Preponderance Of Evidence Research Articles

Moduli and modes in the Mikado model.

We determine how low frequency vibrational modes control the elastic shear modulus of Mikado networks, a minimal mechanical model for semi-flexible fiber networks. From prior work it is known that when the fiber bending modulus is sufficiently small, (i) the shear modulus of 2D Mikado networks scales as a power law in the fiber line density, G ∼ ρα+1, and (ii) the networks also possess an anomalous abundance of soft (low-frequency) vibrational modes with a characteristic frequency ωκ ∼ ρβ/2. While it has been suggested that α and β are identical, the preponderance of evidence indicates that α is larger than theoretical predictions for β. We resolve this inconsistency by measuring the vibrational density of states in Mikado networks for the first time. Supported by these results, we then demonstrate analytically that α = β + 1. In so doing, we uncover new insights into the coupling between soft modes and shear, as well as the origin of the crossover from bending- to stretching-dominated response.

Does synaptic hypometabolism or synaptic dysfunction, originate cognitive loss? Analysis of the evidence.

Elderly persons with currently normal cognition who have cerebral hypometabolism as shown by low uptake of 18fluorine‐fluorodeoxyglucose (18F‐FDG), are at risk of future loss of cognition and, thus, of future Alzheimer's dementia (AD). Reduction of either 18F‐FDG or cognition is assumed to reflect synaptic dysfunction, since synapses account for the majority of glucose use by the brain and cognition depends upon accurate synaptic function. The chronology of the connection between reduced cerebral synaptic function and hypometabolism is, therefore, a critical question, because if synaptic dysfunction came first, then correcting the hypometabolism would likely not benefit synaptic function; but if hypometabolism came first, then correcting the hypometabolism probably would benefit synaptic function. That correction might prevent initiation of the cognitive loss that eventuates in AD and, thereby, would benefit the vast numbers of persons in their eighth to tenth decades of life who are at risk for AD. Among the many citations reviewed in this presentation, seven show hypometabolism that precedes synaptic dysfunction, and two show the reverse. Thus the preponderance of evidence, 78%, suggests that the initiating event is synaptic hypometabolism and that it is 3.5‐fold less likely that synaptic dysfunction is the initiator. In addition, it is inherently unlikely that synaptic dysfunction causes hypometabolism. This conclusion could be tested by a clinical trial whose primary objective would be to assess the benefit to cognition of improving synaptic metabolism in patients who are at risk for cognitive loss.

Azithromycin for severe COVID-19

Azithromycin for severe COVID-19

Editor's Column: “We are the jury”: Steinbeck's America under Threat

Editor's Column: “We are the jury”: Steinbeck's America under Threat

Obstructive sleep apnea is associated with coronary microvascular dysfunction: A systematic review from a clinical perspective.

There is now increasing evidence demonstrating that obstructive sleep apnea (OSA) contributes to microvascular disorder. However, whether OSA is associated with impaired coronary flow reserve is still unclear. Therefore, we conducted this systematic review and meta‐analysis to summarize current evidence. In a systematic review, PubMed, Embase, the Cochrane Library and Web of Science were searched; five observational studies fulfilled the selection criteria and were included in this study. Data were extracted from selected studies and meta‐analysis was performed using random‐effects modelling. In all, 829 OSA patients and 507 non‐OSA subjects were included and assessed for coronary flow reserve (CFR), the clinical indicator of coronary microvascular dysfunction (CMD). For all studies, OSA was significantly associated with reduced CFR. The pooled weighted mean difference (WMD) of CFR was −0.78 (95% confidence interval [CI] −1.25 to −0.32, p ＜ 0.001, I2 = 84.4%). The difference in the apnea–hypopnea index (AHI) between studies can explain 89% of heterogeneity (coef = −0.05, 95% CI −0.12 to 0.02, p = .078) in a meta‐regression, indicating the CFR tended to negatively correlate with severity of OSA. The Egger regression test did not show statistical significance (p = .49). In conclusion, there are plausible biological mechanisms linking OSA and CMD, and the preponderance of evidence from this systematic review suggests that OSA, especially severe OSA, is associated with reduced CFR. Future studies are warranted to further delineate the exact role of OSA in CMD occurrence and development in a prospective setting.

Do we know what they are thinking? Theory of Mind and affect in the classroom

Research on Theory of Mind explores how we develop the capacity to understand that others have thoughts and feelings that differ from our own and how we are compelled to “read” them. However, a preponderance of evidence from the cognitive humanities and cognitive neurosciences tells us that our readings are often misguided or just plain wrong. None of this work has considered how teachers and learners might engage in open conversations about theory to mind to identify misperceptions and enhance their understanding of one another’s thoughts and reactions in the classroom. In this essay, we explore how using what we call “Theory of Minding” as a rhetorical device may invite moments of vulnerability and of clarification when we engage in learning with our students, thus enhancing classroom dynamics. We describe how the idea of Theory of Minding developed, present an initial evaluation of it by students, and situate this technique in the rich literature about affect and pedagogy. We propose that using Theory of Minding in the classroom can be used to encourage more authentic and interactive engagement.

Evaluating the effects of smoking and smoking cessation on alveolar bone in young adults: An interventional prospective study

Introduction: Preponderance of evidence suggests that smoking is one of the most significant risk factors in the development and progression of periodontal diseases. Smoke contains thousands of different compounds like Nicotine, Tar. Lack of education of dentists and hygienists to promote smoking quitting activities is a significant barrier for Motivational Interviewing for smokers. Aim: To evaluate the effect of smoking on alveolar bone in young adults and motivating patients to quit through the Motivational Interviewing. Materials and Methods: Sixty subjects were categorized into three groups. Group 1: smokers, Group 2:non-smokers, Group 3: smokers but willing to quit smoking.For alveolar bone height measurement Image Digitization was done.Smoking cessation was carried out for Group 3. Motivational Interviewing was used to convince the patients for smoking cessations. After six months, Nicoscreen® was used to know whether they quitted smoking or not. Results: Group 1 had statistically significant bone loss in comparison to Group 2 & Group 3 after six months which is attributed to effect of smoking on alveolar bone. Conclusion: Periodontal health is compromised by chronic smoking by an increase alveolar bone loss. Nicoscreen® can be used as a prompt screening tool for smoking cessation. Keywords: Smoking, Motivational interviewing, Smoking cessation.

It is time to retire Goodsall's Rule: the Midline Rule is a more accurate predictor of the true and natural course of anal fistulas.

On May 6, 1887 at a meeting of the West London Medico-Chirurgical Society, original observations attributed to D. H. Goodsall described an association between the secondary (external) sinus opening and the location of the primary (internal) opening of an anal fistula: posterior external sinuses had a midline origin and anterior external sinuses took a straight path to their internal origin-eponymously known as Goodsall's Rule. However, over the last century, published reports support the midline as the primary (internal) origin of all anal fistulas, thus challenging the predictive accuracy of Goodsall's Rule and prompting this expansive review. A literature search was performed for studies describing the relationship between the secondary (external) opening and the primary (internal) opening of anal fistulas, including recent reports of the positive predictive value (PPV) of Goodsall's Rule. The studies were evaluated to determine the validity of Goodsall's observations. The midline was the dominant, primary (internal) opening site of all anal fistulas with up to 95% accuracy. Goodsall's Rule was inaccurate when applied to anal fistulas with an anterior off-midline external sinus opening which tend to mirror posterior off-midline external sinuses and curve to a midline origin, rather than take a straight course to a primary (internal) opening, as predicted by Goodsall. Use of the Midline Rule had superior predictive accuracy, reflected in an increase in overall PPV of the location of the primary (internal) origin from 49% using Goodsall's Rule to 71% using the Midline Rule (57-62% for men, 31-90% for women). Goodsall's Rule falls short in predicting the natural course of anal fistulas with an anterior off-midline external sinus opening, especially for women. Given the increased risk of fecal incontinence related to surgical intervention for anterior-based anal fistulas, especially in women, dependence on Goodsall's Rule to guide the surgeon may result in "disastrous consequences". The preponderance of evidence over the last century favors the Midline Rule as a more accurate predictor of the true and natural course of anal fistulas, regardless of the location of the external sinus opening.

No Influence of Overweight/Obesity on Exercise Lipid Oxidation: A Systematic Review.

Compared to lean counterparts, overweight/obese individuals rely less on lipid during fasting. This deficiency has been implicated in the association between overweight/obesity and blunted insulin signaling via elevated intramuscular triglycerides. However, the capacity for overweight/obese individuals to use lipid during exercise is unclear. This review was conducted to formulate a consensus regarding the influence of overweight/obesity on exercise lipid use. PubMed, ProQuest, ISI Web of Science, and Cochrane Library databases were searched. Articles were included if they presented original research on the influence of overweight/obesity on exercise fuel use in generally healthy sedentary adults. Articles were excluded if they assessed older adults, individuals with chronic disease, and/or exercise limitations or physically-active individuals. The search identified 1205 articles with 729 considered for inclusion after duplicate removal. Once titles, abstracts, and/or manuscripts were assessed, 24 articles were included. The preponderance of evidence from these articles indicates that overweight/obese individuals rely on lipid to a similar extent during exercise. However, conflicting findings were found in eight articles due to the outcome measure cited, participant characteristics other than overweight/obesity and characteristics of the exercise bout(s). We also identified factors other than body fatness which can influence exercise lipid oxidation that should be controlled in future research.

Changing treatment landscape for early cervical cancer: outcomes reported with minimally invasive surgery compared with an open approach.

The aim of the article is to review recent studies that compare the oncologic efficacy of minimally invasive radical hysterectomy with that of open radical hysterectomy. The Laparoscopic Approach to Cervical Cancer (LACC) trial, a randomized study design to test the hypothesis that minimally invasive radical hysterectomy is not inferior to open radical hysterectomy, was stopped early by the data and safety monitoring committee after enrolling 631 of a planned 740 patients. The disease-free survival rate at 4.5 years was 86% among women assigned to minimally invasive surgery and 96.5% in those who underwent open surgery (hazard ratio [HR] 3.74; 95% confidence interval [CI] 1.63-8.58). Minimally invasive surgery was also associated with inferior overall survival (HR 6.00; 95% CI 1.44-12.7). Recent well designed, adequately powered observational studies mostly corroborate the findings of the LACC trial. After a decade of widespread acceptance and increasing popularity, the preponderance of evidence now suggests that minimally invasive radical hysterectomy for cervical cancer confers an excess risk of recurrence and death compared with open abdominal radical hysterectomy.

Lung protection in acute respiratory distress syndrome: what should we target?

Most clinical trials of lung-protective ventilation have tested one-size-fits-all strategies with mixed results. Data are lacking on how best to tailor mechanical ventilation to patient-specific risk of lung injury. Risk of ventilation-induced lung injury is determined by biological predisposition to biophysical lung injury and physical mechanical perturbations that concentrate stress and strain regionally within the lung. Recent investigations have identified molecular subphenotypes classified as hyperinflammatory and hypoinflammatory acute respiratory distress syndrome (ARDS), which may have dissimilar risk for ventilation-induced lung injury. Mechanically, gravity-dependent atelectasis has long been recognized to decrease total aerated lung volume available for tidal ventilation, a concept termed the 'ARDS baby lung'. Recent studies have demonstrated that the aerated baby lung also has nonuniform stress/strain distribution, with potentially injurious forces concentrated in zones of heterogeneity where aerated alveoli are adjacent to flooded or atelectatic alveoli. The preponderance of evidence also indicates that current standard-of-care tidal volume management is not universally protective in ARDS. When considering escalation of lung-protective interventions, potential benefits of the intervention should be weighed against tradeoffs of accompanying cointerventions required, for example, deeper sedation or neuromuscular blockade. A precision medicine approach to lung-protection would weigh. A precision medicine approach to lung-protective ventilation requires weighing four key factors in each patient: biological predisposition to biophysical lung injury, mechanical predisposition to biophysical injury accounting for spatial mechanical heterogeneity within the lung, anticipated benefits of escalating lung-protective interventions, and potential unintended adverse effects of mandatory cointerventions.

Jefferson's Daughters: Three Sisters, White and Black, in a Young America by Catherine Kerrison

Reviewed by: Jefferson's Daughters: Three Sisters, White and Black, in a Young America by Catherine Kerrison Aston Gonzalez (bio) Keywords Thomas Jefferson, Martha Jefferson Randolph, Maria Jefferson Eppes, Harriet Hemings, Sally Hemings, Monticello Jefferson's Daughters: Three Sisters, White and Black, in a Young America. By Catherine Kerrison. (New York: Ballantine Books, 2018. Pp. 448. Cloth, $28.00.) In Jefferson's Daughters, Catherine Kerrison examines an impressive array of historical sources to distinguish the complex lives of Martha [End Page 352] Jefferson Randolph, Mary "Maria" Jefferson Eppes, and Harriet Hemings. The former two women, the daughters of Martha Wayles Jefferson, and the latter, the enslaved daughter of Sally Hemings, led lives that diverged greatly from one another. Aimed mainly at a general audience, the book largely explains in three sections—each roughly dedicated to each daughter—the circumstances foisted upon them, and the decisions they made that sometimes challenged social norms. The three sections of the book move from Martha to Maria to Harriet, and correspondingly from the largest primary-source base to the smallest. Kerrison relies on personal correspondence, so it is not surprising that she provides readers with substantially clearer and more robust views of the lives and inner thoughts of Jefferson's two white daughters. Her voluminous archive supplies glimpses of Martha and Maria's challenges to their father's authority and their assertions of autonomy. Kerrison reconstructs the intimate conversations and friendships between Martha and her friends in the City of Light to bring readers into the world of their Parisian education and entertainment. Impressive are Kerrison's portrayals of Martha's emerging attraction to Catholicism and her apprehension about leaving France for Virginia. Kerrison convincingly presents a picture of a serious, but playful, and intellectually curious daughter whose interest in "male" topics afforded by her progressive Enlightenment education placed her on track to challenge Jefferson's stagnant expectations about women's roles back home. In her interpretation of the life of Jefferson's younger daughter, Maria, Kerrison shifts the focus from her relationship with her father to her relationship with her husband (171). She skillfully analyzes a single sentence written by Maria's husband, Jack Eppes, to Jefferson to show how the couple consulted each other before rejecting Jefferson's repeated proposal that they live very near Monticello. Still, Kerrison overemphasizes Maria's emotional maturity, especially during her childhood, given the evidence presented. The decision to leave Monticello due to her husband's career may instead be evidence of Maria conforming to gendered marriage expectations. Regardless, Kerrison productively shifts the primary focus to Maria as a means of de-centering Jefferson's control over her life. Throughout the book, Kerrison engages numerous bodies of scholarship that provide a foundation and offer an opening for her fresh understanding of Jefferson's daughters. She offers a corrective to scholars who have not taken Maria on her own terms. The thin collection of letters [End Page 353] authored by Maria makes that difficult given all of the correspondence about her, yet Kerrison expertly contextualizes her life and impressively triangulates Maria's agency and constraints. She takes issue with Jefferson biographer Dumas Malone, who claimed that Jefferson "did not succeed in molding his daughter [Maria] in his own image" (87). Given the preponderance of evidence that Kerrison marshals, it seems unlikely this was Jefferson's desire given his belief in innate and intended differences between men and women, regardless of their filial relationship to him. Incorporating the scholarship of architectural historians whose work underscores how the design of Monticello conveyed the intended order sought by Jefferson adds further to Kerrison's comprehensive analysis of Monticello's hierarchies. Furthermore, Kerrison's writing is clear and often witty, especially when she details the lives of Jefferson's white daughters, and immediately undercuts their elite pleasures with the harsh realities of the enslaved people toiling to build Jefferson's idea of himself. On the particular subject of the Hemingses at Monticello, Kerrison is in close conversation with Annette Gordon-Reed's work about the enslaved people at Monticello.1 Just as Martha passed along the lessons of her French education to her children, Sally Hemings likely passed on to her children...

Vision of Research on Human Linear Growth.

The human body grows in length from conception to the maximal adult height over two decades. The shortest male population averages ∼150 cm and the tallest ∼183 cm. Nonetheless the dimensions of head and trunk are highly comparable, with the vast difference in the leg length. Stunting is a personal condition in which an individual has a standing height-for-age (HAZ) of less than two standard deviations of the standard curve median. It is associated with increased mortality, morbidity, and functional deficits. The process of losing relative stature is known as linear growth retardation, first attributed to chronic protein deficiency, then to an assortment of micronutrient deficiencies, and most recently to inflammation from unhygienic environmental conditions. Public health intervention trials responding to each of these possibilities have failed to produce true reversal responses measured in the 10s of centimeters. As to biological insights, there is no convenient way to separate weight from length growth with sonographic monitoring, but a third of infants can be born stunted. Normative growth (standard curves) competes with epigenetic adaptation (programming) as the beacon for in utero growth. Major investments into field trials allow us to discard multiple micronutrients and water/sanitation/hygiene interventions as measures to reverse established stunting. The preponderance of evidence is against catch-up growth during puberty. Future publications will be in the conceptual domain, resolving metrics, while the full range of stimuli and exposures impeding growth will be elucidated. Advances in measurement techniques in anthropometry and immunology and endocrinology will be mobilized to the literature.

A \u201cSwiss paradox\u201d in the United States? Level of spatial aggregation changes the association between income inequality and morbidity for older Americans

Although a preponderance of research indicates that increased income inequality negatively impacts population health, several international studies found that a greater income inequality was associated with better population health when measured on a fine geographic level of aggregation. This finding is known as a “Swiss paradox”. To date, no studies have examined variability in the associations between income inequality and health outcomes by spatial aggregation level in the US. Therefore, this study examined associations between income inequality (Gini index, GI) and population health by geographic level using a large, nationally representative dataset of older adults. We geographically linked respondents’ county data from the 2012 Behavioral Risk Factor Surveillance System to 2012 American Community Survey data. Using generalized linear models, we estimated the association between GI decile on the state and county levels and five population health outcomes (diabetes, obesity, smoking, sedentary lifestyle and self-rated health), accounting for confounders and complex sampling. Although state-level GI was not significantly associated with obesity rates (b = − 0.245, 95% CI − 0.497, 0.008), there was a significant, negative association between county-level GI and obesity rates (b = − 0.416, 95% CI − 0.629, − 0.202). State-level GI also associated with an increased diabetes rate (b = 0.304, 95% CI 0.063, 0.546), but the association was not significant for county-level GI and diabetes rate (b = − 0.101, 95% CI − 0.305, 0.104). Associations between both county-level GI and state-level GI and current smoking status were also not significant. These findings show the associations between income inequality and health vary by spatial aggregation level and challenge the preponderance of evidence suggesting that income inequality is consistently associated with worse health. Further research is needed to understand the nuances behind these observed associations to design informed policies and programs designed to reduce socioeconomic health inequities among older adults.

The Influence of preterm birth beyond infancy: Umbrella review of outcomes of adolescents and adults born preterm.

In recent decades, increased neonatal survival has enabled research of long-term outcomes of those born preterm. The purpose of this article is to present the findings of an umbrella review, an examination of published systematic reviews and meta-analyses, to examine the outcomes of adolescents and adults born preterm. The research was guided by the Joanna Briggs Institute methodology for umbrella reviews. A systematic search of PubMed, CINAHL, and PsycINFO databases with the search years 2010 through September 2018 yielded 16 reviews for inclusion. The 16 reviews included in this umbrella review represent five clinical outcomes: neurodevelopmental (3 reviews), mental/behavioral health (5 reviews), cardiovascular (4 reviews), pulmonary (3 reviews), and life experience outcomes (4 reviews). One review included data for multiple clinical outcomes. This umbrella review highlights the adolescent and adult risks related to cognitive scores, executive function, anxiety, depression, attention-deficit hyperactivity disorder, long-term effects on systolic blood pressure, low-density lipoproteins and cholesterol levels, pulmonary symptoms, including asthma, pulmonary function, radiographic changes in the lungs, sports and leisure participation, and educational attainment and employment. There is a preponderance of evidence that supports targeted screening for a history of preterm birth by all health care providers. This screening should facilitate the promotion of healthy lifestyles and improving psychosocial and neurodevelopmental difficulties through early and continued support services. Curricular and practice standards are advocated to support this change.

The Burden of Proof for Invoking the Public Interest Exception to ITC Exclusion Orders Under Section 337

The U.S. International Trade Commission’s enforcement of Section 337 of the Tariff Act protects domestic industries from the consequences of unfair competitive acts in the importation of goods into the U.S. that infringe on U.S. IP rights. The power of the Commission is limited primarily to issuing exclusion orders against infringing imports into the U.S. Because upon finding of a violation, an exclusion order is presumed to serve the public interest, the alleged infringing importer (respondent) must bear the burden of proving by the preponderance of evidence that statutorily-specified public interest factors justify an exception from issuance of the order. This paper analyzes the statute, regulations, case law, and administrative precedents that allocate the burden of persuasion for these factors onto the respondent. This burden of proof is substantive, including the burden of showing patent holder’s market power, higher prices, lack of alternatives to consumers, infeasibility of design-around the patent holder’s claims, national security imperatives, showing essentiality for standard implementation of patent claims subject to Fair, Reasonable and Non-Discriminatory commitments, and showing that refusal to license such essential patent claims caused a patent “holdup.” It is shown that these exceptions are rare and narrowly applied. Through more than a thousand investigations, the Commission applied the exception only four times.

"Objects Insignificant to Sight": Racial Violence and Empathy in Faulkner's "Pantaloon in Black"

"Objects Insignificant to Sight":Racial Violence and Empathy in Faulkner's "Pantaloon in Black" John Lutz (bio) Way Down South in Dixie(Break the heart of me)Love is a naked shadowOn a gnarled and naked tree. Langston Hughes, "Song for a Dark Girl" Racist ideas are not natural to the human mind. Ibram X. Kendi, How to Be an Antiracist An effort to lay bare the root causes of the empathy deficiency that enables the brutal practice of lynching lies at the very center of William Faulkner's short masterpiece "Pantaloon in Black." First published in 1940 as a chapter in the novel Go Down, Moses, "Pantaloon in Black" confronts the underlying psychological and social forces that legitimize lynching by humanizing its central African American character, Rider. Recent discoveries in neuroscience and social psychology concerning empathy can provide a useful vantage point for understanding Faulkner's critique of racist violence in "Pantaloon in Black" and in Go Down, Moses more generally. The preponderance of evidence from these fields demonstrates that our emotional responses to the pain of others are hardwired into our brains and frequently felt with an involuntary immediacy over which we have little control. Feeling with others is a spontaneous, natural feature of our common humanity, a biological inheritance most likely developed as an adaptive trait in the process of human evolution. However, if our empathic responses to others are indeed a common biological inheritance, then how do we explain the apparent suspension of such responses in the inflicting of racist violence? In his research into empathic accuracy, William Ickes notes how negative frames of reference that "become inflexible, unyielding, and irreconcilable" [End Page 189] can create "an empathic stalemate or, even worse, the death of any mutual understanding" (Ickes 223). This discovery suggests that any internal obstacle to feeling with others might also inhibit our intellectual capacity to understand their lived experience or perspective. Ickes's research bears out the significant role that biases about designated out-groups play in our ability to make accurate inferences about what others think and feel. Citing similar research, Elizabeth A. Segal et al. have investigated how notions of otherness appear to be at the foundation of most barriers to empathy. If we consider a person fully human and on a footing of equality with ourselves, we can more readily consider his or her inner life and thoughts and successfully empathize. But "if we do not view them as fully human, the empathic process will likely be bypassed. Neurological data supports these points" (Segal et al. 89). Essentially, the more that a given set of ideological assumptions transforms others into inhuman objects, the less mirroring of the self and adopting the perspective of these others becomes likely or possible. This tendency of negative frames of reference to block empathy is particularly common in biased perceptions directed at entire groups. As Segal et al. note, "Framing entire groups as others to be feared is a step in the dehumanizing process and obstructs any possibility of empathic insight" (91). In addition, people tend to attribute more complex mental states to targets they like and ascribe complex emotions more readily to members of their in-group than an out-group (Echols and Correll 60).1 In an interesting study measuring emotional reactions to the pain of others, Avenanti et al. used transcranial magnetic stimulation (TMS) to determine whether racial membership or bias modulates the response to the pain of those in other racial groups. Their findings point to a lack of empathic brain response to outgroup members and provide support for the "notion that race-related prejudices can shape social categorization and lead to dehumanized perception of different others" (Avenanti et al. 1021). If racist ideas that dehumanize other individuals or groups block empathy and short-circuit even basic neurological mirroring responses, one would expect to see pronounced empathy deficits in instances of racially-motivated violence. The discoveries of neuroscience and social psychology concerning empathy illuminate and complement Faulkner's antiracist stance in "Pantaloon in Black" in two important respects. First, the existence of empathy as an inherited aspect of our common biological nature undercuts one of the central planks of racist...

Burden and Standard of Proof in Election Petitions without Criminal Allegations

The burden and standard of proof in election petition without criminal allegation is in tandem with the extant Evidence Act, as election petitions is sui generis. The purpose of election laws is to obtain a correct expression of the intent of the voters. However, this paper argues that whereas proof of election petition without criminal allegations requires proof on the preponderance of evidence, the shallow chant of “he who asserts must prove” in the extant law is a conduit pipe for electoral injustice. This paper therefore makes a clarion call for the amendment of the relevant extant law to usher in a legal regime of burden of proof on the pleadings, where whoever asserts the affirmative or positive must prove on the state of the pleadings. 
 
 The rebuttable presumption of the regularity of the conduct of elections and declaration of results, no longer serve the end of justice in our electoral process. This paper therefore argues that the Electoral Act be amended to place the burden of proof of the regularity of elections and declaration of results on the Independent National Electoral Commission (INEC), to meet the desired justice contemplated in the electoral process.

Discussion: The Questionable Role of Antibiotic Irrigation in Breast Augmentation

Discussion: The Questionable Role of Antibiotic Irrigation in Breast Augmentation

Abstract 259: Interplay between Bcl-2 and cFLIP in lymphoma disease progression is a function of an altered redox milieu

Abstract Bcl-2 is associated with chemoresistance and despite the preponderance of evidence linking its anti-apoptotic function to hematologic cancers, it’s now emerging that overexpression of Bcl-2 is a feature shared by a host of cancers. Canonically, the death inhibitory activity of Bcl-2 is associated with its ability to prevent mitochondrial outer membrane permeabilization. However, recent evidence has highlighted a novel facet in the biology of Bcl-2, whereby enforced expression of Bcl-2 resulted in an increase in mitochondrial oxygen consumption and elevated levels of the reactive oxygen species (ROS), superoxide (O2-.). Alleviating the levels of intracellular O2-. sensitized Bcl-2 overexpressing cells to death receptor induced apoptosis via a robust increase in upstream caspase 8 activation. Using a variety of functional mutants of the NOX-activating small GTPase Rac1, we show a clear link between Bcl-2 induced apoptosis resistance and intracellular O2-.. In the search for the molecular target of this inhibitory signal, we now show that Bcl-2 overexpression is associated with an increase in the transcription and protein levels of the receptor inhibitory protein, cFLIP. We employed pharmacological and genetic approaches to modulated intracellular O2-. and present evidence cFLIP is transcriptionally regulated by O2-.; increase in cFLIP promoter activity and mRNA levels. Interestingly, inhibiting glycolysis also resulted in downregulation of cFLIP in a ROS-dependent manner. Notably, primary cells derived from patients with lymphoma also showed a significant downregulation of cFLIP when subjected to conditions that decrease O2-. and elicited enhanced sensitivity to TRAIL-induced apoptosis. Importantly, TCGA and Affy meta-cohorts’ analyses revealed consistent correlation trend: Bcl-2 and cFLIP (CFLAR) were positively correlated; Bcl-2 and SOD1 (superoxide dismutase 1) were negatively correlated. A strong negative correlation was also observed between CFLAR and SOD1. Furthermore, Kaplan-Meier analyses of overall survival (OS) were performed in the in-house High expression of either Bcl-2 or CFLAR conferred poor OS outcome. When stratified by CFLAR and Bcl-2 expressions, cases with higher expression of the two genes had the worst prognosis with the shortest median survival. Notably, DLBCL with high Bcl-2 and low SOD1 had the worst OS outcome, compared against expression levels of Bcl-2 and SOD1. Together, these findings point to a concordance between cFLIP and Bcl-2, which negatively correlates with SOD1 in driving lymphoma progression. Citation Format: Jayshree L. Hirpara, Shazib Pervaiz. Interplay between Bcl-2 and cFLIP in lymphoma disease progression is a function of an altered redox milieu [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 259.