Lineage tracing and analog recording in mammalian cells by single-site DNA writing.

Studying cellular and developmental processes in complex multicellular organisms can require the non-destructive observation of thousands to billions of cells deep within an animal. DNA recorders address the staggering difficulty of this task by converting transient cellular experiences into mutations at defined genomic sites that can be sequenced later in high throughput. However, existing recorders act primarily by erasing DNA. This is problematic because, in the limit of progressive erasure, no record remains. We present a DNA recorder called CHYRON (Cell History Recording by Ordered Insertion) that acts primarily by writing new DNA through the repeated insertion of random nucleotides at a single locus in temporal order. To achieve in vivo DNA writing, CHYRON combines Cas9, a homing guide RNA and the template-independent DNA polymerase terminal deoxynucleotidyl transferase. We successfully applied CHYRON as an evolving lineage tracer and as a recorder of user-selected cellular stimuli.

A Systematic Review of Research on Trauma and Women's Health in the Nurses' Health Study II.

OBJECTIVE: To synthesize research on interpersonal trauma and women's health from the Nurses' Health Study II (NHS II) and to analyze conceptualization of interpersonal trauma across studies. DATA SOURCES: A literature review was conducted in PubMed using a systematic search strategy. STUDY SELECTION: Articles were included in the review if they used data from the NHS II and involved investigations of interpersonal trauma. Theoretical articles, methodologic articles, and other literature reviews involving the NHS II were excluded. Initially, the search returned 61 articles. After exclusions, 45 articles met the criteria for inclusion in the review and data extraction. DATA EXTRACTION: Information was extracted and consolidated in an evidence table. Data included study time frame, sample, definition of trauma, outcomes studied, and journal of publication. DATA SYNTHESIS: Trauma was not operationalized consistently across studies, even though the NHS II assessed trauma experiences in childhood, adolescence, and adulthood. Most investigations focused on childhood abuse, with investigations of childhood sexual abuse overrepresented in comparison to other abuse experiences. Authors conducting studies of trauma at any time in the life course consistently found a negative association with physical and mental health outcomes, which were increased by the presence of posttraumatic stress symptoms. Results from a small number of studies suggested a negative intergenerational impact of trauma on the children of women in the NHS II. CONCLUSION: Interpersonal trauma across the life course was strongly associated with many leading causes of morbidity and mortality among female nurses. Trauma conceptualization and operationalization varied across studies, and future investigations should leverage the full range of trauma measures available in the NHS II data set.

Geospatial analysis of associations among mental health need, housing need, and involuntary psychiatric hospitalizations of people experiencing homelessness in Los Angeles County.

The purpose of this study was to use geospatial indicators of mental health need and homelessness in Los Angeles County Service Planning Areas (SPAs) and a psychiatric sample of adults who were homeless to investigate 1) overlap between SPA level of mental health need and corresponding volume of involuntary psychiatric hospitalizations over time; 2) overlap between SPA level of unsheltered homelessness and corresponding volume of involuntary psychiatric hospitalizations over time; and 3) associations between SPA level of mental health need, SPA level of unsheltered homelessness, and initiation of a mental health conservatorship for grave disability. A sample of 373 adults who were homeless and hospitalized on an involuntary psychiatric hold from 2016 to 2018 were linked to data from the Greater Los Angeles Homeless Count on unsheltered homelessness and from the California Health Interview Survey on need for mental health services and suicidality, using admission zip codes to link variables at the SPA level. Geospatial mapping and bivariate tests were used to examine geographic overlap of SPA mental health need and unsheltered homelessness with volume of involuntary psychiatric admissions over the study period. Multiple logistic regression modeling was used to examine associations of SPA mental health need and unsheltered homelessness with conservatorship initiation. The volume of patients admitted from SPAs with higher levels of mental illness need grew from 2016 to 2018 (Tau = 0.27, P < 0.001; Tau = 0.40, P < 0.001), but there were fewer patients admitted from SPAs with higher levels of unsheltered homelessness over the same years (Tau of -0.33, P < 0.001). Being admitted from SPAs with the highest levels of unsheltered homelessness was associated with higher odds of conservatorship initiation (OR = 1.73, 95% CI = 1.82-16.74). Results suggest a need for targeted mental health and housing services to reach areas of highest need in Los Angeles County.

Mental Health Conservatorship Among Homeless People With Serious Mental Illness.

OBJECTIVE: The purpose of this study was to examine associations between homelessness and length of psychiatric hospitalization and to explore the role of mental health conservatorship in determining discharge location for patients who are homeless and have a grave disability from serious mental illness. METHODS: This observational study used administrative data from a safety-net psychiatric hospital in Los Angeles. The sample included 795 adults (≥18 years) who were hospitalized on an involuntary psychiatric hold between 2016 and 2018. The outcome variables were length of stay (days) and discharge location (home, locked psychiatric facility, unlocked psychiatric facility, unhoused). The predictor variables were homelessness status and whether a mental health conservatorship was initiated during hospitalization. Multiple regression models were used to estimate associations between variables. RESULTS: Homelessness status was associated with 27.5 additional days (SE=3.5 days) of hospitalization in adjusted models. Homeless patients for whom conservatorship was initiated comprised 6% of the sample but 41% of total inpatient days. Among people who were homeless, initiation of a conservatorship was associated with significantly longer length of inpatient stay (mean=154.8 days versus 25.6 days for the whole sample) but also with lower odds of being unhoused at the time of discharge (risk ratio=0.19, 95% confidence interval=0.09-0.34). CONCLUSIONS: A mental health conservatorship can be a mechanism for helping homeless people with a grave disability from mental illness to transition from the streets to residential psychiatric treatment, but it requires substantial resources from facilities that initiate such conservatorships and does not guarantee resolution of long-term supportive housing needs.