Running and Jumping Variables in RD Designs: Evidence Based on Race, Socioeconomic Status, and Birth Weights

Throughout the years spanned by the U.S. Vital Statistics Linked Birth and Infant Death Data (1983-2002), birth weights are measured most precisely for children of white and highly educated mothers. As a result, less healthy children, who are more likely to be of low socioeconomic status, are disproportionately represented at multiples of round numbers. This has crucial implications for any study using a regression discontinuity design in which birth weights are used as the running variable. For example, estimates will be biased in a manner that leads one to conclude that it is “good” to be strictly to the left of any 100-gram cutoff. As such, prior estimates of the effects of very low birth weight classification (Almond, Doyle, Kowalski, and Williams 2010) have been overstated and appear to be zero. This analysis highlights a more general problem that can afflict regression discontinuity designs. In cases where attributes related to the outcomes of interest predict heaping in the running variable, estimated effects are likely to be biased. We discuss approaches to diagnosing and correcting for this type of problem.regression discontinuity, donut RD, birth weight, infant mortality

Bio-based building components: A newly sustainable solution for traditional walls made of Arundo donax and gypsum

To contribute to the use of bio-based materials in the building sector, a novel bio-based wall panel, with a high thermal performance level, is proposed in this work. The panel is based on an ancient rural technique, widely diffused in southern Italy, which makes use of Arundo donax L. canes combined with gypsum plaster to build walls and ceilings of rural buildings. The enhancement of the thermal capacity of these panels by means of the introduction in the canes of a natural wax oleogel (WO) is proposed in this paper. A specific experimental campaign aiming at the comparison of traditional and innovative panels was carried out to assess the enhanced thermal performance of the proposed solution. The maximum value of heat flow absorbed from the panel with WO was 61.08 W/m(2) around a mean panel temperature of 24 & DEG;C, corresponding to the melting temperature range of the WO. The panel without WO at the same temperature absorbed an incoming heat flow of 34.64 W/m(2) which is about 57% of the panel with WO. The panel with WO released at a temperature of about 27.5 & DEG;C, a heat flow of 43.42 W/m(2). At the same temperature of about 27.5 & DEG;C, the panel without WO released a heat flow of 34.38 W/m(2) which is about 80% that of the panel with WO. The results highlighted that the addition of natural WO has enhanced the thermal capacity of the panel facilitating heat dissipation through the borders. These characteristics make the panel a suitable component for internal partitions of controlled temperature zones such as residential rooms, storage food areas, livestock buildings, and where it is necessary to obtain a constant environmental temperature. In particular, the null or low toxicity of the panel's materials allows for partition use, also in hygienically safe environments

Synthesis of Pyrazoles by 1,3-Dipolar Cycloaddition under Aqueous Micellar Catalysis

Ethyl diazoacetate (EDA), which is easily prepared from ethyl glycinate and NaNO2, reacts in situ with alkynes in a water micelle environment without organic solvent to form pyrazoles. The reaction is pH dependent, as in the presence of protic catalysis (H2SO4 4%, pH 3.5) a mixture of 3,5- and 4,5-disubstituted pyrazoles was obtained, while, at pH 5.5, only the 3,5-disubstituted isomer was obtained. The presence of the surfactant TPGS-750-M was crucial to secure clean crude reaction mixtures and high yields of the products. The same protocol was successfully applied to the synthesis of substituted pyrazolines. © 2022 The Author

Heaping-Induced Bias in Regression-Discontinuity Designs

This study uses Monte Carlo simulations to demonstrate that regression-discontinuity designs arrive at biased estimates when attributes related to outcomes predict heaping in the running variable. After showing that our usual diagnostics are poorly suited to identifying this type of problem, we provide alternatives. We also demonstrate how the magnitude and direction of the bias varies with bandwidth choice and the location of the data heaps relative to the treatment threshold. Finally, we discuss approaches to correcting for this type of problem before considering these issues in several non-simulated environments.

Polyphenol characterization and skin-preserving properties of hydroalcoholic flower extract from Himantoglossum robertianum (Orchidaceae)

Himantoglossum robertianum (Loisel.) P. Delforge is a Mediterranean orchid whose propagation in vitro has been achieved, making it eligible as a source of bioactive substances. Flowers were analyzed by light and SEM microscopy and used to obtain a polyphenol-rich, hydroalcoholic flower extract (HFE). HFE was characterized for total phenols, flavonoids and proanthocyanidins, and for polyphenol profile by RP-LC-DAD. Antioxidant assays, in vitro collagenase and elastase inhibition, and MTT and cell motility assays on HaCaT keratinocytes were done. Microscopy showed epidermal cells containing anthocyanins in the flower labellum. Flavonoids (flavones and flavan-3-ols) represented the most abundant compounds (42.91%), followed by scopoletin (33.79%), and phenolic acids (23.3%). Antioxidant assays showed strong activities, rating ORAC > FRAP > TEAC > \u3b2-carotene bleaching > DPPH > iron-chelation. Biological assays showed elastase and collagenase inhibition (up to 42% and 78%, respectively), improvement of HaCaT cell viability after treatment with 500 \u3bcM H2O2 (from 30% to 84% of control), and stimulation of cell migration rate up to 210% of control. In summary, HFE counteracted different free radicals, while protective properties were shown by cell-free and cell-based bioassays, suggesting the possible use of H. robertianum flowers for skin-preserving, repair, and anti-aging applications

HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico Approaches

Protein–protein interactions (PPI) represent attractive targets for drug design. Thus, aiming at a deeper insight into the HSV-1 envelope glycoprotein D (gD), protein–protein docking and dynamic simulations of gD-HVEM and gD-Nectin-1 complexes were performed. The most stable complexes and the pivotal key residues useful for gD to anchor human receptors were identified and used as starting points for a structure-based virtual screening on a library of both synthetic and designed 1,2,3-triazole-based compounds. Their binding properties versus gD interface with HVEM and Nectin-1 along with their structure-activity relationships (SARs) were evaluated. Four [1,2,3]triazolo[4,5-b]pyridines were identified as potential HSV-1 gD inhibitors, for their good theoretical affinity towards all conformations of HSV-1 gD. Overall, this study suggests promising basis for the design of new antiviral agents targeting gD as a valuable strategy to prevent viral attachment and penetration into the host cell

Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences

Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed

Electron transport through single Mn12 molecular magnets

We report transport measurements through a single-molecule magnet, the Mn12 derivative [Mn12O12(O2C-C6H4-SAc)16(H2O)4], in a single-molecule transistor geometry. Thiol groups connect the molecule to gold electrodes that are fabricated by electromigration. Striking observations are regions of complete current suppression and excitations of negative differential conductance on the energy scale of the anisotropy barrier of the molecule. Transport calculations, taking into account the high-spin ground state and magnetic excitations of the molecule, reveal a blocking mechanism of the current involving non-degenerate spin multiplets.Comment: Accepted for Phys. Rev. Lett., 5 pages, 4 figure

Rapamycin-loaded polymeric nanoparticles as an advanced formulation for macrophage targeting in atherosclerosis

Recently, rapamycin (Rapa) represents a potential drug treatment to induce regression of atherosclerotic plaques; however, its use requires site-specific accumulation in the vessels involved in the formation of the plaques to avoid the systemic effects resulting from its indiscriminate biodistribution. In this work, a stable pharmaceutical formulation for Rapa was realized as a dried powder to be dispersed extemporaneously before administration. The latter was constituted by man-nitol (Man) as an excipient and a Rapa-loaded polymeric nanoparticle carrier. These nanoparticles were obtained by nanoprecipitation and using as a starting polymeric material a polycaprolactone (PCL)/α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) graft copolymer. To obtain nanoparti-cles targeted to macrophages, an oxidized phospholipid with a high affinity for the CD36 receptor of macrophages, the 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdia-PC), was added to the starting organic phase. The chemical–physical and technological characterization of the obtained nanoparticles demonstrated that: both the drug loading (DL%) and the entrapment efficiency (EE%) entrapped drug are high; the entrapped drug is in the amorphous state, protected from degradation and slowly released from the polymeric matrix; and the KOdia-PC is on the nanoparticle surface (KP-Nano). The biological characterization demonstrated that both systems are quickly internalized by macrophages while maintaining the activity of the drug. In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug