Comparing principal stratification and selection models in parametric causal inference with nonignorable missingness

Two approaches for dealing with “endogenous selection” problems when estimating causal effects are considered. They are principal stratification and selection models. The main goal is to highlight similarities and differences between the two approaches, by investigating the different nature of their parametric hypotheses. The principal stratification approach focuses on information contained in specific subgroups of units. The aim is to produce valid inference conditional on such subgroups, without an a priori extension of the results to the whole population. Selection models, on the contrary, aim at estimating parameters that should be valid for the whole population, as if the data come from random sampling. A simulation study is conducted to show their different performances, with data generating processes coming from either approach. It is also argued that principal stratification is able to suggest alternative identification strategies not always easily translatable into assumptions of a selection model.     

Herding stochastic autonomous agents via local control rules and online target selection strategies

Autonomous Robots - We propose a simple yet effective set of local control rules to make a small group of “herder agents” collect and contain in a desired region a large ensemble of...     

Thermodynamically Stable SiwCxNyOz Polymer-Like, Amorphous Ceramics Made from Organic Precursors

This communication reports new results on the enthalpy of formation of pseudo-amorphous ceramic compounds constituted from silicon, carbon, oxygen, and nitrogen (SiCNO), made from the polymer route. Again, like the SiCO materials, although with one exception, the enthalpy of formation from crystalline components (SiO₂ cristobalite, β-Si₃N₄, SiC, and excess C) is negative. Some of the alloyed oxygen–nitrogen compositions yield enthalpies that are much more negative (∼100 kJ/g·atom) in comparison with compositions that contain mainly oxygen or nitrogen (∼20 kJ/g·atom). The exception, having a N/O ratio near 2, has a positive value for the enthalpy. This may reflect the presence of nanoclusters of stoichiometric Si₂N₂O instead of the pseudo-amorphous nanodomain structure seen for the other samples.     

Cadmium distribution and effects on ultrastructureand chlorophyll status in photobionts and mycobionts of Xanthoria parietina

In this work, we tried to go deeper inside distribution and toxicity of cadmium (Cd) in the macrolichen Xanthoria parietina (L.) Th. Fr. Thalli of this species were treated with 0 (control), 4.5, 9, 18, or 36 muM Cd for 24 or 48 hours. Transmission electron microscopy, X-ray microanalysis, and electron energy loss spectroscopy were exploited to study distribution and ultrastructural effects of Cd in thalli; spectrophotometric techniques were utilized for measuring Cd effects on chlorophyll (Chl) content; light fluorescence microscopy was used to evaluate Chl autofluorescence. The highest Cd concentration caused ultrastructural alterations both in the mycobiont and in the photobiont, more severe in the latter, decreased total Chl content and progressively quenched Chl autofluorescence. Cell wall immobilization was observed in both bionts, and evidence pointing to a Cd-binding ability by the concentric bodies in the mycobiont was also obtained. Lower Cd concentrations led to slight or even no effects on thallus structures and on Chl content and autofluorescence. The results obtained suggest that: (1) among the two bionts, the algal partner appears to be more susceptible to Cd stress, probably because of the presence of delicate and sensitive components such as the chloroplast and photosynthetic pigments; (2) a concentration threshold exists for the occurrence of evident structural and functional damage in X. parietina thalli exposed to Cd.     

Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.     

Stability of Polymer:PCBM Thin Films under Competitive Illumination and Thermal Stress

The combined effects of illumination and thermal annealing on the morphological stability and photodimerization in polymer/fullerene thin films are examined. While illumination is known to cause fullerene dimerization and thermal stress their dedimerization, the operation of solar cells involves exposure to both. The competitive outcome of these factors with blends of phenyl‐C61‐butyric acid methyl ester (PCBM) and polystyrene (PS), supported on PEDOT:PSS is quantified. UV–vis spectroscopy is employed to quantify dimerization, time‐resolved neutron reflectivity to resolve the vertical composition stratification, and atomic force microscopy for demixing and coarsening in thin films. At the conventional thermal stress test temperature of 85 °C (and even up to the PS glass transition), photodimerization dominates, resulting in relative morphological stability. Prior illumination is found to result in improved stability upon high temperature annealing, compatible with the need for dedimerization to occur prior to structural relaxation. Modeling of the PCBM surface segregation data suggests that only PCBM monomers are able to diffuse and that illumination provides an effective means to control dimer population, and thus immobile fullerene fraction, in the timescales probed. The results provide a framework for understanding of the stability of organic solar cells under operating conditions.     

Interplay between Oxidative Stress and Metabolic Derangements in Non-Alcoholic Fatty Liver Disease: The Role of Selenoprotein P

Background: Pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) are complex and multifactorial. We investigated oxidative stress through the measurement of selenoprotein P (SeP) in serum and we explored its relation to metabolic derangements and liver damage in a group of non-diabetic NAFLD subjects. Methods: 57 NAFLD patients underwent a double-tracer oral glucose tolerance test (OGTT). Insulin resistance (IR) components were calculated at baseline as follows: hepatic-IR = (endogenous glucose production*insulin); peripheral-IR = (glucose rate of disappearance(Rd)); adipose-tissue(AT)-IR as Lipo-IR = (glycerol rate of appearance (Ra)*insulin) or AT-IR = (free fatty acids (FFAs)*insulin). The lipid and amino acid (AA) profiles were assessed by gas chromatography–mass spectrometry. SeP levels were measured by enzyme immunosorbent assay. Results: Circulating SeP correlated with insulin (r_S = 0.28), FFAs (r_S = 0.42), glucose Rd (r_S = −0.33) and glycerol Ra (r_S = −0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (r_S > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (r_S = −0.31), glycine (r_S = −0.44) and branched chain AA (r_S = −0.32), and directly correlated with saturated (r_S = 0.41) and monounsaturated FFAs (r_S = 0.40). Hepatic steatosis and fibrosis increased in subjects with higher levels of SeP. In multivariable regression analysis, SeP was associated with the degree of hepatic fibrosis (t = 2.4, p = 0.022). Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD.     

A Novel KCNA2 Variant in a Patient with Non-Progressive Congenital Ataxia and Epilepsy: Functional Characterization and Sensitivity to 4-Aminopyridine

Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous system, where they regulate neuronal excitability. Recently, heterozygous mutations in KCNA2 have been associated with a spectrum of symptoms extending from epileptic encephalopathy, intellectual disability, and cerebellar ataxia. Patients are treated with a combination of antiepileptic drugs and 4-aminopyridine (4-AP) has been recently trialed in specific cases. We identified a novel variant in KCNA2, E236K, in a Serbian proband with non-progressive congenital ataxia and early onset epilepsy, treated with sodium valproate. To ascertain the pathogenicity of E236K mutation and to verify its sensitivity to 4-AP, we transfected HEK 293 cells with Kv1.2 WT or E236K cDNAs and recorded potassium currents through the whole-cell patch-clamp. In silico analysis supported the electrophysiological data. E236K channels showed voltage-dependent activation shifted towards negative potentials and slower kinetics of deactivation and activation compared with Kv1.2 WT. Heteromeric Kv1.2 WT+E236K channels, resembling the condition of the heterozygous patient, confirmed a mixed gain- and loss-of-function (GoF/LoF) biophysical phenotype. 4-AP inhibited both Kv1.2 and E236K channels with similar potency. Homology modeling studies of mutant channels suggested a reduced interaction between the residue K236 in the S2 segment and the gating charges at S4. Overall, the biophysical phenotype of E236K channels correlates with the mild end of the clinical spectrum reported in patients with GoF/LoF defects. The response to 4-AP corroborates existing evidence that KCNA2-disorders could benefit from variant-tailored therapeutic approaches, based on functional studies.