RESUMEN
Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.
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BACKGROUND: Older companion dogs naturally develop a dementia-like syndrome with biological, clinical and therapeutic similarities to Alzheimer disease (AD). Given there has been no new safe, clinically effective and widely accessible treatment for AD for almost 20 years, an all-new cell therapeutic approach was trialled in canine veterinary patients, and further modelled in aged rats for more detailed neurobiological analysis. METHODS: A Phase 1/2A veterinary trial was conducted in N = 6 older companion dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD). Treatment comprised direct microinjection of 250,000 autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis. Safety was assessed clinically and efficacy using the validated Canine Cognitive Dysfunction Rating Scale (CCDR) at baseline and 3-month post treatment. Intention to treat analysis imputed a single patient that had a surgical adverse event requiring euthanasia. Three dog brains were donated following natural death and histology carried out to quantify Alzheimer pathology as well as immature neurons and synapses; these were compared to a brain bank (N = 12) of untreated aged dogs with and without CCD. Further, an age-related memory dysfunction rat model (N = 16) was used to more closely evaluate intrahippocampal engraftment of canine SKN cells, focusing on mnemonic and synaptic effects as well as donor cell survival, neurodifferentation and electrophysiologic circuit integration in a live hippocampal slice preparation. RESULTS: Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and remarkably, two underwent full syndromal reversal lasting up to 2 years. At post mortem, synaptic density in the hippocampus specifically was nine standard deviations above non-treated dogs, and intensity of new neurons also several fold higher. There was no impact on AD pathology or long-term safety signals. Modelling in aged rats replicated the main canine trial findings: hippocampally-dependent place memory deficits were reversed and synaptic depletion rescued. In addition, this model confirmed donor cell survival and migration throughout the hippocampus, neuronal differentiation in situ, and physiologically-correct integration into pyramidal layer circuits. CONCLUSIONS: With further development, SKN cell therapy may have potential for treating carefully chosen AD patients based on neurosynaptic restoration in the hippocampus.
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Enfermedad de Alzheimer , Tratamiento Basado en Trasplante de Células y Tejidos , Enfermedades de los Perros , Animales , Perros , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/veterinaria , Enfermedades de los Perros/terapia , Hipocampo/patología , Células-Madre Neurales/trasplanteRESUMEN
OBJECTIVES: The 2010 Dietary Guidelines for Americans include reducing consumption of sugar-sweetened beverages. Among the many possible routes of access for youth, school vending machines provide ready availability of sugar-sweetened beverages. The purpose of this study was to determine variation in high school student access to sugar-sweetened beverages through vending machines by geographic location - urban, town or rural - and to offer an approach for analysing school vending machine content. STUDY DESIGN: Cross-sectional observational study. METHODS: Between October 2007 and May 2008, trained coders recorded beverage vending machine content and machine-front advertising in 113 machines across 26 schools in New Hampshire and Vermont, USA. RESULTS: Compared with town schools, urban schools were significantly less likely to offer sugar-sweetened beverages (P = 0.002). Rural schools also offered more sugar-sweetened beverages than urban schools, but this difference was not significant. Advertisements for sugar-sweetened beverages were highly prevalent in town schools. CONCLUSIONS: High school students have ready access to sugar-sweetened beverages through their school vending machines. Town schools offer the highest risk of exposure; school vending machines located in towns offer up to twice as much access to sugar-sweetened beverages in both content and advertising compared with urban locations. Variation by geographic region suggests that healthier environments are possible and some schools can lead as inspirational role models.
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Bebidas/provisión & distribución , Distribuidores Automáticos de Alimentos/estadística & datos numéricos , Instituciones Académicas/estadística & datos numéricos , Edulcorantes/provisión & distribución , Publicidad , Estudios Transversales , Sacarosa en la Dieta , Humanos , New Hampshire , Población Rural , Población Urbana , VermontRESUMEN
OBJECTIVE: We examined having a TV in the bedroom as a risk factor for child overweight. DESIGN: Cross-sectional study. SETTING: School- and telephone-based surveys in New Hampshire and Vermont between 2002 and 2004. PARTICIPANTS: Two thousand three hundred and forty-three children enrolled in public schools, aged 9-12 years, and one of their parents. MAIN EXPOSURES: The child having a TV in the bedroom. MAIN OUTCOME MEASURES: Age- and gender-standardized child body mass index (zBMI). Overweight was defined as equal to or above the 95th percentile for zBMI. RESULTS: Overall, 22.3% (N=523) of the children were overweight, and almost half of all children (48.2%, N=1130) had a TV in their bedroom. Children with a TV in their bedroom had a higher zBMI and were significantly more likely to be overweight compared to those without a TV in their bedroom (27.3 versus 17.7%, respectively; P<0.05). After controlling for sociodemographics, physical activity, frequency of TV or movie watching and internet use, children with a TV in their bedroom who watched at least one session of TV or movies per day were more likely to be overweight compared to those without a TV in their bedroom (odds ratio=1.32, 95% confidence interval: 1.03, 1.70). CONCLUSIONS: Having a TV in the bedroom is a risk factor for child overweight, independent of reported physical activity, participation in team sports, TV or movie watching time and internet use at home. Further study is needed to fully understand the mechanism by which having a TV in the bedroom increases children's risk for overweight.
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Sobrepeso , Televisión , Índice de Masa Corporal , Niño , Conducta Infantil/fisiología , Conducta Infantil/psicología , Estudios Transversales , Ejercicio Físico/fisiología , Femenino , Humanos , Estilo de Vida , Masculino , New Hampshire/epidemiología , Sobrepeso/fisiología , Vigilancia de la Población , Recreación , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Vermont/epidemiologíaRESUMEN
OBJECTIVE: To test the hypothesis that greater exposure to smoking in films is associated with trying smoking among adolescents. DESIGN: Cross sectional survey of 4919 schoolchildren aged 9-15 years, and assessment of occurrence of smoking in 601 films. SETTING: Randomly selected middle schools in Vermont and New Hampshire, USA. MAIN OUTCOME MEASURE: Number of schoolchildren who had ever tried smoking a cigarette. RESULTS: The films contained a median of 5 (interquartile range 1-12) occurrences of smoking. The typical adolescent had seen 17 of 50 films listed. Exposure to smoking in films varied widely: median 91 (49-152) occurrences. The prevalence of ever trying smoking increased with higher categories of exposure: 4.9% among students who saw 0-50 occurrences of smoking, 13.7% for 51-100 occurrences, 22.1% for 101-150, and 31.3% for >150. The association remained significant after adjustment for age; sex; school performance; school; parents' education; smoking by friend, sibling, or parent; and receptivity to tobacco promotions. The adjusted odds ratios of ever trying smoking for students in the higher categories of exposure, compared with students exposed to 0-50 occurrences of smoking in films, were 1.7 (95% confidence interval 1.2 to 2.4), 2.4 (1.7 to 3.4), and 2.7 (2.0 to 3.8). These odds ratios were not substantially affected by adjustment for parenting style or for personality traits of the adolescent. CONCLUSION: In this sample of adolescents there was a strong, direct, and independent association between seeing tobacco use in films and trying cigarettes, a finding that supports the hypothesis that smoking in films has a role in the initiation of smoking in adolescents.
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Conducta del Adolescente/psicología , Conducta Imitativa , Películas Cinematográficas , Fumar/epidemiología , Adolescente , Factores de Edad , Niño , Estudios Transversales , Femenino , Humanos , Masculino , New Hampshire/epidemiología , Oportunidad Relativa , Prevalencia , Psicometría , Factores de Riesgo , Fumar/psicología , Medio Social , Televisión , Vermont/epidemiologíaRESUMEN
OBJECTIVE: To assess the relation between adolescents' favourite movie stars, the portrayal of tobacco use by those stars in contemporary motion pictures, and adolescent smoking. DESIGN AND SETTING: 632 students (sixth to 12th grade, ages 10-19 years) from five rural New England public schools completed a voluntary, self administered survey in October 1996. The survey assessed tobacco use, other variables associated with adolescent smoking, and favourite movie star. In addition, tobacco use by 43 selected movie stars was measured in films between 1994 and 1996. OUTCOME MEASURES: Students were categorised into an ordinal five point index (tobacco status) based on their smoking behaviour and their smoking susceptibility: non-susceptible never smokers, susceptible never smokers, non-current experimenters, current experimenters, and smokers. We determined the adjusted cumulative odds of having advanced smoking status based on the amount of on-screen tobacco use by their favourite film star. RESULTS: Of the 43 stars, 65% used tobacco at least once, and 42% portrayed smoking as an essential character trait in one or more films. Stars who smoked more than twice in a film were considered smokers. For adolescents whose favourite stars smoked in only one film, the odds of being higher on the smoking index was 0.78 (95% confidence interval (CI) 0.53 to 1.15). For adolescents whose favourite stars smoked in two films, the odds of being higher on the smoking index was 1.5 (95% CI 1.01 to 2.32). For adolescents whose favourite stars smoked in three or more films (Leonardo DiCaprio, Sharon Stone, John Travolta), the odds of being higher on the smoking index was 3.1 (95% CI 1.34 to 7.12). Among never smokers (n = 281), those who chose stars who were smokers in three or more films were much more likely to have favourable attitudes toward smoking (adjusted odds ratio 16.2, 95% CI 2.3 to 112). CONCLUSIONS: Adolescents who choose movie stars who use tobacco on-screen are significantly more likely to have an advanced smoking status and more favourable attitudes toward smoking than adolescents who choose non-smoking stars. This finding supports the proposition that the portrayal of tobacco use in contemporary motion pictures, particularly by stars who are admired by adolescents, contributes to adolescent smoking.
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Conducta del Adolescente/psicología , Personajes , Fumar , Televisión , Tabaquismo/epidemiología , Adolescente , Adulto , Niño , Femenino , Humanos , Conducta Imitativa , Masculino , New Hampshire/epidemiología , Reproducibilidad de los Resultados , Autorrevelación , Encuestas y Cuestionarios , Tabaquismo/psicología , Vermont/epidemiologíaRESUMEN
BACKGROUND: The appearance of a cigarette brand in a cinema film gives the brand a certain distinction through its association with the characters and general tone of the film. Through the worldwide distribution of films, brands are promoted globally. We assessed the tobacco-brand appearances in a 10-year sample of contemporary films. METHODS: We viewed the contents of the top 25 US box-office films for each year of release, from 1988 to 1997 (250 films in total). We compared the prevalence of brand appearances for films produced before a voluntary ban on paid product placement by the tobacco industry (1988-90) with films produced after the ban (1991-97). Tobacco-brand appearance was defined as the screen appearance of a brand name, logo, or identifiable trademark on products or product packaging, billboards, store-front advertising, or tobacco promotional items. We defined actor endorsement of a brand as the display of a brand while being handled or used by an actor. FINDINGS: More than 85% of the films contained tobacco use. Tobacco brands appeared in 70 (28%) films. Brand appearances were as common in films suitable for adolescent audiences as they were in films for adult audiences (32 vs 35%), and were also present in 20% of those rated for children. Prevalence of brand appearance did not change overall in relation to the ban. However, there was a striking increase in the type of brand appearance depicted, with actor endorsement increasing from 1% of films before the ban to 11% after. Four US cigarette brands accounted for 80% of brand appearances. Revenues outside the USA accounted for 49% of total revenues for these films, indicating a large international audience. INTERPRETATION: Tobacco-brand appearances are common in films and are becoming increasingly endorsed by actors. The most highly advertised US cigarette brands account for most brand appearances, which suggests an advertising motive to this practice.
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Publicidad/métodos , Películas Cinematográficas/estadística & datos numéricos , Nicotiana , Plantas Tóxicas , Femenino , Humanos , Masculino , Fumar/economía , Factores de Tiempo , Industria del Tabaco/economía , Industria del Tabaco/legislación & jurisprudenciaRESUMEN
OBJECTIVE: To examine e-mail communication between student physicians and schoolchildren, in the context of a school-based tobacco prevention program, as a way to teach communication skills and model physician-patient interactions. DESIGN: Twenty medical students and pediatric residents were partnered with groups of children as part of HealthQuest, a tobacco prevention program implemented in 2 kindergarten through grade 12 Vermont schools. Medical students and residents acted as mentors for their group and provided support to the schoolchildren through e-mail and occasional site visits. E-mail messages were transmitted and stored in a Web server and monitored by preceptors. Content analysis of the messages was performed to identify emerging themes. RESULTS: During the 2-year intervention period, 1187 messages were exchanged between children, teachers, and the student physicians. Thirty-two percent (n = 383) of the messages involved tobacco, of which 54% addressed health effects; 23% were related to social influences of tobacco use, 15% to cessation by parents and others, and 7% to cessation by students. Other categories included nontobacco health issues (n = 135), personal questions (n = 294), and classroom information (n = 735). Many inquiries required medical students and residents to research their answers, and several required collaboration with preceptors, because the questions raised serious medical or psychosocial issues. With feedback, medical students and residents adjusted their responses so that they were appropriate for the developmental level of the children. CONCLUSIONS: The e-mail component of this program provided important learning opportunities for student physicians in tobacco control, child development, communication skills, and developing a physician-patient relationship. This model also offers potential benefits for medically underserved pediatric populations. Arch Pediatr Adolesc Med. 2000;154:1258-1262.
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Redes de Comunicación de Computadores , Pediatría/educación , Relaciones Médico-Paciente , Servicios de Salud Escolar/organización & administración , Prevención del Hábito de Fumar , Estudiantes de Medicina , Niño , Femenino , Educación en Salud/métodos , Humanos , Internado y Residencia , Masculino , Mentores , VermontRESUMEN
BACKGROUND: To inform the development of messages for tobacco prevention programs, we examined seven positive and five negative outcome expectations of smoking as risk factors for smoking uptake. METHODS: A cross-sectional, self-administered survey of 471 students in grades 6-12 who were never or experimental smokers was performed. Logistic regression was used to examine the relationship between outcome expectations and susceptibility to becoming a smoker in the future, a measure of intent and resistance to peer smoking. RESULTS: A total of 36.1% of the sample was susceptible to smoking. All positive outcome expectations showed a strong and significant association with susceptibility. Students were most likely to be susceptible if they believed they would enjoy smoking (OR = 29.4). Three of the five negative outcome expectations were significantly associated with susceptibility, but the strength of these associations was much lower than that observed for the positive expectations (OR = 0.5 to 0.6). A strong belief in the negative outcomes of smoking did not alter the association between susceptibility and positive outcome expectations. CONCLUSIONS: These findings suggest that teaching adolescents and teens about the negative consequences of smoking is unlikely to change their intent to smoke. Preventive efforts should identify ways to address the positive expectations adolescents have about smoking, possibly by offering alternative means for achieving these outcomes.
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Actitud Frente a la Salud , Motivación , Psicología del Adolescente , Prevención del Hábito de Fumar , Adolescente , Niño , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Oportunidad Relativa , Fumar/psicología , VermontRESUMEN
BACKGROUND: Although additional dietary calcium is recommended frequently to reduce the risk of lead poisoning, its role in preventing lead absorption has not been evaluated clinically. OBJECTIVE: The objective was to determine the safety and to estimate the size of the effect of calcium- and phosphorus-supplemented infant formula in preventing lead absorption. DESIGN: One hundred three infants aged 3.5-6 mo were randomly assigned to receive iron-fortified infant formula (465 mg Ca and 317 mg P/L) or the same formula with added calcium glycerophosphate (1800 mg Ca and 1390 mg P/L) for 9 mo. RESULTS: There was no significant difference between groups in the mean ratio of urinary calcium to creatinine, serum calcium and phosphorus, or change in iron status (serum ferritin, total iron binding capacity). At month 4, the median (+/-SD) increase from baseline in blood lead concentration for the supplemented group was 57% of the increase for the control group (0.04 +/- 0.09 compared with 0.07 +/- 0.10 micromol/L; P = 0.039). This effect was attenuated during the latter half of the trial, with an overall median increase in blood lead concentration from baseline to month 9 of 0.12 +/- 0.13 micromol/L for the control group and 0.10 +/- 0.18 micromol/L for the supplemented group (P = 0.284). CONCLUSIONS: Supplementation did not have a measurable effect on urinary calcium excretion, calcium homeostasis, or iron status. The significant effect on blood lead concentrations during the first 4 mo was in the direction expected; however, because this was not sustained throughout the 9-mo period we cannot conclude that the calcium glycerophosphate supplement prevented lead absorption in this population.
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Glicerofosfatos/uso terapéutico , Alimentos Infantiles , Absorción Intestinal/efectos de los fármacos , Intoxicación por Plomo/prevención & control , Plomo/sangre , Calcio/sangre , Calcio/orina , Femenino , Glicerofosfatos/administración & dosificación , Humanos , Lactante , Massachusetts , Proyectos Piloto , Clase SocialRESUMEN
OBJECTIVES: To assess the prevalence of ownership of cigarette promotional items (CPIs) by rural northern New England students and to examine the association between CPI ownership and smoking behavior. DESIGN AND SETTING: Voluntary, self-administered survey of 1265 sixth- through 12th-grade students representing 79% to 95% of all students attending 5 rural New Hampshire and Vermont public schools in October 1996. We examined the association between ownership of a CPI and smoking behavior through regression models and conducted a sensitivity analysis on the findings. MAIN OUTCOME MEASURES: Adjusted odds of being a smoker (lifetime use of > or = 100 cigarettes) and, among never smokers and experimental smokers, adjusted cumulative odds of having higher levels of smoking uptake given CPI ownership. RESULTS: One third of students owned a CPI. Prevalence of ownership did not vary by grade or sex, but was higher among poor-to-average school performers (45.0% vs 21.0% for excellent school performers, P < .001) and children whose friends and family members smoked (43.4% vs 13.8% for students with no family members or friends smoking, P < .001). Cigarette promotional items included articles of clothing (T-shirts, hats, backpacks, and jackets), smoking paraphernalia (lighters and ashtrays), camping gear, and electronics. More than half of CPIs (58.2%) bore the Marlboro logo, and almost one third (31.7%) bore the Camel logo. These items were obtained directly from catalogs or vendors 22.4% of the time. Whereas only 4.5% of students reported bringing a CPI to school with them the day of the survey, 44.5% reported seeing such an item at school the day of the survey. After controlling for confounding factors, such as having friends who smoke, students who owned CPIs were 4.1 times more likely to be smokers than those who did not own CPIs (95% confidence interval [CI], 3.1-5.5). Never and experimental smokers (n = 1008) who owned CPIs were more likely to be in a higher category on the smoking uptake index in grades 6 (cumulative odds ratio [OR = 5.7, 95% CI, 1.9-16.8), 7 (OR = 1.8, 95% CI, 0.9-3.7), 8 (OR = 2.3, 95% CI, 1.1-4.8), and 9 (OR = 2.1, 95% CI, 1.1-3.9), periods when children are most vulnerable to initiating cigarette use. A sensitivity analysis indicated that an unmeasured confounder of CPI ownership and smoking was unlikely to alter our conclusions. CONCLUSIONS: Cigarette promotional items are owned by one third of students in these rural northern New England schools. These items are highly visible in the public school setting, and their ownership is strongly associated with initiation and maintenance of smoking behavior. These data lend support to a ban on CPIs to be included in US Food and Drug Administration regulations to prevent tobacco use among US youth.
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Publicidad , Instituciones Académicas , Fumar , Adolescente , Niño , Femenino , Humanos , Masculino , Población Rural , Medio Social , Encuestas y Cuestionarios , Contaminación por Humo de TabacoRESUMEN
One objective of this clinical trial was to determine whether calcium and phosphorus supplementation of infant formula affects the iron status of healthy full-term infants. One hundred three infants were randomly assigned to receive iron-fortified, cow milk-based infant formula (465 mg Ca and 317 mg P/L) or the same formula with added calcium glycerophosphate (1800 mg Ca and 1390 mg P/L) for 9 mo. Reported calcium intake for supplemented infants was about four times that of control infants, ranging from a mean of 1741 mg/d at baseline to 1563 mg/d at 9 mo. There was no difference by treatment group in mean or median change from baseline of serum ferritin, total-iron-binding capacity, erythrocyte protoporphyrin, or hematocrit at 4 and 9 mo after enrollment. Incidence of iron deficiency was similar for both groups and no infant developed iron deficiency anemia during the trial. This study indicates that the well-documented inhibitory effect of calcium and phosphorus on iron absorption is not clinically important in infants fed iron-fortified infant formula.
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Calcio/farmacología , Alimentos Formulados/normas , Alimentos Infantiles/normas , Hierro/sangre , Fósforo/farmacología , Absorción/efectos de los fármacos , Absorción/fisiología , Calcio/administración & dosificación , Ferritinas/sangre , Alimentos Fortificados , Hematócrito , Humanos , Lactante , Recién Nacido , Plomo/sangre , Fósforo/administración & dosificación , Protoporfirinas/sangreRESUMEN
There has been increasing interest in a targeted approach to the screening and prevention of lead exposure in children. Targeted screening requires an understanding of variation in lead exposure in individual children or by region. In order to better understand variation by region, we studied Rhode Island lead poisoning screening data, examining average lead exposure to children living in 136 Providence County census tracts (CTs). The study population included 17,956 children aged 59 months and under, who were screened between May 1, 1992, and April 30, 1993. We evaluated the relationship between the percentage of children with blood lead > or = 10 micrograms/dL (pe10) and sociodemographic and housing characteristics, derived from United States 1990 Census data, of these CTs. CT descriptors included population density, percentage of households receiving public assistance income, median per capita income, percentage of households female headed, percentage of houses owner occupied, percentage of houses built before 1950, percentage of houses vacant, percentage of population Black, percentage of recent immigrants, and intraurban mobility. On average, 109 children were screened in each census tract; mean screening rate was 44%. There was wide variation in average lead exposure among census tracts, with pe10 ranging from 3 to 60% of screened children (mean 27%). Individual census variables explained between 24 and 67% of the variance in pe10 among CTs. A multiple regression model including percentage screened, percentage of households receiving public assistance, percentage of houses built before 1950, In (percentage of houses vacant), and percentage of recent immigrants explained 83% of variance in pe10. The percentage of houses built before 1950, a variable which models the presence of lead paint in old houses, displayed the largest adjusted effect on pe10 over the range observed for that variable in RI CTs. The percentage of houses vacant was also a highly significant and robust predictor; we suggest that vacancy is an ecological marker for the deterioration of leadbased paint, with higher vacancy neighborhoods containing houses in poorer condition. In Rhode Island, census tracts with high vacancy rates also have high rates of recent immigration, making immigrant groups vulnerable to lead exposure. Small-areas analysis may be useful in directing resources to high risk areas, explaining the sociocultural forces which produce such exposure and analyzing the effects of housing policy over time in states with high screening penetration.
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Intoxicación por Plomo/epidemiología , Preescolar , Demografía , Vivienda , Humanos , Rhode Island/epidemiología , Factores Socioeconómicos , Población UrbanaRESUMEN
OBJECTIVES: To examine the test characteristics of the capillary blood lead screening test as a predictor of elevated venous blood lead levels, using receiver operating characteristic (ROC) curves. To consider a rational capillary blood lead cutoff value in the context of what has been learned about the screening test and what is understood about the clinical course of children with elevated blood lead levels in the mild range (0.48-0.92 mumol/L [10-19 micrograms/dL]). DESIGN: In a clinical trial, 513 urban children aged 6 years and younger were screened for lead exposure. Paired samples of venous blood were drawn from all children. For these children we examine the ROC curves for capillary blood lead levels as a predictor of elevated venous blood lead levels above 2 thresholds, 0.48 and 0.97 mumol/L (10 and 20 micrograms/dL). Contaminated capillary specimens were defined as those in which the capillary result exceeded the venous result by 0.12 mumol/L (2.5 micrograms/dL) or more (n = 49). MAIN OUTCOME MEASURES: Test sensitivity and false-positive rate (equal to 1-specificity) as a function of the capillary screening cutoff value. Area under the ROC curve as a measure of screening test performance. RESULTS: Venous blood lead levels were 0.48 mumol/L (10 micrograms/dL) or more in 20.5% and 0.97 mumol/l (20 micrograms/dL) or more in 2.3% of children. Measurement of capillary blood lead levels performed very well as a screening test with an area under the ROC curve of 0.97 at the 0.48 mumol/L (10-micrograms/dL) threshold and 0.99 at the 0.97-mumol/L (20-micrograms/dL) threshold. For a capillary cutoff value of 0.39 mumol/L (8 micrograms/dL) and an elevated blood lead level threshold of 0.48 mumol/L (10 micrograms/dL), test sensitivity is 100% and the false-positive rate is 23%. Test sensitivity drops to 91%, 63%, and 45% at capillary cutoff values of 0.48, 0.58, and 0.68 mumol/L (10, 12, and 14 micrograms/dL), respectively. The false-positive rate drops to 8%, 2%, and 1% at capillary cutoff values of 0.48, 0.58, and 0.68 mumol/L (10, 12, and 14 micrograms/dL), respectively. Changing the contamination rate by appending or deleting contaminated capillary specimens from the data set had little effect on the area under the ROC curve at either threshold. CONCLUSIONS: In this sample of children, capillary blood lead measurement performed well as a screening test for elevated venous blood lead levels. Altering the capillary specimen contamination rate has little effect on the rest characteristics because much of the misclassification error resulted from random analytic error in the analysis of blood lead levels, which is high compared with the threshold of concern (0.48 mumol/L [10 micrograms/dL]). Because of lack of data on clinical outcomes for children with elevated blood lead levels in the 0.48- to 0.92-mumol/L (10- to 19-micrograms/dL) range, we suggest that the greatest utility be placed on avoiding false-positive misclassification. A clinical capillary screening cutoff value of 0.72 mumol/L (15 micrograms/dL) would avoid most false-positive results and would permit 100% sensitivity in detecting children with blood lead levels of 0.97 mumol/L (20 micrograms/dL) or higher.
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Análisis Químico de la Sangre/estadística & datos numéricos , Plomo/sangre , Capilares , Niño , Preescolar , Reacciones Falso Positivas , Pruebas Hematológicas/estadística & datos numéricos , Humanos , Intoxicación por Plomo/sangre , Intoxicación por Plomo/diagnóstico , Curva ROC , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: This study examined the association between community rates of iron deficiency in children and sociodemographic characteristics of Massachusetts communities. METHODS: Between April 1990 and March 1991, 238 273 Mssachusetts children 6 through 59 months of age were screened; iron deficiency was defined as an erythrocyte protopophyrin concentration of 0.62 micromol/L or higher and a blood lead level of less than 1.2 micromol/L. Sociodemographic data were obtained from the 1990 US Census. RESULTS: Five percent of communities had iron deficiency rates greater than 13.9 per 100 children screened. Iron deficiency rate was positively associated with proportion of Southeast Asians (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.08, 1.12), proportion of Hispanics (OR = 1.008, 95% CI = 1.002, 1.013), and high school incompletion (OR = 1.028, 95% CI = 1.020, 1.035). Similarly, an examination of three Massachusetts cities indicated that the iron deficiency rate was higher for children with Southeast Asian (relative risk [RR] = 3.6, 95% CI = 3.3, 3.8) and Hispanic (RR = 1.6, 95% CI = 1.5, 1.8) surnames than for all other children. CONCLUSIONS: Wide variation exists in iron deficiency rates for children in Massachusetts communities. Community iron deficiency was associated with low socioeconomic status and high proportions of Southeast Asians and Hispanics.
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Anemia Ferropénica/etnología , Factores Socioeconómicos , Anemia Ferropénica/etiología , Preescolar , Escolaridad , Humanos , Lactante , Tamizaje Masivo , Massachusetts/epidemiología , Oportunidad Relativa , Vigilancia de la Población , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate the utility of the Centers for Disease Control and Prevention (CDC) Risk Questionnaire and a behavioral risk factor questionnaire in identifying children with blood lead concentrations of 0.48 mumol/L (10 micrograms/dL) or more. DESIGN: Cross-sectional study of 463 urban Massachusetts children (6 to 72 months of age) screened for lead with venous blood. RESULTS: Twenty-two percent of the children had elevated blood lead concentrations. Of the five CDC questions, only one was significantly associated with an increased adjusted odds ratio for elevated blood lead: having a sibling, housemate, or playmate who was followed up or treated for lead poisoning (odds ratio, 2.7; 95% confidence interval, 1.7 to 4.2; P < .001). Children who had at least one positive or equivocal response to any of the five CDC questions (n = 318 [68.7%]) were not at higher risk than were children who displayed a negative response to all five questions (odds ratio, 1.1; 95% confidence interval, 0.7 to 1.8; P = .69). Of nine behaviors surveyed, two were associated with an increased adjusted odds for elevated blood lead: use of a pacifier (odds ratio, 2.4; 95% confidence interval, 1.3 to 4.4; P = .01) and playing near the outside of the home (odds ratio, 3.4; 95% confidence interval, 2.0 to 5.8; P < .001). CONCLUSIONS: In this population of children, the CDC risk questionnaire did not identify a group at higher risk for lead exposure. We suggest that practitioners in urban communities screen all children according to the same schedule. We conclude that risk factors differ by community and no risk questionnaire developed at the national level should be applied across communities to target screening.
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Conducta Infantil , Exposición a Riesgos Ambientales , Intoxicación por Plomo/etiología , Centers for Disease Control and Prevention, U.S. , Niño , Preescolar , Humanos , Plomo/sangre , Intoxicación por Plomo/sangre , Intoxicación por Plomo/prevención & control , Tamizaje Masivo/métodos , Massachusetts , Prevalencia , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Estados Unidos , Salud UrbanaRESUMEN
We have shown previously that the epidermal growth factor (EGF) receptor is phosphorylated at Ser-1002 and that this phosphorylation is associated with desensitization of the EGF receptor. Ser-1002 is followed immediately by Pro-1003, a residue that may promote the adoption of a specific conformation at this site or severe as a recognition element for the interaction of the EGF receptor with other proteins. To examine these possibilities, we have mutated Pro-1003 of the EGF receptor to a Gly residue and have analyzed the effect of this mutation on EGF-stimulated signaling. Cells expressing the P1003G EGF receptors exhibited higher EGF-stimulated autophosphorylation and synthetic peptide phosphorylation compared to cells expressing wild-type EGF receptors. In addition, the ability of EGF to stimulate PI 3-kinase activity and mitogen-activated protein kinase activity was enhanced in cells expressing the P1003G EGF receptor. Cells expressing P1003G receptors also demonstrated an increased ability to form colonies in soft agar in response to EGF. These results indicate that mutation of Pro-1003 leads to a potentiation of the biological effects of EGF. The findings are consistent with the hypothesis that Pro-1003 plays a role in a form of regulation that normally suppresses EGF receptor function.