The Economics of Crypto-Democracy

Democracy is an economic problem of choice constrained by transaction costs and information costs. Society must choose between competing institutional frameworks for the conduct of voting and elections. These decisions are constrained by the technologies and institutions available. Blockchains are a governance technology that reduces the costs of consensus, coordinating information, and monitoring and enforcing contracts. Blockchain could be applied to the voting and electoral process to form a crypto-democracy. Analysed through the Institutional Possibility Frontier framework, we propose that blockchain lowers disorder and dictatorship costs of the voting and electoral process. In addition to efficiency gains, this technological progress has implications for decentralised institutions of voting. One application of crypto-democracy, quadratic voting, is discussed

Light-Induced Currents at Domain Walls in Multiferroic BiFeO3.

Multiferroic BiFeO3 (BFO) films with spontaneously formed periodic stripe domains can generate above-gap open circuit voltages under visible light illumination; nevertheless the underlying mechanism behind this intriguing optoelectronic response has not been understood to date. Here, we make contact-free measurements of light-induced currents in epitaxial BFO films via detecting terahertz radiation emanated by these currents, enabling a direct probe of the intrinsic charge separation mechanisms along with quantitative measurements of the current amplitudes and their directions. In the periodic stripe samples, we find that the net photocurrent is dominated by the charge separation across the domain walls, whereas in the monodomain samples the photovoltaic response arises from a bulk shift current associated with the non-centrosymmetry of the crystal. The peak current amplitude driven by the charge separation at the domain walls is found to be 2 orders of magnitude higher than the bulk shift current response, indicating the prominent role of domain walls acting as nanoscale junctions to efficiently separate photogenerated charges in the stripe domain BFO films. These findings show that domain-wall-engineered BFO thin films offer exciting prospects for ferroelectric-based optoelectronics, as well as bias-free strong terahertz emitters

High Quality, Low Cost Egg Incubator for BIC Church in Choma, Zambia

The Egg Incubator team is partnering with the Brethren in Christ Church located in Choma, Zambia to design a high-quality, low-cost chicken egg incubator to supply the pastors and church members with a means of food and income. The design will need to take into account the accessibility and cost of the tools and materials. The current prototype features separate heating and humidity systems, a control system to maintain a set temperature and humidity, and tilting egg racks. The heating system consists of two stovetop coils to produce heat and a fan to transfer it to the air. The humidifier utilizes an atomizer in a pan of water to create a mist that mixes with the hot air to create humidity. The control system uses a proportional integral derivative controller (PID) to keep the temperature at 37 ± 1 °C and the humidity at 60–70%. The egg racks are tilted by a motor that runs every 6 hours to prevent the embryos from sticking to the shell. With a fully functioning prototype, the team has begun to incubate 60 real fertilized eggs. During the 21-day incubation process, a final prototype iteration is being designed and will be built on-site in Zambia in May 2022. Funding for this work provided by The Collaboratory for Strategic Partnerships and Applied Research.https://mosaic.messiah.edu/engr2022/1004/thumbnail.jp

Christian-Muslim Relations in a State Church Situation: Politics of Religion and Interfaith Dialogue

No abstract availabl

Advancing medical technology innovation and clinical translation via a model of industry-enabled technical and educational support: Indiana Clinical and Translational Sciences Institute’s Medical Technology Advance Program

The success rate for translation of newly engineered medical technologies into clinical practice is low. Traversing the “translational valleys of death” requires a high level of knowledge of the complex landscape of technical, ethical, regulatory, and commercialization challenges along a multi-agency path of approvals. The Indiana Clinical and Translational Sciences Institute developed a program targeted at increasing that success rate through comprehensive training, education, and resourcing. The Medical Technology Advance Program (MTAP) provides technical, educational, and consultative assistance to investigators that leverages partnerships with experts in the health products industry to speed progress toward clinical implementation. The training, resourcing, and guidance are integrated through the entire journey of medical technology translation. Investigators are supported through a set of courses that cover bioethics, ethical engineering, preclinical and clinical study design, regulatory submissions, entrepreneurship, and commercialization. In addition to the integrated technical and educational resources, program experts provide direct consultation for planning each phase along the life cycle of translation. Since 2008, nearly 200 investigators have gained assistance from MTAP resulting in over 100 publications and patents. This support via medicine–engineering–industry partnership provides a unique and novel opportunity to expedite new medical technologies into clinical and product implementation

Rates of cortical thinning in Alzheimer's disease signature regions associate with vascular burden but not with β-amyloid status in cognitively normal adults at age 70

BACKGROUND: Consistent patterns of reduced cortical thickness have been identified in early Alzheimer's disease (AD). However, the pathological factors that influence rates of cortical thinning within these AD signature regions remain unclear. METHODS: Participants were from the Insight 46 substudy of the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort), a prospective longitudinal cohort study. Linear regression was used to examine associations of baseline cerebral β-amyloid (Aβ) deposition, measured using florbetapir positron emission tomography, and baseline white matter hyperintensity volume (WMHV) on MRI, a marker of cerebral small vessel disease, with subsequent longitudinal changes in AD signature cortical thickness quantified from baseline and repeat MRI (mean [SD] interval 2.4 [0.2] years). RESULTS: In a population-based sample of 337 cognitively normal older white adults (mean [SD] age at baseline 70.5 [0.6] years; 48.1% female), higher global WMHV at baseline related to faster subsequent rates of cortical thinning in both AD signature regions (~0.15%/year faster per 10 mL additional WMHV), whereas baseline Aβ status did not. Among Aβ positive participants (n=56), there was some evidence that greater global Aβ standardised uptake value ratio at baseline related to faster cortical thinning in the AD signature Mayo region, but this did not reach statistical significance (p=0.08). CONCLUSIONS: Cortical thinning within AD signature regions may develop via cerebrovascular pathways. Perhaps reflecting the age of the cohort and relatively low prevalence of Aβ-positivity, robust Aβ-related differences were not detected. Longitudinal follow-up incorporating additional biomarkers will allow assessment of how these relationships evolve closer to expected dementia onset

Associations of β-Amyloid and Vascular Burden With Rates of Neurodegeneration in Cognitively Normal Members of the 1946 British Birth Cohort

OBJECTIVE: To quantify the independent and interactive associations of amyloid-β (Aβ) and white matter hyperintensity volume (WMHV) - a marker of presumed cerebrovascular disease (CVD) - with rates of neurodegeneration, and to examine the contributions of APOE ε4 and vascular risk measured at different stages of adulthood in cognitively normal members of the 1946 British birth cohort. METHODS: Participants underwent brain MRI and florbetapir-Aβ positron emission tomography as part of Insight 46, an observational population-based study. Changes in whole brain, ventricular and hippocampal volume were directly measured from baseline and repeat volumetric T1 MRI using the Boundary Shift Integral. Linear regression was used to test associations with: baseline Aβ deposition; baseline WMHV; APOE ε4; and office-based Framingham heart study-cardiovascular risk scores (FHS-CVS) and systolic blood pressure (BP) at ages 36, 53 and 69 years. RESULTS: 346 cognitively normal participants (mean [SD] age at baseline scan 70.5 [0.6] years; 48% female) had high-quality T1 MRI data from both time-points (mean [SD] scan interval 2.4 [0.2] years). Being Aβ positive at baseline was associated with 0.87 ml/year faster whole brain atrophy (95% CI 0.03, 1.72), 0.39 ml/year greater ventricular expansion (95% CI 0.16, 0.64) and 0.016 ml/year faster hippocampal atrophy (95% CI 0.004, 0.027), while each 10 ml additional WMHV at baseline was associated with 1.07 ml/year faster whole brain atrophy (95% CI 0.47, 1.67), 0.31 ml/year greater ventricular expansion (95% CI 0.13, 0.60) and 0.014 ml/year faster hippocampal atrophy (95% CI 0.006, 0.022). These contributions were independent and there was no evidence that Aβ and WMHV interacted in their effects. There were no independent associations of APOE ε4 with rates of neurodegeneration after adjusting for Aβ status and WMHV, and no clear relationships between FHS-CVS or systolic BP and rates of neurodegeneration when assessed across the whole sample, nor any evidence that they acted synergistically with Aβ. CONCLUSIONS: Aβ and presumed CVD have distinct and additive effects on rates of neurodegeneration in cognitively normal elderly. These findings have implications for the use of MRI measures as biomarkers of neurodegeneration and emphasize the importance of risk management and early intervention targeting both pathways

Neuroimaging, clinical and life course correlates of normal-appearing white matter integrity in 70-year-olds

We investigate associations between normal-appearing white matter (NAWM) microstructural integrity in cognitively normal ∼70-year-olds and concurrently measured brain health and cognition, demographics, genetics and life course cardiovascular health. Participants born in the same week in March 1946 (British 1946 Birth cohort) underwent PET-MRI around age 70. Mean standardized NAWM integrity metrics (fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI) and orientation dispersion index (ODI)) were derived from diffusion MRI. Linear regression was used to test associations between NAWM metrics and (1) concurrent measures, including whole brain volume, white matter hyperintensity volume (WMHV), PET amyloid and cognition; (2) the influence of demographic and genetic predictors, including sex, childhood cognition, education, socioeconomic position, and genetic risk for Alzheimer’s Disease (APOE-ε4); (3) systolic and diastolic blood pressure and cardiovascular health (FHS-CVS) across adulthood. Sex interactions were tested. Statistical significance included false discovery rate correction (5%). 362 participants met inclusion criteria (mean age 70 years, 49% female). Higher WMHV was associated with lower FA (b=-0.09 [95%CI:-0.11, -0.06] p<0.01), NDI (b=-0.17 [-0.22, -0.12] p<0.01), and higher MD (b=0.14 [-0.10, -0.17] p<0.01); amyloid (in men) was associated with lower FA (b=-0.04 [-0.08, -0.01] p=0.03) and higher MD (b=0.06 [0.01,0.11] p=0.02). FHS-CVS in later-life (age 69) was associated with NAWM [lower FA (b=-0.06 [-0.09, -0.02] p<0.01), NDI (b=-0.10 [-0.17, -0.03] p<0.01), and higher MD (b=0.09 [0.04,0.14] p<0.01). Significant sex interactions (p<0.05) emerged for midlife cardiovascular health (age 53) and NAWM at 70: marginal effect plots demonstrated, in women only, NAWM was associated with higher midlife FHS-CVS (lower FA and NDI), midlife systolic (lower FA, NDI, and higher MD), and diastolic (lower FA and NDI) blood pressure, and greater blood pressure change between 43 and 53 years (lower FA and NDI), independently of WMHV. In summary, poorer NAWM microstructural integrity in ∼70-year-olds was associated with measures of cerebral small vessel disease, amyloid (in males) and later-life cardiovascular health, demonstrating how NAWM can provide additional information to overt white matter disease. Our findings further show that greater midlife cardiovascular risk and higher blood pressure were associated with poorer NAWM microstructural integrity in females only, suggesting that women’s brains may be more susceptible to the effects of midlife blood pressure and cardiovascular health

Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis and Tumor Progression in Mouse Models of Lung Cancer and Impacts Tumor-Initiating Cells

The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the interconversion of pyruvate and lactate, is upregulated in human cancers, and is associated with aggressive tumor outcomes. Here we use an inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo. This was accompanied by reactivation of mitochondrial function in vitro, but not in vivo or ex vivo. Finally, using a specific small molecule LDH-A inhibitor, we demonstrated that LDH-A is essential for cancer-initiating cell survival and proliferation. Thus, LDH-A can be a viable therapeutic target for NSCLC, including cancer stem cell-dependent drug-resistant tumors