Wake Forest University
  • Winston-Salem, North Carolina, United States
Recent publications
We survey extant literature on the economics of blockchain fundamentals, with particular focus on Bitcoin, proof-of-work, and proof-of-stake. We formally clarify Bitcoin's economic significance in solving the double-spending problem without a centralized entity. We then transition to the economics literature, highlighting the key endogenous economic interactions among participants in the Bitcoin ecosystem as well as the economics of proof-of-stake and other potential consensus algorithms. Along the way, we discuss various literature that provides important insights regarding fees, forks, and price volatility. We conclude by reflecting on the next generation of blockchain innovations. Expected final online publication date for the Annual Review of Financial Economics, Volume 13 is November 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Entrepreneurial effort has been found to be an important predictor of entrepreneurial passion. The more effort one devotes to entrepreneurial activities, the more passionate one becomes. Our work, however, extends prior research by offering contrasting empirical evidence. Drawing on fit theory and the person-entrepreneurship fit perspective, we propose that for novice individuals, who do not feel a strong fit with entrepreneurship, engaging in entrepreneurial effort would increase the perception of misfit, thereby reducing their entrepreneurial passion. Results from two experimental studies confirm our hypotheses. Our research contributes to the entrepreneurial passion and the person-entrepreneurship fit literatures.
Introduction De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation. Methods Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use. Results Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1). Conclusions Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.
Authenticity facilitates positive human functioning. Yet, previous research has not adequately addressed whether different dimensions of authenticity develop naturally as one ages or whether their development can be facilitated through systematic interventions. These issues must be addressed to better understand the dimensionality of authenticity and its change over time. We conducted a quasi-experimental intervention study with 170 first-year business students (58 treatment and 112 control group participants) at a university in Switzerland over an eight-month period—a critical time when authenticity should naturally develop given young adults' move from their family of origin. A career and personal development program exhibited differential effects on three dimensions of authenticity: (1) authentic living increased only for those in the treatment group, (2) acceptance of external influence decreased in both groups, but with a stronger effect in the treatment group, and (3) no significant changes occurred in either group's self-alienation. These findings suggest that some authenticity dimensions may be more receptive to natural growth, whereas others require systematic interventions or may be notoriously hard to change. The results contribute to the theoretical understanding of authenticity and provide practical insights into its development.
Over an algebraically closed field k of characteristic zero, the Drinfeld double Dn of the Taft algebra that is defined using a primitive nth root of unity q∈k for n≥2 is a quasitriangular Hopf algebra. Kauffman and Radford have shown that Dn has a ribbon element if and only if n is odd, and the ribbon element is unique; however there has been no explicit description of this element. In this work, we determine the ribbon element of Dn explicitly. For any n≥2, we use the R-matrix of Dn to construct an action of the Temperley-Lieb algebra TLk(ξ) with ξ=−(q12+q−12) on the k-fold tensor power V⊗k of any two-dimensional simple Dn-module V. This action is known to be faithful for arbitrary k≥1. We show that TLk(ξ) is isomorphic to the centralizer algebra EndDn(V⊗k) for 1≤k≤2n−2.
In the family of piecewise differentiable expanding Markov transformations, every map preserves a unique absolutely continuous invariant measure. The measure theoretical entropy with respect to this invariant measure depends on the map differentiably. We prove that this entropy functional does not have any nontrivial local critical points. The only critical points are where the functional reaches its global maximum. We also observe that the same statement holds true for the family of sufficiently smooth volume-preserving Anosov maps on a torus. Based on Gallavotti–Cohen Chaotic Hypothesis, these families of chaotic maps may serve as mathematical models of thermodynamic systems where the second law of thermodynamics can be rigorously proved.
One specific instantiation of the storm-and-stress view of adolescence is the idea that “normal” adolescence involves high-risk substance use behaviors. However, although uptake of some substance use behaviors is more common during adolescence than other life stages, it is clear that not all adolescents engage in risky substance use—and among those who do, there is much variation in emotional, behavioral, and contextual precursors of this behavior. One such set of predictors forms the internalizing pathway to substance use disorder, whereby internalizing symptoms in childhood such as negative affect and anxiety set off a chain of consequences culminating in high-risk substance use in late adolescence. However, findings linking internalizing symptoms to substance use are mixed, and it is clear that this link varies across adolescents and contexts. One heretofore unanswered question is whether and how geographic location, specifically whether the adolescent lives in an urban or rural location, moderates this link. The current report is a secondary analysis of data from the Longitudinal Study of Australian Children (LSAC; N = 2,285), in which we examined the link between internalizing symptoms in childhood and initiation of substance use through age 19. Using a multiple event process survival mixture model (MEPSUM), we identified three trajectories of substance use initiation in adolescence: one (65.7% of the sample) characterized by near-complete abstinence until late adolescence, another (27.2%) by earlier initiation of alcohol, nicotine, and cannabis, and another (7.2%) by early initiation of these substances and later initiation of more hazardous drugs such as cocaine and methamphetamine. Although childhood externalizing symptoms increased the risk of being in the second or third class, internalizing symptoms decreased risk when rural and non-rural adolescents were considered together. Few effects of rurality were found, but the negative relationship between internalizing at age 10 and high-risk substance use was only observed among non-rural adolescents. This finding, which was inconsistent with our initial predictions that rurality might confer higher risk for substance use, instead suggests a potentially protective effect of internalizing symptoms for engagement in risky substance use which may differ based on an adolescent’s geographical context.
Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, setting, and participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main outcomes and measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial registration: ClinicalTrials.gov Identifier: NCT00297895.
We report the isolation and characterization of a series of three cobalt(II) bis(phosphine) complexes with varying numbers of coordinated solvent ligands in the axial position. X-ray quality crystals of [Co(dppv)2][BF4]2 (1), [Co(dppv)2(NCCH3)][BPh4]2 (2), and [Co(dppv)2(NCCH3)2][BF4]2 (3) (dppv = cis-1,2-bis(diphenylphosphino)ethylene) were grown under slightly different conditions, and their structures were compared. This analysis revealed multiple crystallization motifs for divalent cobalt(II) complexes with the same set of phosphine ligands. Notably, the 4-coordinate complex 1 is a rare example of a square-planar cobalt(II) complex, the first crystallographically characterized square-planar Co(II) complex containing only neutral, bidentate ligands. Characterization of the different axial geometries via EPR and UV-visible spectroscopies showed that there is a very shallow energy landscape for axial ligation. Ligand field angular overlap model calculations support this conclusion, and we provide a strategy for tuning other ligands to be axially labile on a phosphine scaffold. This methodology is proposed to be used for designing cobalt phosphine catalysts for a variety of oxidation and reduction reactions.
I argue that that an influential strategy for understanding conspiracy theories stands in need of radical revision. According to this approach, called ‘generalism’, conspiracy theories are epistemically defective by their very nature. Generalists are typically opposed by particularists, who argue that conspiracy theories should be judged case-by-case, rather than definitionally indicted. Here I take a novel approach to criticizing generalism. I introduce a distinction between ‘Dominant Institution Conspiracy Theories and Theorists’ and ‘Non-Dominant Institution Conspiracy Theories and Theorists’. Generalists uncritically center the latter in their analysis, but I show why the former must be centered by generalists’ own lights: they are the clearest representatives of their views, and they are by far the most harmful. Once we make this change in paradigm cases, however, various typical generalist theses turn out to be false or in need of radical revision. Conspiracy theories are not primarily produced by extremist ideologies, as generalists typically claim, since mainstream, purportedly non-extremist political ideologies turn out to be just as, if not more responsible for such theories. Conspiracy theories are also, we find, not the province of amateurs: they are often created and pushed by individuals widely viewed as experts, who have the backing of our most prestigious intellectual institutions. While generalists may be able to take this novel distinction and shift in paradigm cases on board, this remains to be seen. Subsequent generalist accounts that do absorb this distinction and shift will look radically different from previous incarnations of the view.
The proteolytic cleavage of C99 by γ-secretase is the last step in the production of amyloid-β (Aβ) peptides. Previous studies have shown that membrane lipid composition, cholesterol concentration, and mutation in the transmembrane helix modified the structures and fluctuations of C99. In this study, we performed atomistic molecular dynamics simulations of the homodimer of the 55-residue congener of the C-terminal domain of the amyloid protein precursor, C99(1-55), in a POPC-cholesterol lipid bilayer, and we compared the conformational ensemble of WT sequence to those of the A2T and D23N variants. These mutations are particularly interesting as the protective Alzheimer's disease (AD) A2T mutation is known to decrease Aβ production, whereas the early onset AD D23N mutation does not affect Aβ production. We found noticeable differences in the structural ensembles of the three sequences. In particular, A2T varies from both WT and D23N by having long-range effects on the population of the extracellular justamembrane helix, the interface between the G29xxx-G33xxx-G37 motifs and the fluctuations of the transmembrane helical topologies.
Background: Endovascular thrombectomy (EVT) is the standard-of-care for proximal large vessel occlusion (LVO) stroke. Data on technical and clinical outcomes in distal vessel occlusions (DVOs) remain limited. Methods: This was a retrospective study of patients undergoing EVT for stroke at 32 international centers. Patients were divided into LVOs (internal carotid artery/M1/vertebrobasilar), medium vessel occlusions (M2/A1/P1) and isolated DVOs (M3/M4/A2/A3/P2/P3) and categorized by thrombectomy technique. Primary outcome was a good functional outcome (modified Rankin Scale ≤2) at 90 days. Secondary outcomes included recanalization, procedure-time, thrombectomy attempts, hemorrhage, and mortality. Multivariate logistic regressions were used to evaluate the impact of technical variables. Propensity score matching was used to compare outcome in patients with DVO treated with aspiration versus stent retriever RESULTS: We included 7477 patients including 213 DVOs. Distal location did not independently predict good functional outcome at 90 days compared with proximal (p=0.467). In distal occlusions, successful recanalization was an independent predictor of good outcome (adjusted odds ratio (aOR) 5.11, p<0.05) irrespective of technique. Younger age, bridging therapy, and lower admission National Institutes of Health Stroke Scale (NIHSS) were also predictors of good outcome. Procedure time ≤1 hour or ≤3 thrombectomy attempts were independent predictors of good outcomes in DVOs irrespective of technique (aOR 4.5 and 2.3, respectively, p<0.05). There were no differences in outcomes in a DVO matched cohort of aspiration versus stent retriever. Rates of hemorrhage and good outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group and attempts in the stent retriever group. Conclusions: Outcomes following EVT for DVO are comparable to LVO with similar results between techniques. Techniques may exhibit different futility metrics; stent retriever thrombectomy was influenced by attempts whereas aspiration was more dependent on procedure time.
Background Implanted and transcutaneous nerve stimulators have shown promise as novel non-pharmacologic treatment for episodic and chronic migraines. The purpose of this study was to summarize the reported efficacy of transcutaneous single nerve stimulators in management of migraine frequency and severity. Methods A systematic review of five databases identified studies treating migraines with transcutaneous stimulation of a single nerve. Random effects model meta-analyses were conducted to establish the effect of preventive transcutaneous nerve stimulation on headache days per month and 0–10 numeric rating scale pain severity of headaches for both individuals with episodic and chronic migraines. Results Fourteen studies, which treated 995 patients, met inclusion criteria, including 7 randomized controlled trials and 7 uncontrolled clinical trials. Transcutaneous nerve stimulators reduced headache frequency in episodic migraines (2.81 fewer headache days per month, 95% CI 2.18–3.43, I² = 21%) and chronic migraines (2.97 fewer headache days per month, 95% CI 1.66–4.28, I² = 0%). Transcutaneous nerve stimulators reduced headache severity in episodic headaches (2.23 fewer pain scale points, 95% CI 1.64–2.81, I² = 88%). Conclusions Preventive use of transcutaneous nerve stimulators provided clinically significant reductions in headache frequency in individuals with chronic or episodic migraines. Individuals with episodic migraines also experienced a reduction in headache pain severity following preventive transcutaneous nerve stimulation.
Obesity is a risk factor for chronic diseases and moderate weight loss is generally recommended. Energy restriction results in the loss of hip bone mineral density (BMD) in older adults, but there is no consistent decline at the lumbar spine (LS), possibly due to vertebral abnormalities although this may also be dependent on the amount of weight loss. In this secondary analysis of weight loss trials investigating BMD and trabecular bone score (TBS) changes over 12–18 months, 92 postmenopausal women (60.8 ± 5.8 years; body mass index 32.7 ± 4.4 kg/m²) without osteoporosis, were divided into two groups: those who lost < 5% body weight (minimal) or ≥ 5% (moderate). Hip and LS–BMD and TBS were measured at baseline, 6 and 12–18 months. Exclusion of vertebral abnormalities (VE) was used to calculate BMD at the spine (LS–BMD–VE) using standard guidelines. Women lost 2.3 ± 2.4% and 8.5 ± 4.7% weight in the minimal and moderate weight loss groups, respectively. Over one third of the women had at least one vertebral abnormality or partially degraded TBS at baseline that worsened after weight loss, increasing to over 50% in this population (p < 0.05). TBS and hip BMD decreased with weight loss (p < 0.05), but LS–BMD did not decrease significantly. However, after excluding vertebral abnormalities, the LS–BMD–VE decreased in the entire population (p < 0.01), and by 1.7 ± 4.3% in the moderate weight loss group. This study suggests that older women without osteoporosis have vertebral abnormalities that obfuscated declines in BMD with weight loss, indicating that bone at the spine is further compromised.
Purpose Understanding real-time relationships between physical activity (PA) and symptoms during chemotherapy (CT) could have important implications for intervention. This study used ecological momentary assessment to examine the relationship between objective PA and symptoms during CT. Methods Breast cancers patients (n = 67; Mage = 48.6 (SD = 10.3)) participated in data collection at three time points during CT: beginning, middle, and end. At each time point, participants answered four prompts assessing symptoms and wore an accelerometer for 10 days (3 days pre-CT, day of CT, and 6 days post-CT). Multilevel linear regression models examined the between- and within-person associations between moderate to vigorous (MVPA) and light-intensity physical activity (LPA) and same and next-day symptom ratings controlling for covariates. Results On days when individuals engaged in more LPA or MVPA, separately, they reported improved affect, anxiety, fatigue, physical functioning (walking and activities of daily living), pain, and cognition that day (p < 0.001 for all). Findings were consistent for next-day symptom ratings with the exception that only previous day LPA was related to next-day fatigue and neither LPA nor MVPA were related to next-day cognition (p < 0.001 for all). No between-person effects were found. Conclusions Within person higher than usual PA on a given day, regardless of intensity, is associated with improved symptoms ratings on the current and next day. Implications for cancer survivors Encouraging breast cancer patients undergoing CT to engage in daily PA could help manage CT-associated symptoms.
Despite being widely applied in drug development, existing in vitro 2D cell-based models are not suitable to assess chronic mitochondrial toxicity. A novel in vitro assay system mimicking in vivo micro-environment for this purpose is urgently needed. The goal of this study is to establish a 3D cell platform as a reliable, sensitive, cost-efficient, and high-throughput assay to predict drug-induced mitochondrial toxicity. We evaluated a long-term culture of human primary urine-derived stem cells (USC) seeded in 3D silk fiber matrix (3D USC-SFM) and further tested chronic mitochondrial toxicity induced by Zalcitabine (ddC, a nucleoside reverse transcriptase inhibitor) as a test drug, compared to USC grown in spheroids. The numbers of USC remain steady in 3D spheroids for 4 weeks and 3D SFM for 6 weeks. However, the majority (95%) of USC survived in 3D SFM, while cell numbers significantly declined in 3D spheroids at 6 weeks. Highly porous SFM provides large-scale numbers of cells by increasing the yield of USC 125-fold/well, which enables the carrying of sufficient cells for multiple experiments with less labor and lower cost, compared to 3D spheroids. The levels of mtDNA content and mitochondrial superoxide dismutase2 [SOD2] as an oxidative stress biomarker and cell senescence genes (RB and P16, p21) of USC were all stably retained in 3D USC-SFM, while those were significantly increased in spheroids. mtDNA content and mitochondrial mass in both 3D culture models significantly decreased six weeks after treatment of ddC (0.2, 2, and 10 μM), compared to 0.1% DMSO control. Levels of complexes I, II, and III significantly decreased in 3D SFM-USC treated with ddC, compared to only complex I level which declined in spheroids. A dose- and time-dependent chronic MtT displayed in the 3D USC-SFM model, but not in spheroids. Thus, a long-term 3D culture model of human primary USC provides a cost-effective and sensitive approach potential for the assessment of drug-induced chronic mitochondrial toxicity.
Organisms live not as discrete entities on which an independent environment acts, but as members of a reproductive lineage in an ongoing series of interactions between that lineage and a dynamic ecological niche. These interactions continuously shape both systems in a reciprocal manner, resulting in the emergence of reliably co-occurring configurations within and between both systems. The enactive approach to cognition describes this relationship as the structural coupling between an organism and its environment; similarly, Developmental Systems Theory emphasizes the reciprocal nature of structurally coupled systems in its analysis of organisms as developmental processes embedded within a developmental system. Through an enactive-developmental systems framing, this paper identifies the organizational features of cognizing systems in order to motivate a picture of how organism and environment co-determine and co-construct one another. I argue that organisms can be characterized as self-organizing, operationally closed, plastic systems ecologically embedded within a developmental system. In virtue of this organizational makeup, organisms actively engage in the modulation and assessment of their coupling with their environment: cognitive strategies that entail contextualized responses to variations across the web of interactions that comprises the developmental system.
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2,694 members
Yuan Li
  • Department of Physics
James B Pease
  • Department of Biology
Dale Dagenbach
  • Department of Psychology
Terry D Blumenthal
  • Department of Psychology
1834 Wake Forest Road, NC 27106, Winston-Salem, North Carolina, United States
Head of institution
Nathan Hatch
(336) 758-5000