Lux et Lex: Volume 2, Number 2

This issue of Lux et Lex, a publication of the Chester Fritz Library at the University of North Dakota, was published in April 1992

Efferent projections of C3 adrenergic neurons in the rat central nervous system

C3 neurons constitute one of three known adrenergic nuclei in the rat central nervous system (CNS). While the adrenergic C1 cell group has been extensively characterized both physiologically and anatomically, the C3 nucleus has remained relatively obscure. This study employed a lentiviral tracing technique that expresses green fluorescent protein behind a promoter selective to noradrenergic and adrenergic neurons. Microinjection of this virus into the C3 nucleus enabled the selective tracing of C3 efferents throughout the rat CNS, thus revealing the anatomical framework of C3 projections. C3 terminal fields were observed in over 40 different CNS nuclei, spanning all levels of the spinal cord, as well as various medullary, mesencephalic, hypothalamic, thalamic, and telencephalic nuclei. The highest densities of C3 axon varicosities were observed in Lamina X and the intermediolateral cell column of the thoracic spinal cord, as well as the dorsomedial medulla (both commissural and medial nuclei of the solitary tract, area postrema, and the dorsal motor nucleus of the vagus), ventrolateral periaqueductal gray, dorsal parabrachial nucleus, periventricular and rhomboid nuclei of the thalamus, and paraventricular and periventricular nuclei of the hypothalamus. In addition, moderate and sparse projections were observed in many catecholaminergic and serotonergic nuclei, as well as the area anterior and ventral to the third ventricle, Lamina X of the cervical, lumbar, and sacral spinal cord, and various hypothalamic and telencephalic nuclei. The anatomical map of C3 projections detailed in this survey hopes to lay the first steps toward developing a functional framework for this nucleus

Detecting Illicit Drug Ads in Google+ Using Machine Learning

Opioid abuse epidemics is a major public health emergency in the US. Social media platforms have facilitated illicit drug trading, with significant amount of drug advertisement and selling being carried out online. In order to understand dynamics of drug abuse epidemics and design efficient public health interventions, it is essential to extract and analyze data from online drug markets. In this paper, we present a computational framework for automatic detection of illicit drug ads in social media, with Google+ being used for a proof-of-concept. The proposed SVM- and CNN-based methods have been extensively validated on the large dataset containing millions of posts collected using Google+ API. Experimental results demonstrate that our methods can efficiently identify illicit drug ads with high accuracy. Both approaches have been extensively validated using the dataset containing millions of posts collected using Google+ API. Experimental results demonstrate that both methods allow for accurate identification of illicit drug ads

A Single Dermatome Clinical Prediction Rule for Independent Walking 1 Year After Spinal Cord Injury

Objective: To derive and validate a simple, accurate CPR to predict future independent walking ability after SCI at the bedside that does not rely on motor scores and is predictive for those initially classified in the middle of the SCI severity spectrum. Design: Retrospective cohort study. Binary variables were derived, indicating degrees of sensation to evaluate predictive value of pinprick and light touch variables across dermatomes. The optimal single sensory modality and dermatome was used to derive our CPR, which was validated on an independent dataset. Setting: Analysis of SCI Model Systems dataset. Participants: Individuals with traumatic SCI. The data of 3679 participants (N=3679) were included with 623 participants comprising the derivation dataset and 3056 comprising the validation dataset. Interventions: Not applicable. Main Outcome Measures: Self-reported ability to walk both indoors and outdoors. Results: Pinprick testing at S1 over lateral heels, within 31 days of SCI, accurately identified future independent walkers 1 year after SCI. Normal pinprick in both lateral heels provided good prognosis, any pinprick sensation in either lateral heel provided fair prognosis, and no sensation provided poor prognosis. This CPR performed satisfactorily in the middle SCI severity subgroup. Conclusions: In this large multi-site study, we derived and validated a simple, accurate CPR using only pinprick sensory testing at lateral heels that predicts future independent walking after SCI

The Longitudinal Effects of Comorbid Health Burden on Functional Outcomes for Adults With Moderate to Severe Traumatic Brain Injury

Objective: To evaluate the impact of physical, mental, and total health condition burden on functional outcome and life satisfaction up to 10 years after moderate to severe traumatic brain injury (TBI). Setting: Six TBI Model Systems centers. Participants: Three hundred ninety-three participants in the TBI Model Systems National Database. Design: Retrospective cohort study. Main measures: Self-reported physical and mental health conditions at 10 years postinjury. Functional Independence Measure Motor and Cognitive subscales and the Satisfaction With Life Scale measured at 1, 2, 5, and 10 years. Results: In 10-year longitudinal individual growth curve models adjusted for covariates and inverse probability weighted to account for selection bias, greater physical and mental health comorbidity burden was negatively associated with functional cognition and life satisfaction trajectories. Physical, but not mental, comorbidity burden was negatively associated with functional motor trajectories. Higher total health burden was associated with poorer functional motor and cognitive trajectories and lower life satisfaction. Conclusions: This study offers evidence that comorbidity burden negatively impacts longitudinal functional and life satisfaction outcomes after TBI. The findings suggest that better identification and treatment of comorbidities may benefit life satisfaction, functional outcome, reduce healthcare costs, and decrease reinjury. Specific guidelines are needed for the management of comorbidities in TBI populations

GANDALF: Generative Adversarial Networks with Discriminator-Adaptive Loss Fine-tuning for Alzheimer's Disease Diagnosis from MRI

Positron Emission Tomography (PET) is now regarded as the gold standard for the diagnosis of Alzheimer's Disease (AD). However, PET imaging can be prohibitive in terms of cost and planning, and is also among the imaging techniques with the highest dosage of radiation. Magnetic Resonance Imaging (MRI), in contrast, is more widely available and provides more flexibility when setting the desired image resolution. Unfortunately, the diagnosis of AD using MRI is difficult due to the very subtle physiological differences between healthy and AD subjects visible on MRI. As a result, many attempts have been made to synthesize PET images from MR images using generative adversarial networks (GANs) in the interest of enabling the diagnosis of AD from MR. Existing work on PET synthesis from MRI has largely focused on Conditional GANs, where MR images are used to generate PET images and subsequently used for AD diagnosis. There is no end-to-end training goal. This paper proposes an alternative approach to the aforementioned, where AD diagnosis is incorporated in the GAN training objective to achieve the best AD classification performance. Different GAN lossesare fine-tuned based on the discriminator performance, and the overall training is stabilized. The proposed network architecture and training regime show state-of-the-art performance for three- and four- class AD classification tasks.Comment: Accepted for publication at the MICCAI 2020 conferenc

Iron Phosphate Glass-Containing Hanford Waste Simulant

Resolution of the nation’s high level tank waste legacy requires the design, construction, and operation of large and technically complex one-of-a-kind processing waste treatment and vitrification facilities. While the ultimate limits for waste loading and melter efficiency have yet to be defined or realized, significant reductions in glass volumes for disposal and mission life may be possible with advancements in melter technologies and/or glass formulations. This test report describes the experimental results from a small-scale test using the research scale melter (RSM) at Pacific Northwest National Laboratory (PNNL) to demonstrate the viability of iron phosphate-based glass with a selected waste composition that is high in sulfates (4.37 wt% SO3). The primary objective of the test was to develop data to support a cost-benefit analysis as related to the implementation of phosphate-based glasses for Hanford low activity waste (LAW) and/or other high-level waste streams within the U.S. Department of Energy complex. The testing was performed by PNNL and supported by Idaho National Laboratory, Savannah River National Laboratory, and Mo-Sci Corporation

Identification of a Human Monoclonal Antibody to Replace Equine Diphtheria Anti-toxin for the Treatment of Diphtheria

Diphtheria anti-toxin (DAT) has been used to treat Corynebacterium diphtheriae infection for over one hundred years. While the global incidence of diphtheria has declined in the 20th century, the disease remains endemic in many parts of the world and significant outbreaks still occur. Diphtheria anti-toxin is an equine polyclonal antibody with considerable side effects that is in critically short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we cloned human monoclonal antibodies (HuMabs) directly from antibody secreting cells of human volunteers immunized with Td vaccine. We isolated a diverse panel of HuMabs that recognized diphtheria toxoid and recombinant protein fragments of diphtheria toxin. Forty-one unique HuMabs were expressed in 293T cells and tested for neutralization of diphtheria toxin in in vitro cytotoxicity assays. The lead candidate HuMab, 315C4 potently neutralized diphtheria toxin with an EC50 of 0.65 ng/mL. Additionally, 25 μg of 315C4 completely protected guinea pigs in an in vivo lethality model. In comparison, 1.6 IU of DAT was necessary for full protection resulting in an estimated relative potency of 64 IU/mg for 315C4. We further established that our lead candidate HuMab binds to the receptor binding domain of diphtheria toxin and blocks the toxin from binding to the putative receptor, heparin binding-epidermal growth factor like growth factor. The discovery of a specific and potent neutralizing antibody against diphtheria toxin holds promise as a potential human therapeutic and is being developed for human use