People linked through social ties are known to have interdependent health. Our aim was to investigate such collateral health effects in the context of offspring mortality after a parent's death in children aged 10 -59 years. The data (N = 3,753,368) were from a linkedregisters database that contains the total Swedish population. In minor children, we found elevations in mortality risks associated with a parent's death. Adult offspring experienced a reduced mortality risk recently after a parent's death, which over time approached, and in some instances even exceeded, that of the general population. Mother's death tended to have a stronger influence than father's death, unnatural parental deaths had a stronger effect than natural ones, and male offspring were more vulnerable than female offspring.Research has shown that people linked through social ties have interdependent health. Illness or death in one person may consequently influence the health of another person to whom the he or she is connected (Berkman

These findings corroborate and extend earlier findings suggesting elevated mortality risks also following the death of an adult child.

A defective form of the AIRE protein causes autoimmune destruction of target organs by disturbing the immunological tolerance of patients with a rare monogenic disease, autoimmune polyendocrinopathy (APE)-candidiasis (C)-ectodermal dystrophy (ED), APECED. Recently, experiments on knockout mice revealed that AIRE controls autoimmunity by regulating the transcription of peripheral tissue-restricted antigens in thymic medullary epithelial cells. Thus, AIRE provides a unique model for molecular studies of organ-specific autoimmunity. In order to analyze the molecular and cellular consequences of 16 disease-causing mutations in vitro, we studied the subcellular localization, transactivation capacity, homomultimerization, and complex formation of several mutant AIRE polypeptides. Most of the mutations altered the nucleus-cytoplasm distribution of AIRE and disturbed its association with nuclear dots and cytoplasmic filaments. While the PHD zinc fingers were necessary for the transactivation capacity of AIRE, other regions of AIRE also modulated this function. Consequently, most of the mutations decreased transactivation. The HSR domain was responsible for the homomultimerization activity of AIRE; all the missense mutations of the HSR and the SAND domains decreased this activity, but those in other domains did not. The AIRE protein was present in soluble high-molecular-weight complexes. Mutations in the HSR domain and deletion of PHD zinc fingers disturbed the formation of these complexes. In conclusion, we propose an in vitro model in which AIRE transactivates transcription through heteromeric molecular interactions that are regulated by homomultimerization and conditional localization of AIRE in the nucleus or in the cytoplasm.

WHAT'S KNOWN ON THIS SUBJECT: Many children experience the death of a parent during childhood. The long-term consequences of this life event, including school performance, and the importance of the psychosocial circumstances of the home have not been well elucidated in previous studies.WHAT THIS STUDY ADDS: Both maternal and paternal deaths during childhood were associated with lower grades and school failure. Many of the associations (and especially for death due to external causes) were associated with socioeconomic disadvantage and psychosocial problems in the family. abstract OBJECTIVES: Parental death during childhood has been linked to increased mortality and mental health problems in adulthood. School failure may be an important mediator in this trajectory. We investigated the association between parental death before age 15 years and school performance at age 15 to 16 years, taking into account potentially contributing factors such as family socioeconomic position (SEP) and parental substance abuse, mental health problems, and criminality.

ObjectiveTo investigate whether the daily workload per nurse (Oulu Patient Classification (OPCq)/nurse) as measured by the RAFAELA system correlates with different types of patient safety incidents and with patient mortality, and to compare the results with regressions based on the standard patients/nurse measure.SettingWe obtained data from 36 units from four Finnish hospitals. One was a tertiary acute care hospital, and the three others were secondary acute care hospitals.ParticipantsPatients’ nursing intensity (249 123 classifications), nursing resources, patient safety incidents and patient mortality were collected on a daily basis during 1 year, corresponding to 12 475 data points. Associations between OPC/nurse and patient safety incidents or mortality were estimated using unadjusted logistic regression models, and models that adjusted for ward-specific effects, and effects of day of the week, holiday and season.Primary and secondary outcome measuresMain outcome measures were patient safety incidents and death of a patient.ResultsWhen OPC/nurse was above the assumed optimal level, the adjusted odds for a patient safety incident were 1.24 (95% CI 1.08 to 1.42) that of the assumed optimal level, and 0.79 (95% CI 0.67 to 0.93) if it was below the assumed optimal level. Corresponding estimates for patient mortality were 1.43 (95% CI 1.18 to 1.73) and 0.78 (95% CI 0.60 to 1.00), respectively. As compared with the patients/nurse classification, models estimated on basis of the RAFAELA classification system generally provided larger effect sizes, greater statistical power and better model fit, although the difference was not very large. Net benefits as calculated on the basis of decision analysis did not provide any clear evidence on which measure to prefer.ConclusionsWe have demonstrated an association between daily workload per nurse and patient safety incidents and mortality. Current findings need to be replicated by future studies.

Previous findings have suggested that the loss of a family member is associated with mortality among bereaved family members. The least-studied familial relationship in the bereavement literature is that of siblings, although loss of a sibling may also involve health consequences. The authors conducted a follow-up study based on data from the Swedish total population register, covering the period 1981-2002. Using Cox regression, mortality risk ratios for bereaved and nonbereaved persons aged 18-69 years were estimated. All-cause mortality and cause-specific mortality (unnatural causes, natural causes, cardiovascular disease, cancer, suicide, accidents, and all other causes) were examined. In men, the mortality risk for bereaved persons versus nonbereaved persons was 1.26 (95% confidence interval: 1.22, 1.30), and in women it was 1.33 (95% confidence interval: 1.28, 1.39). An elevated mortality risk associated with a sibling's death was found in all age groups studied, but the association was generally stronger at younger ages and could be observed predominantly after more than 1 year of follow-up. There was also an increased mortality risk if the sibling had died from a discordant main cause, which may strengthen the possibility that the association observed is not due to confounding alone.

We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of patients with AML, and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five patients with AML to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled the identification of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3 inhibitors. Integration of molecular profiling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommendations, providing a paradigm for individualized implementation of functional precision cancer medicine. Significance: Oncogenomics data can guide clinical treatment decisions, but often such data are neither actionable nor predictive. Functional ex vivo drug testing contributes significant additional, clinically actionable therapeutic insights for individual patients with AML. Such data can be generated in four days, enabling rapid translation through FPMTB. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275

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