In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients

Purpose Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. Methods Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t1/2), time to 1% (Time1%), and calculated weekly dose (Dose1%). Bias and precision of these estimates were assessed to determine which LSS was adequate. Results For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: −5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time1%, except for t1/2 (range: 27.1% to 44.7%) and Dose1% (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose1% using LSS with the last sample taken on day 3 (LSS 6 and 10). Conclusion Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively.

Omani experience with the use of factor IX Fc fusion protein

We describe our local experience in the management of haemophilia B patients with factor IX Fc fusion protein. Two children with haemophilia B were managed with the use of a personalised/tailored dosing schedule of factor IX Fc fusion protein. Compared with the standard half-life factor IX, prophylaxis with factor IX Fc fusion protein was cost-effective, with much less injections, better bleeding control, improved tolerability or no inhibitor development.

Adverse Childhood Experiences Associated with Greater Internalization of Weight Stigma in Women with Excess Weight

Adverse childhood experiences (ACEs) may be an early life factor associated with adult weight stigma via biological (e.g., stress response), cognitive (e.g., self-criticism/deprecation), and/or emotional (e.g., shame) mechanisms. This pilot study investigated relationships between ACEs and internalized and experienced weight stigma in adult women with overweight/obesity and explored differential relationships between weight stigma and ACE subtypes (i.e., abuse, neglect, household dysfunction). Adult women (68% white, Mage = 33 ± 10 years, MBMI = 33.7 ± 7.2 kg/m2) completed measures of ACEs (ACE Questionnaire), internalized weight stigma (IWS; Weight Bias Internalization Scale—Modified; WBIS—M), and lifetime experiences of weight stigma (yes/no). Data were analyzed with linear and logistic regression (n = 46), adjusting for age, race, and body mass index (BMI). Linear regressions revealed a positive association between ACE and WBIS—M scores (β = 0.40, p = 0.006), which was driven by Abuse-type ACEs (β = 0.48, p = 0.009). Relationships between WBIS—M scores and Neglect- and Household-Dysfunction-type ACEs did not reach significance (β = 0.20, p = 0.173; β = −0.16, p = 0.273). Though descriptive statistics revealed greater rates of experienced weight stigma endorsement by those with high-3+ ACEs (81%) vs. medium-1–2 ACEs (67%) or low/no-0 ACEs (60%), ACE scores were not significantly associated with experienced weight stigma in logistic regression (Wald = 1.36, p = 0.244, OR = 1.324, 95%, CI = 0.825–2.125). ACEs may be an early life factor that increase the risk for internalizing weight stigma in adulthood. Larger studies should confirm this relationship and follow-up on descriptive findings suggesting a potential association between ACEs and experienced weight stigma.

Foreign E-commerce Practitioners in “Taobao Village”: Isolation and Integration

This research mainly analyzes the actual situation of social integration of migrant E-commerce practitioners in Xintang Town of Guangdong Province through field survey. According to the survey, the overall level of social integration is relatively low, and there are three isolation barriers, namely time, space and psychology.Regarding the influencing factors of social integration level, it is concluded through the principal component analysis that five main factors impacting the social integration of migrant E-commerce practitioners are life factor, business factor, housing factor, social factor and individual factor. By establish a multiple logistic analysis model, it is found that type of friends, interest protection and frequency of recreational activities would impact the social integration of migrant E-commerce practitioners most significantly among all factors.

Studi Kelayakan Operasi Berdasarkan Uji Dissolve Gas Analysis pada Transformator Distribusi 150 kV Gardu Induk Cibabat Cimahi

The role of insulation media in high voltage equipment is an important component in maintaining the ongoing distribution of electric power from random interference during operation. Insulation media used in high voltage equipment are air, solid, oil, or gas. All of these media will experience a decrease in performance along with the operating time and service life factor of the equipment. Therefore, the role of maintenance is very important. One method of diagnosis of damage to insulating oil is Dissolve Gas Analysis (DGA). DGA diagnosis is conducted to determine the rate of gas growth in the insulating oil in parts per million (ppm). Some DGA methods are Total Dissolve Combustible Gas (TDCG), Duval’s Triangle, and Roger’s Ratio. A sampling of transformer oil isolation in this study was conducted on three transformer units in the 150 kV / 20 kV Cibabat Cimahi Substation. Oil samples are tested through data processing based on IEEE Std C57.104-2008 standards and SPLN T5.004-5: 2017. DGA test results in the laboratory of PT. PLN (Persero) UPT Bandung shows the results of TDCG transformer unit 1 in condition 2 with the amount of flammable gas at 821 ppm, for transformer unit 2 in condition 1 with the amount of combustible gas 694 ppm and transformer unit 3 in condition 2 with combustible gas 1117 ppm so that each gas growth rate for transformer unit 1 is -1.36 ppm/day, transformer unit 2 is -1.03 ppm/day and transformer unit is 3 0.95 ppm/day.