Preventive Group Training Improves Children’s Outcomes after Divorce: A Dutch Quasi-experimental Study

Worldwide, many children experience parental separation and divorce. This has a significant impact on their well-being, and emotional and behavioral functioning, and calls for prevention. To assess the effects of the Children of Divorce Intervention Program in the Netherlands (CODIP-NL) on 6- to 8-year-olds, we performed a quasi-experimental effect study. The study compared children receiving CODIP-NL (intervention: I, n = 104), children not receiving CODIP-NL but having divorced parents (divorced control: DC, n = 37), and children belonging to non-divorced families (non-divorced control: NDC, n = 138). Outcomes pertained to children’s positive functioning, emotional and behavioral problems, and well-being. We assessed pre- to post-test differences in change in mother-reported outcomes between the intervention and control groups, and pre- to post-test differences in group leader reports. The intervention led to increases in mother-reported positive functioning (d = 0.97 I vs. DC; d = 1.04 I vs. NDC), and well-being (d = 1.00 I vs. DC; d = 0.84 I vs. NDC). Mother-reported child emotional and behavioral problems decreased after participation (total difficulties, d = 0.73 I vs. DC; d = 0.49 I vs. NDC). Group leader-reported pre- to post-test differences (p ≤ 0.001) pointed in the same directions. Findings support further implementation of CODIP to support children’s positive functioning and well-being, and to decrease emotional and behavioral problems after their parents’ divorce.

The Determinant of Student Decision to Continue Their Study on Postgraduate Sharia Economic Study Program of Uin Alauddin Makassar

This research aims to examine and partially and simultaneously the effects of (1) socialization, (2) study program accreditation, (3) tuition fees, and (4) job opportunities for students' decisions to continue their education on Postgraduate Sharia Economic Study Program of UIN Alauddin Makassar. This research is an ex-post facto research that examines causal associative relationships with a quantitative approach. The sampling technique is done by proportional random sampling. Techniques of analysis and processing of research data using multiple linear regression analysis. The results show that socialization partially does not have an effect, study program accreditation has a positive and significant effect, tuition fees has a positive and significant effect, and job opportunities do not have an effect, and simultaneously socialization, accreditation, tuition fees, and job opportunities have effect on students' decisions to continue their education in the Postgraduate Sharia Economic Study Program of UIN Alauddin Makassar. It indicates that the all factors in this study can be determined as the factors for the students to choose Postgraduate Sharia Economic Study Program in UIN Alauddin Makassar; thus, in order to increase the decisions of other students, the university needs to increase aspects that this research has been conducted. The recommendation for future researchers is conducting research with other variables to know other reasons and aspects of students to continue their study at Postgraduate Sharia Economic Study Program of UIN Alauddin Makassar.

Effect of Selective Lateral Chromium Doping by RF Magnetron Sputtering on the Structural, and Opto-Electrical Properties of Nickel Oxide

In this study, chromium (Cr)-doped nickel oxide (NiO) thin films were deposited by employing selective lateral doping of Cr in NiO by radio-frequency magnetron sputtering at different doping times ranging from 0 s (undoped) to 80 s. The structural, optical, and electrical properties of the resulting Cr-doped NiO thin films were investigated. Structural investigation from XRD patterns indicated that the grown Cr-doped NiO layer crystallized in a cubic phase. Broadening of the diffraction peak with increasing doping time from 0 s to 80 s led to a reduction in the crystallite size that varied from 23.52 nm to 14.65 nm. Compared with the undoped NiO, the diffraction peak along the (200) plane shifted from left to right as a function of doping time. This result indicated that Cr+3 could easily enter the NiO lattice. Results from the Hall-effect study disclosed that electrical properties of Cr-doped NiO was highly dependent on doping time. The conductivity of NiO was increased with doping time, and the highest conductivity (8.73 × 10−2 Scm−1) was achieved at a doping time of 80 s. Finally, optical investigations revealed that as doping time increased, the optical bandgap of Cr-doped NiO films dropped from 3.43 eV to 3.28 eV. The highest Urbach energy at higher doping time indicated that crystallinity became poorer, and the degree of defects increased with increasing doping time.

An Enterohepatic Recirculation Population Pharmacokinetic and MIC-1 Pharmacokinetic-Pharmacodynamic Model for the MDM2 Inhibitor Navtemadlin (KRT-232) in Healthy Subjects

Background: Murine double minute 2 (MDM2) is the primary negative regulator of the tumor suppressor protein, p53. Navtemadlin (KRT-232), a potent and selective, orally available MDM2 inhibitor restores p53 activity to drive apoptosis of cancer cells in TP53 WT malignancies. Navtemadlin is currently being evaluated in a phase 3 trial of patients with relapsed or refractory myelofibrosis, as well as in numerous phase 1b/2 trials in various hematologic malignancies and solid tumors. Serum macrophage inhibitor cytokine-1 (MIC-1) is a pharmacodynamic (PD) marker of p53-mediated activity in patients treated with navtemadlin (Allard et al. HemaSphere. 2020). Using pharmacokinetic (PK) and PD data from a healthy subject food effect study (Wong et al. Blood. 2020), we developed a population PK (PPK) model that characterized enterohepatic recirculation (EHR) as a half-life extending element in the PK profiles of navtemadlin and its major acyl glucuronide metabolite M1. MIC-1 PD data were incorporated into the model to quantify plasma concentration-driven MIC-1 excursions and to simulate PK and PD across time and dose in healthy subjects. Methods: PPK and PK-PD models were developed using the first-order conditional estimation with interaction (FOCE-I) method in NONMEM 7.4, with model covariates selected using a stepwise forward addition and backward elimination method based on a 5% significance level. Model quality was checked by inspecting model parameters and confidence intervals, as well as standard residual-based and simulation-based diagnostics, and prediction-corrected visual predictive checks. Navtemadlin plasma concentration and MIC-1 serum concentration-time data from the food effect study (KRT-232-105) were modeled (N=30 subjects after a single 60 mg navtemadlin dose). Candidate PPK semi-mechanistic models that described EHR with multi-compartment structures (gut, central, and peripheral compartments for navtemadlin, and central and gallbladder [GB] compartments for M1), first-order elimination, and mealtime effects on GB emptying were tested. Post hoc parameter estimates from the final PPK model were used to generate individual predicted navtemadlin plasma concentrations for the PK-PD model. Based on exploratory plots, the pharmacological mechanism of action of navtemadlin, and a bile acid recycling model (Guiastrennec et al. CPT Pharmacometrics Syst Pharmacol. 2018), an indirect response equation was selected for the MIC-1 effect compartment (Figure 1a). Results: Navtemadlin and M1 plasma concentrations, including a second peak attributed to EHR at ~8-12 h, were well described by a model with central and peripheral compartments, constant basal M1 release rate into bile (KBR BASAL), and incremental mealtime GB emptying rate (KBR MEAL, Figure 1a). Figure 1b shows simulated navtemadlin and M1 amounts in various compartments over time. Median oral clearance of navtemadlin was estimated at 36.35 L/h. Estimated median apparent oral clearance of navtemadlin in healthy subjects was higher than PPK estimates for patients with advanced solid tumors (24.9 L/h [Ma et al. Blood. 2019]). The median central and peripheral volumes of navtemadlin were 159 L and 390 L, respectively. Navtemadlin exposure was higher in healthy female subjects relative to male subjects. Between-subject variability in clearance was 31%. Typical MIC-1 maximum stimulatory effect (S max) was estimated at 6.82, close to the median maximum ratio of MIC-1 to baseline MIC-1 (7.29) in the observed data. SC 50 was estimated at 85.22 ng/mL, with a Hill coefficient of 2.02, indicating a relatively steep increase in MIC-1 serum concentration with increasing navtemadlin concentration. For both PPK and PK-PD models, diagnostic plots confirmed an adequate fit. Subjects with lower baseline MIC-1 had a larger response and reached a maximum MIC-1 concentration later. Older subjects had the largest covariate impact, with a higher MIC-1 response. Conclusion: A two-compartment PPK model with basal and incremental mealtime GB emptying rates captured concentration-time data for navtemadlin and its metabolite M1. EHR was evident and navtemadlin reabsorption following hydrolysis of biliary M1 in the intestine contributed to navtemadlin half-life. An indirect stimulatory PK-PD model effectively described the relationship between navtemadlin and MIC-1 in healthy subjects. Figure 1 Figure 1. Disclosures Zhang: Certara, Inc.: Current Employment; Milad Pharmaceutical Consulting, LLC.: Ended employment in the past 24 months. Wong: Kartos Therapeutics: Current Employment; AbbVie Biotherapeutics: Current equity holder in publicly-traded company. Slatter: Telios Pharma: Current holder of stock options in a privately-held company; Kartos Therapeutics: Current Employment, Current holder of stock options in a privately-held company; AstraZeneca: Current equity holder in publicly-traded company; Amgen: Divested equity in a private or publicly-traded company in the past 24 months. OffLabel Disclosure: Yes, navtemadlin (KRT-232) is an investigational small molecule MDM2 inhibitor.

Study of new elastomeric composite systems containing wood ash based alternative filler

The presented paper deals with the preparation of the new types of elastomeric composite systems containing an alternative filler based on wood ash or fly ash. Wood ash (fly ash) is generated as the waste from the process of wood pellets burning in the pellet boilers. The results of the EDX analysis confirmed that CaO and SiO2 are the most represented components of wood ash, which contains commonly used white fillers, such as kaolin or silica. Therefore, wood ash was used as an alternative ecological filler in a function of a partial replacement for the commonly used carbon black filler in the elastomer systems. Rheological properties and cure characteristics of prepared elastomer composite systems and tensile properties of resulting vulcanizates have been studied. The prepared elastomeric systems were also subjected to a Payne effect study. The obtained results showed the degree of filler - filler interactions as well as the degree of mutual interactions between alternative filler particles and elastomeric matrix.