The treatment recommendation based on a network meta-analysis (NMA) is usually the single treatment with the highest expected value (EV) on an evaluative function. We explore approaches that recommend multiple treatments and that penalise uncertainty, making them suitable for risk-averse decision-makers. We introduce loss-adjusted EV (LaEV) and compare it to GRADE and three probability-based rankings. We define properties of a valid ranking under uncertainty and other desirable properties of ranking systems. A two-stage process is proposed: the first identifies treatments superior to the reference treatment; the second identifies those that are also within a minimal clinically important difference (MCID) of the best treatment. Decision rules and ranking systems are compared on stylised examples and 10 NMAs used in NICE (National Institute of Health and Care Excellence) guidelines. Only LaEV reliably delivers valid rankings under uncertainty and has all the desirable properties. In 10 NMAs comparing between 5 and 41 treatments, an EV decision maker would recommend 4–14 treatments, and LaEV 0–3 (median 2) fewer. GRADE rules give rise to anomalies, and, like the probability-based rankings, the number of treatments recommended depends on arbitrary probability cutoffs. Among treatments that are superior to the reference, GRADE privileges the more uncertain ones, and in 3/10 cases, GRADE failed to recommend the treatment with the highest EV and LaEV. A two-stage approach based on MCID ensures that EV- and LaEV-based rules recommend a clinically appropriate number of treatments. For a risk-averse decision maker, LaEV is conservative, simple to implement, and has an independent theoretical foundation.

Objectives/Goals: The extracellular matrix (ECM) of the sinoatrial node (SAN) is critical for maintaining automaticity in hiPSC-derived pacemaking cardiomyocytes (PCMs) under cyclic strain. We aim to determine the ECM ligands responsible for cell-ECM mediated mechanotransduction and the resulting phenotype in PCMs. Methods/Study Population: HiPSCs are differentiated to PCM and replated on substrate with 5 or 15 kPa PDMS that are coated with 5 or 25 ug/cm of either collagen I or fibronectin at sub-confluent density to restrict junction engagement to only costameres. Then, PCM are subjected to 10% cyclic mechanical strain at 1 Hz for 48 hours, with static culture as control. PCMs from all conditions are subsequently fixed and stained for cardiomyocyte-specific troponin T (TnT), pacemaking HCN4 channel, and pro-pacemaking transcription factors (Shox2, Isl1, Tbx3, Tbx18). Additionally, PCM cell size will also be assessed. Results/Anticipated Results: Considering the amount of hypertrophy and myofilament in CMs correlates with mechanical strain, we expect a reduced degree of mechanotransduction in hiPSC-PCM on collagen I with a stiffness 15 kPa to induce smaller cell size with fewer myofilament and an upregulation of HCN4 and pro-pacemaking transcription factors than those on 5 kPa and those on fibronectin of either 5 or 15 kPa after cyclic strain. This is because COL1 is reported to have a lower signaling threshold but a limited sensitivity to force which contributes to the diminished mechanotransduction signaling. Discussion/Significance of Impact: Effects of the microenvironment on hiPSC-PCMs via costamere mechanotransduction may provide insights for engineering biopacemakers with a suitable ECM, to potentially preserve automaticity in hiPSC-PCMs and sustain long-term pacemaking function, making biopacemakers a step closer to reality.

We have structured our response around 3 rough categories of commentary themes: those that provided illustrations of existing person-centric research, those that provided novel ideas about extending the viewpoint to traditional research areas, and those that criticized our neglect of issues of morality and power differences. In our response, we clarify and reiterate our position as advocating a science of first-person work experience. In doing so, we differentiate our agenda from others labeled person-centric but not first-person experiential in the way we describe it. We also differentiate our position from a primary interest in worker treatment and well-being, except as part of work experience, and defend that difference.

In this essay we argue for a more person-centric direction for research in industrial–organizational (I–O) psychology. We argue that the prevailing paradigm within I–O treats workers as objects and in so doing limits the ability to develop a deep and continued understanding of the important ways in which humans relate to work. In response, we think there is a need for a more coherent focus on the worker and on the subjective experience of working. After describing the current paradigm we suggest an alternative—a person-centric work psychology that takes the worker as its focus and worker experience as a topic of study.

The present study examined the impact of children's maltreatment experiences on the emergence of externalizing problem presentations among children during different developmental periods. The sample included 788 youth and their caregivers who participated in a multisite, prospective study of youth at-risk for maltreatment. Externalizing problems were assessed at ages 4, 8, and 12, and symptoms and diagnoses of attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder were assessed at age 14, during interviews with youth and caregivers. Information about maltreatment allegations was coded from official records. Latent transition analysis identified three groups of youth with similar presentations of externalizing problems (“well adjusted,” “hyperactive/oppositional,” and “aggressive/rule-breaking”) and transitions between groups from ages 4, 8, and 12. A “defiant/deceitful” group also emerged at age 12. Girls were generally more likely to present as well adjusted than boys. Children with recent physical abuse allegations had an increased risk for aggressive/rule-breaking presentations during the preschool and preadolescent years, while children with sexual abuse or neglect allegations had lower probabilities of having well-adjusted presentations during middle childhood. These findings indicate that persistently severe aggressive conduct problems, which are related to the most concerning outcomes, can be identified early, particularly among neglected and physically and sexually abused children.

The purpose of this study was to evaluate whether children with a history of disorganized attachment in infancy were more likely than children without a history of disorganized attachment to exhibit symptoms of posttraumatic stress disorder (PTSD) at school age following trauma exposure. The sample consisted of 78 8.5-year-old children from a larger, ongoing prospective study evaluating the effects of intrauterine cocaine exposure (IUCE) on children's growth and development from birth to adolescence. At the 12-month visit, children's attachment status was scored from videotapes of infant–caregiver dyads in Ainsworth's strange situation. At the 8.5-year visit, children were administered the Violence Exposure Scale—Revised, a child-report trauma exposure inventory, and the Diagnostic Interview for Children and Adolescents by an experienced clinical psychologist masked to children's attachment status and IUCE status. Sixteen of the 78 children (21%) were classified as insecure–disorganized/insecure–other at 12 months. Poisson regressions covarying IUCE, gender, and continuity of maternal care indicated that disorganized attachment status at 12 months, compared with nondisorganized attachment status, significantly predicted both higher avoidance cluster PTSD symptoms and higher reexperiencing cluster PTSD symptoms. These findings suggest that the quality of early dyadic relationships may be linked to differences in children's later development of posttraumatic stress symptoms following a traumatic event.

The purpose of this study was to evaluate whether children with a history of disorganized attachment in infancy were more likely than children without a history of disorganized attachment to exhibit symptoms of posttraumatic stress disorder (PTSD) at school age following trauma exposure. The sample consisted of 78 8.5-year-old children from a larger, ongoing prospective study evaluating the effects of intrauterine cocaine exposure (IUCE) on children's growth and development from birth to adolescence. At the 12-month visit, children's attachment status was scored from videotapes of infant–caregiver dyads in Ainsworth's strange situation. At the 8.5-year visit, children were administered the Violence Exposure Scale—Revised, a child-report trauma exposure inventory, and the Diagnostic Interview for Children and Adolescents by an experienced clinical psychologist masked to children's attachment status and IUCE status. Sixteen of the 78 children (21%) were classified as insecure–disorganized/insecure–other at 12 months. Poisson regressions covarying IUCE, gender, and continuity of maternal care indicated that disorganized attachment status at 12 months, compared with nondisorganized attachment status, significantly predicted both higher avoidance cluster PTSD symptoms and higher reexperiencing cluster PTSD symptoms. These findings suggest that the quality of early dyadic relationships may be linked to differences in children's later development of posttraumatic stress symptoms following a traumatic event.