Model-based lamotrigine clearance changes during pregnancy: clinical implication

Objective: The objective of the study was to characterize changes in the oral clearance (CL/F) of lamotrigine (LTG) over the course of pregnancy and the postpartum period through a model-based approach incorporating clinical characteristics that may influence CL/F, in support of developing clinical management guidelines. Methods: Women receiving LTG therapy who were pregnant or planning pregnancy were enrolled. Maternal blood samples were collected at each visit. A pharmacokinetic analysis was performed using a population-based, nonlinear, mixed-effects model. Results: A total of 600 LTG concentrations from 60 women (64 pregnancies) were included. The baseline LTG CL/F was 2.16 L/h with a between-subject variability of 40.6%. The influence of pregnancy on CL/F was described by gestational week. Two subpopulations of women emerged based on the rate of increase in LTG CL/F during pregnancy. The gestational age-associated increase in CL/F displayed a 10-fold higher rate in 77% of the women (0.118 L/h per week) compared to 23% (0.0115 L/h per week). The between-subject variability in these slopes was 43.0%. The increased CL/F at delivery declined to baseline values with a half-life of 0.55 weeks. Interpretation The majority of women had a substantial increase in CL/F from 2.16 to 6.88 L/h by the end of pregnancy, whereas 23% of women had a minimal increase. An increase in CL/F may correspond to decreases in LTG blood concentrations necessitating the need for more frequent dosage adjustments and closer monitoring in some pregnant women with epilepsy. Postpartum doses should be tapered to preconception dose ranges within 3 weeks of delivery

Enhancing easy-plane anisotropy in bespoke Ni(II) quantum magnets

We examine the crystal structures and magnetic properties of several S = 1 Ni(II) coordination compounds, molecules and polymers, that include the bridging ligands HF2-, AF62- (A = Ti, Zr) and pyrazine or non-bridging ligands F-, SiF62-, glycine, H2O, 1-vinylimidazole, 4-methylpyrazole and 3-hydroxypyridine. Pseudo-octahedral NiN4F2, NiN4O2 or NiN4OF cores consist of equatorial Ni-N bonds that are equal to or slightly longer than the axial Ni-Lax bonds. By design, the zero-field splitting (D) is large in these systems and, in the presence of substantial exchange interactions (J), can be difficult to discriminate from magnetometry measurements on powder samples. Thus, we relied on pulsed-field magnetization in those cases and employed electron-spin resonance (ESR) to confirm D when J 0) and range from ≈ 8-25 K. This work reveals a linear correlation between the ratio d(Ni-Lax)/d(Ni-Neq) and D although the ligand spectrochemical properties may also be important. We assert that this relationship allows us to predict the type of magnetocrystalline anisotropy in tailored Ni(II) quantum magnets

Machine learning uncovers the most robust self-report predictors of relationship quality across 43 longitudinal couples studies

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner’s ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person’s own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships

Innovation in State Level Veterans Services: A Comprehensive Review, Case Highlights, and an Agenda for Enhanced State Impact

This technical report provides a comprehensive analysis of all 50 states. It gives insight into leading practices in veteran service delivery, describes how innovative policy is diffusing across state governments, and highlights ten of the top states in providing services to veterans at the state level

Security-Enhanced Serial Communications

Industrial Control Systems (ICS) are widely used by critical infrastructure and are ubiquitous in numerous industries including telecommunications, petrochemical, and manufacturing. ICS are at a high risk of cyber attack given their internet accessibility, inherent lack of security, deployment timelines, and criticality. A unique challenge in ICS security is the prevalence of serial communication buses and other non-TCP/IP communications protocols. The communication protocols used within serial buses often lack authentication and integrity protections, leaving them vulnerable to spoofing and replay attacks. The bandwidth constraints and prevalence of legacy hardware in these systems prevent the use of modern message authentication and integrity techniques, such as those provided by Transport Layer Security (TLS). Our approach seeks to address the challenges of providing authentication to serial communications while keeping the existing serial communications bus in place and adding minimal hardware. Here we demonstrate the integration of field-programmable gate arrays (FPGAs) on the bus to inject message authentication codes into an out-of-band (OOB) communications channel, leveraging Power Line Communication (PLC) techniques. Our results show that simple solutions can be integrated into existing serial communications to provide necessary security features in critically important systems. The presented solution is inexpensive, scales well, is modular and extensible, and has low temporal overhead. Providing authenticated serial communications for critical infrastructure systems will improve their ability to resist cyber attacks

Implementation Assessment of Executive Order 13518: The Veterans Employment Initiative (Full Technical Report)

This report documents the results of a year-long, independent study to assess the policy implementation of the government’s Veterans Employment Initiative (VEI). The study considers the initiative’s efficacy and impact; identifies successful practices, implementation strategies, and opportunities for improvement; and offers recommendations to senior policymakers and agency leaders on how best to position the initiative for future success

Implementation Assessment of Executive Order 13518: The Veterans Employment Initiative

A year-long study to assess the implementation of Executive Order (EO) 13518, Veterans Employment in the Federal Government. Signed on November, 9, 2009, EO 13518 created the Veterans Employment Initiative (VEI), one of the most comprehensive efforts in U.S. history to increase veterans’ employment in U.S. federal agencies

Implementation Assessment of Executive Order 13518: The Veterans Employment Initiative (Executive Summary)

This is the Executive Summary of a report which documents the results of a year-long, independent study to assess the policy implementation of the government’s Veterans Employment Initiative (VEI). The study considers the initiative’s efficacy and impact, identifies successful practices, strategies and opportunities for improvement. This assessment also offers recommendations to senior policymakers and agency leaders on how to best position the VEI for future success