Moderator analysis in single-experimental design (SCED) meta-analysis allows for fine-grained analysis allowing explanation of variability in intervention effectiveness between studies in addition to between participants. This is desirable for the field of cognitive therapy as individual SCED study participant characteristics might explain participant’s responsiveness to interventions. This stands in contrast to traditional group design meta-analysis in which moderator analysis is limited to exploring study level characteristics. If traditional meta-analytic techniques were to be used, as in group design studies (i.e., using study average moderators), then the unique benefits of synthesizing SCED studies are missed. In this manuscript, three-level meta-analysis for synthesis of SCED effect sizes with inclusion of moderators is introduced and an empirical demonstration using SCED studies focusing on cognitive behavioral therapy (CBT) is provided. The goal is to provide applied SCED meta-analysis with appropriate methodology to conduct moderator analysis which can result in more fine-grained evidence. This approach can support a more comprehensive understanding of the conditions under which, and the participants for whom, interventions may be recommended.
Advanced distribution management systems (ADMS) increasingly rely on smart inverter (SI)-based resources for voltage regulation and optimization in modern distribution grids. However, conventional Volt-Var (Q-V) droop settings prescribed by IEEE-1547 remain static, limiting adaptive coordination and often resulting in unfair photovoltaic (PV) curtailments. This paper proposes a fairness-aware and adaptive optimization model to determine SI Volt-Var droop settings with variable breakpoints, ensuring IEEE 1547 compatibility within a multi-period distribution optimal power flow (DOPF) formulation. The framework builds upon an established Current-Voltage AC Optimal Power Flow (IVACOPF) model and introduces new power loss constraints to enhance accuracy. The framework supports fairness-aware curtailment policies, including egalitarian, proportional, and priority-based schemes, with the latter reformulated to eliminate conditional expressions for solver compatibility. Simulations on a modified 33-bus feeder with 15-min resolution profiles and hourly breakpoint updates demonstrate significant improvements in voltage regulation and reactive power control. The model converges within four min, making it suitable for operational use.
PURPOSE:Stereotactic body radiation therapy is standard of care for inoperable early-stage non-small cell lung cancer. Here, we report the long-term outcomes of 30 Gy in 1 fraction (arm 1) versus 60 Gy in 3 fractions (arm 2). METHODS AND MATERIALS:This was a multi-institutional randomized, phase 2, 2-arm clinical trial. Medically inoperable patients with peripheral clinical T1-T2/N0M0 disease were enrolled. All patients had biopsy-confirmed disease. Patients were stratified by performance status and randomized to arm 1 or arm 2. The primary endpoint was thoracic grade 3 or higher adverse events per the Common Terminology Criteria for Adverse Events. Secondary endpoints included freedom from local failure, freedom from distal failure, progression-free (PFS) and overall survival (OS). RESULTS:Between September 2008 and April 2015, 98 patients were randomized. Median survival was 40.3 months. There were no new attributable adverse events within the additional follow-up period. There were no differences in time to local failure, time to distant failure, PFS, or OS (P = .14, .17, .98, and .78, respectively). CONCLUSIONS:This randomized phase 2 study demonstrated that 30 Gy in 1 fraction was equivalent to 60 Gy in 3 fractions in terms of toxicity, local failure, distant failure, PFS, and OS.
Mitochondrial and lysosomal abnormalities co-occur in aging-related diseases with progressive tissue atrophy. It remains unclear whether these two pathogenic pathways affect tissue homeostasis independently, convergently or epistatically. We show that mitochondrial protein import stress causes vacuolar damage in yeast, manifested by V-ATPase disassembly, and vacuolar deacidification and fragmentation. In a mouse model of mitochondrial protein import stress induced by overloading of the nuclear-encoded ANT1 protein, we observe progressive muscle atrophy independent of bioenergetic defects. Like in yeast mutants with severe vacuolar damage, genes involved in amino acid uptake/biosynthesis, one-carbon metabolism, lysosomal biogenesis and iron homeostasis are activated in the skeletal muscle of Ant1-transgenic mice. The affected muscles accumulate glycogen, lipofuscin and poorly processed multivesicular bodies. Despite activation of lysosomal repair and lysophagic pathways, autophagic flux is severely stalled. During aging, various proteolytic cathepsins are increasingly released from the lysosomal lumen into the cytosol. Together with proteasomal activation, this may contribute to unbalanced proteostasis, reduced myofiber size and skeletal muscle atrophy. Our study therefore discovered an evolutionarily conserved mitochondria-to-lysosome proteotoxic axis that affects tissue mass homeostasis during aging.
Agency and communion are two core motivational themes in narrative identity, reflecting drives for independent control and relatedness, respectively. Despite significant attention to the salience of these narrative themes, no previous research has examined thematic change or associations with well-being and developmental outcomes in late midlife. In a diverse sample of 128 adults transitioning from middle to later adulthood, life story interviews were conducted at three time points (ages 55, 60, and 65, approximately). Five autobiographical scenes from each participant per wave were coded for agency and communion, for a total of 1,913 scenes. At the between-person level, adults who were highly generative and reported greater ego integrity at age 65 tended to tell life stories marked by fulfilled agency and communion. Higher levels of these themes across the three waves were also linked to greater well-being and life satisfaction at age 65. There was no significant within-person change in agency or communion across the three waves of this longitudinal study, and the small changes that did occur did not predict well-being or developmental outcomes assessed at age 65. Taken together, the findings suggest that fulfilled agency and communion function as enduring markers of narrative identity that significantly relate to adjustment in late midlife.
