Associations between tobacco 21 and state flavour restrictions with young adult tobacco use.

BACKGROUND: States have recently enacted tobacco-related age and flavour restrictions in addition to federal T21 laws. Little is known about the independent effects of these policies on young adult tobacco use. METHODS: Linking 2011-2022 Behavioural Risk Factor Surveillance System data on 2 696 870, 18-59 years from 50 states and DC with policy data, we conducted probit regression models to evaluate the associations between state and federal T21 laws and state flavour restrictions with cigarettes, electronic nicotine delivery system (ENDS) and smokeless tobacco use. Models were adjusted for sociodemographics, additional tobacco policies, COVID-19-related factors, year and state. We tested two-way and three-way interactions between age, state T21 and federal T21 laws. RESULTS: Although we did not find evidence that state T21 laws were associated with cigarette, smokeless tobacco or ENDS use overall, the federal T21 law was associated with lower use of all three tobacco products by 0.39-0.92 percentage points. State flavour restrictions were associated with lower use of cigarettes by 0.68 (-1.27 to -0.09) and ENDS by 0.56 (-1.11 to -0.00) percentage points, but not with smokeless tobacco. A three-way interaction revealed that state and federal T21 laws together were associated with a lower prevalence of ENDS use among 18-20 years, but there were no differences in cigarette use from both policies combined versus either alone. CONCLUSION: State and federal T21 laws are broadly effective at reducing adult tobacco use, while state flavour restrictions specifically lower use of cigarettes and ENDS.

Impact of School Shootings on Adolescent School Safety, 2009-2019.

Objectives. To examine the impact of school shootings on indicators of adolescent school safety in the United States. Methods. We linked 2009-2019 Youth Risk Behavior Survey data on 211 236 adolescents aged 14 to 18 years from 24 school districts with data on high school shootings from the Center for Homeland Defense and Security. We conducted 2-way fixed-effects logistic regression models to assess the impact of shootings on self-report of 3 indicators of school safety: avoiding school because of feeling unsafe, carrying a weapon at school, and being threatened or injured with a weapon at school. Results. High school shootings were associated with adolescents having 20% greater odds of avoiding school because of feeling unsafe (adjusted odd ratio [AOR] = 1.20; 95% confidence interval [CI] = 1.11, 1.29) than those who had not. Findings were slightly attenuated in sensitivity analyses that tested exposure to shootings at any school in the district or state. High school shootings were associated with a statistically nonsignificant (P = .08) elevated risk of carrying a weapon at school (AOR = 1.11; 95% CI = 0.99, 1.25). Conclusions. The negative ramifications of school shootings extend far beyond the event itself to adolescents' concerns about school safety. (Am J Public Health. 2023;113(4):438-441. https://doi.org/10.2105/AJPH.2022.307206).

Associations between ACA-related policies and a clinical recommendation with HPV vaccine initiation.

PURPOSE: We examined associations between the 2010 Affordable Care Act (ACA) provisions, 2011 Advisory Committee on Immunization Practices (ACIP) recommendation, and 2014 ACA-related health insurance reforms with HPV vaccine initiation rates by sex and health insurance type. METHODS: Using 2009-2015 public and private health insurance claims for 551,764 males and females aged 9-26 years (referred to as youth) from Maine, New Hampshire, and Massachusetts, we conducted linear regression models to examine the associations between three policy changes and HPV vaccine initiation rates by sex and health insurance type. RESULTS: In 2009, HPV vaccine initiation rates for males and females were 0.003 and 0.604 per 100 enrollees, respectively. Among males, the 2010 ACA provisions and ACIP recommendation were associated with significant increases in HPV vaccine uptake among those with private plans (0.207 [0.137, 0.278] and 0.419 [0.353, 0.486], respectively) and Medicaid (0.157 [0.083, 0.230] and 0.322 [0.257, 0.386], respectively). Among females, the 2010 ACA provisions were associated with significant increases in HPV vaccine uptake among Medicaid enrollees only (0.123 [0.033, 0.214]). The ACA-related health insurance reforms were associated with significant increases in HPV vaccine uptake for male and female Medicaid enrollees (0.257 [0.137, 0.377] and 0.214 [0.102, 0.327], respectively), but no differences among privately insured youth. By 2015, there were no differences in HPV vaccine initiation rates between males (0.278) and females (0.305). CONCLUSIONS: Both ACA provisions and the ACIP recommendation were associated with significant increases in HPV vaccine initiation rates among privately and publicly insured males in three New England states, closing the gender gap. In contrast, females and youth with private insurance did not exhibit the same changes in HPV vaccine uptake over the study period.

Associations between insurance-related affordable care act policy changes with HPV vaccine completion.

BACKGROUND: Although all 11- or 12-year-olds in the US were recommended to receive a 3-dose series of the human papillomavirus (HPV) vaccine within a 12-month period prior to 2016, rates of completion of the HPV vaccine series remained suboptimal. The effects of the Affordable Care Act (ACA), including private insurance coverage with no cost-sharing and health insurance expansions, on HPV vaccine completion are largely unknown. The aim of this study was to examine the associations between the ACA's 2010 provisions and 2014 insurance expansions with HPV vaccine completion by sex and health insurance type. METHODS: Using 2009-2015 public and private health insurance claims from Maine, New Hampshire, and Massachusetts, we identified 9-to-26-year-olds who had at least one HPV vaccine dose. We conducted a logistic regression model to examine the associations between the ACA policy changes with HPV vaccine completion (defined as receiving a 3-dose series within 12 months from the date of initiation) as well as interactions by sex and health insurance type. RESULTS: Over the study period, among females and males who initiated the HPV vaccine, 27.6 and 28.0%, respectively, completed the series within 12 months. Among females, the 2010 ACA provision was associated with a 4.3 percentage point increases in HPV vaccine completion for the privately-insured (0.043; 95% CI: 0.036-0.061) and a 5.7 percentage point increase for Medicaid enrollees (0.057; 95% CI: 0.032-0.081). The 2014 health insurance expansions were associated with a 9.4 percentage point increase in vaccine completion for females with private insurance (0.094; 95% CI: 0.082-0.107) and a 8.5 percentage point increase for Medicaid enrollees (0.085; 95% CI: 0.068-0.102). Among males, the 2014 ACA reforms were associated with a 5.1 percentage point increase in HPV vaccine completion for the privately-insured (0.051; 95% CI: 0.039-0.063) and a 3.4 percentage point increase for Medicaid enrollees (0.034; 95% CI: 0.017-0.050). In a sensitivity analysis, findings were similar with HPV vaccine completion within 18 months. CONCLUSIONS: Despite low HPV vaccine completion overall, both sets of ACA provisions were associated with increases in completion among females and males. Our results suggest that expanding Medicaid across the remaining states could increase HPV vaccine completion among publicly-insured youth and prevent HPV-related cancers.

BRCA1/2 Testing in Massachusetts Among Women With Private Insurance or Medicaid, 2011-2015.

PURPOSE: Testing for BRCA1/2 mutations has increased among privately insured women in the United States. However, little is known about testing rates or trends among women with Medicaid. We sought to determine whether BRCA1/2 testing rates differed between women with private insurance compared with women with Medicaid in a state where both insurance types cover the test, and to compare testing trends from 2011 to 2015. METHODS: We conducted a retrospective cohort study of medical claims from January 2011 through June 2015. We included Massachusetts women aged 18-64 with private insurance or Medicaid and at least 12 months of continuous enrollment. We used multivariable linear regression to examine the association of insurance type, age, and time with testing rates. RESULTS: Mean monthly BRCA1/2 testing rates were lower among women with Medicaid compared with those with private insurance. Among privately insured women, mean monthly rates rose from 9.3 per 100,000 in 2011 to 18.4 per 100,000 in 2015, while among Medicaid-insured women, rates increased from 3.7 to 14.7. There was no difference in the monthly rate of increase in both groups (P=0.07). In adjusted analyses, rates were lower among Medicaid-insured women (7 fewer tests per month than privately insured women, P<0.001), and differed by age, with women aged 44-54 most likely to receive testing and women 18-34 the least likely. CONCLUSION: BRCA1/2 testing rates were lower among women insured by Medicaid compared with those with private insurance, though rates increased from 2011 to 2015 among both groups of women at a similar rate.

State-Level Changes in Firearm Laws and Workplace Homicide Rates: United States, 2011 to 2017.

Objectives. To test whether year-over-year strengthening of state-level firearm laws is associated with decreases in workplace homicide rates.Methods. In this time-series ecological study of working people in all 50 US states, we used federal data on workplace homicides by state and year from 2011 to 2017, linked to an index of state-year firearm laws, to characterize the regulatory environment (overall and within legislative categories). We used generalized linear regression to model associations between changes in firearm laws and changes in workplace homicide rates the following year.Results. From 2011 to 2017, more than 3000 people died as a result of workplace homicides; over that period, 23 states strengthened firearm regulations and 23 weakened them. We modeled the impact of states strengthening laws within the interquartile range (IQR; equivalent to adding 20.5 firearm laws). This change was associated with a 3.7% reduction in the workplace homicide rate (95% confidence interval [CI] = -3.86, -3.51). Positive IQR changes in specific categories of firearm laws-concealed carry permitting (-5.79%; 95% CI = -6.09, -3.51), domestic violence-related restrictions (-5.31%; 95% CI = -5.57, -5.05), and background checks (-5.07%; 95% CI = -5.32, -4.82)-were also associated with significant reductions.Conclusions. Strengthening state-level firearm laws may reduce the population-level mortality and morbidity burden posed by workplace homicides.

Associations Between Gun Laws and Suicides.

We examined the impact of a state gun law environment on suicides overall and within demographic subgroups. We linked 211,766 firearm suicides and 204,625 nonfirearm suicides in the 50 states of the United States for 2005-2015 to the population in each state, year, race/ethnicity, sex, and age, as well as to an index of state-level gun control. Difference-in-differences, zero-inflated, negative-binomial models were used to evaluate the impact of strengthening gun control on firearm and nonfirearm suicides. We subsequently stratified by sex and tested for interactions with race/ethnicity and age. We found 25 states strengthened gun control by an average of 6 points. Such an increase may result in a 3.3% (incidence rate ratio = 0.967; 95% confidence interval: 0.938, 0.996) decrease in firearm suicides. Although no impact on nonfirearm suicides was found overall, interaction models showed an increase in nonfirearm suicides among black men, white women, black women, and older individuals. Strengthening gun control may reduce firearm suicides overall but may increase nonfirearm suicides in some populations. The results indicate stricter gun laws should be advocated for and that additional policies are needed for populations who shifted to nonfirearm suicides.

Impact of state tobacco control policies on birth defects.

While research has demonstrated the effects of tobacco control policies on birth outcomes, there is little known about their impact on birth defects. Using 2005-2015 natality data on 26,334,854 singletons from 47 US states and District of Columbia linked to state-level cigarette taxes and smoke-free restaurant legislation, we examined the impact of tobacco control policies on birth defects by maternal race/ethnicity and education. We found that among white women with less than a high school degree, every $1.00 increase in cigarette taxes reduced prenatal smoking by 3.48 percentage points and reduced the risk of their infant having any birth defect by 0.0023 percentage points. Tax increases also reduced the risk of cyanotic heart defects, cleft palate, gastroschisis, and limb reduction. We found no evidence for associations between the enactment of smoke-free legislation, prenatal smoking and birth defects. Our findings suggest that state cigarette taxes are a population-level intervention that can help reduce prenatal smoking and the risk of birth defects.

A quasi-experimental evaluation of marijuana policies and youth marijuana use.

BACKGROUND: Marijuana use carries risks for adolescents' well-being, making it essential to evaluate effects of recent marijuana policies. OBJECTIVES: This study sought to delineate associations between state-level shifts in decriminalization and medical marijuana laws (MML) and adolescent marijuana use. METHODS: Using data on 861,082 adolescents (14 to 18+ years; 51% female) drawn from 1999 to 2015 state Youth Risk Behavior Surveys (YRBS), difference-in-differences models assessed how decriminalization and MML policy enactment were associated with adolescent marijuana use, controlling for tobacco and alcohol policy shifts, adolescent characteristics, and state and year trends. RESULTS: MML enactment was associated with small significant reductions (OR = 0.911, 95% CI [0.850, 0.975]) of 1.1 percentage points in current marijuana use, with larger significant declines for male, Black, and Hispanic (2.7-3.9 percentage points) adolescents. Effects of MML increased significantly with each year of exposure (OR = 0.980, 95% CI [0.968, 0.992]). In contrast, decriminalization was not associated with significant shifts in use for the sample as a whole, but predicted significant declines in marijuana use among 14-year olds and those of Hispanic and other ancestry (1.7-4.4 percentage points), and significant increases among white adolescents (1.6 percentage points). Neither policy was significantly associated with heavy marijuana use or the frequency of use, suggesting that heavy users may be impervious to such policy signals. CONCLUSION: As the first study to concurrently assess unique effects of multiple marijuana policies, results assuage concerns over potential detrimental effects of more liberal marijuana policies on youth use.

Associations Between State Tobacco Control Policies and Adolescent ENDS Use.

BACKGROUND: Despite an increase in adolescent use of electronic nicotine delivery systems (ENDS), little is known about the role of tobacco control policies on ENDS use. OBJECTIVE: For aim 1, we examined how trends in adolescent use of cigarettes were affected by the introduction of ENDS; for aim 2, we examined the associations between ENDS age restrictions, cigarette taxes, and smoke-free legislation and adolescent use of ENDS and cigarettes. DESIGN AND SETTING: Repeated cross-sections of the 1999-2015 Youth Risk Behavior Surveys linked to state-level tobacco control policies. PARTICIPANTS: 938 486 adolescents aged 14 to 18 years from 45 states. MAIN OUTCOME MEASURES: For aim 1, we examined adolescent use of cigarettes. For aim 2, we examined adolescent use of ENDS, only ENDS, and cigarettes. RESULTS: We found there was an overall decreasing trend in adolescent use of cigarettes, but the actual decline was greater than the predicted decline for 17- and 18-year-olds. While we found no associations between ENDS use and ENDS age restrictions or cigarette taxes, ENDS use was 3.8 percentage points higher in those states with smoke-free legislation for combustible tobacco products. CONCLUSIONS: Our findings highlight that ENDS age restrictions may not be adequate to curb ENDS use and additional local- and state-level policies governing ENDS are needed.

Impact of tobacco control policies on adolescent smokeless tobacco and cigar use: a difference-in-differences approach.

BACKGROUND: While increasing cigarette taxes has been a major policy driver to decrease smoking, taxes on other tobacco products have received less attention. Our aims were to evaluate the impact of chewing tobacco/cigar taxes, cigarette taxes, and smoke-free legislation on adolescent male and female use of smokeless tobacco and cigars. METHODS: We analyzed data on 499,381 adolescents age 14-18 years from 36 US states in the Youth Risk Behavior Surveys (1999-2013) linked to state-level tobacco control policies. We conducted difference-in-differences regression models to assess whether changes in taxes and the enactment of smoke-free legislation were associated with smokeless tobacco use and, separately, cigar use. Models were stratified by adolescent sex. RESULTS: We found that chewing tobacco taxes had no effect on smokeless tobacco use and cigar taxes had no effect on cigar use. In contrast, among males a 10% increase in cigarette taxes was associated with a 1.0 percentage point increase (0.0010, 95% CI 0.0003-0.0017) in smokeless tobacco use. A 10% increase in cigarette taxes was also associated with a 1.5 percentage point increase (0.0015, 95% CI 0.0006-0.0024) in cigar use among males and a 0.7 percentage point increase (0.0007, 95% CI 0.0001-0.0013) in cigar use among females. There was some evidence that smoke-free legislation was associated with an 1.1 percentage point increase (0.0105, 95% CI 0.0015-0.0194) in smokeless tobacco use among males only, but no effect of smoke-free legislation on cigar use for males or females. CONCLUSIONS: Higher state cigarette taxes are associated with adolescents' use of cheaper, alternative tobacco products such as smokeless tobacco and cigars. Reducing tobacco use will require comprehensive tobacco control policies that are applied equally to and inclusive of all tobacco products.

A modified γ-retrovirus vector for X-linked severe combined immunodeficiency.

BACKGROUND: In previous clinical trials involving children with X-linked severe combined immunodeficiency (SCID-X1), a Moloney murine leukemia virus-based γ-retrovirus vector expressing interleukin-2 receptor γ-chain (γc) complementary DNA successfully restored immunity in most patients but resulted in vector-induced leukemia through enhancer-mediated mutagenesis in 25% of patients. We assessed the efficacy and safety of a self-inactivating retrovirus for the treatment of SCID-X1. METHODS: We enrolled nine boys with SCID-X1 in parallel trials in Europe and the United States to evaluate treatment with a self-inactivating (SIN) γ-retrovirus vector containing deletions in viral enhancer sequences expressing γc (SIN-γc). RESULTS: All patients received bone marrow-derived CD34+ cells transduced with the SIN-γc vector, without preparative conditioning. After 12.1 to 38.7 months of follow-up, eight of the nine children were still alive. One patient died from an overwhelming adenoviral infection before reconstitution with genetically modified T cells. Of the remaining eight patients, seven had recovery of peripheral-blood T cells that were functional and led to resolution of infections. The patients remained healthy thereafter. The kinetics of CD3+ T-cell recovery was not significantly different from that observed in previous trials. Assessment of insertion sites in peripheral blood from patients in the current trial as compared with those in previous trials revealed significantly less clustering of insertion sites within LMO2, MECOM, and other lymphoid proto-oncogenes in our patients. CONCLUSIONS: This modified γ-retrovirus vector was found to retain efficacy in the treatment of SCID-X1. The long-term effect of this therapy on leukemogenesis remains unknown. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01410019, NCT01175239, and NCT01129544.).

Effect of the Affordable Care Act on Disparities in Breastfeeding: The Case of Maine.

OBJECTIVES: To evaluate the Affordable Care Act (ACA) breastfeeding provision and test whether changes in coverage affected women differently according to health insurance status. METHODS: We used the All-Payer Claims Database from Maine (2012-2014) to compare health insurance claims for lactation classes and breast pumps between women with private insurance and women with Medicaid (1) before the ACA breastfeeding provision, (2) after the provision came into effect, and (3) after health insurance expansion through the Marketplace. RESULTS: We found limited change in claims for lactation classes over the study period. By contrast, the number of claims for breast pumps among women with private insurance increased from 70 claims in the third quarter of 2012 to 629 claims 1 year later and 803 claims in the third quarter of 2014. Women with Medicaid had only 11 claims for breast pumps over the entire study period. CONCLUSIONS: This 11-fold rise in claims for breast pumps by women with private insurance suggests that these women will likely increase breastfeeding initiation or duration; however, without additional support for women with Medicaid, disparities in breastfeeding may increase.

Invited Commentary: An Interdisciplinary Approach for Policy Evaluation.

Evidence-based policymaking is becoming the norm, but how do we acquire the evidence to inform policies? In their article in the present issue of the Journal, Basu et al. (Am J Epidemiol. 2016;183(6):531-538) used difference-in-difference-in-differences models and a synthetic control approach to examine the effects of the 1996 welfare reforms on health outcomes among single mothers. In the present commentary, we discuss the limitations of observational studies for policy evaluation. Difference-in-differences models, from the field of economics, offer a rigorous approach to cope with those limitations.

Reduction in emergency department visits for children's asthma, ear infections, and respiratory infections after the introduction of state smoke-free legislation.

Despite the benefits of smoke-free legislation on adult health, little is known about its impact on children's health. We examined the effects of tobacco control policies on the rate of emergency department (ED) visits for childhood asthma (N=128,807), ear infections (N=288,697), and respiratory infections (N=410,686) using outpatient ED visit data in Massachusetts (2001-2010), New Hampshire (2001-2009), and Vermont (2002-2010). We used negative binomial regression models to analyze the effect of state and local smoke-free legislation on ED visits for each health condition, controlling for cigarette taxes and health care reform legislation. We found no changes in the overall rate of ED visits for asthma, ear infections, and upper respiratory infections after the implementation of state or local smoke-free legislation or cigarette tax increases. However, an interaction with children's age revealed that among 10-17-year-olds state smoke-free legislation was associated with a 12% reduction in ED visits for asthma (adjusted incidence rate ratios (aIRR) 0.88; 95% CI 0.83, 0.95), an 8% reduction for ear infections (0.92; 0.88, 0.97), and a 9% reduction for upper respiratory infections (0.91; 0.87, 0.95). We found an overall 8% reduction in ED visits for lower respiratory infections after the implementation of state smoke-free legislation (0.92; 0.87, 0.96). The implementation of health care reform in Massachusetts was also associated with a 6-9% reduction in all children's ED visits for ear and upper respiratory infections. Our results suggest that state smoke-free legislation and health care reform may be effective interventions to improve children's health by reducing ED visits for asthma, ear infections, and respiratory infections.

Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency.

Defects in perforin lead to the failure of T and NK cell cytotoxicity, hypercytokinemia, and the immune dysregulatory condition known as familial hemophagocytic lymphohistiocytosis (FHL). The only curative treatment is allogeneic hematopoietic stem cell transplantation which carries substantial risks. We used lentiviral vectors (LV) expressing the human perforin gene, under the transcriptional control of the ubiquitous phosphoglycerate kinase promoter or a lineage-specific perforin promoter, to correct the defect in different murine models. Following LV-mediated gene transfer into progenitor cells from perforin-deficient mice, we observed perforin expression in mature T and NK cells, and there was no evidence of progenitor cell toxicity when transplanted into irradiated recipients. The resulting perforin-reconstituted NK cells showed partial recovery of cytotoxicity, and we observed full recovery of cytotoxicity in polyclonal CD8(+) T cells. Furthermore, reconstituted T cells with defined antigen specificity displayed normal cytotoxic function against peptide-loaded targets. Reconstituted CD8(+) lymphoblasts had reduced interferon-γ secretion following stimulation in vitro, suggesting restoration of normal immune regulation. Finally, upon viral challenge, mice with >30% engraftment of gene-modified cells exhibited reduction of cytokine hypersecretion and cytopenias. This study demonstrates the potential of hematopoietic stem cell gene therapy as a curative treatment for perforin-deficient FHL.

TCR-engineered T cells: a model of inducible TCR expression to dissect the interrelationship between two TCRs.

TCR gene modified T cells for adoptive therapy simultaneously express the Tg TCR and the endogenous TCR, which might lead to mispaired TCRs with harmful unknown specificity and to a reduced function of TCR-Tg T cells. We generated dual TCR T cells in two settings in which either TCR was constitutively expressed by a retroviral promoter while the second TCR expression was regulable by a Tet-on system. Constitutively expressed TCR molecules were reduced on the cell surface depending on the induced TCR expression leading to strongly hampered function. Besides that, using fluorescence resonance energy transfer we detected mispaired TCR dimers and different pairing behaviors of individual TCR chains with a mutual influence on TCR chain expression. The loss of function and mispairing could not be avoided by changing the TCR expression level or by introduction of an additional cysteine bridge. However, in polyclonal T cells, optimized TCR formats (cysteineization, codon optimization) enhanced correct pairing and function. We conclude from our data that (i) the level of mispairing depends on the individual TCRs and is not reduced by increasing the level of one TCR, and (ii) modifications (cysteineization, codon optimization) improve correct pairing but do not completely exclude mispairing (cysteineization).

Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.

Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and essential feature of the retroviral life cycle, establishes the infection permanently. Current antiretroviral combination drug therapy cannot cure HIV infection. However, expressing an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre), shown to excise integrated proviral DNA in vitro, may provide a novel and highly promising antiviral strategy. We report here the conditional expression of Tre-recombinase from an advanced lentiviral self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful transgene expression, resulting in accurate provirus excision in the absence of cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are demonstrated in vivo, particularly in humanized Rag2⁻/⁻γc⁻/⁻ mice engrafted with either Tre-transduced primary CD4⁺ T cells, or Tre-transduced CD34⁺ hematopoietic stem and progenitor cells (HSC). Taken together, our data support the use of Tre-recombinase in novel therapy strategies aiming to provide a cure for HIV.

Modified lentiviral LTRs allow Flp recombinase-mediated cassette exchange and in vivo tracing of "factor-free" induced pluripotent stem cells.

Methods for generating induced pluripotent stem cells (iPSCs) for disease modeling and cell therapies have progressed from integrating vectors to transient delivery of reprogramming factors, avoiding permanent genomic modification. A major limitation of unmodified iPSCs is the assessment of their distribution and contribution to adverse reactions in autologous cell therapy. Here, we report that polycistronic lentiviral vectors with single Flp recombinase (Flp) recognition target (FRT) sites can be used to generate murine iPSCs that are devoid of the reprogramming cassette but carry an intergenic 300-bp long terminal repeat sequence. Performing quantitative polymerase chain reaction on this marker, we could determine genetic identity and tissue contribution of iPSC-derived teratomas in mice. Moreover, we generated iPSCs carrying heterospecific FRT twin sites, enabling excision and recombinase-mediated cassette exchange (RMCE) of the reprogramming cassette for another expression unit of choice. Following screening of iPSCs for "safe harbor" integration sites, expression cassettes were introduced by RMCE into various previously silenced loci of selected single-copy iPSCs. Analysis of DNA methylation showed that RMCE reverted the local epigenetic signature, which allowed transgene expression in undifferentiated iPSCs and in differentiated progeny. These findings support the concept of creating clonotypically defined exchangeable and traceable pluripotent stem cells for disease research and cell therapy.

Evaluating the impact of the Baby-Friendly Hospital Initiative on breast-feeding rates: a multi-state analysis.

OBJECTIVE: To evaluate the impact of the Baby-Friendly Hospital Initiative (BFHI) on breast-feeding initiation and duration overall and according to maternal education. DESIGN: Quasi-experimental study using data from five states (Alaska, Maine, Nebraska, Ohio, Washington) that participated in the Pregnancy Risk Assessment Monitoring System from 1999 to 2009. Using differences-in-differences models that included year and hospital fixed effects, we compared rates of breast-feeding initiation and duration (any and exclusive breast-feeding for ≥4 weeks) before and after BFHI accreditation between mothers who gave birth in hospitals that were accredited or became accredited and mothers from matched non-BFHI facilities. We stratified analyses into lower and higher education groups. SETTING: Thirteen BFHI hospitals and nineteen matched non-BFHI facilities across five states in the USA. SUBJECTS: Mothers (n 11 723) who gave birth in BFHI hospitals and mothers (n 13 604) from nineteen matched non-BFHI facilities. RESULTS: Although we did not find overall differences in breast-feeding initiation between birth facilities that received BFHI accreditation compared with non-Baby-Friendly facilities (adjusted coefficient = 0·024; 95 % CI -0·00, 0·51), breast-feeding initiation increased by 3·8 percentage points among mothers with lower education who delivered in Baby-Friendly facilities (P = 0·05), but not among mothers with higher education (adjusted coefficient = 0·002; 95 % CI -0·04, 0·05). BFHI accreditation also increased exclusive breast-feeding for ≥4 weeks by 4·5 percentage points (P = 0·02) among mothers with lower education who delivered in BFHI facilities. CONCLUSIONS: By increasing breast-feeding initiation and duration among mothers with lower education, the BFHI may reduce socio-economic disparities in breast-feeding.