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This study aims to compare the developmental-behavioral profiles of 2-year-olds of mothers who experienced postpartum and/or current depression with profiles of toddlers of mothers without depression at either time using population-based Rhode Island data. Weighted data from Rhode Island Department of Health's Pregnancy Risk Assessment Monitoring System and Rhode Island's follow-up Toddlers Wellness Overview Survey distributed to mothers giving birth between 2006 and 2008 were analyzed. Compared with non-depressed mothers, those with any depression following childbirth reported more concerns with their toddlers' receptive language, social-emotional development, and their sleep and feeding behaviors. When adjusted for demographics, persistent depression remained associated with social-emotional (adjusted odds ratio [aOR] = 7.53, 2.78-20.34) and feeding concerns (aOR = 3.13, 1.36-7.22), and current depression was associated with social-emotional concerns (aOR = 2.52, 1.26-5.01). We conclude that pediatric providers should explore maternal mental health as a mediating and potentially modifiable factor beyond the postpartum period when toddlers present with developmental-behavioral challenges., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Major depressive disorder (MDD) is a serious psychiatric disorder that in extreme cases can lead to suicide. Evidence suggests that alterations in the kynurenine pathway (KP) contribute to the pathology of MDD. Activation of the KP leads to the formation of neuroactive metabolites, including kynurenic acid (KYNA) and quinolinic acid (QUIN). To test for changes in the KP, postmortem anterior cingulate cortex (ACC) was obtained from the National Institute of Health NeuroBioBank. Gene expression of KP enzymes and relevant neuroinflammatory markers were investigated via RT-qPCR (Fluidigm) and KP metabolites were measured using liquid chromatography-mass spectrometry in tissue from individuals with MDD (n = 44) and matched nonpsychiatric controls (n = 36). We report increased IL6 and IL1B mRNA in MDD. Subgroup analysis found that female MDD subjects had significantly decreased KYNA and a trend decrease in the KYNA/QUIN ratio compared to female controls. In addition, MDD subjects that died by suicide had significantly decreased KYNA in comparison to controls and MDD subjects that did not die by suicide, while subjects that did not die by suicide had increased KYAT2 mRNA, which we hypothesise may protect against a decrease in KYNA. Overall, we found sex- and suicide-specific alterations in the KP in the ACC in MDD. This is the first molecular evidence in the brain of subgroup specific changes in the KP in MDD, which not only suggests that treatments aimed at upregulation of the KYNA arm in the brain may be favourable for female MDD sufferers but also might assist managing suicidal behaviour., (© 2023. The Author(s).)

The glutamatergic system may be central to the neurobiology and treatment of major depressive disorder (MDD) and psychosis. Despite the success of N-methyl-D-aspartate receptor (NMDAR) antagonists for the treatment of MDD, little is known regarding the expression of these glutamate receptors in MDD. In this study we measured gene expression, via qRT-PCR, of the major NMDAR subunits, in the anterior cingulate cortex (ACC) in MDD subjects with and without psychosis, and non-psychiatric controls. Overall, GRIN2B mRNA was increased in both MDD with (+32%) and without psychosis (+40%) compared to controls along with a trend increase in GRIN1 mRNA in MDD overall (+24%). Furthermore, in MDD with psychosis there was a significant decrease in the GRIN2A:GRIN2B mRNA ratio (-19%). Collectively these results suggest dysfunction of the glutamatergic system at the gene expression level in the ACC in MDD. Increased GRIN2B mRNA in MDD, along with an altered GRIN2A:GRIN2B ratio in psychotic depression, suggests a disruption to NMDAR composition could be present in the ACC in MDD; this could lead to enhanced signalling via GluN2B-containing NMDARs and greater potential for glutamate excitotoxicity in the ACC in MDD. These results support future research into GluN2B antagonist-based treatments for MDD., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cannabidiol (CBD) is a non-intoxicating cannabinoid with antipsychotic-like properties, however it's potential to prevent schizophrenia development has not been thoroughly investigated. Brain maturation during adolescence creates a window where CBD could potentially limit the development of schizophrenia. The neuregulin 1 transmembrane domain heterozygous ( Nrg1 TM HET) mutant mouse shows face, predictive, and construct validity for schizophrenia. Here we sought to determine if CBD given in adolescence could prevent the development of the schizophrenia-relevant phenotype, as well as susceptibility to the psychoactive cannabinoid Δ 9 -tetrahydrocannabinol (THC) in Nrg1 TM HET mice. Adolescent male Nrg1 mutants and wild type-like (WT) animals were administered 30 mg/kg CBD i.p. daily for seven weeks, and were tested for locomotion, social behavior, sensorimotor gating and cognition, and sensitivity to acute THC-induced behaviors. GAD67, GluA1, and NMDAR1 protein levels were measured in the hippocampus, striatum, and prefrontal cortex. Chronic adolescent CBD increased locomotion in animals regardless of genotype, was anxiolytic, and increased social behavior when animals were tested for their acute THC response. CBD did not alleviate the schizophrenia-relevant hyperlocomotive phenotype of Nrg1 mutants, nor deficits in social behaviors. Nrg1 mutant mice treated with CBD and THC showed no habituation to a startle pulse, suggesting CBD increased vulnerability to the startle habituation-reducing effects of THC in mutant mice. CBD increased levels of GluA1, but reduced levels of GAD67 in the hippocampus of Nrg1 mutants. These results suggest adolescent CBD is not effective as a preventative of schizophrenia-relevant behavioral deficits in mutants and may actually contribute to pathological changes in the brain that increase sensitivity to THC in particular behavioral domains., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Visini, Brown, Weston-Green, Shannon Weickert, Chesworth and Karl.)

Background: Many short-read genome assemblies have been found to be incomplete and contain mis-assemblies. The Vertebrate Genomes Project has been producing new reference genome assemblies with an emphasis on being as complete and error-free as possible, which requires utilizing long reads, long-range scaffolding data, new assembly algorithms, and manual curation. A more thorough evaluation of the recent references relative to prior assemblies can provide a detailed overview of the types and magnitude of improvements., Results: Here we evaluate new vertebrate genome references relative to the previous assemblies for the same species and, in two cases, the same individuals, including a mammal (platypus), two birds (zebra finch, Anna's hummingbird), and a fish (climbing perch). We find that up to 11% of genomic sequence is entirely missing in the previous assemblies. In the Vertebrate Genomes Project zebra finch assembly, we identify eight new GC- and repeat-rich micro-chromosomes with high gene density. The impact of missing sequences is biased towards GC-rich 5'-proximal promoters and 5' exon regions of protein-coding genes and long non-coding RNAs. Between 26 and 60% of genes include structural or sequence errors that could lead to misunderstanding of their function when using the previous genome assemblies., Conclusions: Our findings reveal novel regulatory landscapes and protein coding sequences that have been greatly underestimated in previous assemblies and are now present in the Vertebrate Genomes Project reference genomes., (© 2022. The Author(s).)

Background: False duplications in genome assemblies lead to false biological conclusions. We quantified false duplications in popularly used previous genome assemblies for platypus, zebra finch, and Anna's Hummingbird, and their new counterparts of the same species generated by the Vertebrate Genomes Project, of which the Vertebrate Genomes Project pipeline attempted to eliminate false duplications through haplotype phasing and purging. These assemblies are among the first generated by the Vertebrate Genomes Project where there was a prior chromosomal level reference assembly to compare with., Results: Whole genome alignments revealed that 4 to 16% of the sequences are falsely duplicated in the previous assemblies, impacting hundreds to thousands of genes. These lead to overestimated gene family expansions. The main source of the false duplications is heterotype duplications, where the haplotype sequences were relatively more divergent than other parts of the genome leading the assembly algorithms to classify them as separate genes or genomic regions. A minor source is sequencing errors. Ancient ATP nucleotide binding gene families have a higher prevalence of false duplications compared to other gene families. Although present in a smaller proportion, we observe false duplications remaining in the Vertebrate Genomes Project assemblies that can be identified and purged., Conclusions: This study highlights the need for more advanced assembly methods that better separate haplotypes and sequence errors, and the need for cautious analyses on gene gains., (© 2022. The Author(s).)

Background: Studies in vertebrate genomics require sampling from a broad range of tissue types, taxa, and localities. Recent advancements in long-read and long-range genome sequencing have made it possible to produce high-quality chromosome-level genome assemblies for almost any organism. However, adequate tissue preservation for the requisite ultra-high molecular weight DNA (uHMW DNA) remains a major challenge. Here we present a comparative study of preservation methods for field and laboratory tissue sampling, across vertebrate classes and different tissue types., Results: We find that storage temperature was the strongest predictor of uHMW fragment lengths. While immediate flash-freezing remains the sample preservation gold standard, samples preserved in 95% EtOH or 20-25% DMSO-EDTA showed little fragment length degradation when stored at 4°C for 6 hours. Samples in 95% EtOH or 20-25% DMSO-EDTA kept at 4°C for 1 week after dissection still yielded adequate amounts of uHMW DNA for most applications. Tissue type was a significant predictor of total DNA yield but not fragment length. Preservation solution had a smaller but significant influence on both fragment length and DNA yield., Conclusion: We provide sample preservation guidelines that ensure sufficient DNA integrity and amount required for use with long-read and long-range sequencing technologies across vertebrates. Our best practices generated the uHMW DNA needed for the high-quality reference genomes for phase 1 of the Vertebrate Genomes Project, whose ultimate mission is to generate chromosome-level reference genome assemblies of all ∼70,000 extant vertebrate species., (© The Author(s) 2022. Published by Oxford University Press GigaScience.)

The presence of distinct stem cells that maintain the interfollicular epidermis is highly debated. Here, we report a population of keratinocytes, marked by Thy1, in the basal layer of the interfollicular epidermis. We find that epidermal cells expressing differential levels of Thy1 display distinct transcriptional signatures. Thy1 + keratinocytes do not express T cell markers, express a unique transcriptional profile, cycle significantly slower than basal epidermal progenitors and display significant expansion potential in vitro. Multicolor lineage tracing analyses and mathematical modeling reveal that Thy1 + basal keratinocytes do not compete neutrally alike interfollicular progenitors and contribute long-term to both epidermal replenishment and wound repair. Importantly, ablation of Thy1 + cells strongly impairs these processes, thus indicating the non-redundant function of Thy1 + stem cells in the epidermis. Collectively, these results reveal a distinct stem cell population that plays a critical role in epidermal homeostasis and repair., (© 2022. The Author(s).)

Evidence, largely obtained from peripheral studies, suggests that alterations in the kynurenine pathway contribute to the aetiology of depression and disorders involving psychosis. Stimulation of the kynurenine pathway leads to the formation of neuroactive metabolites, including kynurenic acid (predominantly in astrocytes) and quinolinic acid (predominantly in microglia), which are antagonists and agonists of the glutamate NMDA receptor, respectively. In this study, we measured gene expression via qRT-PCR of the main kynurenine pathway enzymes in the anterior cingulate cortex (ACC) in people with major depressive disorder and matched controls. In parallel, we tested for diagnostic differences in gene expression of relevant glial markers. We used total RNA isolated from the ACC from depression subjects with psychosis (n = 12) and without psychosis (n = 12), and non-psychiatric controls (n = 12) provided by the Stanley Medical Research Institute. In the ACC, KYAT1 (KAT I), AADAT (KAT II), and the astrocytic SLC1A2 (EAAT2) mRNAs, were significantly increased in depression, when combining those with and without psychosis. The increased KYAT1 and AADAT mRNA indicates that depression is associated with increased activation of the kynurenic acid arm of the kynurenine pathway in the ACC, suggesting an astrocyte response in depression. Considering EAAT2 and KATs increase astrocytic glutamate uptake and production of the NMDA receptor antagonist kynurenic acid, the observed increases of these markers may relate to changes in glutamatergic signalling in depression. These results suggest dysfunction of the kynurenine pathway in the brain in depression and point to the kynurenine pathway as a possible driver of glutamate dysfunction in depression., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To identify initial diagnoses associated with elevated risk of chronic prescription opioid use., Design: Population-based, retrospective cohort study., Setting: State of Rhode Island., Participants: Rhode Island residents with an initial opioid prescription dispensed between 1 April 2019 and 31 March 2020., Primary Outcome Measure: Subsequent chronic prescription opioid use, defined as receiving 60 or more days' supply of opioids in the 90 days following an initial opioid prescription., Results: Among the 87 055 patients with an initial opioid prescription, 3199 (3.7%) subsequently became chronic users. Patients who become chronic users tended to receive a longer days' supply, greater quantity dispensed, but a lower morphine milligram equivalents on the initial opioid prescription. Patients prescribed an initial opioid prescription for diseases of the musculoskeletal system and connective tissue (adjusted OR (aOR): 5.9, 95% CI: 4.7 to 7.6), diseases of the nervous system (aOR: 6.3, 95% CI: 4.9 to 8.0) and neoplasms (aOR: 5.6, 95% CI: 4.2 to 7.5) had higher odds of subsequent chronic prescription opioid use, compared with a referent group that included all diagnosis types with fewer than 15 chronic opioid users, after adjusting for confounders., Conclusions: By focusing interventions and prescribing guidelines on specific types of diagnoses that carry a high risk of chronic prescription opioid use and diagnoses that would benefit equally or more from alternative management approaches, states and healthcare organisations may more efficiently decrease inappropriate opioid prescribing while improving the quality of patient care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: No case definition exists that allows public health authorities to accurately identify opioid overdoses using emergency medical services (EMS) data. We developed and evaluated a case definition for suspected nonfatal opioid overdoses in EMS data., Methods: To identify suspected opioid overdose-related EMS runs, in 2019 the Rhode Island Department of Health (RIDOH) developed a case definition using the primary impression, secondary impression, selection of naloxone in the dropdown field for medication given, indication of medication response in a dropdown field, and keyword search of the report narrative. We developed the case definition with input from EMS personnel and validated it using an iterative process of random medical record review. We used naloxone administration in consideration with other factors to avoid misclassification of opioid overdoses., Results: In 2018, naloxone was administered during 2513 EMS runs in Rhode Island, of which 1501 met our case definition of a nonfatal opioid overdose. Based on a review of 400 randomly selected EMS runs in which naloxone was administered, the RIDOH case definition accurately identified 90.0% of opioid overdoses and accurately excluded 83.3% of non-opioid overdose-related EMS runs. Use of the case definition enabled analyses that identified key patterns in overdose locations, people who experienced repeat overdoses, and the creation of hotspot maps to inform outbreak detection and response., Practice Implications: EMS data can be an effective tool for monitoring overdoses in real time and informing public health practice. To accurately identify opioid overdose-related EMS runs, the use of a comprehensive case definition is essential.

The Rhode Island Department of Health (RIDOH) uses emergency department data to monitor nonfatal opioid overdoses in Rhode Island. In April 2019, RIDOH detected an increase in nonfatal opioid overdoses in Woonsocket, Rhode Island, and sent an alert to state and local partners (eg, fire departments, emergency departments, faith leaders) with guidance on how to respond. To guide community-level, strategic response efforts, RIDOH analyzed surveillance data to identify overdose patterns, populations, and geographic areas most affected. During April-June 2019, nonfatal opioid overdoses in Woonsocket increased 463% (from 13 to 73) when compared with the previous 3 months. Because of the sustained increase in nonfatal opioid overdoses, RIDOH brought together community partners at a meeting in June 2019 to discuss RIDOH opioid overdose data and coordinate next steps. Data analyses were essential to framing the discussion and allowed community partners at the event to identify an unexpected increase in cocaine-involved nonfatal opioid overdoses in Woonsocket. Many patients with cocaine-involved nonfatal overdoses also had fentanyl in their system, and input from community partners suggested that many patients were unaware of using fentanyl. Community response actions included targeting harm reduction services (eg, distribution of naloxone, mobile needle exchange); deploying peer recovery support specialists to overdose hotspots to connect people to treatment and recovery resources; placing harm reduction messaging in high-traffic areas; and targeted social media messaging. After the meeting, nonfatal opioid overdoses returned to pre-outbreak levels. This case study provides an example of how timely opioid overdose data can be effectively used to detect a spike in nonfatal opioid overdoses and inform a strategic, community-level response.

Objective: Both small for gestational age (SGA) birthweight and pregnancies complicated by maternal hypertension (HTN) are independently associated with poorer childhood learning outcomes, however the relative contribution of each remains unknown., Study Design: A retrospective cohort was created in which 2014-2017 third grade Rhode Island Department of Education data were linked to Rhode Island Department of Health birth certificate data. The study population was composed of non-anomalous, singleton births between 22- and 42-weeks' gestation. Reading and math proficiency were compared among four groups: 1) appropriate for gestational age (AGA) and no maternal HTN (referent), 2) AGA with HTN, 3) SGA without HTN and 4) SGA with HTN., Main Outcome Measures: Bivariable and multivariable log-binomial regression were used to examine the association between subject proficiency and pregnancy complication, adjusting for potential confounders., Results: Of the 23,097 who met inclusion criteria, 1004 (4%) were AGA with HTN, 1575 (7%) were SGA without HTN and 176 (1%) were SGA with HTN. Overall, when adjusted for maternal age, gestational age, sex and socioeconomic factors, only children born SGA without HTN had reduced reading proficiency (relative risk (RR) 0.86 95% confidence interval (CI) 0.78, 0.92) and math proficiency (RR 0.88 95% CI 0.82, 0.94) compared to children born AGA without HTN., Conclusion: In a diverse, statewide cohort, only SGA without HTN was associated with lower reading and math proficiency compared to uncomplicated pregnancies. This suggests that only decreased fetal growth from causes other than HTN is associated with risk of poorer school-age outcomes, and has implications for early resource allocation., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Major depression is a serious psychiatric disorder, occurring in up to 20 % of the population. Despite its devastating burden, the neurobiological changes associated with depression are not fully understood. A growing body of evidence suggests the kynurenine pathway is implicated in the pathophysiology of depression. In this review, we bring together the literature examining elements of the kynurenine pathway in depression and explore the implications for the pathophysiology and treatment of depression, while highlighting the gaps in the current knowledge. Current research indicates an increased potential for neurotoxic activity of the kynurenine pathway in peripheral blood samples but an increased activation of the putative neuroprotective arm in some brain regions in depression. The disconnect between these findings requires further investigation, with a greater research effort on elucidating the central effects of the kynurenine pathway in driving depression symptomology. Research investigating the benefits of targeting the kynurenine pathway centred on human brain findings and the heterogenous subtypes of depression will help guide the identification of effective drug targets in depression., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Modern sequencing technologies should make the assembly of the relatively small mitochondrial genomes an easy undertaking. However, few tools exist that address mitochondrial assembly directly., Results: As part of the Vertebrate Genomes Project (VGP) we develop mitoVGP, a fully automated pipeline for similarity-based identification of mitochondrial reads and de novo assembly of mitochondrial genomes that incorporates both long (> 10 kbp, PacBio or Nanopore) and short (100-300 bp, Illumina) reads. Our pipeline leads to successful complete mitogenome assemblies of 100 vertebrate species of the VGP. We observe that tissue type and library size selection have considerable impact on mitogenome sequencing and assembly. Comparing our assemblies to purportedly complete reference mitogenomes based on short-read sequencing, we identify errors, missing sequences, and incomplete genes in those references, particularly in repetitive regions. Our assemblies also identify novel gene region duplications. The presence of repeats and duplications in over half of the species herein assembled indicates that their occurrence is a principle of mitochondrial structure rather than an exception, shedding new light on mitochondrial genome evolution and organization., Conclusions: Our results indicate that even in the "simple" case of vertebrate mitogenomes the completeness of many currently available reference sequences can be further improved, and caution should be exercised before claiming the complete assembly of a mitogenome, particularly from short reads alone.

Background: Operative vaginal delivery rates continue to drop nationally with many citing neonatal safety concerns as a primary driver of this decrease. Previous evidence on short-term neonatal outcomes does not support this concern., Objective: This study aimed to better understand the impact of delivery mode on childhood educational outcomes., Study Design: A statewide retrospective cohort was created in which third grade Rhode Island Department of Education data for 2014 to 2017 were linked to Rhode Island Department of Health birth certificate data. Children's third grade reading and math proficiencies were compared by the mode of delivery listed in their birth certificates. The study population was limited to children who were term, singleton births without congenital anomalies. The mode of delivery was classified as operative vaginal (forceps or vacuum), primary cesarean, or spontaneous vaginal delivery. Children born via repeat cesarean delivery were excluded. Bivariate analyses were conducted to assess differences in demographic variables between mothers and children by mode of delivery and between reading and math proficiencies and mode of delivery. Bivariable and multivariable log-binomial regression was used to examine the association between subject proficiency and predictors including mode of delivery, gestational age, sex, race/ethnicity, and lunch subsidy., Results: Of the 18,247 children who met the inclusion criteria, 6% were delivered by operative vaginal delivery, 19% by primary cesarean delivery, and the remaining 75% by spontaneous vaginal delivery. After adjustment for confounders including gestational age at delivery, child's race/ethnicity, sex, and socioeconomic factors, there was no difference in reading proficiency (adjusted risk ratio, 1.03; 95% confidence interval, 0.96-1.10) or math proficiency (adjusted risk ratio, 1.01; 95% confidence interval, 0.95-1.08) in those born by operative vaginal delivery compared with primary cesarean delivery, and no difference was found in either proficiency when spontaneous vaginal delivery was compared with primary cesarean delivery (reading, adjusted risk ratio, 0.97; 95% confidence interval, 0.93-1.01; math, adjusted risk ratio, 0.98; 95% confidence interval, 0.94-1.01)., Conclusion: Operative vaginal delivery was not associated with differences in later childhood educational outcomes after adjusting for baseline differences. This should assuage previous concerns about long-term safety outcomes after operative vaginal delivery and may assist in shared decision making when operative vaginal or primary cesarean delivery is being considered., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Although labor induction at 39 weeks of gestation has been shown to reduce the number of cesarean deliveries, compared with expectant management, without increasing neonatal morbidity in nulliparous, low-risk women, the association between induction at 39 weeks and longer-term childhood cognitive outcomes is not certain., Objective: To evaluate educational outcomes of children born by induction at 39 or 40 weeks compared with those whose mothers were expectantly managed beyond those weeks., Design, Setting, and Participants: This statewide cohort study was conducted in Rhode Island. The participants included children of nulliparous women who were born at 39 weeks of gestation or later and then completed third-grade math and reading tests during the 2014 to 2017 academic year. Data analysis was performed from July 2019 to October 2019., Exposures: Induction of labor compared with expectant management., Main Outcomes and Measures: Third-grade math and reading test scores and proficiency (based on achievement level) among children born after induction in the 39th or 40th week were compared with scores for those who remained in utero beyond that same gestational week. The hypothesis was that induction in the 39th or 40th week would not be associated with differences in math or reading scores or proficiency compared with expectant management past the 39th or 40th week of gestation., Results: Of the 6393 children meeting the inclusion criteria (mean [SD] age, 8.00 [0.22] years; 3208 boys [50.2%]; 376 [5.8%] black; 1280 [22.0%] Hispanic), 455 were delivered by induction in the 39th week and 610 were delivered by induction in the 40th week. There were no differences in mean math or reading test scores or in the frequency of math or reading proficiency between children delivered by induction at 39 or 40 weeks compared with those whose mothers were expectantly managed (overall mean [SD] math score, 744 [33]; overall mean [SD] reading score, 743 [38]; 2945 children [46%] achieved proficiency in math and 2833 [44%] achieved proficiency in reading). After adjusting for plausible confounders (race/ethnicity, maternal education, hypertension, diabetes, and socioeconomic status), induction continued to be associated with similar proficiency in math and reading compared with expectant management. For children born by induction at 39 weeks, the adjusted relative risks were 1.07 (95% CI, 0.97-1.18) for math proficiency and 0.98 (95% CI, 0.88-1.08) for reading proficiency. For children born by induction at 40 weeks, the adjusted relative risks were 0.97 (95% CI, 0.88-1.08) for math proficiency and 0.98 (95% CI, 0.89-1.08) for reading proficiency., Conclusions and Relevance: These findings suggest that the offspring of nulliparous women for whom labor is induced at 39 or 40 weeks have similar third-grade educational outcomes compared with the offspring of mothers who underwent expectant management past those gestational ages.

Background: The Rhode Island Department of Health (RIDOH) has administered the Health Information Technology (HIT) Survey since 2009 to report clinician-level process measures relating to HIT adoption and use., Methods: RIDOH administers the Rhode Island HIT Survey to all licensed independent practitioners. Descriptive analyses examined HIT adoption and the clinician experience working with HIT., Results: Most physician and Advanced Practice Provider (APP) respondents report using an EHR (92.5% and 94.3%) and e-prescribing medications (84.1% and 81.6%). Less than half of physicians (40.9% or n=565) and APPs (35.4% or n=195) who prescribe controlled substances currently submit controlled substance prescriptions electronically. A higher percentage of physicians, compared to APPs, reported experiencing HIT-related stress (80.9% and 66.6%). The overall prevalence of physicians reporting symptoms of burnout was 29.7% (n=539) but varied between specialties., Discussion: As of 2019, the majority of Rhode Island physicians have adopted EHRs and e-prescribing. Adoption plateaued after 2012, and challenges persist in integrating existing technology into practice.

Background: The timing of social service benefit issuance is thought to be associated with increased drug overdose fatalities. However, the extent to which this excess mortality is concentrated in communities with higher levels of benefit receipt has not been studied. We sought to examine if benefit receipt at the neighborhood level was associated with spatiotemporal patterns of overdose fatalities., Methods: We conducted a retrospective review of all accidental overdose deaths recorded in Rhode Island from 2014 to 2016 (n = 838). Overdose incident locations were geocoded to the census block group level. Clusters of census block groups with excess overdose mortality at the beginning of a month were identified using spatial scan methods. Logistic regression models were fit to identify characteristics associated with the inclusion of a census block group within a cluster., Results: Increased rates of overdose fatalities at the beginning of a month were observed relative to the end of a preceding month (Ratio: 1.17; 95% CI: 1.04, 1.38). The proportions of residents receiving cash public assistance or Supplemental Security Income were not associated with excess mortality at the beginning of a month; however, the proportion of residents living in unaffordable housing was (OR: 1.42; 95% CI: 1.05, 1.91)., Conclusion: Despite previous research on benefit check issuance and overdose, welfare receipt was not associated with excess overdose mortality at the beginning of a month at the neighborhood level. Future research on housing cost burden and its influence on overdose death risk at the individual level is needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Context: National data on the epidemiology of firearm injuries and circumstances of firearm deaths are difficult to obtain and often are nonreliable. Since firearm injury and death rates and causes can vary substantially between states, it is critical to consider state-specific data sources., Objective: In this study, we illustrate how states can systematically examine demographic characteristics, firearm information, type of wound, toxicology tests, precipitating circumstances, and costs to provide a comprehensive picture of firearm injuries and deaths using data sets from a single state with relatively low rates of firearm injury and death., Design: Cross-sectional study., Setting: Firearm-related injury data for the period 2005-2014 were obtained from the Rhode Island emergency department and hospital discharge data sets; death data for the same period were obtained from the Rhode Island Violent Death Reporting System., Main Outcome Measure: Descriptive statistics were used. Healthcare Cost and Utilization Project cost-to-charge ratios were used to convert total hospital charges to costs., Results: Most firearm-related emergency department visits (55.8%) and hospital discharges (79.2%) in Rhode Island were from assaults; however, most firearm-related deaths were suicides (60.1%). The annual cost of firearm-related hospitalizations was more than $830 000. Most decedents who died because of firearms tested positive for illicit substances. Nearly a quarter (23.5%) of firearm-related homicides were due to a conflict between the decedent and suspect. More than half (59%) of firearm suicide decedents were reported to have had current mental or physical problems prior to death., Conclusions: Understanding the state-specific magnitude and patterns (who, where, factors, etc) of firearm injury and death may help inform local injury prevention efforts. States with similar data sets may want to adopt our analyses. Surveillance of firearm-related injury and death is essential. Dissemination of surveillance findings to key stakeholders is critical in improving firearm injury prevention. States that are not part of the National Violent Death Reporting System (NVDRS) could work with their other data sources to obtain a better picture of violent injuries and deaths to make the best use of resources.

[Full article available at http://rimed.org/rimedicaljournal-2019-03.asp].

Background: Sexual minority students have higher risk for health-related behaviors. We examined 5 domains including 34 health risk behaviors and health conditions among sexual minorities and unsure students in Rhode Island. We also included sexual contact of heterosexually identified students to capture heterosexually identified students who may be considered sexual minorities by their behavior., Methods: We used the 2007-2015 Rhode Island Youth Risk Behavior Survey data (N = 14,264). We categorized students into 4 groups: students self-identified as heterosexual and reported no sexual contact with same sex only or both sexes (group 1); self-identified as heterosexual and reported sexual contact with same sex only or both sexes (group 2); self-identified as lesbian, gay, bisexual (group 3); and responded as unsure (group 4). We used multivariable adjusted logistic regression analyses to evaluate associations of sexual minority and unsure students with 34 health risk behaviors and health conditions accounting for complex sampling design., Results: Students in groups 2-4 were more likely to engage in health-risk behaviors including violent behaviors, attempted suicide, substance use, and no physical activity than their peers., Conclusions: As sexual minority youth continue to report higher rates of health-related risk behaviors, targeted evidence-based prevention approaches must focus on reducing these risk behaviors among those youth., (© 2018, American School Health Association.)

Unintentional opioid overdoses are a growing public health epidemic in the United States. Rhode Island is also faced with a challenging crisis of drug overdose deaths. The State Unintentional Drug Overdose Reporting Surveillance (SUDORS) data from the second half of 2016 were used to present opioid overdose deaths and characteristics in Rhode Island. During July-December 2016, 142 individuals died of opioid overdose in Rhode Island. People who died by opioid overdose were more likely to be 25-65 years old, male, and non-Hispanic white. The most common precipitating circumstances were substance abuse (88%), current mental health problems (43%), and physical health problems (27.5%). Over 83% of decedents had 2 or more substances attribute to causing their death, with fentanyl (71.1%) as the most common substance. Only 36.6% of decedents had naloxone administered. Fatal opioid overdose data are important for understanding this public health crisis and can guide overdose intervention efforts.

Apoptosis culminates in the activation of caspase-3, which plays an important role in implementing the cell death program. Here, we reveal a non-apoptotic role of caspase-3 as a key regulator of cell proliferation and organ size. Caspase-3 is specifically activated in the proliferating cells of the sebaceous gland, but does not instruct cell elimination. Deletion or chemical inhibition of caspase-3 diminishes cell proliferation, decreases cell number and reduces sebaceous gland size in vivo. Exploring the underlying mechanism, we demonstrate that α-catenin is cleaved by caspase-3, thus facilitating the activation and nuclear translocation of yes-associated protein (YAP), a vital regulator of organ size. Accordingly, activation of caspase-3 leads to YAP-dependent organ size augmentation. Finally, we show that X-linked inhibitor of apoptosis protein (XIAP) serves as an endogenous feedback antagonist for the caspase-3/YAP signaling module. Taken together, we report here a molecular mechanism wherein the apoptotic machinery is refocused to regulate cell proliferation and orchestrate organ size., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Information on homicide firearms can be used to help state and local communities understand the problems of violence and decrease injuries and deaths. However, it is difficult to collect these data. To our knowledge, in the public health arena, the National Violent Death Reporting System (NVDRS) is the only system that collects detailed firearm information. The Rhode Island State Crime Laboratory (RISCL) can provide detailed information about the firearms and cartridge cases\bullets involved in firearm deaths. With help from the RISCL, the firearm information related to homicides in Rhode Island has improved dramatically. In 2015, information on caliber/gauge increased by 80%, the firearm type by 50%, the make by 50%, and the model by 20%. By documenting the process of using information from the RISCL, it is hoped that this process can be used as a model by other states when reporting on violent deaths.

[Full article available at http://rimed.org/rimedicaljournal-2018-02.asp].

Zika virus infection during pregnancy can cause serious birth defects, including microcephaly and brain abnormalities (1). Population-based birth defects surveillance systems are critical to monitor all infants and fetuses with birth defects potentially related to Zika virus infection, regardless of known exposure or laboratory evidence of Zika virus infection during pregnancy. CDC analyzed data from 15 U.S. jurisdictions conducting population-based surveillance for birth defects potentially related to Zika virus infection.* Jurisdictions were stratified into the following three groups: those with 1) documented local transmission of Zika virus during 2016; 2) one or more cases of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents; and 3) less than one case of confirmed, symptomatic, travel-associated Zika virus disease reported to CDC per 100,000 residents. A total of 2,962 infants and fetuses (3.0 per 1,000 live births; 95% confidence interval [CI] = 2.9-3.2) (2) met the case definition. † In areas with local transmission there was a non-statistically significant increase in total birth defects potentially related to Zika virus infection from 2.8 cases per 1,000 live births in the first half of 2016 to 3.0 cases in the second half (p = 0.10). However, when neural tube defects and other early brain malformations (NTDs) § were excluded, the prevalence of birth defects strongly linked to congenital Zika virus infection increased significantly, from 2.0 cases per 1,000 live births in the first half of 2016 to 2.4 cases in the second half, an increase of 29 more cases than expected (p = 0.009). These findings underscore the importance of surveillance for birth defects potentially related to Zika virus infection and the need for continued monitoring in areas at risk for Zika., Competing Interests: No conflicts of interest were reported.

Violence against women is a public health issue. Monitoring assault-related injury and homicide death among women is imperative for understanding this public health issue. We used data from the 2014 Rhode Island emergency department (ED), hospital discharge (HD), and 2004-2014 Rhode Island violent death reporting system (RIVDRS) to provide a broad picture for violence against women injuries and deaths in Rhode Island. ED visit and HD data show that the majority of female assault injuries occurred among women aged 25-44, resided in the core cities, and had public insurance. RIVDRS data showed that over half of the homicides among women were aged 25-64; nearly two in five were non-Hispanic black or Hispanic. Precipitating circumstances include intimate partner violence, a preceding argument or a conflict, and precipitated by another crime. Evidence-informed interventions need to target high-risk populations and urban areas to effectively reduce violence against women. [Full article available at http://rimed.org/rimedicaljournal-2017-12.asp].

Context: Drug overdoses are a growing public health problem in the United States. Rhode Island is also confronted with a serious epidemic of drug overdose deaths and ranks sixth worst in the United States for age-adjusted drug overdose death rate., Objective: To monitor trends of drug overdose-related emergency department (ED) visits, hospitalizations, and deaths and classify the drug overdoses by demographics, discharge status, intent, and specific drug involved to plan for health care resource allocation, mental health services, drug abuse treatment, prevention, and policies., Design: Cross-sectional study., Setting: The 2005-2014 ED, hospital discharge, and death data were used for this study., Main Outcome Measure: Age-adjusted rates were calculated by using age-specific Rhode Island 2010 standard population. Healthcare Cost and Utilization Project cost-to-charge ratios were used to convert total hospital charges to costs. The descriptive analysis was performed., Results: Hospitalizations generally represent the most severe cases; there are substantially fewer cases than are seen in the ED, and their characteristics are different from ED visits. More than half of the ED cases were an unintentional injury by drug overdose, but more than half of the hospital discharge data cases were a suicide/self-inflicted injury by drug overdose. There were typically much more females than males that result in a hospital admission. In Rhode Island, there were 249 drug overdose deaths in 2014. Drug overdose fatalities were more likely to be young, male, white, and those who reside in suburban regions., Implications: Nonfatal and fatal drug overdose data are important for understanding the scope, incidence, and breadth of this public health epidemic and can guide overdose intervention efforts. In Rhode Island, policy makers can use drug overdose data to target high-risk subpopulations to reduce overdose injuries and fatalities. The Rhode Island study can be shared with other states., Conclusions: Regardless of the type of drug, overdoses remain a public health crisis in Rhode Island. It is a dynamic epidemic and needs partnership among public health, behavioral health, public safety, clinic, pharmacy, and communities. The ability to track drug overdose in real time will be an essential tool to respond to the constantly evolving drug overdose epidemic in Rhode Island quickly and effectively.

Cells in healthy tissues acquire mutations with surprising frequency. Many of these mutations are associated with abnormal cellular behaviours such as differentiation defects and hyperproliferation, yet fail to produce macroscopically detectable phenotypes. It is currently unclear how the tissue remains phenotypically normal, despite the presence of these mutant cells. Here we use intravital imaging to track the fate of mouse skin epithelium burdened with varying numbers of activated Wnt/β-catenin stem cells. We show that all resulting growths that deform the skin tissue architecture regress, irrespective of their size. Wild-type cells are required for the active elimination of mutant cells from the tissue, while utilizing both endogenous and ectopic cellular behaviours to dismantle the aberrant structures. After regression, the remaining structures are either completely eliminated or converted into functional skin appendages in a niche-dependent manner. Furthermore, tissue aberrancies generated from oncogenic Hras, and even mutation-independent deformations to the tissue, can also be corrected, indicating that this tolerance phenomenon reflects a conserved principle in the skin. This study reveals an unanticipated plasticity of the adult skin epithelium when faced with mutational and non-mutational insult, and elucidates the dynamic cellular behaviours used for its return to a homeostatic state.

Community violence, including assault and homicide, is a public health problem. We provide a profile of assault-related injury and homicide death in Rhode Island to better understand assault/homicide. The 2014 emergency department (ED) visit data, hospital discharge (HD) data, and 2004-2014 Rhode Island Violent Death Reporting System (RIVDRS) data were used for this study. Most assault injuries and homicide deaths were among persons who were 25-44 years old, male, black and Hispanic, living in urban regions, self-pay or public insurance user, and never married. Almost 63% of the homicide decedents tested positive for some illicit substance. Precipitating circumstances include a preceding argument or a conflict, another crime, intimate partner violence, and drug involvement. RIVDRS did not provide an estimate for mental illness related homicides (e.g. command hallucinations). ED, HD, and RIVDRS data can provide a profile of assault injury and homicide death for public health authorities in RI. Interventions need to focus on high-risk populations and areas to effectively prevent assault-related injury and homicide. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. During mammalian skin repair, cells respond by migrating and proliferating to close the wound. However, the coordination of cellular repair behaviours and their effects on homeostatic functions in a live mammal remains unclear. Here we capture the spatiotemporal dynamics of individual epithelial behaviours by imaging wound re-epithelialization in live mice. Differentiated cells migrate while the rate of differentiation changes depending on local rate of migration and tissue architecture. Cells depart from a highly proliferative zone by directionally dividing towards the wound while collectively migrating. This regional coexistence of proliferation and migration leads to local expansion and elongation of the repairing epithelium. Finally, proliferation functions to pattern and restrict the recruitment of undamaged cells. This study elucidates the interplay of cellular repair behaviours and consequent changes in homeostatic behaviours that support tissue-scale organization of wound re-epithelialization.

The Rhode Island Violent Death Reporting System (RIVDRS) collects comprehensive surveillance data on violent deaths to support violence prevention programs in Rhode Island and nationwide. Successful collection of firearm information is critical to understanding gun violence in public health. A recent quality improvement (QI) project was performed to improve gun information collection in the RIVDRS program. Our aim was to increase the presence of firearm model information for 2014 suicides from 50% to 80% by December 31, 2015. We used the 2014 RIVDRS data and the Plan-Do-Study-Act cycle for this project. Our efforts achieved a 50% increase in the number of firearm model reporting. If we work more closely with police departments, they may understand the data importance, and be more likely to include the firearm information in their reports. We describe this process and provide lessons learned that can be generalizable to other states' violent death reporting system. [Full article available at http://rimed.org/rimedicaljournal-2017-02.asp].

Introduction: Mortality from injuries, particularly violent injuries, is more common among the young. Although traditional epidemiologic measures describe burden of death using rate-related mortalities, this method may not accurately represent burden of premature death. Years of life lost (YLLs) incorporate time discounting and age weighting to more accurately estimate the burden of death. To the authors' knowledge, there has been no examination of YLLs using the Rhode Island Violent Death Reporting System data. This study's objective was to assess the burden of violent death in Rhode Island in terms of YLLs., Methods: This study used 2006-2013 Rhode Island Violent Death Reporting System data. YLLs as a result of premature violent deaths were assessed overall and by age, sex, race/ethnicity, and manner of death. Data were analyzed in 2015., Results: Suicide made the largest contribution to the overall YLLs (61.3%), followed by homicide (24.0%), whereas undetermined intent deaths captured by the system accounted for 14.8% of YLLs. In Rhode Island, people aged 25-44 years had the highest YLLs due to suicide, and Hispanics had the highest YLLs due to homicide/legal intervention. By comparison, using crude mortality rate calculations, people aged 45-64 years had the highest suicide mortality rate and non-Hispanic blacks had the highest homicide mortality rate., Conclusions: YLL calculations provide a different picture than crude mortality-based assessments of the population at highest risk for violent death. This study demonstrates the strengths of using YLL to assess the burden of violent death at the state level., (Published by Elsevier Inc.)

Adult tissues replace lost cells via pools of stem cells. However, the mechanisms of cell self-renewal, commitment, and functional integration into the tissue remain unsolved. Using imaging techniques in live mice, we captured the lifetime of individual cells in the ear and paw epidermis. Our data suggest that epidermal stem cells have equal potential to either divide or directly differentiate. Tracking stem cells over multiple generations reveals that cell behavior is not coordinated between generations. However, sibling cell fate and lifetimes are coupled. We did not observe regulated asymmetric cell divisions. Lastly, we demonstrated that differentiating stem cells integrate into preexisting ordered spatial units of the epidermis. This study elucidates how a tissue is maintained by both temporal and spatial coordination of stem cell behaviors., (Copyright © 2016, American Association for the Advancement of Science.)

Identifying and understanding the root causes of preventable hospitalization (PH) is important for improving health outcomes and reducing unnecessary healthcare costs. Thus far, however, the desire to address this issue has been impeded by a general lack of research on factors associated with PH. To begin to address this gap, we propose an evidence-based logic model of individual, environmental, and systemic factors related to PH. We aim to use this logic model to design public health interventions to reduce PH in the State of Rhode Island and to stimulate an industry-wide discussion of the problem and its possible solutions.

Background: Incarceration is simultaneously a public health opportunity and a public health concern. We examined the association between maternal/partner incarceration in the year prior to birth and perinatal smoking., Methods: We pooled 2006-2010 data from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment and Monitoring System. Controlling for age, race/ethnicity, education, marital status and other stressors, we assessed prevalence and heaviness of perinatal smoking., Findings: Women who reported incarceration of themselves or their partners in the year prior to delivery were more likely to smoke during the last trimester of pregnancy (adjusted OR (AOR) 1.51 (95% CI 1.36 to 1.67)), and they were more likely to smoke more than 10 cigarettes a day compared to smokers who did not report incarceration (AOR 1.35 (95% CI 1.10 to 1.65)). Patterns were similar for the 3 months prior to pregnancy and postbirth smoking., Conclusions: Incarceration of a parent in the 12 months before birth is associated with increased risk of fetal and newborn exposure to smoking. The criminal justice system can be utilised by public health practitioners to target perinatal smoking reduction interventions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)