The Effect of Smart Contracts on Online Investment Decisions: An Experimental Study in ICOs

The imbalance of internal and external knowledge for investments in Initial Coin Offerings (ICO) leads to an information asymmetry, where issuers may further exploit a moral hazard as a resulting mismatch of time and interest during lock-up situations. The existing regulatory vacuum is mirrored by literature, as scholars deliver insights on effective means of signaling. However, research on smart contracts as immutable mechanisms and effective signals to mitigate risks for online investments remains an untapped subject, whilst market demand for solutions to an existing agency problem remains high. To respond to a pressing research question, this study conducted a randomized between-subjects online experiment with a sample of 391 participants. Results include a significant positive effect of the implementation of smart contracts on investor decisions in a present lock-up situation

Polymer particles for the intra-articular delivery of drugs to treat osteoarthritis

Osteoarthritis (OA) is a leading cause of chronic disability. It is a progressive disease, involving pathological changes to the entire joint, resulting in joint pain, stiffness, swelling, and loss of mobility. There is currently no disease-modifying pharmaceutical treatment for OA, and the treatments that do exist suffer from significant side effects. An increasing understanding of the molecular pathways involved in OA is leading to many potential drug targets. However, both current and new therapies can benefit from a targeted approach that delivers drugs selectively to joints at therapeutic concentrations, while limiting systemic exposure to the drugs. Delivery systems including hydrogels, liposomes, and various types of particles have been explored for intra-articular drug delivery. This review will describe progress over the past several years in the development of polymer-based particles for OA treatment, as well as their in vitro, in vivo, and clinical evaluation. Systems based on biopolymers such as polysaccharides and polypeptides, as well as synthetic polyesters, poly(ester amide)s, thermoresponsive polymers, poly(vinyl alcohol), amphiphilic polymers, and dendrimers will be described. We will discuss the role of particle size, biodegradability, and mechanical properties in the behavior of the particles in the joint, and the challenges to be addressed in future research

Melt chemistry and redox conditions control titanium isotope fractionation during magmatic differentiation

Titanium offers a burgeoning isotope system that has shown significant promise as a tracer of magmatic processes. Recent studies have shown that Ti isotopes display significant mass-dependent variations linked to the crystallisation of Fe-Ti oxides during magma differentiation. We present a comprehensive set of Ti isotope data for a range of differentiation suites from alkaline (Ascension Island, Afar and Heard Island), calc-alkaline (Santorini) and tholeiitic (Monowai seamount and Alarcon Rise) magma series to further explore the mechanics of Ti isotope fractionation in magmas. Whilst all suites display an increase in δ49/47Ti (deviation in 49Ti/47Ti of a sample relative to the OL-Ti reference material) during magma differentiation relative to indices such as increasing SiO2 and decreasing Mg#, our data reveal that each of the three magma series have contrasting δ49/47Ti fractionation patterns over comparable ranges of SiO2 and Mg#. Alkaline differentiation suites from intraplate settings display the most substantial range of variation (δ49/47Ti = +0.01 to +2.32‰), followed by tholeiites (−0.01 to +1.06‰) and calc-alkaline magmas (+0.06 to +0.64‰). Alkaline magmas possess high initial melt TiO2 contents which enables early saturation of ilmenite + titanomagnetite and a substantial degree of oxide crystallisation, whereas tholeiitic and calc-alkaline suites crystallise fewer oxides and have titanomagnetite as the dominant oxide phase. Positive slopes of FeO*/TiO2 vs. SiO2 during magma differentiation are related to high degrees of crystallisation of Ti-rich oxides (i.e. ilmenite). Bulk solid-melt Ti isotope fractionation factors co-vary with the magnitude of the slope of FeO*/TiO2 vs. SiO2 during magma differentiation.This indicates that the modal abundance and composition of the Fe-Ti oxide phase assemblage, itself is controlled by melt composition, governs Ti isotope fractionation during magma differentiation. In addition to this overall control, hydrous, oxidised calc-alkaline suites display a resolvable increase in δ49/47Ti at higher Mg# relative to drier and more reduced tholeiitic arc suites. These subparallel Ti isotope fractionation patterns are best explained by the earlier onset of oxide segregation in arc magmas with a higher oxidation state and H2O content. This indicates the potential of Ti isotopes to be utilised as proxies for geodynamic settings of magma generation

Hemiretinal vein occlusion 12-month outcomes are unique with vascular endothelial growth factor inhibitors: data from the Fight Retinal Blindness! Registry

BACKGROUND/AIMS To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care. METHODS A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits. RESULTS At baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; p<0.001). Mean change in CST in HRVO (-231 µm) was similar to CRVO (-259 µm; p=0.33) but greater than BRVO eyes (-151 µm; p=0.003). The groups had similar median burdens of eight injections and nine visits. CONCLUSIONS HRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes

Defining a Minimum Set of Standardized Patient-centered Outcome Measures for Macular Degeneration

Purpose To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. Design Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). Methods Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice. Results Standardized measurement of the following outcomes is recommended: visual functioning and quality of life (distance visual acuity, mobility and independence, emotional well-being, reading and accessing information); number of treatments; complications of treatment; and disease control. Proposed data collection sources include administrative data, clinical data during routine clinical visits, and patient-reported sources annually. Recording the following clinical characteristics is recommended to enable risk adjustment: age; sex; ethnicity; smoking status; baseline visual acuity in both eyes; type of macular degeneration; presence of geographic atrophy, subretinal fibrosis, or pigment epithelial detachment; previous macular degeneration treatment; ocular comorbidities. Conclusions The recommended minimum outcomes and pragmatic reporting standards should enable standardized, meaningful assessments and comparisons of macular degeneration treatment outcomes. Adoption could accelerate global improvements in standardized data gathering and reporting of patient-centered outcomes. This can facilitate informed decisions by patients and health care providers, plus allow long-term monitoring of aggregate data, ultimately improving understanding of disease progression and treatment responses

“Sexual” Population Structure and Genetics of the Malaria Agent P. falciparum

The population genetics and structure of P. falciparum determine the rate at which malaria evolves in response to interventions such as drugs and vaccines. This has been the source of considerable recent controversy, but here we demonstrate the organism to be essentially sexual, in an area of moderately high transmission in the Lower Shire Valley, Malawi. Seven thousand mosquitoes were collected and dissected, and genetic data were obtained on 190 oocysts from 56 infected midguts. The oocysts were genotyped at three microsatellite loci and the MSP1 locus. Selfing rate was estimated as 50% and there was significant genotypic linkage disequilibrium (LD) in the pooled oocysts. A more appropriate analysis searching for genotypic LD in outcrossed oocysts and/or haplotypic LD in the selfed oocysts found no evidence for LD, indicating that the population was effectively sexual. Inbreeding estimates at MSP1 were higher than at the microsatellites, possibly indicative of immune action against MSP1, but the effect was confounded by the probable presence of null mutations. Mating appeared to occur at random in mosquitoes and evidence regarding whether malaria clones in the same host were related (presumably through simultaneous inoculation in the same mosquito bite) was ambiguous. This is the most detailed genetic analysis yet of P. falciparum sexual stages, and shows P. falciparum to be a sexual organism whose genomes are in linkage equilibrium, which acts to slow the emergence of drug resistance and vaccine insensitivity, extending the likely useful therapeutic lifespan of drugs and vaccines