Antibody Seroprevalence, Infection and Surveillance for SARS-CoV-2 in Residents and Staff of New Jersey Long-Term Care Facilities.

Early in the pandemic, New Jersey (NJ) long-term care facilities (LTCFs) witnessed severe COVID-19 illness. With limited surveillance to characterize the scope of infection, we estimated the prevalence of antibody to the SARS-CoV-2 nucleocapsid protein among residents and staff, to describe the epidemiology, and to measure antibody distribution by prior PCR/antigen status and symptomatology. 10 NJ LTCFs of 20 solicited with diverse geography and bed-capacities were visited between October 2020 and March 2021. A single serum was tested for total N-antibody (ELISA) by the state laboratory. Residents' demographics and clinical history were transcribed from the patient record. For staff, this information was solicited directly from employees, supplemented by prior PCR/antigen results from facilities. 62% of 332 residents and 46% of 661 staff tested N-antibody positive. In a multivariable logistic regression in residents, odds ratios for older age and admission prior before March 1, 2020 were significant. Among the staff, odds ratios for older age, ethnic-racial group, nursing-related job, and COVID-19 symptoms were significantly associated with N-antibody positivity. In a sub-analysis in five better record-keeping LTCFs, 90% of residents and 85% of staff with positive PCR/antigen results were seropositive for N-antibody, yet 25% of residents and 22% of staff were N-antibody positive but PCR/antigen and symptoms negative. The high rate of clinically unsuspected infections likely contributed to the spread. These findings argue for robust surveillance, regular screening of asymptomatic individuals, and vaccinating both residents and staff to abate the pandemic. The data also provide guidance to prevent future outbreaks.

Adaptation of the Flu-FIT Program for Patient-Aligned Care Teams: A Quality Improvement Project.

The Flu-FIT program aims to increase colorectal cancer screening rates by offering a home fecal immunochemical test (FIT) at the time of annual influenza immunization. This program was piloted at a VA campus in New Jersey during the 2018-2019 influenza season, with a 9% increase in colorectal cancer screening rates. In the 2019-2020 season, the program was implemented in 6 primary care teams; 6 additional teams maintaining standard of care served as a comparison group. A total of 816 patients aged 50 to 75 years were eligible for participation; 509 patients were available for analysis, 242 in the Flu-FIT group and 267 in the comparison group. The Flu-FIT group patients were 2.4 times more likely to accept FIT kits (95% confidence interval: 1.6-3.6, P = .001). The colorectal cancer screening rates increased 77.0% to 81.9% in the Flu-FIT group and 77.0% to 79.8% in the comparison group (P > .05).

The Impact of HIV Infection on TB Disparities Among US-Born Black and White Tuberculosis Patients in the United States.

BACKGROUND/OBJECTIVES: US-born non-Hispanic black persons (blacks) (12% of the US population) accounted for 41% of HIV diagnoses during 2008-2014. HIV infection significantly increases TB and TB-related mortality. TB rate ratios were 6 to 7 times as high in blacks versus US-born non-Hispanic whites (whites) during 2013-2016. We analyzed a sample of black and white TB patients to assess the impact of HIV infection on TB racial disparities. METHODS: In total, 552 black and white TB patients with known HIV/AIDS status were recruited from 10 US sites in 2009-2010. We abstracted data from the National TB Surveillance System, medical records, and death certificates and interviewed 477 patients. We estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations of TB with HIV infection, late HIV diagnosis (≤3 months before or any time after TB diagnosis), and mortality during TB treatment. RESULTS: Twenty-one percent of the sample had HIV/AIDS infection. Blacks (AOR = 3.4; 95% CI, 1.7-6.8) and persons with recent homelessness (AOR = 2.5; 95% CI, 1.5-4.3) had greater odds of HIV infection than others. The majority of HIV-infected/TB patients were diagnosed with HIV infection 3 months or less before (57%) or after (4%) TB diagnosis. Among HIV-infected/TB patients, blacks had similar percentages to whites (61% vs 57%) of late HIV diagnosis. Twenty-five percent of HIV-infected/TB patients died, 38% prior to TB diagnosis and 62% during TB treatment. Blacks did not have significantly greater odds of TB-related mortality than whites (AOR = 1.1; 95% CI, 0.6-2.1). CONCLUSIONS: Black TB patients had greater HIV prevalence than whites. While mortality was associated with HIV infection, it was not significantly associated with black or white race.

Blood Lead Concentrations of Children in the United States: A Comparison of States Using Two Very Large Databases.

OBJECTIVES: To determine whether there are substantial differences by state between 2 large datasets in the proportion of children with elevated blood lead levels (BLLs); to identify states in which the percentage of elevated BLLs is high in either or both datasets; and to compare the percentage of elevated BLLs in individual states with those of children living in Flint, Michigan, during the months when these children were exposed to lead-contaminated drinking water. STUDY DESIGN: Tables of BLLs for individual states from the Quest Diagnostics and the Centers for Disease Control and Prevention datasets for 2014-2015, containing more than 3 million BLLs of young children?

Geographic Differences in the Contribution of ubiA Mutations to High-Level Ethambutol Resistance in Mycobacterium tuberculosis.

Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% ± 6.5% of the African EMB-resistant isolates but in only 9.5% ± 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.

The Epidemiology of Infant Mortality in the Greater Newark, New Jersey Area: A New Look at an Old Problem.

REVIEW: This research had institutional review board approval from the University of Medicine and Dentistry of New Jersey and the State of New Jersey Department of Health and Senior Services. IRB #0120110286 BACKGROUND: The death rate during the first year of life, or infant mortality rate (IMR), is a key indicator of a nation's health. Many factors affect IMR in the United States, including race and ethnicity. The 2020 U.S. Healthy People IMR target goal has been revised to 6.0 deaths per 1,000 births. In 2006, the IMR in New Jersey was 5.5 deaths per 1,000 births, ranging from 4.4 for Caucasians, to 11.5 for African Americans. OBJECTIVE: This study is designed to determine whether IMRs vary by zip code in the greater Newark region and identify maternal/infant characteristics associated with elevated IMRs. METHODS: A descriptive study was conducted using New Jersey Department of Health (NJDOH) birth certificate data and U.S. Census data by zip code in the greater Newark area. IMRs were analyzed by zip code and by characteristics of mothers and infants. RESULTS: IMRs vary by zip code of residence. The lowest and highest IMRs were in zip codes 07105 and 07102, respectively, both located within the city of Newark. Maternal characteristics associated with high IMR, in multivariable analysis, include: lack of prenatal care, single marital status, and non-Hispanic black race. Demographic characteristics associated with high IMRs were: low mean household income and a large percentage of the population living below poverty level. CONCLUSIONS: Race/ethnicity, marital status, and zip code of residence show significant impact upon infant mortality. Poverty and race/ethnicity are associated with increased IMRs and track to ZIP code.

Preventing Infectious Pulmonary Tuberculosis Among Foreign-Born Residents of the United States.

OBJECTIVES: We described risk factors associated with infectious tuberculosis (TB) and missed TB-prevention opportunities in foreign-born US residents, who account for almost two thirds of the nation's TB patients. METHODS: In a cross-sectional study at 20 US sites of foreign-born persons diagnosed with TB in 2005 through 2006, we collected results of sputum smear microscopy for acid-fast bacilli (a marker for infectiousness) and data on visa status, sociodemographics, TB-related care seeking, and latent TB infection (LTBI) diagnosis opportunities. RESULTS: Among 980 persons with pulmonary TB who reported their visa status, 601 (61%) were legal permanent residents, 131 (13.4%) had temporary visas, and 248 (25.3%) were undocumented. Undocumented persons were more likely than permanent residents to have acid-fast bacilli-positive smears at diagnosis (risk ratio = 1.3; 95% confidence interval = 1.2, 1.4). Of those diagnosed 1 year or more after arrival, 57.3% reported LTBI screening opportunities; fewer than 25% actually were. Undocumented persons reported fewer LTBI screening opportunities and were less likely to be tested. CONCLUSIONS: Progress toward TB elimination in the United States depends upon expanding opportunities for regular medical care and promotion of LTBI screening and treatment among foreign-born persons.

Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype?

BACKGROUND: Some children with autism spectrum disorders (ASD) are characterized by fluctuating behavioral symptoms following immune insults, persistent gastrointestinal (GI) symptoms, and a lack of response to the first-line intervention measures. These children have been categorized as the ASD-inflammatory subtype (ASD-IS) for this study. We reported a high prevalence of non-IgE mediated food allergy (NFA) in young ASD children before, but not all ASD/NFA children reveal such clinical features of ASD-IS. This study addressed whether behavioral changes of ASD-IS are associated with innate immune abnormalities manifested in isolated peripheral blood (PB) monocytes (Mo), major innate immune cells in the PB. METHODS: This study includes three groups of ASD subjects (ASD-IS subjects (N = 24), ASD controls with a history of NFA (ASD/NFA (N = 20), and ASD/non-NFA controls (N = 20)) and three groups of non-ASD controls (non-ASD/NFA subjects (N = 16), those diagnosed with pediatric acute onset-neuropsychiatric syndrome (PANS, N = 18), and normal controls without NFA or PANS (N = 16)). Functions of purified PB Mo were assessed by measuring the production of inflammatory and counter-regulatory cytokines with or without stimuli of innate immunity (lipopolysaccharide (LPS), zymosan, CL097, and candida heat extracts as a source of ß-lactam). In ASD-IS and PANS subjects, these assays were done in the state of behavioral exacerbation ('flare') and in the stable ('non-flare') condition. ASD-IS children in the 'flare' state revealed worsening irritability, lethargy and hyperactivity. RESULTS: 'Flare' ASD-IS PB Mo produced higher amounts of inflammatory cytokines (IL-1ß and IL-6) without stimuli than 'non-flare' ASD-IS cells. With zymosan, 'flare' ASD-IS cells produced more IL-1ß than most control cells, despite spontaneous production of large amounts of IL-1ß. Moreover, 'flare' ASD-IS Mo produced less IL-10, a counterregulatory cytokine, in response to stimuli than 'non-flare' cells or other control cells. These changes were not observed in PANS cells. CONCLUSIONS: We observed an imbalance in the production of inflammatory (IL-1ß and IL-6) and counterregulatory (IL-10) cytokines by 'flare' ASD-IS monocytes, which may indicate an association between intrinsic abnormalities of PB Mo and changes in behavioral symptoms in the ASD-IS subjects.

Dynamic antibody responses to the Mycobacterium tuberculosis proteome.

Considerable effort has been directed toward controlling tuberculosis, which kills almost two million people yearly. High on the research agenda is the discovery of biomarkers of active tuberculosis (TB) for diagnosis and for monitoring treatment outcome. Rational biomarker discovery requires understanding host-pathogen interactions leading to biomarker expression. Here we report a systems immunology approach integrating clinical data and bacterial metabolic and regulatory information with high-throughput detection in human serum of antibodies to the entire Mycobacterium tuberculosis proteome. Sera from worldwide TB suspects recognized approximately 10% of the bacterial proteome. This result defines the M. tuberculosis immunoproteome, which is rich in membrane-associated and extracellular proteins. Additional analyses revealed that during active tuberculosis (i) antibody responses focused on an approximately 0.5% of the proteome enriched for extracellular proteins, (ii) relative target preference varied among patients, and (iii) responses correlated with bacillary burden. These results indicate that the B cell response tracks the evolution of infection and the pathogen burden and replicative state and suggest functions associated with B cell-rich foci seen in tuberculous lung granulomas. Our integrated proteome-scale approach is applicable to other chronic infections characterized by diverse antibody target recognition.

Proteome-scale antibody responses and outcome of Mycobacterium tuberculosis infection in nonhuman primates and in tuberculosis patients.

BACKGROUND: Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. METHODS: Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. RESULTS: Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. CONCLUSIONS: Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.

Injury to Cone Synapses by Retinal Detachment: Differences from Rod Synapses and Protection by ROCK Inhibition.

Attachment of a detached retina does not always restore vision to pre-injury levels, even if the attachment is anatomically successful. The problem is due in part to long-term damage to photoreceptor synapses. Previously, we reported on damage to rod synapses and synaptic protection using a Rho kinase (ROCK) inhibitor (AR13503) after retinal detachment (RD). This report documents the effects of detachment, reattachment, and protection by ROCK inhibition on cone synapses. Conventional confocal and stimulated emission depletion (STED) microscopy were used for morphological assessment and electroretinograms for functional analysis of an adult pig model of RD. RDs were examined 2 and 4 h after injury or two days later when spontaneous reattachment had occurred. Cone pedicles respond differently than rod spherules. They lose their synaptic ribbons, reduce invaginations, and change their shape. ROCK inhibition protects against these structural abnormalities whether the inhibitor is applied immediately or 2 h after the RD. Functional restoration of the photopic b-wave, indicating cone-bipolar neurotransmission, is also improved with ROCK inhibition. Successful protection of both rod and cone synapses with AR13503 suggests this drug will (1) be a useful adjunct to subretinal administration of gene or stem cell therapies and (2) improve recovery of the injured retina when treatment is delayed.

Prevalence and Disparities in the Detection of Autism Without Intellectual Disability.

BACKGROUND: Intellectual ability predicts functional outcomes for children with autism spectrum disorder (ASD). It is essential to classify ASD children with and without intellectual disability (ID) to aid etiological research, provide services, and inform evidence-based educational and health planning. METHODS: Using a cross-sectional study design, data from 2000 to 2016 active ASD surveillance among 8-year-olds residing in the New York-New Jersey Metropolitan Area were analyzed to determine ASD prevalence with and without ID. Multivariable Poisson regression models were used to identify trends for ASD with ID (ASD-I) and without ID (ASD-N). RESULTS: Overall, 4661 8-year-olds were identified with ASD. Those that were ASI-I were 1505 (32.3%) and 2764 (59.3%) were ASD-N. Males were 3794 (81.4%), 946 (20.3%) were non-Hispanic Black (Black), 1230 (26.4%) were Hispanic, and 2114 (45.4%) were non-Hispanic white (white). We observed 2-fold and 5-fold increases in the prevalence of ASD-I and ASD-N, respectively, from 2000-2016. Black children were 30% less likely to be identified with ASD-N compared with white children. Children residing in affluent areas were 80% more likely to be identified with ASD-N compared with children in underserved areas. A greater proportion of children with ASD-I resided in vulnerable areas compared with children with ASD-N. Males had higher prevalence compared with females regardless of ID status; however, male-to-female ratios were slightly lower among ASD-I compared with ASD-N cases. CONCLUSIONS: One-in-3 children with ASD had ID. Disparities in the identification of ASD without ID were observed among Black and Hispanic children as well as among children residing in underserved areas.

A multisite assessment of the quantitative capabilities of the Xpert MTB/RIF assay.

RATIONALE: The Xpert MTB/RIF is an automated molecular test for Mycobacterium tuberculosis that estimates bacterial burden by measuring the threshold-cycle (Ct) of its M. tuberculosis-specific real-time polymerase chain reaction. Bacterial burden is an important biomarker for disease severity, infection control risk, and response to therapy. OBJECTIVES: Evaluate bacterial load quantitation by Xpert MTB/RIF compared with conventional quantitative methods. METHODS: Xpert MTB/RIF results were compared with smear-microscopy, semiquantiative solid culture, and time-to-detection in liquid culture for 741 patients and 2,008 samples tested in a multisite clinical trial. An internal control real-time polymerase chain reaction was evaluated for its ability to identify inaccurate quantitative Xpert MTB/RIF results. MEASUREMENTS AND MAIN RESULTS: Assays with an internal control Ct greater than 34 were likely to be inaccurately quantitated; this represented 15% of M. tuberculosis-positive tests. Excluding these, decreasing M. tuberculosis Ct was associated with increasing smear microscopy grade for smears of concentrated sputum pellets (r(s) = -0.77) and directly from sputum (r(s) =-0.71). A Ct cutoff of approximately 27.7 best predicted smear-positive status. The association between M. tuberculosis Ct and time-to-detection in liquid culture (r(s) = 0.68) and semiquantitative colony counts (r(s) = -0.56) was weaker than smear. Tests of paired same-patient sputum showed that high viscosity sputum samples contained ×32 more M. tuberculosis than nonviscous samples. Comparisons between the grade of the acid-fast bacilli smear and Xpert MTB/RIF quantitative data across study sites enabled us to identify a site outlier in microscopy. CONCLUSIONS: Xpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis.

A national study of socioeconomic status and tuberculosis rates by country of birth, United States, 1996-2005.

BACKGROUND: Tuberculosis (TB) in developed countries has historically been associated with poverty and low socioeconomic status (SES). In the past quarter century, TB in the United States has changed from primarily a disease of native-born to primarily a disease of foreign-born persons, who accounted for more than 60% of newly-diagnosed TB cases in 2010. The purpose of this study was to assess the association of SES with rates of TB in U.S.-born and foreign-born persons in the United States, overall and for the five most common foreign countries of origin. METHODS: National TB surveillance data for 1996-2005 was linked with ZIP Code-level measures of SES (crowding, unemployment, education, and income) from U.S. Census 2000. ZIP Codes were grouped into quartiles from low SES to high SES and TB rates were calculated for foreign-born and U.S.-born populations in each quartile. RESULTS: TB rates were highest in the quartiles with low SES for both U.S.-born and foreign-born populations. However, while TB rates increased five-fold or more from the two highest to the two lowest SES quartiles among the U.S.-born, they increased only by a factor of 1.3 among the foreign-born. CONCLUSIONS: Low SES is only weakly associated with TB among foreign-born persons in the United States. The traditional associations of TB with poverty are not sufficient to explain the epidemiology of TB among foreign-born persons in this country and perhaps in other developed countries. TB outreach and research efforts that focus only on low SES will miss an important segment of the foreign-born population.

Poisonings After a Hurricane: Lessons From the New Jersey Poison Information and Education System (NJPIES) During and Following Hurricane Sandy.

OBJECTIVE: Hurricane Sandy made landfall in New Jersey on October 29, 2012, resulting in widespread power outages and gasoline shortages. These events led to potentially toxic exposures and the need for information related to poisons/toxins in the environment. This report characterizes the New Jersey Poison Information and Education System (NJPIES) call patterns in the days immediately preceding, during, and after Hurricane Sandy to identify areas in need of public health education and prevention. METHODS: We examined NJPIES case data from October through December 2012. Most Sandy-related calls had been coded as such by NJPIES staff. Additional Sandy-related cases were identified by performing a case narrative review. Descriptive analyses were performed for timing, case frequencies, exposure substances, gender, caller site, type of information requests, and other data. RESULTS: The most frequent Sandy-related exposures were gasoline and carbon monoxide (CO). Gasoline exposure cases were predominantly males and CO exposure cases, females (P < 0.0001). Other leading reasons for Sandy-related calls were poison information, food poisoning/spoilage information, and water contamination. CONCLUSIONS: This analysis identified the need for enhanced public health education and intervention to improve the handling of gasoline and encourage the proper use of gasoline-powered generators and cleaning and cooking equipment, thus reducing toxic exposures.

Prevalence of autism spectrum disorder in a large, diverse metropolitan area: Variation by sociodemographic factors.

Autism spectrum disorder (ASD) prevalence estimates have varied by region. In this study, ASD prevalence, based on active case finding from multiple sources, was determined at the county and school district levels in the New Jersey metropolitan area. Among children born in 2008, residing in a four-county area and enrolled in public school in 2016, ASD prevalence was estimated to be 36 per 1000, but was significantly higher in one region-54 per 1000 and greater than 70 per 1000, in multiple school districts. Significant variation in ASD prevalence by race/ethnicity, socioeconomic status (SES), and school district size was identified. Highest prevalence was in mid-SES communities, contrary to expectation. Prevalence among Hispanic children was lower than expected, indicating a disparity in identification. Comprehensive surveillance should provide estimates at the county and town levels to appreciate ASD trends, identify disparities in detection or treatment, and explore factors influencing change in prevalence. LAY SUMMARY: We found autism prevalence to be 3.6% in New Jersey overall, but higher in one region (5.4%) and in multiple areas approaching 7.0%. We identified significant variation in autism spectrum disorder (ASD) prevalence by race/ethnicity, socioeconomic status (SES) and school district size. Mapping prevalence in smaller, well-specified, regions may be useful to better understand the true scope of ASD, disparities in ASD detection and the factors impacting ASD prevalence estimation.

Disparities in Early Intervention Program Participation by Children With Autism Spectrum Disorder in a US Metropolitan Area, 2006 to 2016.

Importance: Multiple studies have shown the value of early interventions for autism spectrum disorder (ASD). In the US, the Early Intervention Program (EIP) is mandated by law (Part C of the Individuals With Disabilities Education Act [IDEA]) to provide services to all young children with delays or disabilities. However, the extent to which children with ASD participate in this key service system is unknown. Objectives: To evaluate EIP use by children with ASD from 2006 to 2016 and to describe the factors associated with EIP participation. Design, Setting, and Participants: This cross-sectional study used repeated data collected from 2006 to 2016 by active ASD surveillance of the New York-New Jersey metropolitan area as reported in the New Jersey Autism Study. The New Jersey Autism Study identified 4050 children aged 8 years with ASD from 2006 to 2016. Demographic and clinical data were collected and participation in an EIP was assessed through active surveillance. Data were analyzed from June to December 2021. Exposure: Sociodemographic factors associated with the outcome of EIP participation. Main Outcomes and Measures: Participation in an EIP assessed at age 8 years. Demographic, ecological, and clinical factors, as well as temporal patterns, were examined by using standard and multilevel logistic regression models. Results: Among 4050 children aged 8 years with ASD by active surveillance, 1887 (46.6%) received EIP services. Of these children, 3303 (81.6%) were boys; 1105 (27.3%) were Hispanic, 801 (19.8%) were non-Hispanic Black, 1816 (44.8%) were non-Hispanic White, and 328 (8.1%) were non-Hispanic other (included Alaska Native or American Indian and Asian or Pacific Islander). In adjusted regression models, non-Hispanic Black children with ASD had lower odds of EIP participation (adjusted odds ratio [AOR], 0.67; 95% CI, 0.54-0.84) compared with their non-Hispanic White peers, and children residing in affluent areas had higher odds of receiving EIP services (AOR, 1.71; 95% CI, 1.36-2.15) compared with children residing in underserved areas. Children with ASD born in 2008 had higher odds of EIP participation than children born in 1998 (AOR, 2.64; 95% CI, 2.07-3.36). Conclusions and Relevance: Early identification of ASD is an important public health priority and receipt of EIP services may improve ASD outcomes. Approximately half of the population of children aged 8 years with ASD received EIP services between 2006 and 2016, and EIP participation by children with ASD increased during the 10-year period. However, receipt of EIP services was marked by strong socioeconomic status- and race and ethnicity-based disparities. Universal ASD screening and additional strategies are needed to address disparities and to increase access to EIP services.

ROCK inhibition reduces morphological and functional damage to rod synapses after retinal injury.

Retinal detachment (RD) causes damage, including disjunction, of the rod photoreceptor-bipolar synapse, which disrupts vision and may contribute to the poor visual recovery observed after retinal reattachment surgery. We created a model of iatrogenic RD in adult female pigs to study damage to the rod-bipolar synapse after injury and the ability of a highly specific Rho-kinase (ROCK) inhibitor to preserve synaptic structure and function. This model mimics procedures used in humans when viral vectors or cells are injected subretinally for treatment of retinal disease. Synaptic disjunction by retraction of rod spherules, quantified by image analysis of confocal sections, was present 2 h after detachment and remained 2 days later even though the retina had spontaneously reattached by then. Moreover, spherule retraction occurred in attached retina 1-2 cms from detached retina. Synaptic damage was significantly reduced by ROCK inhibition in detached retina whether injected subretinally or intravitreally. Dark-adapted full-field electroretinograms were recorded in reattached retinas to assess rod-specific function. Reduction in synaptic injury correlated with increases in rod-driven responses in drug-treated eyes. Thus, ROCK inhibition helps prevent synaptic damage and improves functional outcomes after retinal injury and may be a useful adjunctive treatment in iatrogenic RD and other retinal degenerative diseases.

The challenge of multisite epidemiologic studies in diverse populations: design and implementation of a 22-site study of tuberculosis in foreign-born people.

OBJECTIVES: We designed a population-based study of the epidemiology of tuberculosis among foreign-born people in the U.S. and Canada. Challenges included standardizing recruitment and data entry at 22 sites, enrolling individuals who did not speak English and may be undocumented, and obtaining clearance from 36 institutional review boards (IRBs). METHODS: We used stratified sampling to recruit patients through the Tuberculosis Epidemiologic Studies Consortium, a research consortium funded by the Centers for Disease Control and Prevention. Because recruitment sites were overseen by more than 30 local IRBs, we developed a simple process to designate a central IRB. We translated instruments into 10 main languages, arranged for fast translation of consent "short forms" into other languages, used one telephone interpretation service at all sites, and provided extensive interviewer training including mock interviews with simulated patients. RESULTS: We interviewed 1,696 participants in 19 states and provinces. Participants from 99 countries were interviewed in 40 languages. Twenty-three percent did not speak English at all; 64% needed an interpreter. More than 20% of participants reported they were undocumented. Participants' age, gender, and birthplaces were broadly similar to the target populations. One-third of local IRBs used the central IRB. CONCLUSIONS: Special confidentiality protections, substantial resources for translation and interpretation, and a centralized IRB made possible the recruitment of a representative sample of foreign-born people. The approaches may be applicable to studies of other diseases in multinational populations in the U.S. and Canada.