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Romantic Humility: Literature, Ethico-Politics, and Emotion, 1780-1820
No full textWhat we now call “liberal individualism”—that is, the belief in the inalienable rights and freedom of the individual—first emerged in the Enlightenment and Romantic periods in Europe, and continues to be a defining feature of Western democracies. The liberal valorization of freedom as the sovereign moral concept was a consequence of Enlightenment philosophy, scientific progress, and secularization, which led to the view that human life is self-contained and without an externally defined purpose, and that human relations can be understood by considering society simply as an aggregate of individuals who are each driven by desire and self-interest. Values previously safeguarded by divine authority devolved into matters of choice by the individual will, and many observers have suggested that this change resulted in a moral lassitude that, paradoxically, made it more difficult to realize the Enlightenment ideals of universal liberty, rights, and justice. Arguments grounded in premises of natural freedom and rights often end up rationalizing absolute authoritarian power, as we see, for example, in the philosophy of Thomas Hobbes.This dissertation examines how British writers of the Romantic period such as Olaudah Equiano, William Godwin, and Mary Shelley responded to this moral dilemma of liberal individualism by developing a new understanding of humility in their works. The meaning of humility in the West has been fundamentally shaped by the Jewish and Christian traditions that view humility as a spiritual quality that disposes an individual toward reverence for and submission to God. As a quality that goes against the Enlightenment emphasis on human reason and agency, humility underwent a steady devaluation in the eighteenth century and onward, perceived, for example, as a “monkish kind of virtue” by David Hume and a “slave morality” by Friedrich Nietzsche. This study argues that instead of returning to the religiously infused concept of humility, British Romantic authors developed a new form of humility for the secular age, one that not only preserves human agency but also emphasizes the need for human action for collective good. This humility does not focus on self-abasement but on a selfless mood, predicated on an immanent framework derived from Stoicism and the philosophy of Baruch Spinoza, which were influential in the eighteenth century. In three chapters, this study shows how Equiano, Godwin, and Shelley’s instantiations of Romantic humility respectively illuminate Romantic humility as it informs human relations, historical progress, and human-nonhuman relations. In so doing, this study shows that Romanticism cannot be viewed simply as an extension of Enlightenment individualism but also as an era of collectivist humility.</p
The spino-pelvic ratio: a novel global sagittal parameter associated with clinical outcomes in adult spinal deformity patients.
No full textPurposeAnalysis of interactions of spinal alignment metrics may uncover novel alignment parameters, similar to PI-LL. This study utilized a data-driven approach to hypothesis generation by testing all possible division interactions between spinal alignment parameters.MethodsThis study was a retrospective cohort analysis. In total, 1439 patients with baseline ODI were included for hypothesis generation. In total, 666 patients had 2-year postoperative follow-up and were included for validation. All possible combinations of division interactions between baseline metrics were assessed with linear regression against baseline ODI.ResultsFrom 247 raw alignment metrics, 32,398 division interactions were considered in hypothesis generation. Conceptually, the TPA divided by PI is a measure of the relative alignment of the line connecting T1 to the femoral head and the line perpendicular to the sacral endplate. The mean TPA/PI was 0.41 at baseline and 0.30 at 2 years postoperatively. Higher TPA/PI was associated with worse baseline ODI (p 0.4). The R-squared for ODI against categorical TPA/PI alone (0.154) was directionally higher than that for each of the individual Schwab modifiers (SVA: 0.138, PI-LL 0.111, PT 0.057).ConclusionThis study utilized a data-driven approach for hypothesis generation and identified the spino-pelvic ratio (TPA divided by PI) as a promising measure of sagittal spinal alignment among ASD patients. Patients with SPR > 0.2 exhibited inferior ODI scores.Level of evidenceIII
Adult Scoliosis Deformity Surgery: Comparison of Outcomes Between One Versus Two Attending Surgeons.
No full textStudy designRetrospective review of prospectively collected data.ObjectiveAssess outcomes of adult spinal deformity (ASD) surgery performed by one versus two attending surgeons.Summary of background dataASD centers have developed two attending teams to improve efficiency; their effects on complications and outcomes have not been reported.MethodsPatients with ASD with five or more levels fused and more than 2-year follow-up were included. Estimated blood loss (EBL), length of stay (LOS), operating room (OR) time, complications, quality of life (Health Related Quality of Life), and x-rays were analyzed. Outcomes were compared between one-surgeon (1S) and two-surgeon (2S) centers. A deformity-matched cohort was analyzed.ResultsA total of 188 patients in 1S and 77 in 2S group were included. 2S group patients were older and had worse deformity based on the Scoliosis Research Society-Schwab classification (P 0.05). 2S patients had more three-column osteotomies (3CO; P ConclusionNo significant differences were found in LOS, OR time, or EBL between the 1S and 2S groups, even when matching for severity of deformity. 2S group had less BMP-2 use, fewer intraoperative complications but more postoperative complications.Level of evidence2
Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment.
No full textIntroductionMenthol, through its cooling and pleasant sensory effects, facilitates smoking and tobacco product initiation, resulting in the high popularity of mint/menthol-flavored E-cigarettes. More recently, E-cigarette vendors started marketing synthetic cooling agents as additives that impart a cooling effect but lack a characteristic minty odor. Knowledge about content of synthetic coolants in US-marketed E-cigarette products and associated health risks is limited.Aims and methodsE-liquid vendor sites were searched with the terms "koolada", "kool/cool", "ice", or WS-3/WS-23, denoting individual cooling agents, and relevant refill E-liquids were purchased. "Ice" flavor varieties of Puffbar, the most popular disposable E-cigarette brand, were compared with non-"Ice" varieties. E-liquids were characterized, and synthetic coolants quantified using GC/MS. Margin of exposure (MOE), a risk assessment parameter, was calculated to assess the risk associated with synthetic coolant exposure from E-cigarette use.ResultsWS-3 was detected in 24/25 refill E-liquids analyzed. All Puffbar flavor varieties contained either WS-23 (13/14) or WS-3 (5/14), in both "Ice"- and non-"Ice" flavors. Modeling consumption of WS-3 from vaped E-liquids, resulted in MOEs below the safe margin of 100 for most daily use scenarios. MOEs for WS-23 were ConclusionsSynthetic cooling agents (WS-3/WS-23) were present in US-marketed E-cigarettes, at levels that may result in consumer exposures exceeding safety thresholds set by regulatory agencies. Synthetic coolants are not only found in mint- or menthol-flavored products but also in fruit- and candy-flavored products, including popular disposable E-cigarette products such as Puffbar.ImplicationsSynthetic cooling agents are widely used in "kool/cool"- and "ice"-flavored E-liquids and in E-liquids without these labels, both as a potential replacement for menthol or to add cooling "notes" to nonmenthol flavors. These agents may be used to bypass current and future regulatory limits on menthol content in tobacco products, and not just E-cigarettes. Because synthetic cooling agents are odorless, they may not fall under the category of "characterizing flavor", potentially circumventing regulatory measures based on this concept. Regulators need to consider the additional health risks associated with exposure to synthetic cooling agents
<i>Bcl2l1</i> Deficiency in Osteoblasts Reduces the Trabecular Bone Due to Enhanced Osteoclastogenesis Likely through Osteoblast Apoptosis.
No full textBcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generated osteoblast-specific Bcl2l1-deficient (Bcl2l1fl/flCre) mice using 2.3-kb Col1a1 Cre. Trabecular bone volume and the trabecular number were lower in Bcl2l1fl/flCre mice of both sexes than in Bcl2l1fl/fl mice. In bone histomorphometric analysis, osteoclast parameters were increased in Bcl2l1fl/flCre mice, whereas osteoblast parameters and the bone formation rate were similar to those in Bcl2l1fl/fl mice. TUNEL-positive osteoblastic cells and serum TRAP5b levels were increased in Bcl2l1fl/flCre mice. The deletion of Bcl2l1 in osteoblasts induced Tnfsf11 expression, whereas the overexpression of Bcl-XL had no effect. In a co-culture of Bcl2l1-deficient primary osteoblasts and wild-type bone-marrow-derived monocyte/macrophage lineage cells, the numbers of multinucleated TRAP-positive cells and resorption pits increased. Furthermore, serum deprivation or the deletion of Bcl2l1 in primary osteoblasts increased apoptosis and ATP levels in the medium. Therefore, the reduction in trabecular bone in Bcl2l1fl/flCre mice may be due to enhanced bone resorption through osteoblast apoptosis and the release of ATP from apoptotic osteoblasts, and Bcl2l1 may inhibit bone resorption by preventing osteoblast apoptosis
Analysis of Rare Events and Multi-Object Radiomics in Medical Imaging
No full textIntroduction: Medical imaging is essential in oncology for detecting, diagnosing, and treating cancer, and monitoring treatment effectiveness. Radiomics and machine learning are techniques that use computer algorithms to extract and analyze a vast number of quantitative features from medical images, which can lead to more accurate diagnoses and treatment plans. However, technical challenges, such as rare events and multi-object radiomics need to be addressed to fully realize the potential of these techniques in medical imaging and improve patient outcomes. Two examples of technical challenges in medical imaging are (1) the rare occurrence of a positive cancer diagnosis relative to the screened population, and (2) the difficulty of applying radiomics to multiple tumors in the same image, as seen in cases of multiple brain metastases. Methods: (1) To evaluate the diagnostic performance of lung cancer screening (LCS) on low dose CT (LDCT), We retrospectively enrolled patients who received LCS via LDCT within our healthcare system between 1/1/2015-6/30/20. Our LCS program is a high-volume, ACR-recognized LCS program that houses a structured reporting registry of Lung-RADS scores. Using data from the electronic health record, we defined a malignant pulmonary nodule (i.e., lung cancer) as a pathology-proven diagnosis of lung cancer (via tissue obtained from a needle biopsy, bronchoscopy, or surgical biopsy). We determined the rate of screen-detected lung cancers, as well as all lung cancers diagnosed within one year after a LCS exam. The diagnostic performance of LCS was determined based on receiver operating characteristic analysis. Relevant clinical and demographic characteristics were analyzed as potential confounding factors, including age, sex, race/ethnicity, and smoking history. Predictive modeling on support vector machine (SVM) was performed and compared to standard-of-care Lung-RADS. (2) To explore radiomic feature aggregation methods in patients with metastatic brain cancer, seventy-eight relevant radiomic features were extracted from 449 unique metastases from 159 unique patients treated with stereotactic radiosurgery (SRS) using SPGR or T1+c MRI scans. MRI scans were normalized and discretized into 64 gray levels. Three different aggregation techniques were evaluated to compare radiomic feature results: (1) simple average, (2) weighted average by tumor volume, and (3) weighted average of the three largest metastases by volume. Univariate Kaplan-Meier analysis was performed based on the median value of each feature for three distinct clinical endpoints: overall survival, intracranial progression-free survival (ICPFS), and extracranial progression-free survival (ECPFS). In addition, this study considered molecular drivers (including EGFR, ALK, BRAF, KRAS, PD-L1, ROS1) and some clinical/demographic factors (age at SRS, KPS, number of metastases and NSCLC type) as potential confounding variables, evaluated for radiogenomic association based on Fisher's Exact Test. Results: (1) 5,150 LCS exams were performed on 3,326 unique patients. The average age at LCS was 65.4±6.2 years, with 51.4% (1709/3,326) being male. The sensitivity and specificity of LCS were 93.1% and 83.8% respectively. Patients with positive Lung-RADs scores and patients who were current smokers had a higher likelihood of screen-detected lung cancer than former smokers (p<0.001 and p=0.017 respectively). The sensitivity plus specificity of one-class training on SVM outperformed standard-of-care Lung-RADS alone. (2) Radiomic texture features Small Zone Emphasis (p=0.014) and Correlation (p=0.018) demonstrated a significant association with ICPFS and ECPFS, respectively, regardless of the feature aggregation technique. The radiomic morphological feature Compactness was also significant for these endpoints, suggesting that both tumor shape and volume-corrected texture provide complementary prognostic value. The EGFR mutation was found to be associated with 11 prognostically-relevant radiomic features for ECPFS, with the strongest association for the feature of Correlation (p=0.010).Conclusions: (1) LCS has high sensitivity, modest specificity, and relatively low PPV, the latter suggesting a need for improvements in classification of "positive" LCS results. Screen-detected lung cancers were likely in currently smoking patients. (2) This exploratory study identified several associations between radiomic features and clinical endpoints, providing insight into their potential prognostic value. Molecular drivers were also identified as confounding variables, emphasizing the importance of further radiogenomic analyses in brain metastases.
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Dorsal thoracic arachnoid web and the "scalpel sign": a distinct clinical-radiologic entity.
No full textArachnoid webs are intradural extramedullary bands of arachnoid tissue that can extend to the pial surface of the spinal cord, causing a focal dorsal indentation of the cord. These webs tend to occur in the upper thoracic spine and may produce a characteristic deformity of the cord that we term the "scalpel sign." We describe 14 patients whose imaging studies demonstrated the scalpel sign. Ten of 13 patients who underwent MR imaging demonstrated T2WI cord signal-intensity changes, and 7 of these patients also demonstrated syringomyelia adjacent to the level of indentation. Seven patients underwent surgery, with 5 demonstrating an arachnoid web as the cause of the dorsal indentation demonstrated on preoperative imaging. Although the webs themselves are rarely demonstrated on imaging, we propose that the scalpel sign is a reliable indicator of their presence and should prompt consideration of surgical lysis, which is potentially curative
Persisting neurobehavioral effects of developmental copper exposure in wildtype and metallothionein 1 and 2 knockout mice.
No full textBackgroundMetallothioneins (MT) are small proteins, which are crucial for the distribution of heavy and transition metals. Previously, we found in mice that knockout of MT 1 and 2 genes (MTKO) impaired spatial learning and potentiated the learning impairment caused by developmental mercury exposure. The current study examined the neurocognitive and neurochemical effects of MTKO with the developmental copper (Cu) supplementation.MethodsWildtype (WT) and MTKO mice were given supplemental Cu (0, 10 or 50 mg/l) in their drinking water during gestation and until weaning. When the mice were young adults they were trained on the win-shift 8-arm radial maze test of spatial learning and memory. After cognitive testing, their brains were analyzed for norepinepherine, dopamine and serotonin levels.ResultsIn the spatial learning test, wildtype mice showed the normal sex difference with males performing more accurately than the females. This effect was eliminated by MTKO and restored by moderate Cu supplementation during development. In neurochemical studies, MTKO caused a significant overall increase in serotonin in all of the regions studied: the frontal cortex, posterior cortex, hippocampus, striatum, midbrain, and brainstem. MTKO also caused a significant increase in norepinepherine in the brainstem and hippocampus. In wildtype mice, Cu supplementation during development caused a significant decline in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex. These effects were blocked by MTKO.ConclusionsThe normal sex difference in spatial working memory accuracy, which was eliminated by MTKO, was restored by moderate copper supplementation. MTKO increased serotonin across all brain areas studied and increased norepinepherine only in the hippocampus and brainstem. MTKO blocked copper-induced decreases in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex
Effects of Oxidative Stress on Airway Epithelium Permeability in Asthma and Potential Implications for Patients with Comorbid Obesity.
No full text20 million adults and 4.2 million children in the United States have asthma, a disease resulting in inflammation and airway obstruction in response to various factors, including allergens and pollutants and nonallergic triggers. Obesity, another highly prevalent disease in the US, is a major risk factor for asthma and a significant cause of oxidative stress throughout the body. People with asthma and comorbid obesity are susceptible to developing severe asthma that cannot be sufficiently controlled with current treatments. More research is needed to understand how asthma pathobiology is affected when the patient has comorbid obesity. Because the airway epithelium directly interacts with the outside environment and interacts closely with the immune system, understanding how the airway epithelium of patients with asthma and comorbid obesity is altered compared to that of lean asthma patients will be crucial for developing more effective treatments. In this review, we discuss how oxidative stress plays a role in two chronic inflammatory diseases, obesity and asthma, and propose a mechanism for how these conditions may compromise the airway epithelium
The Theognidea in Reperformance: A Rhetorical Rereading
No full textThe Theognidea is the most significant work of archaic Greek elegy, but questions of its origins have long dominated its study. This dissertation reads the Theognidea as the product of widespread, rhetorically motivated sympotic performance and gives equal interpretive weight to each performance, whether it be the putative “original” or a reperformance. I find that many features that had been regarded as cruxes would have instead been assets for symposiasts hoping to repurpose the poetry. In the first chapter, I take up the problem of poem divisions. There is no authoritative scheme of poem divisions. Indeed, there are almost as many different schemes of poem division as there are versions of the texts, as I show in the results of a survey of the poem divisions made by 16 manuscripts, 21 editions, and two schemas proposed in a monograph. I argue that this variation is not a problem, but instead a reflection of the malleability of the text, a feature that would have been useful in sympotic reperformance. In the second chapter, I argue that the doublets are demonstrations of the adaptability of the poetry to new contexts, whether or not they are actual transcriptions of reperformance. I argue that the change in medium from dynamic, sympotic performance to fixed, page poetry has created interpretive problems which can be solved with the introduction of a born-digital edition of the collection.
In the third chapter, I discuss the use of five value terms (agathos, esthlos, kalos, kakos, and deilos) which occur with notable frequency in the collection. I find that the status of “good” or “bad” described by these terms is a matter of discernment rather than the result of objectively identifiable indicators like birth or wealth; moreover, the status is regarded as impermanent. The frequent use and inconsistent application of these terms is a reflection of the fact that these terms were both valuable and contestable. In the fourth chapter I build upon the unsettled social picture of the third chapter with an examination of the use of friendship language in the Theognidea. I find that friendship is predominantly described on a one-on-one level and characterized by a lack of trust. If organized friend groups (hetaireiai) did exist, they do not seem to have held much sway over the interpersonal relationships of the symposiasts who performed this poetry.
The final two chapters are concerned with how this new reading ought to affect our understanding of author and audience in the poetry. In the fifth chapter, I examine passages in which the speaker of the poetry makes claims to authorship. I find that these claims are consistent with the immediate rhetorical needs of the symposion and do not preclude reuse. I argue that Theognis, as identified in previous readings, is best understood as an implied author. I close with an examination of how the implied authors of the collection has been understood. In the sixth chapter, I describe the differences between the ancient and modern audiences of the poetry. I survey the extensive use of address in the collection to show that the audience is quite literally an element of the poetry, and I discuss how these vocatives could be used in reperformance. I conclude with a rumination on the role that modern readers play as audience members. I find that it is ultimately impossible for readers now to fully inhabit the role of audience envisioned when it was performed in the symposion.</p