Triangle Universities Nuclear Laboratory

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    An assessment of frailty as a tool for risk stratification in adult spinal deformity surgery.

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    OBJECTIVE The goal of this study was to analyze the value of an adult spinal deformity frailty index (ASD-FI) in preoperative risk stratification. Preoperative risk assessment is imperative before procedures known to have high complication rates, such as ASD surgery. Frailty has been associated with risk of complications in trauma surgery, and preoperative frailty assessments could improve the accuracy of risk stratification by providing a comprehensive analysis of patient factors that contribute to an increased risk of complications. METHODS Using 40 variables, the authors calculated frailty scores with a validated method for 417 patients (enrolled between 2010 and 2014) with a minimum 2-year follow-up in an ASD database. On the basis of these scores, the authors categorized patients as not frail (NF) ( 0.5 points). The correlation between frailty category and incidence of complications was analyzed. RESULTS The overall mean ASD-FI score was 0.33 (range 0.0-0.8). Compared with NF patients (n = 183), frail patients (n = 158) and SF patients (n = 109) had longer mean hospital stays (1.2 and 1.6 times longer, respectively; p < 0.001). The adjusted odds of experiencing a major intraoperative or postoperative complication were higher for frail patients (OR 2.8) and SF patients ( 4.1) compared with NF patients (p < 0.01). For frail and SF patients, respectively, the adjusted odds of developing proximal junctional kyphosis (OR 2.8 and 3.1) were higher than those for NF patients. The SF patients had higher odds of developing pseudarthrosis (OR 13.0), deep wound infection (OR 8.0), and wound dehiscence (OR 13.4) than NF patients (p < 0.05), and they had 2.1 times greater odds of reoperation (p < 0.05). CONCLUSIONS Greater patient frailty, as measured by the ASD-FI, was associated with worse outcome in many common quality and value metrics, including greater risk of major complications, proximal junctional kyphosis, pseudarthrosis, deep wound infection, wound dehiscence, reoperation, and longer hospital stay

    Persistent quantum beats and long-distance entanglement from waveguide-mediated interactions.

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    We study photon-photon correlations and entanglement generation in a one-dimensional waveguide coupled to two qubits with an arbitrary spatial separation. To treat the combination of nonlinear elements and 1D continuum, we develop a novel Green function method. The vacuum-mediated qubit-qubit interactions cause quantum beats to appear in the second-order correlation function. We go beyond the Markovian regime and observe that such quantum beats persist much longer than the qubit lifetime. A high degree of long-distance entanglement can be generated, increasing the potential of waveguide-QED systems for scalable quantum networking

    The health impact of adult cervical deformity in patients presenting for surgical treatment: Comparison to United States population norms and chronic disease states based on the EuroQuol-5 dimensions questionnaire

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    BACKGROUND: Although adult cervical spine deformity (ACSD) is associated with pain and disability, its health impact has not been quantified in comparison to other chronic diseases. OBJECTIVE: To perform a comparative analysis of the health impact of symptomatic ACSD to US normative and chronic disease values using EQ-5D (EuroQuol-5 Dimensions questionnaire) scores. METHODS: ACSD patients presenting for surgical treatment were identified from a prospectively collected multicenter database. Baseline demographics and EQ-5D scores were collected and compared with US normative and disease state values. RESULTS: Of 121 ACSD patients, 115 (95%) completed the EQ-5D (60% women, mean age 61 years, previous spine surgery in 44%). Diagnoses included kyphosis with mid-cervical (63.4%), cervico-thoracic (23.5%), or thoracic (8.7%) apex and primary coronal deformity (4.3%). The mean ACSD EQ-5D index was 0.511 (standard definition = 0.224), which is 34% below the bottom 25th percentile (0.780) for similar age- and gender-matched US normative populations. Mean ACSD EQ-5D index values were worse than the bottom 25th percentile for several other disease states, including chronic ischemic heart disease (0.708), malignant breast cancer (0.708), and malignant prostate cancer (0.708). ACSD mean index values were comparable to the bottom 25th percentile values for blindness/low vision (0.543), emphysema (0.508), renal failure (0.506), and stroke (0.463). EQ-5D scores did not significantly differ based on cervical deformity type (P =.66). CONCLUSION: The health impact of symptomatic ACSD is substantial, with negative impact across all EQ-5D domains. The mean ACSD EQ-5D index was comparable to the bottom 25th percentile values for blindness/low vision, emphysema, renal failure, and stroke

    An innovative educational program for addressing health disparities in translational cancer research.

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    North Carolina Central University (NCCU) and Duke Cancer Institute implemented an NCI-funded Translational Cancer Disparities Research Partnership to enhance translational cancer research, increase the pool of underrepresented racial and ethnic group (UREG) researchers in the translational and clinical research workforce, and equip UREG trainees with skills to increase diversity in clinical trials. The Cancer Research Education Program (C-REP) provided training for UREG graduate students and postdoctoral fellows at Duke and NCCU. An innovative component of C-REP is the Translational Immersion Experience (TIE), which enabled Scholars to gain knowledge across eight domains of clinical and translational research (clinical trials operations, data monitoring, regulatory affairs, UREG accrual, biobanking, community engagement, community outreach, and high-throughput drug screening). Program-specific evaluative metrics were created for three broad domains (clinical operations, basic science/lab research, and population-based science) and eight TIE domains. Two cohorts (n = 13) completed pre- and post-surveys to determine program impact and identify recommendations for program improvement. Scholars reported statistically significant gains in knowledge across three broad domains of biomedical research and seven distinct areas within TIE. Training in translational research incorporating immersions in clinical trials operation, biobanking, drug development, and community engagement adds value to career development of UREG researchers

    Sucrose Nonfermenting 1-Related Protein Kinase 1 Phosphorylates a Geminivirus Rep Protein to Impair Viral Replication and Infection.

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    Geminiviruses are single-stranded DNA viruses that infect a wide variety of plants and cause severe crop losses worldwide. The geminivirus replication initiator protein (Rep) binds to the viral replication origin and catalyzes DNA cleavage and ligation to initiate rolling circle replication. In this study, we found that the Tomato golden mosaic virus (TGMV) Rep is phosphorylated at serine-97 by sucrose nonfermenting 1-related protein kinase 1 (SnRK1), a master regulator of plant energy homeostasis and metabolism. Phosphorylation of Rep or the phosphomimic S97D mutation impaired Rep binding to viral DNA. A TGMV DNA-A replicon containing the Rep S97D mutation replicated less efficiently in tobacco (Nicotiana tabacum) protoplasts than in wild-type or Rep phosphorylation-deficient replicons. The TGMV Rep-S97D mutant also was less infectious than the wild-type virus in Nicotiana benthamiana and was unable to infect tomato (Solanum lycopersicum). Nearly all geminivirus Rep proteins have a serine residue at the position equivalent to TGMV Rep serine-97. SnRK1 phosphorylated the equivalent serines in the Rep proteins of Tomato mottle virus and Tomato yellow leaf curl virus and reduced DNA binding, suggesting that SnRK1 plays a key role in combating geminivirus infection. These results established that SnRK1 phosphorylates Rep and interferes with geminivirus replication and infection, underscoring the emerging role for SnRK1 in the host defense response against plant pathogens

    An Uncommon Cause Of Altered Mental Status In A Patient With Systemic Lupus Erythematosus

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    Introduction: Altered mental status is one of the most common presentations that leads to an admission to intensive care unit. Posterior reversible encephalopathy syndrome (PRES), which is commonly encountered in association with various medical conditions, is an uncommon but probably under-diagnosed cause of this presentation. Case report: A 51-year-old woman was admitted to our ICU because of alteration of consciousness. She was in her usual state of health the night before although she complained of a mild headache. She became unarousable on the following morning and her husband immediately brought her to our institution. She had a significant history of SLE that was diagnosed five years ago with malar rash, photosensitivity rash, polyarthritis, positive ANA and anti-smith antibody. Her only current medication was hydroxychloroquine. Upon admission, she was found to be hypertensive with BP of 170/90 mmHg. Neurological examination was remarkable for GCS of five without any focal neurological deficit. Laboratory investigations were remarkable for an elevation of creatinine (2.4 mg/dL from baseline of 1.0 mg/dL) and an abnormal urinalysis with numerous dysmorphic RBCs and WBCs. CT brain demonstrated ill-defined hypodensity in the subcortical white matter of both posterior parietal lobes. A subsequent MRI brain revealed T2 hyper-intense signal in cortex and subcortical white matter of the same lobes (Figure). She was diagnosed with PRES and was immediately treated with intravenous labetalol. Her BP gradually came down to normal range and her mental status gradually improved as she became completely alert and oriented on the fourth day of admission. She underwent renal biopsy during this admission which revealed type IV lupus nephritis. Treatment with steroid and cyclophosphamide was initiated. Comment: Patient with PRES usually presents with headache, seizure, nausea, confusion or coma in a more severe case. A broad range of medical conditions, including hypertension, eclampsia, use of immunosuppressive agent, and autoimmune disorders has been implicated as causes of this syndrome. Neuroimaging is crucial to the diagnosis. Typical findings include symmetrical edema of white matter predominantly in the parieto-occipital lobes. These abnormalities are best depicted by MRI (hyper-intense signal on T2 and FLAIR technique). Prognosis is favorable as the neurological deficit is usually reversible in days to weeks after blood pressure control, as seen in this patient. However, delay in initiating the appropriate treatment can lead to a permanent neurological damage. Thus, physician should have a high index of suspicion for this syndrome especially in patients with known associated illnesses

    Plasmonic Nanoplatforms and Surface-enhanced Raman Spectroscopy for in vivo Sensing: from Plants to Animals

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    In this thesis, we present an overview of the development and application of surface-enhanced Raman scattering (SERS) and plasmonic nanoplatforms developed in our laboratory for sensing applications. Plasmonic nanomaterials, such as gold nanostars (AuNS) a hallmark particle pioneered by the Vo-Dinh group, increase inherently weak Raman signals from molecules providing an intense and unique SERS spectrum allowing for targets to be sensitively detected and easily identified. For this work, we investigated biosensing in plants and murine models using plasmonic nanoplatforms. In the first part of the work, we developed a wide variety of plasmonics-active substrates and nanoparticle-based sensing systems including inverse molecular sentinels (iMS) utilizing two platforms silver-coated gold nanostars (AuNS@Ag) and nanorods (AuNR@Ag). The AuNS@Ag were decorated onto fiber-optrodes for chemical fiber sensing and monitoring of genomic biomarkers in plants for renewable bioenergy research. Rapid chemical sensing of illegal food additives proves to be a challenge at the site of exposure thus requiring the need for in situ fiber detection. Also, the fiber sensing approach is necessary for facilitating field analyses of microRNAs since the gold standard methods can only be performed in laboratory settings on the timescale of days. The fiber-optrodes were capable of functioning as chemical and biological sensors for analytes such as illegal food additives and plant microRNAs. The work is also aimed at microRNA sensing but directly inside of plant tissue with spatial and temporal resolutions that PCR cannot achieve. Thus, the silver-coated nanorod (AuNR@Ag) was developed with the purpose of infiltrating plant cells. We designed the plasmonic nanorod to have a dimension smaller than the plant cell wall exclusion limit to permit cellular uptake, while improving SERS properties through a silver coating on the particle. We confirmed particle uptake in plant cells using a multi-modal approach consisting of confocal microscopy, transmission electron microscopy, and x-ray fluorescence microscopy. Dye coated AuNR@Ag served as a strong contrast agent for two-photon imaging, photoacoustic imaging, and Raman mapping during in vivo experiments in Tobacco leaves. The AuNR@Ag was further functionalized with iMS technology and was applied for sensing for microRNA targets in leaf tissue. To our knowledge, this is the first demonstration of intracellular SERS sensing in vivo of leaf tissue treated with the AuNR@Ag nanoprobes. In another chapter of the work, we used standoff shifted-excitation difference spectroscopy (SERDS) for remote detection of biomarkers in plants under ambient light conditions. Monitoring plant molecular targets in field conditions remain an elusive task for standard optical methods such as fluorescence and Raman spectroscopy. However, recent developments in nanoprobe technology and remote optical techniques have ushered in a novel mechanism for highly specific molecular monitoring of living organisms at different stages of growth and other phenotypic cues. We have successfully demonstrated nanoprobe detection in a live plant leaf at a minimal distance of 2 meters. This work brings the remote monitoring of plant genetic biomarkers closer to in vivo tracking and analysis without the need of a dark laboratory as required by traditional optical sensing. Applications of plasmonic AuNS for bioimaging of tumors in combination with SERDS is also presented. During surgery accurately removing the entire tumor without harming surrounding healthy tissue is critical; however, due to the lack of intraoperative imaging techniques, surgeons rely on visual and physical inspection to identify tumors. To address this problem, we established the first use of SERDS for in vivo tumor detection in a murine model under ambient light conditions, mimicking an intraoperative environment.   </p

    GEMS Phase I Report: Oyster Reef Restoration

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    Billions of dollars will be spent on large-scale restoration of Gulf ecosystems over the coming decades, but there is no shared platform to guide assessment and reporting of restoration progress and effectiveness for the broad set of environmental, social, and economic goals shared by the many institutions working in the Gulf. The diversity of these goals—including habitat restoration, water quality improvement, marine resource protection, community resilience, and economic revitalization—means that a variety of metrics are needed to fully evaluate the effectiveness of restoration projects. A set of common models and metrics relevant across projects, programs, and locations can facilitate effective project planning and evaluation. While there are existing efforts to collate and standardize ecological and biophysical metrics for Gulf restoration projects (GOMA Monitoring Community of Practice; NRDA Monitoring and Adaptive Management Manual), there is no current effort to do the same for the social, economic, and human well-being outcomes of restoration. This project aims to do that. The GEMS (Gulf of Mexico Ecosystem Service Logic Models and Socio-Economic Indicators) project aims to advance standardized metrics of restoration success by developing ecosystem service logic models (ESLMs) with stakeholders from the five Gulf states, relevant federal agencies, and technical experts. ESLMs trace the effects of restoration strategies as they influence ecological and social systems to create outcomes that are important to people. The use of logic models is recommended by the National Academies of Science as best practice for monitoring plan design; these models can provide a practical and transferable approach for measuring success at different scales. The GEMS team will develop ESLMs and metrics for a wide range of coastal restoration approaches over the course of the project. This report presents the results of the first phase of the GEMS project, which focused on oyster reef restoration. The Phase II report of the GEMS project identifies metrics available to monitor the social and economic outcomes of a wide variety of coastal projects funded in the Gulf, using ESLMs to illustrate how these projects’ impacts cascade through the biophysical system to result in social and economic outcomes

    METROPOLIZED FOREST RECOMBINATION FOR MONTE CARLO SAMPLING OF GRAPH PARTITIONS

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    We develop a new Markov chain on graph partitions that makes relatively global moves yet is computationally feasible to be used as the proposal in the Metropolis-Hastings method. Our resulting algorithm is able to sample from a specified measure on partitions or spanning forests. Being able to sample from a specified measure is a requirement of what we consider as the gold standard in quantifying the extent to which a particular map is a gerrymander. Our proposal chain modifies the recently developed method called recombination (ReCom), which draws spanning trees on joined partitions and then randomly cuts them to repartition. We improve the computational efficiency by augmenting the statespace from partitions to spanning forests. The extra information accelerates the computation of the forward and backward proposal probabilities which are required for the Metropolis-Hastings algorithm. We demonstrate this method by sampling redistricting plans on several measures of interest and find promising convergence results on several key observables of interest. We also explore some limitations in the measures that are efficient to sample from and investigate the feasibility of using parallel tempering to extend this space of measures

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