Two years of newborn screening for Duchenne muscular dystrophy as a part of the statewide Early Check research program in North Carolina.

PURPOSE: Current and emerging treatments for Duchenne muscular dystrophy (DMD) position DMD as a candidate condition for newborn screening (NBS). In anticipation of the nomination of DMD for universal NBS, we conducted a prospective study under the Early Check voluntary NBS research program in North Carolina, United States. METHODS: We performed screening for creatine kinase-MM (CK-MM), a biomarker of muscle damage, on residual routine newborn dried blood spots (DBS) from participating newborns. Total creatine kinase testing and next generation sequencing of an 86-neuromuscular gene panel that included DMD were offered to parents of newborns who screened positive. Bivariate and multivariable analyses were performed to assess effects of biological and demographic predictors on CK-MM levels in DBS. RESULTS: We screened 13,354 newborns and identified 2 males with DMD. The provisional 1626 ng/mL cutoff was raised to 2032 ng/mL to improve specificity, and additional cutoffs (900 and 360 ng/mL) were implemented to improve sensitivity for older and low-birthweight newborns. CONCLUSION: Population-scale screening for elevated CK-MM in DBS is a feasible approach to identify newborns with DMD. Inclusion of birthweight- and age-specific cutoffs, repeat creatine kinase testing after 72 hours of age, and DMD sequencing improve sensitivity and specificity of screening.

Improved Dried Blood Spot PCR Assay for Universal Congenital Cytomegalovirus Screening in Newborns.

Congenital cytomegalovirus (cCMV) is the most common perinatal infection, the leading cause of nongenetic sensorineural hearing loss, and one of the leading causes of neurodevelopmental impairment in the developed world. Early identification via newborn screening (NBS) would benefit the many undiagnosed infants who are either asymptomatic or mildly to moderately symptomatic, of whom 20% develop sequelae. The sensitivity of a recently developed PCR-based method to detect CMV in dried blood spots (DBS) is less than 80% and requires significantly more specimen than any other NBS test. We sought to improve the analytical sensitivity of the screening method by using droplet digital PCR and direct PCR and decreasing the amount of specimen utilized. The methods were tested with CMV-spiked filters, DBS from CMV-spiked cord blood, and DBS from neonates with cCMV. The results showed that the analytical sensitivity of all modified methods was equivalent to that of the reference method, with consistent CMV detection at high viral loads and inconsistent detection at low viral loads. IMPORTANCE Implementation of screening for cCMV in public health programs is hindered by feasibility challenges, including limited specimen availability and an insufficiently sensitive DBS-based screening assay. We report on efforts to improve the currently available DBS-based molecular assay to increase its feasibility of implementation in newborn screening programs. Although the analytical sensitivity of the modified methods was similar at the lower IU, equivalent CMV detection was achieved using one punch instead of the required three punches for the reference method. This reduction in sample size has the potential to substantially improve feasibility of NBS for cCMV. A population-based study is needed to further evaluate the clinical sensitivity of the improved assay.

Evaluation of the GSP Creatine Kinase-MM Assay and Assessment of CK-MM Stability in Newborn, Patient, and Contrived Dried Blood Spots for Newborn Screening for Duchenne Muscular Dystrophy.

Duchenne Muscular Dystrophy (DMD) is a fatal X-linked disorder with a birth prevalence of 19.8:100,000 males worldwide. Elevated concentration of the muscle enzyme creatine kinase-MM (CK-MM) allows for presymptomatic screening of newborns using Dried Blood Spots (DBS). We evaluated imprecision and carryover of the FDA-approved PerkinElmer GSP Neonatal CK-MM kit over multiple runs, days, and operators, followed by quantification of CK-MM loss in stored newborn, contrived, and non-newborn patient DBS resulting from exposure to ambient versus low humidity (50-day trial), and high humidity and high temperature (8-day trial). Imprecision %CV was ≤14% for all verification comparisons and over 6 months of testing. On average, the mean CK-MM recovery after 50 days was >80% of initial concentration for all sample types stored in low humidity and <80% in ambient humidity. After 8 days of storage in high humidity and high temperature, the mean recovery for newborn samples was <80%. Verification results for the GSP Neonatal CK-MM assay were concordant with kit parameters and the assay performed consistently over 6 months. CK-MM degradation in ambient storage can be mitigated by reducing exposure to humidity. Assessment of DBS shipping and storage conditions is recommended prior to implementing DMD screening.

Spray dried extract of Calophyllum brasiliense Cambés produces a potent hypoglycemic effect and improves total serum cholesterol and triglycerides in diabetic rats / El extracto secado por pulverización de Calophyllum brasiliense cambés produce un potente efecto hipoglucémico y mejora el colesterol sérico total y los triglicéridos en ratas diabéticas / O extrato seco por aspersão de Calophyllum brasiliense Cambés produz um potente efeito hipoglicemiante e melhora o colesterol total e triglicérideos em ratos diabéticos

SUMMARY Introduction: The species Calophyllum brasiliense Cambés (Calophyllaceae) is widespread throughout Central and South America. The stem bark infusion is used for lowering blood glucose. Aim: To optimize the spray dry extract ofthis plant using a D-optimal experimental design. Materials and methods: As factors were used the air-drying speed (3.5-4.5 m3/h), the feed flow rate of the suspension (5-11 mL/ min), and the inlet air temperature (90-130 °C). The dried extract was characterized by measuring the phenolics and flavonoids content, moisture, the water activity, apparent densities, flowability, and compressibility. The antioxidant activity, the inhibitory activity of lipase and alpha-glycosidase, and the antiglycant activity of the spray dried extract (SDE) were evaluated. Subsequently, the hypoglycemic activity was evaluated in rats by monitoring the blood glucose level, triglycerides, and cholesterol. Results: Inlet air temperature and feed flow rate were the factors that most affected the yield and phenolic content. SDE showed a potent antioxidant effect (IC50 1.83 μg/mL), a potent a-glycosidase (IC50 74.45 μg/mL) and pancreatic lipase (IC50 27.33 μg/mL) inhibition. A potent antiglycation effect (IC50 9.45^g/mL) was also observed. Conclusion: the SDE showed a potent hypoglycemic effect at 100 mg/kg. These results suggest that SDE could activate four important pathways that can contribute to diabetes control.

Resumen Introducción: la especie Calophyllum brasiliense (Calophyllaceae) está muy extendida en Centro y Suramérica. La infusión del tronco reduce los niveles de glucosa en sangre. bjetivo: optimizar el extracto seco por aspersión (SDE) de esta planta utilizando un diseño experimental D-óptimal. Materiales y métodos: como factores se utilizaron la velocidad del gas secante (aire, 3,5-4,5 m3/h), la temperatura de entrada del aire fue 90-130 °C y la velocidad de alimentación, 5-11 mL/min. Se determinó el contenido de fenoles y flavonoides en el extracto seco, la humedad residual, la actividad del agua, las densidades aparentes, fluidez y compresibilidad. Se evaluó la actividad antioxidante e inhibidora de lipasa y alfa-glicosidasa y la actividad antiglicante. También se evaluó la actividad hipoglicemiante midiendo glucosa en sangre, triglicéridos y colesterol. Resultados: la temperatura del aire de entrada y la velocidad de alimentación afectaron, significativamente, el rendimiento y contenido de fenoles. El SDE mostró un potente efecto antioxidante (IC50 1,83 μg/mL), una potente inhibición de a-glicosidasa (IC50 74,45 μg/mL) y de lipasa pancreática (IC50 27,33 μg/ mL). Se observó un fuerte efecto antiglicante (IC50 9,45 μg/mL). Conclusiones: el SDE mostró un potente efecto hipoglicemiante a 100 mg/kg. Estos resultados sugieren que el SDE podría actuar activando cuatro vías importantes para el control de la diabetes.

RESUMO Introdução: a espécie Calophyllum brasiliense (Calophyllaceae) é amplamente distribuída na América do Sul e Central. A infusão da casca do caule reduz os níveis de glicose no sangue. Objetivo: otimizar o extrato seco por pulverização (SDE) desta planta usando um planejamento experimental D-ótimo. Materiais e métodos: a velocidade do gás de secagem ar (3,5-4,5 m3/h), a temperatura de entrada do ar (90-130 °C) e a taxa de alimentação (5-11 mL/min) foram usados como fatores. Foi determinado o teor de fenóis e flavonóides no extrato seco, a umidade residual, a atividade de água, as densidades aparentes, a fluidez e a compressibilidade. Avaliou-se a atividade antioxidante e a atividade inibitória de lipase e alfa-glicosidase, e a atividade antiglicante do extrato seco. A atividade hipoglicêmica foi avaliada em ratos diabeticos, medindo a glicose no sangue, triglicerídeos e colesterol. Resultados: a temperatura de entrada do ar e a taxa de alimentação afetaram significativamente o desempenho e o conteúdo de fenois. O SDE mostrou um potente efeito antioxidante (IC50 1,83 μg/mL), uma significativa inibição de a-glicosidase (IC50 74,45 ig/mL) e da lipase pancreática (IC50 27,33 μg/mL). Um forte efeito antiglicante também foi observado (IC50 9,45 μg/mL). O SDE mostrou um forte efeito hipogli-cemiente à concentração de 100 mg/kg. Conclusões: Esses resultados sugerem que o SDE poderia atuar ativando quatro vias importantes para o controle do diabetes.

A Voluntary Statewide Newborn Screening Pilot for Spinal Muscular Atrophy: Results from Early Check.

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of 12,065 newborns and identified one newborn with 0 copies of SMN1 and two copies of SMN2, consistent with severe early onset of SMA. We also detected one false positive result, likely stemming from an unrelated blood disorder associated with a low white blood cell count. We evaluated the timing of NBS for babies enrolled prenatally (n = 932) and postnatally (n = 11,133) and reasons for delays in screening and reporting. Although prenatal enrollment led to faster return of results (median = 13 days after birth), results for babies enrolled postnatally were still available within a timeframe (median = 21 days after birth) that allowed the opportunity to receive essential treatment early in life. We evaluated an SMA q-PCR screening method at two separate time points, confirming the robustness of the assay. The pilot project provided important information about SMA screening in anticipation of forthcoming statewide expansion as part of regular NBS.

Cnidoscolus aconitifolius: therapeutic use and phytochemical properties. Literature review / Cnidoscolus aconitifolius: usos terapéuticos y propiedades fitoquímicas. Revisión de la literatura

Abstract Introduction: Medicinal plants have been traditionally used to cure or alleviate infectious and non-infectious diseases. They are widely accepted due to their low cost and low toxicity indexes. These plants are frequently used in cases involving skin irritation, superficial wounds, insect bites, and snake bites. Objective: To compile available evidence on the main therapeutic uses and phytochemical components of Cnidoscolus aconitifolius (popularly known as chaya), a plant that grows in tropical regions of Mexico and Central America. Materials and methods: A literature review of studies on C. aconitifolius published until 2017 was conducted in the BIREME, PubMed/Medline, Elsevier and SciELO databases. Descriptors "Cnidoscolus" and "aconitifolius" were used for the literature search, and no language restrictions were applied. Results: 82 articles were retrieved after completing the initial search. Once the studies were filtered by title (descriptors in the title) and duplicates were removed, 18 articles were reviewed. Based on the information found, it was possible to confirm that this plant has multiple health benefits. Conclusions: The traditional therapeutic use of Cnidoscolus aconitifolius is backed by scientific evidence. Therefore, further research aimed at identifying new phytochemical properties of this plant should be conducted to establish alternative therapies for treating different conditions.

Resumen Introducción. El uso tradicional de plantas medicinales para tratar diferentes enfermedades, ya sean infecciosas o no, es ampliamente aceptado debido a su bajo costo y sus bajos índices de toxicidad. Estas plantas son frecuentemente usadas en casos que involucran irritaciones de la piel, heridas superficiales, picaduras de insectos y mordeduras de víboras. Objetivo. Recopilar la información disponible sobre los principales usos terapéuticos y los componentes fitoquímicos de Cnidoscolus aconitifolius, una planta conocida popularmente como chaya y que crece en regiones tropicales de México y Centroamérica. Materiales y métodos. Se realizó una revisión de la literatura sobre C. aconitifolius publicada hasta 2017 en las bases de datos BIREME, PubMed/Medline, Elsevier y SciELO. Para la búsqueda se emplearon los descriptores "Cnidoscolus" y "aconitifolius", y no se aplicaron filtros de idioma. Resultados. Se identificaron 82 artículos luego de completar la búsqueda inicial. Después de filtrar los estudios por título (presencia de descriptores de búsqueda en el título) y remover duplicados, se incluyeron 18 artículos en la revisión. De acuerdo a la información encontrada, fue posible confirmar que esta planta ofrece diversos beneficios para la salud. Conclusiones. El uso terapéutico tradicional de la chaya está sustentado por evidencia científica, por lo que se sugiere realizar más investigaciones centradas en la identificación de nuevas propiedades fitoquímicas de esta planta y, así, establecer alternativas terapéuticas para distintas afecciones.

Analytical Comparison of Antibody-drug Conjugates Based on Good Manufacturing Practice Strategies.

The production of antibody-drug conjugates (ADCs) has been in great demand in the field of cancer therapeutics. Although cysteine-based conjugation is the most common and well known process for producing ADCs, multiple analytical methods are required for accurate drug-antibody ratio (DAR) determination due to the heterogeneity of the ADCs. Here we report various analytical methods for DAR analysis of traditional cysteine-based ADCs; additionally, apply a good manufacturing practice (GMP) strategy to produce a four hundred milligram ADC batch for use in good laboratory practice (GLP) studies. The work described herein not only evaluates several analytical performances but also provides guidance for future phase appropriate ADC production while establishing a unique analytical strategy.

Proof of site-specificity of antibody-drug conjugates produced by chemical conjugation technology: AJICAP first generation.

Antibody-drug conjugates (ADCs) have become major biopharmaceutical drugs in the field of oncology. Traditional ADCs possess a stochastic distribution of cytotoxic payloads linked to several different amino acid residues of the antibody. This heterogeneous nature of stochastic ADCs results in a complex conjugation-site characterization. To improve upon traditional ADC technology, we have developed a chemical conjugation platform, termed AJICAP™, for site-specific modification of native antibodies using a class of IgG Fc-affinity reagents (Yamada et al., 2019). Here, we report further investigation focusing on peptide mapping of the AJICAP™-ADC to confirm the exact conjugation position of the first generation AJICAP™-ADC. Neutral pH pretreatment for peptide mapping prevented undesired PTMs such as succinimide ring hydrolysis. Mirroring comparison using the purified ADC visibly indicated that Lys248 in the Fc region was conjugated to the drug-linker. MS/MS analysis also provided evidence to support Lys248 conjugation. Finally, extracted ion-chromatogram methodology suggested the site-specificity of AJICAP™ conjugation. Purified ADCs by preparative HIC-HPLC showed clear visual results and more than 93% sequence coverage by a single enzymatic digestion. The analytical strategy described herein demonstrated a robust analytical methodology for revealing the conjugation site of ADCs.

Good Manufacturing Practice Strategy for Antibody-Drug Conjugate Synthesis Using Site-Specific Chemical Conjugation: First-Generation AJICAP.

The development of antibody-drug conjugates (ADCs) is in great demand in the oncology field. With the goal of maximizing the therapeutic index, the conjugation technology to produce ADCs has been shifted to a site-specific manner; however, it is still challenging to establish robust and scalable synthetic processes. We have developed a chemical conjugation platform termed AJICAP for site-specific ADC synthesis using IgG Fc-affinity peptides. Here, we report the preparation of site-specific ADCs based on first-generation AJICAP technology for use in good laboratory practice studies. Analysis of the final ADC product was conducted using validated systems and good manufacturing practice. This work may not only prompt further biological studies of AJICAP-ADC but also establish a strategy to provide well-documented manufacturing data to enable new drug application filings (e.g., investigational new drug applications) for site-specific ADCs.

Comparison of Analytical Methods for Antibody-Drug Conjugates Produced by Chemical Site-Specific Conjugation: First-Generation AJICAP.

Antibody-drug conjugates (ADCs) have become a major class of oncology biopharmaceuticals. Traditional ADCs have a stochastic distribution of cytotoxic drugs attached at several different sites on the antibody. The heterogeneous nature of stochastic ADCs results in a complex compositional analysis. To improve on traditional ADC technology, we have developed a chemical conjugation platform termed "AJICAP" for the site-specific modification of native antibodies using a class of IgG Fc affinity reagents. Here we report further investigation focusing on several analyses of a first-generation AJICAP-ADC (Angew. Chem., Int. Ed. 2019, 58, 5592-5597). For drug-antibody ratio (DAR) determination, we examined and compared six different analytical methods. To the best of our knowledge, this is the first report of a comparison of analytical techniques to measure the DAR for ADCs produced by a site-specific technology such as AJICAP. Furthermore, a rapid analytical process for confirmation of the site selectivity of AJICAP conjugation was established by SEC-Q-TOF-MS. The analytical strategy reported here can be applied to the DAR determination of site-specific ADCs.

Inhibition of Megakaryocyte Differentiation by Antibody-Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia.

Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MK) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers. Effects of AGS-16C3F, T-DM1, and control ADCs on maturing megakaryocytes were evaluated in an in vitro system in which human hematopoietic stem cells (HSC) were differentiated into MKs. AGS-16C3F, like T-DM1, did not affect platelets directly, but inhibited MK differentiation by the activity of Cys-mcMMAF, its active metabolite. FcγRIIA did not appear to play an important role in ADC cytotoxicity to differentiating MKs. AGS-16C3F, cytotoxic to MKs, did not bind to FcγRIIA on MKs. Blocking the interaction of T-DM1 with FcγRIIA did not prevent the inhibition of MK differentiation and IgG1-mcMMAF was not as cytotoxic to MKs despite binding to FcγRIIA. Several lines of evidence suggest that internalization of AGS-16C3F into MKs is mediated by macropinocytosis. Macropinocytosis activity of differentiating HSCs correlated with cell sensitivity to AGS-16C3F. AGS-16C3F was colocalized with a macropinocytosis marker, dextran-Texas Red in differentiating MKs. Ethyl isopropyl amiloride (EIPA), a macropinocytosis inhibitor, blocked internalization of dextran-Texas Red and AGS-16C3F. These data support the notion that inhibition of MK differentiation via macropinocytosis-mediated internalization plays a role in ADC-induced thrombocytopenia. Mol Cancer Ther; 16(9); 1877-86. ©2017 AACRSee related article by Zhao et al., p. 1866.

Prevalence of musculoskeletal disorders and rheumatic diseases in Cuenca, Ecuador: a WHO-ILAR COPCORD study.

The aim of this study was to determine the prevalence of musculoskeletal pain and rheumatic diseases in subjects over 18 years of age from the canton of Cuenca, Ecuador. Cross-sectional analytical community-based study was conducted in subjects over 18 years of age using the validated Community-Oriented Program for the Control of Rheumatic Diseases (COPCORD) questionnaire. Random sampling was used. The questionnaire was administered by standardized health workers. Subjects were visited house by house. Subjects positive for musculoskeletal (MSK) pain in the last 7 days and at some point in life were assessed by rheumatologists to confirm the diagnosis. A total of 4877 subjects participated, with an average age of 42.8 (SD 18.8) years of age; 59.7 % were women; 69.7 % lived in urban areas. 32.5 % reported MSK pain in the last 7 days and 45.7 % at some point in life. The prevalence of knee osteoarthritis was 7.4 %, hand osteoarthritis 5.3 %, low back pain 9.3 %, rheumatoid arthritis 0.8 %, fibromyalgia 2 %, gout 0.4 %, and lupus 0.06 %. Subjects from rural areas reported experiencing more MSK pain in the last 7 days and at some point in life, lower income, poorer health-care coverage, and increased physical activity involving repetitive tasks such as lifting weights or cooking with firewood. MSK pain prevalence was high. Osteoarthritis and low back pain were the most common diseases. Age, sex, physical activity, repetitive tasks, living in a rural area, and lack of health-care coverage were found to be associated with MSK pain.

Trombocitopenia inducida por heparina en hemodiálisis tratada con argatroban / Heparin-induced thrombocytopenia in haemodialysis treated with argatroban

Se presenta el caso de un paciente con un diagnóstico de probabilidad de trombocitopenia inmune inducida por heparina (TIH II) con base en criterios clínicos y test de ELISA positivo, en que la urgencia terapéutica fue determinante ante la gravedad del proceso. La suspensión de heparina y la administración de argatroban solventaron la ineficacia de la diálisis debida a coagulación repetida del circuito y catéter, permitiendo el paso a diálisis peritoneal sin mayores contratiempos. Consideramos prioritaria la toma de decisiones antes de certificar la seguridad diagnóstica (AU)

We present the case of a patient diagnosed with likely immune heparin-induced thrombocytopenia (HIT II) based on clinical criteria and a positive ELISA test, in which emergency treatment was crucial, given the seriousness of the process. The discontinuation of heparin and administration of argatroban resolved inefficiency of dialysis resulting from repeated coagulation of the circuit and catheter, allowing peritoneal dialysis without further setbacks. We consider decision-making to be a priority before certifying diagnostic confidence (AU)

Heparin-induced thrombocytopenia in haemodialysis treated with argatroban.

We present the case of a patient diagnosed with likely immune heparin-induced thrombocytopenia (HIT II) based on clinical criteria and a positive ELISA test, in which emergency treatment was crucial, given the seriousness of the process. The discontinuation of heparin and administration of argatroban resolved inefficiency of dialysis resulting from repeated coagulation of the circuit and catheter, allowing peritoneal dialysis without further setbacks. We consider decision-making to be a priority before certifying diagnostic confidence.

ICF profiling of patients with traumatic brain injury: an international professional survey.

PURPOSE: A worldwide internet survey was conducted (1) to identify problems of individuals with traumatic brain injury (TBI) addressed by health professionals and (2) to summarize these problems using the International Classification of Functioning, Disability and Health (ICF). METHOD: A pool of professionals involved in the TBI rehabilitation process that included physicians, nurses, physical therapists, occupational therapists, social workers and psychologists were surveyed to identify problems in functioning and contextual factors of individuals with TBI using open-ended questions. All answers were translated ("linked") to the ICF based on established rules. The frequencies of the linked ICF categories were reported stratified based on context. RESULTS: One-hundred thirty seven professionals from the six World Health Organization regions identified 5656 concepts. 92.66% could be linked to the ICF; 33.03% were related to the domain of body functions, 27.28% to activities and participation, 10.98% to structures and 21.38% to environmental factors. CONCLUSIONS: The complexity of TBI was described through the identification of a wide variety of ICF categories. ICF language proved to be a neutral framework allowing the comparison of answers between different professionals in different world regions. IMPLICATIONS FOR REHABILITATION: People that suffered a traumatic brain injury (TBI) may have a variety of sequelae that impair functioning. The International Classification of Functioning, Disability and Health (ICF) can help in providing information regarding the identification of patients problems and needs as well as planning, implementing and coordinating the rehabilitation process. The ICF provides a frame of reference process illustrated as the rehabilitation cycle that can help during the rehabilitation process in goal setting bringing together the clinicians' and patient's perspectives in a patient oriented biopsychosocial approach. In the field of TBI rehabilitation, activity limitations and participation restrictions are broadly affected as reported by the professionals interviewed and highly influenced by cognitive and moreover behavioral problems.

INTERNATIONAL MIGRATION AND THE EDUCATION OF CHILDREN: EVIDENCE FROM LIMA, PERU.

The issue of whether emigration has consequences for the education of children who remain behind in the country of origin occupies an increasingly prominent place in the agendas of both scholars and policy makers. The conventional wisdom is that the emigration of family members may benefit children by relaxing budget constraints through remittances that can be used to cover educational expenses. However, the empirical evidence on the overall effect of migration is inconclusive. This is due in part to a substantive emphasis on remittances in the literature, as well as the inability of some studies to deal satisfactorily with the endogeneity of household migration decisions in comparing outcomes across migrant and non-migrant households. Using Peruvian data from the Latin American Migration Project (LAMP), we apply an innovative instrumental variable technique to evaluate the overall effect of migration on educational attainment and schooling disruption among the children of immigrants. In contrast to conventional wisdom, our results suggest that a higher household risk of immigration has deleterious consequences for the education of children who remain behind.