related negative emotional state) as soldiers undergo the transition from active duty to veteran status, as well as to prevent/reduce alcohol misuse and depression in this population. To date: the assessments (screening, baseline, pre-separation (delivered up to 2 times) and post-separation (delivered 12 times)are nearing finalization;the internet-delivered brief intervention component (delivered 3 times to a portion of the participants in the study) is also nearing completion.
ABSTRACT
The combination of alcohol use and negative emotional states has been identified as a particularly toxic combination for suicide risk. The current study proposes to examine changes in (a) alcohol use/misuse and (b) depression (as the primary suicide-related negative emotional state) as soldiers undergo the transition from active duty to veteran status, as well as to prevent/reduce alcohol misuse and depression in this population. To date: the assessments (screening, baseline, pre-separation (delivered up to 2 times) and postx2;separation (delivered 12 times)are nearing finalization;the internet-delivered brief intervention component (delivered 3 times to a portion of the participants in the study) is also nearing completion.
ABSTRACT
Posttraumatic guilt and shame are common among Veterans and have been implicated in the development and maintenance of posttraumatic distress and a range of adverse outcomes, including posttraumatic stress disorder (PTSD), depression and suicidality, and alcohol/substance use disorders. There is a pressing need for effective treatments targeting transdiagnostic mechanisms such as guilt. We developed Trauma Informed Guilt Reduction (TrIGR) therapy as a therapeutic tool to help Veterans accurately appraise deployment-related guilt and to re-identify and re-engage with their values. The overall objective of this study is to examine the efficacy of TrIGR in reducing deployment-related guilt. The overarching hypothesis is that TrIGR will reduce guilt, shame, and related distress, and these improvements will be significantly greater than in the comparison condition, Supportive Care Therapy (SCT). The study is a Stage 2 randomized, controlled trial of TrIGR compared to SCT. Recruitment of participants takes place at two VA Medical Centers (San Diego, CA and Providence, RI). 150 OEF/OIF Veterans will be randomized to TrIGR or SCT (at least 75 in San Diego). All eligible participants complete an in-person baseline assessment, receive 6 sessions of TrIGR or SCT in individual format, complete brief bi-weekly self-report measures during treatment, and complete follow-up assessments immediately post-treatment, and 3- and 6-months later.
ABSTRACT
The overall objective of this study is to provide definitive evidence that early weight bearing is safe in patients with operatively treated ankle fracture injuries and results in better outcomes. We hypothesize that clinical complications will be similar in patients in the early and delayed WB group and that patients in the Early WB Group will return to usual major activity (i.e. work, active duty, school) sooner and achieve better functional outcomes than those in the Delayed WB Group. As a consequence, the number of work days lost and costs associated with lost productivity will be lower for the Early versus the Delayed WB group. We will also conduct a pilot study of early vs. delayed weight bearing in patients surgically treated for unicondylar plateau fractures. Smaller clinical series and biomechanical date indicate that early weight bearing is safe and patients with these injuries may benefit from early weight bearing as well. A study of these injuries will provide important information with regard to safety and outcomes that is currently lacking and provide data to help power a definitive trial.
ABSTRACT
The purpose of our prospective cohort study is to address important knowledge gaps on resiliency in the rehabilitation of adults with lower-extremity injuries. Specific aims are to develop and test a resiliency instrument that is relevant to active duty military Service Members. The proposed project will leverage the infrastructure of the Maximizing Outpatient Rehabilitation Effectiveness (MORE) study that is currently being conducted at Brooke Army Medical Center. The first year of the project focused on selecting items from three well-established resiliency instruments that have been validated in civilian populations. Interviews and focus groups were conducted in up to 28 active duty military Service Members. A pre-test of the MORE resiliency instrument in 60 Service Members was conducted which finalized the instrument. Currently, we are testing the MORE resiliency instrument in 310 Service Members to determine reliability and construct and predictive validity of the instrument in active duty Service Members with lower-extremity injury. This project has HRPO approval and has enrolled 77 out of the 310 participants for the testing cohort phase of the project.
ABSTRACT
An estimated 20,000 military service members sustained extremity injury in the recent wars in Iraq and Afghanistan. This high number of limb injured Service Personnel catalyzed advancements in lower limb bracing technology and a focus on therapy to maximize utilization of these devices. This is a considerable problem in the Veteran and private sectors as well. It is presently unclear whether these newer (i.e. advanced) braces improve comfort and function in those with limb injury compared to bracing options formerly in use. The cost of newer devices and the associated fabrication time is rapidly climbing and some reimbursors are not paying for these newer devices. For instance, a conventional ankle-foot-orthosis has a reimbursable cost of approximately $1400. Alternatively, newer advanced bracing systems such as the Intrepid Dynamic Exoskeletal Orthosis (IDEO), are approximately twice the cost of conventional devices to fabricate. Reimbursement costs are not yet widely agreed upon, if accepted at all. If the devices truly improve function and comfort, then the initial high costs of provision may be justified. The primary objective of this clinical trial is to determine if different types of leg/foot braces will improve comfort and function in persons who have sustained injury affecting their lower limb.
ABSTRACT
The purpose of this project is to conduct a RCT trial examining the efficacy of the TEACCH School Transition to Employment and Postsecondary Education (T-STEP) Program. 60 Community college students (18-21 years of age) with autism spectrum disorder will participate in either the T-STEP Program or manualized counseling services (career, academic, self-counseling) with both proximal (executive function, social communication, and emotion regulation) and distal (employment, postsecondary education success) outcomes measured. The long-term impact of this intervention is to promote a more positive quality of life for young adults with high functioning ASD including increased postsecondary education completion, employment, self-determination, and decreased difficulties with coping and depression. Due to the COVID-19 epidemic preventing in person interactions, we have adapted the protocol to conduct online interventions. This adapted protocol has received approval from all regulatory bodies and the adapted intervention and RCT trial will begin in the second year of funding.
ABSTRACT
The overarching aim of this proposal is to develop, deliver, and investigate the efficacy of MBAT-Team (MBAT-T) as a tool to promoteindividual cognitive performance, resilience, interpersonal interactions, and team-level operational performance. The MBAT-T programwill be tested and compared to the standard MBAT for individuals (MBAT-I) and a no-training control group. We hypothesize thatMBAT-T will benefit squads across all 3 key domains: cognitive performance and resilience, interpersonal interactions, and team-leveloperational performance. We have received approval from the University of Miami IRB and HRPO (Army), have secured a site for theproject, and are on track regarding the coordination with the testing sites, research consultants and delivery of the practicum to the trainerswho will be delivering the MBAT program. The creation of the MBAT-Team course materials and trainer materials are near completion,and significant progress has been made on the preparation and development of the neurobehavioral testing battery for the project. Insummary, our timely success reaching our project milestones over this past year leave us well positioned for continued success in theexecution of this project in the coming year(s).
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APICS-01 seeks to address clinical and operational knowledge gap for acute lung injury (ALI) survivors by defining patterns of unmet needs, resource utilization, readmissions, and long-term functional outcomes among ICU survivors. We will employ a prospective, multi-center, observational study of outcomes and healthcare utilization among 200 ALI survivors which are directly relevant to a military population. In the first year of award, APICS-01 secured all approvals, finalized all study materials, and initiated enrollment ahead of schedule. Enrollment is currently at 64 (ahead of a projected 50 at this point). Analysis of data will not occur until after enrollment is closed. Findings to date are of a highly effective multicenter collaborative performing a high-quality clinical study ahead of schedule. The screening activities are functioning well, the eligibility criteria are working well, and the enrollment curves are solid.
ABSTRACT
This study is designed to measure the change in patients diagnosed with Parkinson's disease (PD) before, during and after a 12-week exercise program. The focus of this study is the glymphatic system. The glymphatic system is a recently discovered novel waste clearance pathway, in patients with Parkinson's Disease (PD). The glymphatic system acts as a waste-clearance system in the brain of vertebrate animals. The glymphatic system has been proposed in which new clearance pathways involving communication between paravascular spaces, interstitial fluid, and ultimately meningeal and dural lymphatic vessels exists, and we have provided evidence that this system may be dysfunctional in patients with Parkinson's disease with cognitive disorders. Early research suggest glymphatic function increases following exercise, this response is believed to clear beta-amyloid in the brain and may mediate the neurobehavioral response to exercise in PD. This study will use cognitive exams, neurological exams as well as specialized imaging to record data points and evaluate the glymphatic function after exercise.
ABSTRACT
Chemo resistance is a major cause of the high mortality of ovarian cancer. For example, although high-grade serous ovarian carcinoma (HGSOC) initially responds well to platinum-based chemotherapy, relapse often occurs with decreased chemotherapeutic sensitivity. Substantial evidence suggests that cancer stem-like cells (CSC) contribute to chemotherapy resistance. Putative epithelial ovarian cancer (EOC) CSCs are typically characterized by increased aldehyde dehydrogenase (ALDH) activity due to concomitant upregulation of the ALDH1A1 gene. It has been demonstrated preclinically that suppression of ALDH activity by ALDH1A1 knock-down sensitizes EOC cells to chemotherapy, demonstrating the functional importance of ALDH activity in EOC chemo resistance. We have furthermore shown that BRD4 (BET) inhibition reduces ALDH activity, thereby eradicating CSCs. The mechanism of suppression of ALDH activity is through down regulation of the ALDH1A1 super-enhancer associated non-coding enhancer RNA (eRNA). Notably, BRD4 genomic locus 19p13.12 is often amplified in HGSOC (~20%), and amplification/overexpression correlates with a poor prognosis in HGSOC patients. Therefore, we hypothesize that BRD4/BET inhibition may overcome chemotherapy resistance, and plan a phase I clinical trial to evaluate the combination of BET inhibitor INCB57643 (Incyte, Inc.) with carboplatin into establish MTD, tolerability, and preliminary efficacy of the combination. We propose embedded correlative science to identify populations most likely to respond to therapy. Our central hypothesis is that platinum resistance can be overcome through eliminating ALDH positive cancer stem-like cells by targetingBRD4 through BET inhibition. The goals of the proposal are: 1) To conduct a Phase I clinical trial of combined BET inhibitor (INCB57643) and carboplatin inpatients with platinum-resistant HGSOC. 2) To identify companion biomarkers that correlate with response to combination therapy in HGSOC patients.
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The present study consists of the application of 1 ma anodal HD tDCS over the preSMA for 20 minutes a session for 10 sessions over a two week period. The treatment is hypothesized to lead to improvement in verbal retrieval, detectable in both performance measures of verbal retrieval tasks and in ERP markers of verbal retrieval processing. Our objective is to determine if 10 sessions of 1 ma anodal HD tDCS to the preSMA for 20 minutes a session are an effective treatment for verbal retrieval deficits in GWI. We have established the research team, laboratory setting, obtained approval of all regulatory documents for the study, and established recruiting procedures. In the first half of the year, we screened 8 veterans and enrolled 5 in the baseline testing and treatment phase of the study. We were required to halt in person human subject research for the second half of the year due to the Covid-19 pandemic.
ABSTRACT
In patient surveys, Raynaud Phenomenon (RP) is the highest-ranked disease-specific symptom affecting patient quality of life. Many promising vasoactive classes of drugs have been evaluated for RP, but none have received FDA approval for this indication. This project is designed to address four critical knowledge gaps that may influence clinical trial design: 1) What is the soundest approach to measure RP attack frequency/severity? Is the paper diary or a new smart phone application more functional and preferred? 2) What should be used as the patient- reported outcome (PRO)? 3) What is the magnitude of the effect of seasonal change on RP activity and severity? 4) What is the best provocation test to study vascular reactivity in early phase and proof-of-concept RP trials? We will use a prospective, observational cohort study design of 160 SSc-RP patients followed every 3 months over one year to accomplish all Specific Aims. Simultaneously, we will recruit 500 patients for a cross-sectional questionnaire study so that we may perform item response theory analysis and validation of the new ASRAP PRO.
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We and others previously described an enrichment for somatic and germline alterations in DNA damage repair (DDR) genes among men with metastatic prostate cancer. Several recent clinical studies have indicated many of these patients could benefit from precision medicine strategies with PARP inhibitors and DNA damaging agents. In this project, our teams would investigate genomic, transcriptomic and protein-related functional signatures for a more accurate sub-classification of prostate cancers associated to DDR defects, aiming for a more precise patient care. The project is divided in 3 main aims: 1) testing the prognostic value of somatic DDR defects in a retrospective cohort of tumor biopsies, 2)developing multi-omics signatures based on prospective analyses of metastatic biopsies and3) clinical validation of these biomarkers in a clinical trial using carboplatin as DNA damaging chemotherapy.
ABSTRACT
Caregiving for individuals with Alzheimers disease and related dementias (ADRD) and Traumatic Brain Injury-related dementia has been associated with increased risk of both psychiatric morbidity and mortality, including higher risks of depression, anxiety, poor quality of life, and even early mortality. Although there are several beneficial interventions for caregivers of persons with AD, interventions that can help build skills to recognize and manage stress as well as enhance compassion in caregivers are urgently needed. The purpose of this study is to evaluate the effectiveness of proposed intervention, Practice of Acceptance, Awareness, and Compassion in Caregiving (PAACC) that integrates mindfulness training with caregiving skills training. Several studies have shown effectiveness of mindfulness in decreasing caregiver burden in caregivers of individuals with cognitive deficits, but most of them did not provide caregiving skills training with mindfulness. Our study hypothesis is that intervention such as PAACC which combines education, skill building, and mindfulness practices will enhance caregiving skills and will reduce caregiver stress as well as increase quality of life of the care recipient. The objective of the study will be accomplished by conducting a randomized control trial to test effectiveness of PAACC and compare it with existing cognitive behavior-based intervention called Resources for Enhancing Alzheimers Caregiver Health (REACH).
ABSTRACT
Aberrant threat monitoring has been established as a risk and a maintaining factor in anxiety and stress-related disorders. The goals of the current grant are to establish the efficacy of a promising 2nd generation eye-tracking-based ABM protocol in: a) reducing risk for deployment-related stress symptoms (focus on prevention);b) enhancing performance of infantry soldiers (focus on performance);and c)reducing stress-related symptoms following combat (focus on treatment). These goals will be tackled through three randomized controlled trials. Together the findings will provide an effective evidence-based means to support soldiers' performance and psychological adjustment throughout the deployment cycle. Specific aims and design: Study1: The overarching goal is to test the efficacy of an eye-tracking-based cognitive training procedure in reducing risk for post-combat stress-related psychopathology. To this end, we will conduct a RCT with three arms (N=540 IDF infantry soldiers). Specific aims are: (1) To determine whether GCFT is superior to RT-based ABMT and a RT-based neutral control condition in enhancing vigilance toward threat;(2) To determine whether GCFT is superior to RT-based ABMT and a NC condition in reducing risk for post-combat stress-related disorders;and (3) To test whether change in threat-related attention mediates change in symptoms post combat. Study 2: The overarching goal is to test the efficacy of an eye-tracking-based cognitive training procedure in enhancing military performance of infantry soldiers. To this end, we will conduct a RCT with three arms (N=180 IDF infantry soldiers). Specific aims are: (1)To determine whether GCFT is superior to RT-based ABMT and N-CFC in enhancing vigilance toward threat;(2) To determine whether GCFT is superior to RT-based ABMT and N-CFC in enhancing military performance in infantry soldiers;and (3) To test whether change inthreat-related attention mediates change in military performance.