bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing compressed mass spectra in electroweak supersymmetry with Recursive Jigsaw Reconstruction
Authors: Santoni M.
Published: May 2018

Abstract

The lack of evidence for the production of colored supersymmetric particles at the LHC has increased interest in searches for superpartners of the electroweak SM gauge bosons, namely the neutralinos and charginos. These are challenging due to the weak nature of the production process, and the existing discovery reach has significant gaps in due to the difficulty of separating the supersymmetric signal from SM diboson events that produce similar final states and kinematics. We apply the Recursive Jigsaw Reconstruction technique to study final states enriched in charged leptons and missing transverse momentum, focusing on compressed topologies with direct production of charginos and neutralinos decaying to the lightest neutral supersymmetric particle through the emission of W and Z bosons. After presenting prototype analysis designs for future LHC runs, we demonstrate that its detectors have the potential to probe a significant amount of unexplored parameter space for chargino-neutralino associated production within the next few years, and show that the very challenging successful search for chargino pair production with compressed spectra might be possible by the end of the LHC lifetime.
Introduction to surface engineering Peter A. Dearnley
Authors: Brookes Kenneth J.A.
Published: May 2018

This is an excellent book. It is, moreover, comprehensive without being, or claiming to be, exhaustive. Thus it will continue to fulfil its remit even in the light of further developments or discoveries, whereas otherwise it might soon have seemed obsolete or obsolescent. Unsurprisingly, in view of the author’s varied experience at Sandvik Hard Materials and elsewhere, much of this well-illustrated book is of immediate interest to readers in the important hardmetals industry. With its many references, it’s also very much an anthology of previous research, and most powder metallurgists will gain from having this useful manual on their bookshelf.

Since my review is aimed specifically at those engaged in the PM industry, I’ve looked at each chapter in turn and attempted to indicate its PM significance.
Cardiovascular Responses During Resistance Exercise in Patients With Parkinson Disease
Authors: Miyasato Roberto S. , Silva‐Batista Carla , Peçanha Tiago , Low David A. , de Mello Marco T. , Piemonte Maria E.P. , Ugrinowitsch Carlos , Forjaz Cláudia L.M. , Kanegusuku Hélcio
Published: May 2018

Background

Patients with Parkinson disease (PD) present cardiovascular autonomic dysfunction that impairs blood pressure control. However, cardiovascular responses during resistance exercise are unknown in these patients.

Objective

To investigate cardiovascular responses during resistance exercise performed with different muscle masses in patients with PD.

Design

Prospective, repeated‐measures.

Setting

Exercise Hemodynamic Laboratory, School of Physical Education and Sport, University of São Paulo.

Participants

Thirteen patients with PD (4 women, 62.7 ± 1.3 years, stages 2‐3 of the modified Hoehn and Yahr scale; “on” state of medication) and 13 paired control patients without PD (7 women, 66.2 ± 2.0 years).

Interventions

Both groups performed, in a random order, bilateral and unilateral knee extension exercises (2 sets, 10‐12 maximal repetition, 2‐minute intervals).

Main Outcome Measurements

Systolic blood pressure (SBP) and heart rate (HR) were assessed before (pre) and during the exercises.

Results

Independent of set and exercise type, SBP and HR increases were significantly lower in PD than the control group (combined values: +45 ± 2 versus +73 ± 4 mm Hg and +18 ± 1 versus +31 ± 2 bpm, P = .003 and .007, respectively). Independently of group and set, the SBP increase was greater in the bilateral than the unilateral exercise (combined values: +63 ± 4 versus +54 ± 3 mm Hg, P = .002), whereas the HR increase was similar. In addition, independently of group and exercise type, the SBP increase was greater in the second than the first set (combined values: +56 ± 4 versus +61 ± 4 mm Hg, P = .04), whereas the HR increases were similar.

Conclusions

Patients with PD present attenuated increases in SBP and HR during resistance exercise in comparison with healthy subjects. These results support that resistance exercise is safe and well tolerated for patients with PD from a cardiovascular point of view supporting its recommendation for this population.

Level of Evidence

II
Patients With Chronic Spinal Pain Benefit From Pain Neuroscience Education Regardless the Self‐Reported Signs of Central Sensitization: Secondary Analysis of a Randomized Controlled Multicenter Trial
Authors: Malfliet Anneleen , Kregel Jeroen , Meeus Mira , Danneels Lieven , Cagnie Barbara , Roussel Nathalie , Nijs Jo
Published: May 2018

Background

Pain neuroscience education is effective in chronic pain management. Central sensitization (ie, generalized hypersensitivity) is often explained as the underlying mechanism for chronic pain, because of its clinical relevance and influence on pain severity, prognosis, and treatment outcome.

Objectives

To examine whether patients with more or fewer symptoms of central sensitization respond differently to pain neuroscience education.

Design

A secondary analysis of a multicenter, triple‐blind randomized controlled trial.

Setting

University Hospital Ghent and University Hospital Brussels, Belgium.

Patients

120 persons with chronic spinal pain with high or low self‐reported symptoms of central sensitization.

Interventions

Pain neuroscience education or neck/back school. Both interventions were delivered in 3 sessions: 1 group session, 1 online session, and 1 individual session.

Main Outcome Measures

disability (primary), pain catastrophizing, kinesiophobia, illness perceptions, and hypervigilance.

Results

Pain disability did not change in any group (P = .242). Regarding secondary outcomes: significant interaction effects were found for pain catastrophizing (P‐values: P = .02 to P = .05), kinesiophobia (P = .02), and several aspects of illness perceptions (chronicity: P = .002; negative consequences: P = .02; personal control: P = .02; and cyclicity: P = .02). Bonferroni post hoc analysis showed that only the pain neuroscience education group (high and low self‐reported symptoms of central sensitization) showed a significant improvement regarding kinesiophobia (P < .001, medium effect sizes), perceived negative consequence (P = .004 and P < .001, small to medium effect sizes), and perceived cyclicity of the illness (P = .01 and P = .01, small effect sizes). Pain catastrophizing only significantly reduced in people with high self‐reported central sensitization symptoms (P < .05).

Conclusion

Pain neuroscience education is useful in all patients with chronic spinal pain as it improves kinesiophobia and the perceived negative consequences and cyclicity of the illness regardless the self‐reported signs of central sensitization. Regarding pain catastrophizing, pain neuroscience education is more effective in patients with high self‐reported symptoms of central sensitization.

Level of Evidence

I
2355
Authors: Webster Gregory , Olson Rachael S. , Schoppen Zachary J. , Giancola Nicholas , George Alfred L.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Sudden death in the young (SDY) occurs in people between 1 and 40 years of age who do not have a known premortem risk factor for early death. Cardiovascular diseases account for the majority of causes of SDY. Sequencing of genes associated with congenital arrhythmia susceptibility and familial cardiomyopathy reveals pathogenic variants in 30% of postmortem cases (often called “molecular autopsy”). However, better data are needed to determine the prevalence of phenotype and genotype abnormalities in surviving relatives. METHODS/STUDY POPULATION: A retrospective cohort study was performed at a tertiary pediatric center including all subjects with a family history of SDY. Cases were identified using ICD-9 codes (798.1 or .9, V17.41, V17.49, V19.8, V61.07), search of cardiology databases, and by recursive identification of all family members of a subject. Phenotype data was independently reviewed by a pediatric cardiologist. Genotype results were available when obtained by the original treating physician. RESULTS/ANTICIPATED RESULTS: Cardiac evaluations were performed in 279 subjects from 175 families, of whom 117 subjects (42%) were first-degree relatives of the proband. Mean age of the subject at time of evaluation was 9 years (SD 5.9). Most probands were over 18 years at the time of SDY: 1–4 years of age (9%); 5–12 (5%); 13–17 (16%); 18–24 (18%); 25–40 (42%). A final diagnosis was determined in 55 families (20%), and a variant in a gene potentially causative of SDY was discovered in 20/55 (36%) of those families. Variants were classified as 50% pathogenic/likely pathogenic, 50% variants of unknown significance. Cardiac testing (ECG, echo, EST, signal averaged ECG, cardiac MRI, or EP study) was abnormal in 124/279 subjects (44%). Among those with abnormal studies, 57/124 (46%) were from a family where a final diagnosis could be determined (LQT 43%, HCM 21%, ARVC 4%, other cardiomyopathy 19%, WPW 5%, CPVT 2%). However, 67/279 of total subjects (24%) had at least 1 abnormal study and a final diagnosis was not determined in the family. DISCUSSION/SIGNIFICANCE OF IMPACT: An abnormal phenotype is common among relatives referred for cardiac evaluation after SDY. While testing identifies a family diagnosis in 20% of families, many patients have abnormal cardiac testing and no clear diagnosis can be made. An improved postmortem protocol for phenotype testing in relatives of a SDY victim and improved postmortem genetic testing may lead to a higher diagnosis rate and improved risk determination in surviving family members.
2464
Authors: Dowla Shima , Ashraf Ambika , Aslibekyan Stella
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to characterize children with nonalcoholic fatty liver disease (NAFLD) living in the Southeastern United States. METHODS/STUDY POPULATION: This retrospective electronic medical record chart review was conducted on a random sample of 206 children identified with NAFLD. Patients were included if they met the following criteria: confirmed NAFLD through either an ultrasound or liver biopsy or clinical suspicion of fatty liver disease alongside elevated alanine aminotransferase (ALT) in the absence of other etiologies causing elevated transaminases. Patients were excluded if they had hepatitis or other documented liver disease. Data collected at initial presentation included age, gender, ethnicity, height, weight, body mass index (BMI), BMI percentile, blood pressure, HbA1c, aspartate aminotransferase (AST), ALT, γ-glutamyl transferase (GGT), total cholesterol, total triglycerides, low-density lipoprotein, and high-density lipoprotein. Statistical analysis: for descriptive statistics, frequency counts and percentages alongside means, standard deviation, range, min/max values for the continuous variables were calculated. RESULTS/ANTICIPATED RESULTS: This study included 206 children diagnosed with NAFLD. Subjects were primarily male (n=136, 66%) and Caucasian (n=133, 66%), followed by Hispanic (n=42, 21%), Black (n=25, 12%), and Asian (n=2, 1%). Mean age at diagnosis was 12.3±3.5 years. Mean weight (lbs), height (in), and BMI (kg/m2) of subjects at diagnosis were 192±77 lbs, 61.7±6.6 in, 34.6±9.7 kg/m2, respectively. Patients had an average systolic blood pressure of 124±15.4 mmHg and diastolic blood pressure of 69.6±10.6 mmHg. Mean ALT was 91.8±67.2 U/L, AST was 61±38.8 U/L, and GGT was 55.1±64.6 U/L. Mean HbA1c was 5.8±1.4%, cholesterol was 176±36.3 mg/dL, triglycerides were 200±134 mg/dL, low-density lipoprotein was 107.6±32.1 mg/dL, and high-density lipoprotein was 39.9±8.4 mg/dL. DISCUSSION/SIGNIFICANCE OF IMPACT: In addition to having significantly elevated liver enzymes, children with NAFLD had several derangements in their metabolic profile, most notably high triglyceride levels and HbA1c values in the prediabetic range. Although lifestyle modification is the gold standard treatment for NAFLD, pharmacotherapy may need to be included to address metabolic syndrome.
2472
Authors: Phillips Debra , Ngwenya Laura , Huang Michael , Saeng Hong Oi ,   The TRACK-TBI Study Investigators
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: About 75% of the estimated 2.5 million traumatic brain injuries (TBIs) diagnosed annually classify as mild TBI (mTBI); yet cognitive impairments associated with poor patient outcomes can persist for weeks to years. mTBI symptoms are difficult to measure objectively and often remain undiagnosed in the context of an unknown cognitive baseline. Formal neuropsychological exams hold limited utility due to their extensive resource burden. We aimed to define the clinical importance of a 4-question assessment of subjective cognitive complaints (SCC) in predicting return to work at 6 months following mTBI. METHODS/STUDY POPULATION: mTBI participants from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study were included. A self-report affirmation to at least 1 of 4 subjective cognitive symptoms yielded positive SCC. Regression analysis was used to determine factors associated with return to work by 6-months. RESULTS/ANTICIPATED RESULTS: Of 479 enrolled participants with mTBI, 271 (57%) had complete follow-up data. Of which, 156 (58%) had at least sheltered employment at enrollment. Thirty-four (22%) of workers had no return to work at 6-months. Demographics, prior education, presenting injury severity, work status, and post-traumatic stress disorder were associated with return to work. SCC was associated with lower odds of return to work by 6-months (OR=0.11, p=0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: We suggest a concise 4-question assessment of SCC may be clinically relevant in estimating the likelihood of return to work by 6 months post-mTBI.
2311
Authors: Arun Gupta Vedant , Sousa Matthew , Annabathula Rahul , Leung Steve , Sorrell Vincent L.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Cardiac complications are common after hospital admission for sepsis, and elevated troponin has been associated with increased all-cause mortality. However, little is known about clinical or imaging factors that predict these cardiac events. Coronary artery calcification (CAC) is an easily identifiable imaging finding, even on nongated CT scans. The goal of this study is to identify if CAC predicts all cause mortality and acute myocardial infarction. METHODS/STUDY POPULATION: This is a single center, nonconcurrent cohort study including 899 patients who were admitted for sepsis and had a detectable TnI level from January 2013 to December 2013. Patients with a CT scan of the chest or abdomen done for other clinical indications within 6 months of this admission were reviewed for the presence or absence of CAC. Medical records were individually reviewed for mortality and type I acute myocardial infarctions at 1 year. RESULTS/ANTICIPATED RESULTS: In total, 144 patients (mean age 57±14.8 years, 48% female) were included in the analysis. CAC was seen in 59% of these scans. Compared to those without detectable CAC, the CAC group had similar APACHE score (18 vs. 16.6, p=0.259), peak TnI (3.64 vs. 2.11 mg/dL, p=0.363), aspirin (63% vs. 51%, p=0.144), and β blocker use (90% vs. 85%, p=0.357) and had higher statin use (48% vs. 27%, p=0.013). CAC was associated with increased all-cause mortality (59.5% vs. 38.9%, p=0.016) and type I myocardial infarctions (10.6% vs. 1.7%, p=0.039) compared with those without CAC. DISCUSSION/SIGNIFICANCE OF IMPACT: Coronary artery calcification is often seen when patients present with a noncardiac acute illness, such as sepsis, often making a new diagnosis for these patients. Mortality and acute MI after sepsis can be predicted by coronary calcification, and identify patients who should be targeted for therapy and close follow-up.
2544
Authors: Billingsley Hayley , Carbone Salvatore , Canada Justin M. , Buckley Leo , Dixon Dave L. , Kadariya Dinesh , Dessie Sofanit , Van Tassell Benjamin W. , Abbate Antonio , Siddiqui Mohammad
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease in the United States characterized by fat accumulation, inflammation, and fibrosis. Higher amounts of fat-free mass (FFM) and lower amounts of fat mass (FM) have been associated with better outcomes in several chronic diseases, recently also in NASH. Body composition is highly influenced by diet. However, the role of diet on body composition in patients with NASH is largely unknown. We hypothesized that consumption of polyunsaturated fatty acids (PUFA), healthy fatty acids mainly found in fish, nuts, and some vegetable oils, is associated with improved body composition, specifically greater FFM and lower FM, in NASH patients. METHODS/STUDY POPULATION: In total, 13 patients with histologically confirmed NASH underwent body composition testing via bioelectrical impedance analysis to estimate FFM% (% of body weight), FM% (% of body weight), and FFM/FM ratio. PUFA and saturated fat consumption was determined by standardized 5-pass 24-hour dietary recall. Correlations were computed using the Spearman rank test. RESULTS/ANTICIPATED RESULTS: Median body mass index (BMI) was 35.7 kg/m2 (32.8–42.7), median age of the sample was 50 years (46.3–57.3), and 73% were female. Median percent of calories from polyunsaturated fat was 6.8% (5.4–9.6). Percent of calories from PUFA was positively and significantly associated with greater FFM% (R=0.56, p=0.049), lower FM% (R=−0.59, p=0.035), and greater FFM/FM ratio (R=0.58, p=0.037). Additionally, a higher PUFA to saturated fatty acids ratio was also significantly correlated with greater FFM% (R=0.58, p=0.039), lower FM% (R=−0.64, p=0.020), and greater FFM/FM ratio (R=0.57, p=0.043). DISCUSSION/SIGNIFICANCE OF IMPACT: In patients with NASH, the consumption of PUFA is associated with higher FFM and lower FM, which suggests a protective role of these nutrients on body composition. A larger study on patients with NASH is warranted to confirm our findings on PUFA consumption and body composition, as well as to determine whether these effects will improve clinical outcomes.
2164
Authors: Aponte Michell R. , González-Viruet Maribella , Wojna Valerie
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: HIV is a chronic disease that affects the immune system. HIV+ people live more thanks to effective antiretroviral treatments. The scientific data demonstrate that HIV+ is associated to the cognitive impairment presented in the 50% of the patient. The objective of this study is to determine the correlation between emotional dysfunction and perceived stigma in HIV+ women and its effects HIV-associated neurocognitive disorders (HAND). METHODS/STUDY POPULATION: HIV+ women will be recruited form the Hispanic Longitudinal Cohort and evaluated questionnaires for emotional dysfunction and stigma, neuropsychological tests, and MRI. RESULTS/ANTICIPATED RESULTS: We anticipated that women with HIV+ will experience higher levels of emotional dysfunction (ie, fear) and perceived stigma when compared with the control group. Women with HIV infection will present an association between emotional dysfunction most like fear and perceived stigma when compared with the control group. This correlation will be associated with HAND. The women with HIV infection will present circuit integrity dysfunction associated with emotional dysfunction and perceived stigma as determined by DTI and connectivity (MRI). DISCUSSION/SIGNIFICANCE OF IMPACT: HIV stigma and emotional dysfunction have a negative impact in quality of life (QOL). This effect can be improved with several treatment interventions with eventual improvement in adherence, emotional control, and QOL.
2353
Authors: Hoffman Megan , Maas Jennifer , Johnson Lisa
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To increase knowledge and application of clinical research coordinator competencies among Research Professionals at the University of Minnesota. METHODS/STUDY POPULATION: The UMN’s CTSI developed and piloted a Foundations for Research Professionals training program comprised of: a baseline assessment, 7 online modules, 4 in-person training sessions, video and reading assignments and a post assessment, which totaled 30–35 hours of training and covered the following topics: preparing for a study, study management, participant recruitment and engagement, assessing capacity to consent and the informed consent process. This course also provides valuable resources and connections to online references and materials. The competencies for this program were based on work of the Joint Task Force for Clinical Trial Competency. RESULTS/ANTICIPATED RESULTS: 30 clinical research professionals completed the pilot program and averaged an increase of 6.5% from baseline assessment to post assessment. Participants were asked to rate their confidence on a variety of role-based competencies at the time of preassessments and postassessments. Trends show an increase in confidence for all competency areas after completion of the training program. DISCUSSION/SIGNIFICANCE OF IMPACT: Developing a workforce of competent research professionals is integral to improve the efficiency, quality, and ethics of research. The Foundations for Research Professionals training program increased knowledge of clinical research coordinator competencies. We will assess impact on application of the competencies 6 months after completion of the program. Our next steps include offering the training program as a 2-week session on an ongoing basis for new coordinators at the University of Minnesota.
2419
Authors: Carrera Alberto M. , De Jesús-Ojeda Lizbelle , Estape Estela , Soto de Laurido Lourdes E.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Goal—broaden the academic offer to enhance clinical and translational research productivity and cost effectiveness. Objective—implement a distance learning program on conducting proficient research management. METHODS/STUDY POPULATION: Needs assessment attested students’ interest in enrolling and willingness to recruit graduates by the research industry and academia. A master of science in clinical research management and regulatory compliance (MS-CRMRC) was developed using the Core Competency Domains for Clinical Research Professional. Experts from research academia, pharmaceutical industry, composed a Proposal Development Committee. RESULTS/ANTICIPATED RESULTS: Access of a distance learning MS-CRMRC program for students with time constrains. Competent research professional graduates working side by side with the principal investigator on onsite teamwork management, to streamline research processes in compliance to regulations. DISCUSSION/SIGNIFICANCE OF IMPACT: Improvement of clinical and translational research productivity and efficient use of grants funds prevails as a generalized concern. The MS-CRMRC offers an accessible alternative to empower the research enterprise by developing knowledgeable skilled professionals to tackle this need.
2430
Authors: Rubio Doris , Norman Marie , Seto Todd , Quarshie Alexander , Shaheen Magda , Bailey Stephanie , Perry George , Soto Lourdes
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To diversify the biomedical research workforce by training postdoctoral scholars and junior faculty from 6 Minority Serving Institutions (MSIs) on practical research skills such as Critical and Creative Thinking, Formulating the Problem, Asking the Right Question, Grant Writing, and Team Science METHODS/STUDY POPULATION: In collaboration with our partners, we identified 11 topics where trainees lack research funding. Next, we identified instructors for these topics. We converted the topics to online module with modules ranging from 2 to 8 weeks. In working with an online education expert, we developed innovative online training using Moodle as the content management system. Scholars complete readings, videos, self-assessments and participate in discussion board each week. In addition, we have weekly synchronous sessions for each module. All scholars are required to take the grant writing module and 8 other modules. After each module, trainees complete a brief survey to evaluate the module. The leaders at the MSI participated in an intensive face-to-face training session on how to be a career coach so that they could be career coaches for the LEADS Scholars at their home institutions. RESULTS/ANTICIPATED RESULTS: In the first year, we selected 13 LEADS Scholars. All but 3 scholars elected to take every module. The 3 scholars did not enroll in the Peer Reviewing module. Results of the brief survey at the end of each module indicate that the scholars value each of the modules and rate them very highly. When 1 scholar wanted to leave the program, we decided to have a conference call with all of the LEADS Scholars to determine what was working and what was not working with the program. All scholars recognized the value of LEADS. Some scholars felt that the weekly synchronous session was too demanding as they have competing demands on their time. We consulted with the leadership at the MSI and decided to modify the requirements of the program such that every synchronous call was not required for successful completion of the module and to earn a badge. Scholars need to have at least 9 badges to earn a certificate. In addition to the training, we decided that scholars would also benefit from mock reviews of their grants. This will help them submit successful grants. We learned that the best way to serve the needs of the scholars is to work iteratively with the scholars and leadership to develop a successful program that most effectively meets their needs of the scholars and helps them launch a successful career. DISCUSSION/SIGNIFICANCE OF IMPACT: Postdoctoral scholars and junior faculty from MSI need practical research training to help launch their research career. We suspect that this is true of many institutions and plan to develop these modules so that they can be widely disseminated to other institutions.
2078
Authors: Ye Yi , Kim Jihwan , Schmidt Brian L. , Albertson Donna G. , Aouizerat Bradley E.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: We hypothesize that both NGF and TNF-α contribute to oral cancer pain by upregulating pro-nociceptive inflammatory cytokines. METHODS/STUDY POPULATION: In total, 48 oral cancer patients were evaluated and their pain scores were measured using a validated oral cancer pain questionnaire. Presence of perineural invasion (PNI) was identified from patients’ pathology reports. We utilized The NIH Cancer Genome Atlas (TCGA) Head and Neck Cancer cohort to investigate the association between pain and genes related to NGF, TNF-α, and their receptors (TRKA, P75, TNF-α receptor 1, and TNF-α receptor 2) in oral cancer samples by employing PNI as a surrogate for pain. Demographic characteristics, clinical characteristics, and genes were analyzed using logistic regression models. A xenograft cancer pain model was created by inoculating human oral cancer cells (HSC-3) into the mouse hind paw. Mice (n=6 per group) were treated with anti-NGF alone, anti-TNF-α alone, a combination of anti-NGF and anti-TNF-α, or PBS (vehicle control). Nociceptive behaviors were measured using an electronic paw withdrawal assay. Paw volume was measured using a plethysmometer. Cytokines in the paw tissues were measured using a multiplex assay kit with 28 cytokines. RESULTS/ANTICIPATED RESULTS: Oral cancer patients with PNI report significantly more pain compared with patients without PNI in our patient cohort (p<0.05). From analysis of TCGA data, we found that PNI is significantly associated with lymphovascular invasion, pathological nodal invasion, and pathological tumor staging (all p<0.05). In adjusted models, we observed that the NGF receptor p75NTR (NGFR) and the TNF-α receptor 1 (TNFRSF1A) were associated with PNI (both p<0.05) and significantly correlated to each other (r=0.25, p<0.001). High levels of TNF-α were present in HSC-3 cell lines and the mouse xenograft cancers. In mice with cancer pain, combined treatment with anti-NGF and anti-TNF-α together provided more effective pain control compared with either anti-NGF or anti-TNF-α treatment alone (p<0.05). We found significantly increased levels of MIP3a, IL-1b, IL-2, IL-4, IL-28b, IL-23, IL17a, IL-31, and IL-33 in cancer mice compared with normal mice (all p<0.05). The combination therapy significantly reduced cytokines MIP3a, IL-1b, IL-4, IL-28b, IL-31, and IL-33 (all p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: We show that targeting both NGF and TNF-α provides more effective pain relief in an oral cancer model. These results suggest that therapeutic strategies aimed at both pathways could yield improved pain management for oral cancer patients.
2092
Authors: Evan Gruenbaum Shaun , Dhaher Roni , Rapuano Amedeo , Eid Tore
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: We previously developed a translationally relevant model of temporal lobe epilepsy (TLE) in which glutamine synthetase is irreversibility inhibited by methionine sulfoximine (MSO), resulting in spontaneous seizures and dentate hilar neuron loss. The objective of this study was to determine the effects of chronic BCAA ingestion on neuronal viability in the dentate hilus in the MSO model of TLE. METHODS/STUDY POPULATION: Sixteen rats were randomly divided into 2 groups: 8 rats drank a 4% aqueous solution of all 3 BCAAs (BCAA group) ad libitum for 31 days, and the other 8 rats drank regular water (control group) for the same period. After 10 days of drinking, a microinfusion cannula (Alzet osmotic pump, model 2004) was surgically implanted in the right dentate gyrus to continuously infuse MSO at a rate of 0.625 g/hour for 28 days. After 31 days of drinking, rats were perfused transcardially with 0.9% NaCl followed by 4% paraformaldehyde in phosphate buffer. The brains were removed and fixed, sectioned on a Vibratome at 50-μm thickness, and were mounted on a gelatin-coated slides and stained with NeuN. Neuron counts in the hilar region were performed ipsilateral and contralateral to the infusion site using a stereological technique. RESULTS/ANTICIPATED RESULTS: Rats in the BCAA group had 37% fewer neurons in the ipsilateral dentate hilus than the control group (5.8×10−4±6.8×10−5 vs. 8.9×10−4±5.6×10−5 cells, respectively, p<0.01). Similarly, rats in the BCAA group had 39% fewer neurons in the contralateral dentate hilus than the control group (5.0×10−4±5.8×10−5 vs. 7.0×10−4±3.4×10−5 cells, respectively, p=0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that chronic ingestion of BCAAs aggravates hilar neuronal loss in a translationally relevant rodent model of MTLE. This study gives important insight into how BCAAs may affect neuronal viability. Although the role of BCAAs on seizure activity is poorly understood, these results suggest that BCAAs may play an important role in neurochemical modulation and neurotoxicity.
2371
Authors: Varkki Chacko Ravi , Kim Kenny , Jung Kate , Shulman Gordon , Corbetta Maurizio , Leuthardt Eric
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Attention is a cognitive function that binds perception and behavior. Recent evidence suggests that attention involves phase-amplitude coupling (PAC) of neural signals. PAC occurs when the amplitude of one frequency (frequency for amplitude) is maximal at particular phases of another frequency (frequency for phase). However, some studies suggest PAC improves attention, while others maintain that PAC inhibits attention. The present study seeks to determine whether PAC promotes or inhibits neural signals that underlie attention. METHODS/STUDY POPULATION: Six adult epilepsy patients with implanted electrodes participated in a cued attention task. Subjects participated in a cued attention task where they oriented attention to one side of the screen at a time and discriminated between stimuli as fast as possible with mouse clicks. Perception-related electrodes discriminated the location and/or shape of the target. These were determined with a cluster-based permutation test. Behavior-related electrodes predicted reaction time (RT) with neural activity prior to target appearance. These were determined with correlations between PAC and RT. PAC was calculated using the modulation index (MI). RESULTS/ANTICIPATED RESULTS: We found 47 perception-related electrodes that discriminated location and/or shape of target (p<0.05, FDR corrected). We found 27 behavior-related electrodes where PAC prior to the target predicted RT (p<0.05 FDR corrected). There was little overlap between the perception-related and behavior-related electrodes (3%). PAC also did not discriminate left-sided and right-sided cues. In addition, behavior-related electrodes had less local neural activity and higher PAC during the period of cued attention than perception-related electrodes. DISCUSSION/SIGNIFICANCE OF IMPACT: PAC minimally facilitates perceptual aspect of visual attention. However, PAC facilitate response speed. We suggest that PAC might improve response speed by “quieting” task irrelevant neural activity. For the same reason, PAC is absent in electrodes that are actively processing meaningful streams of visual data. These findings highlight separable aspects of the human attention system and how PAC contributes to both. Future directions include determining differences in PAC for attentional disorders like ADHD and neurological neglect.
2117
Authors: Angkustsiri Kathleen , Simon Tony J. , Hastings Paul D.
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Chromosome 22q11.2 deletion syndrome (22q) has a prevalence almost as common as Down syndrome. 22q is well known for medical complications, including congenital heart disease and immune dysfunction. However, children with 22q also have borderline cognitive abilities, are at high risk for ADHD and anxiety, and have poor independent living skills (adaptive function). Parenting is one modifiable factor that has been found in typically developing populations to promote independent functioning and protect against the development of anxiety disorders. This study investigates the associations between parenting, anxiety, and adaptive functioning in 22q. METHODS/STUDY POPULATION: Parent-child (ages 4–11) dyads participated in an ongoing study involving observed parenting during challenging tasks plus questionnaires of parenting, child anxiety, and child functioning. In total, 52 dyads [22q=25; typical development (TD)=27] have enrolled to date. Parents completed questionnaires, including the Parenting Styles and Dimensions Questionnaire (PSDQ), Spence Children’s Anxiety Scale, and Adaptive Behavior Assessment System for Children (ABAS-II). PSDQ dimensions of interest included Parental Psychological Control (PPC: the management of child behavior through the manipulation of emotions, expectations, and independence), Authoritative, Authoritarian, and Permissive, and the subscales of these broad dimensions. Scores were compared using t-tests and multiple regression models were used to investigate the relationships between 1-parenting and anxiety and 2-parenting and adaptive function. RESULTS/ANTICIPATED RESULTS: Mean age was 7.8+2.1 years. Full Scale IQ (TD: 112.3 vs. 22q: 82; p<0.001) and ABAS-II Global Adaptive Composite (TD: 102.7 vs. 22q: 69.2; p<0.001) were significantly higher in the TD group. Parents in the 22q group reported higher levels of PSDQ PPC (22q: 2.3 vs. TD: 2.1; p=0.06), specifically overprotection (22q: 3.7 vs. TD: 3.3; p=0.04), and lower Authoritative parenting (22q: 4.1 vs. TD: 4.4; p=0.03), across the subscales. There were no differences in Authoritarian or Permissive parenting. Children with 22q had higher Spence Total Anxiety scores (22q: 62.5 vs. TD: 47.4; p<0.001). Self-reported PPC and group (R2=0.3, F3,48=8.1, p<0.001) predicted child anxiety with a main effect of PPC (β=16, p=0.02). Group tended to moderate the association between PPC and anxiety (β=−17.5, p<0.10), with PPC predicting anxiety for the 22q group (r=0.35, p<0.09), but not the TD group (r=−0.08, ns). At this time, a relationship between PPC and child ABAS-II GAC in 22q (r=−0.14; p=0.5) is not identified. DISCUSSION/SIGNIFICANCE OF IMPACT: Children with 22q are at high risk for anxiety and poor adaptive outcomes. These results suggest that parents of children with 22q use higher levels of PPC, which is correlated with increased child anxiety. These analyses also provide support for parenting interventions to improve anxiety in children with 22q and possibly mitigate the serious mental health risk in this population.
2181
Authors: Neu Matthew , Knight Sara
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Although the clinical utility of whole genome sequencing (WGS) is increasing, a gap exists between what WGS can deliver in quantity of genomic information and what results can be interpreted that patients and community members would find meaningful. Given the potential for incidental findings and variants of uncertain significance, an emphasis should be placed on understanding patient preferences towards receiving WGS results. To identify the current knowledge base on WGS preferences, we performed a scoping review. METHODS/STUDY POPULATION: A search on PubMed using terms “WES,” “WGS,” “genome sequencing,” ”attitudes,” and “preferences” identified survey research between 2012 and 2016. Summaries of population, sample, variables, and results were tabulated. RESULTS/ANTICIPATED RESULTS: Of 13 studies identified, 6 surveyed community members, 6 included medical professionals, and 2 surveyed cohorts with a specific medical condition. Only 1 study used a nationally representative sample and no study focused on a medically underserved population. Patients were most interested in receiving medically actionable results, yet preferred to have access to all available data if desired. Genetics professionals are more conservative with the return of incidental and uncertain findings. DISCUSSION/SIGNIFICANCE OF IMPACT: Existing surveys have limited representation of the US public. Future studies focused on medically underserved populations would provide a deeper understanding of attitudes and preferences toward WGS.
2349
Authors: Han Rowland , Yan Yan , Kulkarni Abhaya , Park T.S. , Smyth Matthew , Strahle Jennifer , Limbrick David
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: To create a composite index, referred to as the Pediatric Hydrocephalus Severity Index (PHSI), to classify the severity of disease at baseline and predict outcomes among children treated for hydrocephalus. METHODS/STUDY POPULATION: The Hydrocephalus Outcome Questionnaire will be administered in person or online to the parents of 150 patients between the ages of 5 and 18 years who are followed at the Neurosurgery Clinic at St. Louis Children’s Hospital for hydrocephalus. Patients must have been diagnosed and treated for hydrocephalus at least 6 months prior to the survey date. Potential participants are excluded if their health status changed during the 4 weeks prior to survey date, as determined by the child’s parents. Potential risk factors (see anticipated results) will be identified on retrospective medical record review. We will create a clinical prediction rule, called the PHSI, to stratify patients on likelihood of experiencing a poor long-term outcome after surgical treatment. Participants will be classified as “good” or “poor” outcome based on thresholds set for questionnaire results. We will use a combination of bivariate analysis and clinical reasoning to restrict the number of factors for further analysis, and multivariate logistic regression to build a predictive model for poor outcome. Creation of the PHSI will involve assigning integer values to adjusted odds ratios for significant risk factors at a 95% confidence level. RESULTS/ANTICIPATED RESULTS: Risk factors that we anticipate will be predictive of long-term clinical outcome include signs and symptoms at onset (bulging fontanel, splayed sutures, papilledema, up-gaze palsy, headache, vomiting, lethargy), head circumference above the 97th percentile, frontal-occipital horn ratio greater than 0.4, etiology of meningitis or neonatal intraventricular hemorrhage, central nervous system comorbidities (seizures, Chiari malformation, scoliosis, periventricular leukomalacia), preoperative infection or sepsis, and frequent shunt revisions or infections. We hypothesize that a PHSI will be a valuable tool for stratifying patients in future research studies, as well as aiding prognosis in clinical situations. DISCUSSION/SIGNIFICANCE OF IMPACT: A validated composite PHSI would be a major advance in clinical hydrocephalus research and practice. A PHSI would allow investigators to stratify patients based on initial presentation for clinical research studies, which may in turn lead to the establishment of more standardized treatment guidelines. It would also facilitate studies investigating differential utilization of healthcare resources based on disease severity. Clinically, a PHSI would better equip physicians to counsel parents on what to expect for their child or future healthcare resource requirements.
2321
Authors: Ota Koji , Zhou Dalee , Zippin Jonathan
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: Our objective is to study the role of soluble adenylyl cyclase in the melanocyte regulation of pigment in response to ultraviolet radiation. Melanocytes are specialized cells that produce melanin in organelles called melanosomes, and melanin determines the pigmentation of hair and skin. cAMP is a master regulator of pigmentation and transmembrane class of adenylyl cyclases are essential for expression of important enzymes involved in melanogenesis. However, pigmentation is also controlled by melanosomal pH, which regulates melanogenesis, tyrosinase activity, and melanosome maturation. The relationship between melanosomal pH and cAMP has been elusive. Soluble adenylyl cyclase is a noncanonical source of cAMP that is not responsive to G proteins but rather functions as a pH sensor. We recently demonstrated that loss of soluble adenylyl cyclase (sAC) activity leads to increased melanosomal pH as well as increased pigmentation in cells and hair. We expanded our research to investigate the role of sAC in the intrinsic response of melanocytes to ultraviolet radiation. METHODS/STUDY POPULATION: We utilized sACfl/fl (wild type) and sACKO mouse melanocytes and compared their change in pigmentation in response to ultraviolet radiation. Melanin was used as a measure of pigmentation. We irradiated these cells at differing doses of UVB (0, 1, 2, or 3 mJ/cm2) daily for 3 days. After UVB treatment, cells were observed and the surviving cell numbers were determined. Cells were then analyzed for melanin content using spectroscopy. RESULTS/ANTICIPATED RESULTS: We found that while both sACfl/fl and sACKO cells had increased melanin content in response to UVB, the melanin content of sACKO cells increased more compared with sACfl/fl cells (p=0.001 at daily dose of 3 mJ/cm2). In addition, sACKO cells required less UVB dose to induce a response. We also observed that sACKO cells show increased cell death compared with sACfl/fl cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Although both sACfl/fl and sACKO cells can induce melanin production in response to UV, our results suggest that sACKO cells are more sensitive. We believe that this increased response in sACKO cells is due to increased melanosomal pH. In addition, sACKO cells show increased cell death, suggesting that sAC is important in the damage response secondary to UV exposure. UV plays a wide range of roles in skin biology such as contributing to cancer risk and pigmentation. Since pigmentation is essential for the protection of the skin from UV insult, further investigation of possible mechanisms in which sAC can influence pigmentation in response to UV is warranted.
2427
Authors: Maimouni Sara , Lee Mi-Hye , Byers Stephen
Published: May 2018

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to examine bioenergetic phenotype of retinoic acid receptor responder 1 (RARRES1)-depleted epithelial cells and to facilitate the discovery of personalized metabo-therapeutics in the context of cancers characterized with loss of or low expression of RARRES1. METHODS/STUDY POPULATION: Anoikis assay and annexinV labeling were used to assess drug resistance and apoptotic phenotype in RARRES1-depleted epithelial cells. Metabolomics, AMP kinase activity, mito-tracker, and extracellular flux assays were used to examine the bioenergetic profile of RARRES1-depleted epithelial cells. Extracellular flux assays were used to assess the phenotype of RARRES1-depleted epithelial cells treated with or without metformin. RESULTS/ANTICIPATED RESULTS: RARRES1 is a major regulator of mitochondrial function. Its depletion in tumors induces an oxidative phosphorylation dependent phenotype and subsequently increases ATP abundance in the cell, enhances anabolic pathways and increases survival. Treatment with FDA approved mitochondrial respiration inhibitor, metformin, reversed the metabolic phenotype of RARRES1 depleted-epithelial cells. Metformin could be the ideal therapeutics to reduce tumor burden in cancers with loss of or low expression of RARRES1. DISCUSSION/SIGNIFICANCE OF IMPACT: Bioenergetic dynamics are emerging as a basis for understanding the pathology of cancer. The malignancy progresses as its metabolic pattern and mitochondrial respiration become more dysfunctional. The regulatory pathways of bioenergetic dynamics are currently poorly understood, and the characterization of proteins implicated in those processes must be assessed. One understudied protein and tumor suppressor is RARRES1. RARRES1 is induced by retinoic acid (a major metabolic regulator) and functions as a putative carboxypeptidase inhibitor. Understanding the connection between this carboxypeptidase inhibitor and intermediary metabolism will enlighten our understanding of the bioenergetic profile of cells and facilitate the discovery of personalized metabo-therapeutics in the context of cancer.