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PROBLEM/CONDITION Autism spectrum disorder (ASD). PERIOD COVERED 2018. DESCRIPTION OF SYSTEM The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts active surveillance of ASD. This report focuses on the prevalence and characteristics of ASD among children aged 8 years in 2018 whose parents or guardians lived in 11 ADDM Network sites in the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. In 2018, children met the case definition if their records documented 1) an ASD diagnostic statement in an evaluation (diagnosis), 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. RESULTS For 2018, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 16.5 in Missouri to 38.9 in California. The overall ASD prevalence was 23.0 per 1,000 (one in 44) children aged 8 years, and ASD was 4.2 times as prevalent among boys as among girls. Overall ASD prevalence was similar across racial and ethnic groups, except American Indian/Alaska Native children had higher ASD prevalence than non-Hispanic White (White) children (29.0 versus 21.2 per 1,000 children aged 8 years). At multiple sites, Hispanic children had lower ASD prevalence than White children (Arizona, Arkansas, Georgia, and Utah), and non-Hispanic Black (Black) children (Georgia and Minnesota). The associations between ASD prevalence and neighborhood-level median household income varied by site. Among the 5,058 children who met the ASD case definition, 75.8% had a diagnostic statement of ASD in an evaluation, 18.8% had an ASD special education classification or eligibility and no ASD diagnostic statement, and 5.4% had an ASD ICD code only. ASD prevalence per 1,000 children aged 8 years that was based exclusively on documented ASD diagnostic statements was 17.4 overall (range: 11.2 in Maryland to 29.9 in California). The median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota. Among the 3,007 children with ASD and data on cognitive ability, 35.2% were classified as having an intelligence quotient (IQ) score ≤70. The percentages of children with ASD with IQ scores ≤70 were 49.8%, 33.1%, and 29.7% among Black, Hispanic, and White children, respectively. Overall, children with ASD and IQ scores ≤70 had earlier median ages of ASD diagnosis than children with ASD and IQ scores >70 (44 versus 53 months). INTERPRETATION In 2018, one in 44 children aged 8 years was estimated to have ASD, and prevalence and median age of identification varied widely across sites. Whereas overall ASD prevalence was similar by race and ethnicity, at certain sites Hispanic children were less likely to be identified as having ASD than White or Black children. The higher proportion of Black children compared with White and Hispanic children classified as having intellectual disability was consistent with previous findings. PUBLIC HEALTH ACTION The variability in ASD prevalence and community ASD identification practices among children with different racial, ethnic, and geographical characteristics highlights the importance of research into the causes of that variability and strategies to provide equitable access to developmental evaluations and services. These findings also underscore the need for enhanced infrastructure for diagnostic, treatment, and support services to meet the needs of all children.

Irreversible electroporation (IRE) is a non-thermal tissue ablative technology that has emerging applications in surgical oncology and regenerative surgery. To advance its therapeutic usefulness, it is important to understand the mechanisms through which IRE induces cell death and the role of the innate immune system in mediating subsequent regenerative repair. Through intravital imaging of the liver in mice, we show that IRE produces distinctive tissue injury features, including delayed yet robust recruitment of neutrophils, consistent with programmed necrosis. IRE treatment converts the monocyte/macrophage balance from pro-inflammatory to pro-reparative populations, and depletion of neutrophils inhibits this conversion. Reduced generation of pro-reparative Ly6CloF4/80hi macrophages correlates with lower numbers of SOX9+ hepatic progenitor cells in areas of macrophage clusters within the IRE injury zone. Our findings suggest that neutrophils play an important role in promoting the development of pro-reparative Ly6Clo monocytes/macrophages at the site of IRE injury, thus establishing conditions of regenerative repair.

Focal adhesion kinase (FAK) is an important mediator of extracellular matrix–integrin mechano-signal transduction that regulates cell motility, survival, and proliferation. As such, FAK is being investigated as a potential therapeutic target for malignant and fibrotic diseases, and numerous clinical trials of FAK inhibitors are underway. The function of FAK in nonmalignant, nonmotile epithelial cells is not well understood. We previously showed that hepatocytes demonstrated activated FAK near stiff collagen tracts in fibrotic livers. In this study, we examined the role of liver epithelial FAK by inducing fibrotic liver disease in mice with liver epithelial FAK deficiency. We found that mice that lacked FAK in liver epithelial cells developed more severe liver injury and worse fibrosis as compared with controls. Increased fibrosis in liver epithelial FAK-deficient mice was linked to the activation of several profibrotic pathways, including the hedgehog/smoothened pathway. FAK-deficient hepatocytes produced increased Indian hedgehog in a manner dependent on matrix stiffness. Furthermore, expression of the hedgehog receptor, smoothened, was increased in macrophages and biliary cells of hepatocyte-specific FAK-deficient fibrotic livers. These results indicate that liver epithelial FAK has important regulatory roles in the response to liver injury and progression of fibrosis., Liver epithelial-specific FAK-deficient mice develop worse liver injury and fibrosis compared to controls, indicating that FAK has a regulatory role.

Autism spectrum disorder (ASD).2014.The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence of autism spectrum disorder (ASD) among children aged 8 years whose parents or guardians reside within 11 ADDM sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). ADDM surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by professional service providers in the community. Staff completing record review and abstraction receive extensive training and supervision and are evaluated according to strict reliability standards to certify effective initial training, identify ongoing training needs, and ensure adherence to the prescribed methodology. Record review and abstraction occurs in a variety of data sources ranging from general pediatric health clinics to specialized programs serving children with developmental disabilities. In addition, most of the ADDM sites also review records for children who have received special education services in public schools. In the second phase of the study, all abstracted information is reviewed systematically by experienced clinicians to determine ASD case status. A child is considered to meet the surveillance case definition for ASD if he or she displays behaviors, as described on one or more comprehensive evaluations completed by community-based professional providers, consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autistic disorder; pervasive developmental disorder-not otherwise specified (PDD-NOS, including atypical autism); or Asperger disorder. This report provides updated ASD prevalence estimates for children aged 8 years during the 2014 surveillance year, on the basis of DSM-IV-TR criteria, and describes characteristics of the population of children with ASD. In 2013, the American Psychiatric Association published the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which made considerable changes to ASD diagnostic criteria. The change in ASD diagnostic criteria might influence ADDM ASD prevalence estimates; therefore, most (85%) of the records used to determine prevalence estimates based on DSM-IV-TR criteria underwent additional review under a newly operationalized surveillance case definition for ASD consistent with the DSM-5 diagnostic criteria. Children meeting this new surveillance case definition could qualify on the basis of one or both of the following criteria, as documented in abstracted comprehensive evaluations: 1) behaviors consistent with the DSM-5 diagnostic features; and/or 2) an ASD diagnosis, whether based on DSM-IV-TR or DSM-5 diagnostic criteria. Stratified comparisons of the number of children meeting either of these two case definitions also are reported.For 2014, the overall prevalence of ASD among the 11 ADDM sites was 16.8 per 1,000 (one in 59) children aged 8 years. Overall ASD prevalence estimates varied among sites, from 13.1-29.3 per 1,000 children aged 8 years. ASD prevalence estimates also varied by sex and race/ethnicity. Males were four times more likely than females to be identified with ASD. Prevalence estimates were higher for non-Hispanic white (henceforth, white) children compared with non-Hispanic black (henceforth, black) children, and both groups were more likely to be identified with ASD compared with Hispanic children. Among the nine sites with sufficient data on intellectual ability, 31% of children with ASD were classified in the range of intellectual disability (intelligence quotient [IQ]70), 25% were in the borderline range (IQ 71-85), and 44% had IQ scores in the average to above average range (i.e., IQ85). The distribution of intellectual ability varied by sex and race/ethnicity. Although mention of developmental concerns by age 36 months was documented for 85% of children with ASD, only 42% had a comprehensive evaluation on record by age 36 months. The median age of earliest known ASD diagnosis was 52 months and did not differ significantly by sex or race/ethnicity. For the targeted comparison of DSM-IV-TR and DSM-5 results, the number and characteristics of children meeting the newly operationalized DSM-5 case definition for ASD were similar to those meeting the DSM-IV-TR case definition, with DSM-IV-TR case counts exceeding DSM-5 counts by less than 5% and approximately 86% overlap between the two case definitions (kappa = 0.85).Findings from the ADDM Network, on the basis of 2014 data reported from 11 sites, provide updated population-based estimates of the prevalence of ASD among children aged 8 years in multiple communities in the United States. The overall ASD prevalence estimate of 16.8 per 1,000 children aged 8 years in 2014 is higher than previously reported estimates from the ADDM Network. Because the ADDM sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States. Consistent with reports from previous ADDM surveillance years, findings from 2014 were marked by variation in ASD prevalence when stratified by geographic area, sex, and level of intellectual ability. Differences in prevalence estimates between black and white children have diminished in most sites, but remained notable for Hispanic children. For 2014, results from application of the DSM-IV-TR and DSM-5 case definitions were similar, overall and when stratified by sex, race/ethnicity, DSM-IV-TR diagnostic subtype, or level of intellectual ability.Beginning with surveillance year 2016, the DSM-5 case definition will serve as the basis for ADDM estimates of ASD prevalence in future surveillance reports. Although the DSM-IV-TR case definition will eventually be phased out, it will be applied in a limited geographic area to offer additional data for comparison. Future analyses will examine trends in the continued use of DSM-IV-TR diagnoses, such as autistic disorder, PDD-NOS, and Asperger disorder in health and education records, documentation of symptoms consistent with DSM-5 terminology, and how these trends might influence estimates of ASD prevalence over time. The latest findings from the ADDM Network provide evidence that the prevalence of ASD is higher than previously reported estimates and continues to vary among certain racial/ethnic groups and communities. With prevalence of ASD ranging from 13.1 to 29.3 per 1,000 children aged 8 years in different communities throughout the United States, the need for behavioral, educational, residential, and occupational services remains high, as does the need for increased research on both genetic and nongenetic risk factors for ASD.

Children with Autism Spectrum Disorders (ASD) may be characterized as "complex" (those with microcephaly and/or dysmorphology) or "essential" (those with neither of these two). Previous studies found subjects in the complex group exhibited lower IQ scores, poorer response to behavioral intervention, more seizures and more abnormal EEGs and brain MRIs compared to the essential group. The objective of this study was to determine if there are differences in complex versus essential subjects based on several developmental/psychological measures as well as certain medical comorbidities. This study utilized data from 1,347 individuals (2-17 years old) well-characterized subjects enrolled in Autism Treatment Network (ATN) Registry. Head circumference measurement and the Autism Dysmorphology Measure (ADM) were used by trained physicians to classify subjects as complex or essential. Significantly lower scores were seen for complex subjects in cognitive level, adaptive behavior and quality of life. Complex subjects showed significantly increased physician-documented GI symptoms and were on a higher number of medications. No significant differences in autism severity scores, behavioral ratings and parent-reported sleep problems were found. After adjusting for multiple comparisons made, adaptive scores remained significantly lower for the complex group, and the complex group used a significantly higher number of medications and had increased GI symptoms. Complex and essential autism subtypes may have distinct developmental and medical correlates and thus underlines the importance of looking for microcephaly and dysmorphology, when evaluating a child with autism. Determining this distinction in autism may have implications in prognosis, identifying medical co-morbidities, directing diagnostic evaluations and treatment interventions. Autism Res 2017, 10: 1344-1352. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Background The safety and efficacy of irreversible electroporation (IRE) in treating hepatic, biliary, and pancreatic malignancies are active areas of clinical investigation. In addition, recent studies have shown that IRE may enable regenerative surgery and in vivo tissue engineering. To use IRE effectively in these clinical applications, it is important to understand how different tissue microenvironments impact the response to IRE. In this study, we characterize the electrical and histological properties of non-fibrotic and fibrotic liver parenchyma before and after IRE treatment. Methods Electrical resistivity and histology of fibrotic liver from C57BL/6 mice fed a 0.1% 3,5-diethylcarbonyl-1,4-dihydrocollidine (DDC) diet were compared to those of non-fibrotic liver from matched control mice before and after IRE treatment. Results At baseline, the electrical resistivity of fibrotic liver was lower than that of non-fibrotic liver. Post-IRE, resistivity of non-fibrotic liver declined and then recovered back to baseline with time, correlating with hepatocyte repopulation of the ablated parenchyma without deposition of fibrotic scar. In contrast, resistivity of fibrotic liver remained depressed after IRE treatment, correlating with persistent inflammation. Conclusion Non-fibrotic and fibrotic liver respond to IRE differently. The underlying tissue microenvironment is an important modifying factor to consider when designing IRE protocols for tissue ablation.

Background Children with intellectual disability (ID), characterized by impairments in intellectual functioning and adaptive behavior, benefit from early identification and access to services. Previous U.S. estimates used administrative data or parent report with limited information for demographic subgroups. Objective Using empiric measures we examined ID characteristics among 8-year-old children and estimated prevalence by sex, race/ethnicity, geographic area and socioeconomic status (SES) area indicators. Methods We analyzed data for 8-year-old children in 9 geographic areas participating in the 2014 Autism and Developmental Disabilities Monitoring Network. Children with ID were identified through record review of IQ test data. Census and American Community Survey data were used to estimate the denominator. Results Overall, 11.8 per 1,000 (1.2%) had ID (IQ ≤ 70), of whom 39% (n = 998) also had autism spectrum disorder. Among children with ID, 1,823 had adaptive behavior test scores for which 64% were characterized as impaired. ID prevalence per 1,000 was 15.8 (95% confidence interval [95% CI], 15.0–16.5) among males and 7.7 (95% CI, 7.2–8.2) among females. ID prevalence was 17.7 (95% CI, 16.6–18.9) among children who were non-Hispanic black; 12.0 (95% CI, 11.1–13.0), among Hispanic; 8.6 (95% CI, 7.1–10.4), among non-Hispanic Asian; and 8.0 (95% CI, 7.5–8.6), among non-Hispanic white. Prevalence varied across geographic areas and was inversely associated with SES. Conclusions ID prevalence varied substantively among racial, ethnic, geographic, and SES groups. Results can inform strategies to enhance identification and improve access to services particularly for children who are minorities or living in areas with lower SES.

This study examined associations between ASD diagnosis retention and non-ASD co-occurring conditions (CoCs) by child sex. The sample included 7077 males and 1487 females who had an ASD diagnosis documented in their school or health records in a population-based ASD surveillance system for 8-year-old children. ASD diagnosis retention status was determined when an initial ASD diagnosis was not later ruled out by a community professional. We found that ASD diagnosis remains fairly stable, with only 9% of children who had an initial documented ASD diagnosis later being ruled-out. Although most of the associations between the ASD diagnosis retention status and CoCs are similar in both sexes, the co-occurrence of developmental diagnoses (e.g., intellectual disability or sensory integration disorder) was predictive of ASD diagnostic changes in males, whereas the co-occurrence of specific developmental (e.g., personal/social delay) and neurological diagnosis (e.g., epilepsy) was associated with ASD diagnostic change in females. More ASD-related evaluations and less ASD-related impairment were associated with later ASD rule outs in both sexes. Our findings highlight that CoCs can complicate the diagnostic picture and lead to an increased likelihood of ambiguity in ASD diagnosis. Using sensitive and appropriate measures in clinical practice is necessary for differential diagnosis, particularly when there are co-occurring developmental conditions.

Problem/condition Autism spectrum disorder (ASD). Period covered 2016. Description of system The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). Interpretation The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. Public health action These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.

Given the increased prevalence of autism spectrum disorders (ASD), it is likely that busy primary care providers (PCP) are providing care to individuals with ASD in their practice. Autism Speaks provides a wealth of educational, medical, and treatment/intervention information resources for PCPs and families, including at least 32 toolkits. This article serves to familiarize PCPs and families on the different toolkits that are available on the Autism Speaks website. This article is intended to increase physicians’ knowledge on the issues that families with children with ASD frequently encounter, to increase their ability to share evidence-based information to guide treatment and care for affected families in their practice.

Plant and animal parents may respond to environmental conditions such as resource stress by altering traits of their offspring via heritable non-genetic effects. While such transgenerational plasticity can result in progeny phenotypes that are functionally pre-adapted to the inducing environment, it is unclear whether such parental effects measurably enhance the adult competitive success and lifetime reproductive output of progeny, and whether they may also adversely affect fitness if offspring encounter contrasting conditions. In glasshouse experiments with inbred genotypes of the annual plant Polygonum persicaria , we tested the effects of parental shade versus sun on (a) competitive performance of progeny in shade, and (b) lifetime reproductive fitness of progeny in three contrasting treatments. Shaded parents produced offspring with increased fitness in shade despite competition, as well as greater competitive impact on plant neighbours. Inherited effects of parental light conditions also significantly altered lifetime fitness: parental shade increased reproductive output for progeny in neighbour and understorey shade, but decreased fitness for progeny in sunny, dry conditions. Along with these substantial adaptive and maladaptive transgenerational effects, results show complex interactions between genotypes, parent environment and progeny conditions that underscore the role of environmental variability and change in shaping future adaptive potential. This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.

Children with Autism Spectrum Disorders (ASD) may be characterized as "complex" (those with microcephaly and/or dysmorphology) or "essential" (those with neither of these two). Previous studies found subjects in the complex group exhibited lower IQ scores, poorer response to behavioral intervention, more seizures and more abnormal EEGs and brain MRIs compared to the essential group. The objective of this study was to determine if there are differences in complex versus essential subjects based on several developmental/psychological measures as well as certain medical comorbidities. This study utilized data from 1,347 individuals (2-17 years old) well-characterized subjects enrolled in Autism Treatment Network (ATN) Registry. Head circumference measurement and the Autism Dysmorphology Measure (ADM) were used by trained physicians to classify subjects as complex or essential. Significantly lower scores were seen for complex subjects in cognitive level, adaptive behavior and quality of life. Complex subjects showed significantly increased physician-documented GI symptoms and were on a higher number of medications. No significant differences in autism severity scores, behavioral ratings and parent-reported sleep problems were found. After adjusting for multiple comparisons made, adaptive scores remained significantly lower for the complex group, and the complex group used a significantly higher number of medications and had increased GI symptoms. Complex and essential autism subtypes may have distinct developmental and medical correlates and thus underlines the importance of looking for microcephaly and dysmorphology, when evaluating a child with autism. Determining this distinction in autism may have implications in prognosis, identifying medical co-morbidities, directing diagnostic evaluations and treatment interventions. Autism Res 2017, 10: 1344-1352. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Research Findings: Family conflict is known to be associated with poor development for young children, but many children appear resilient. This study examined the extent to which high-quality center care during early childhood protects children from these negative consequences. Children participating in center-based sites of the Early Head Start (EHS) Research and Evaluation study were grouped based on their treatment status: 305 children receiving EHS services, and 305 children not receiving EHS services. Family conflict was positively associated with aggressive behavior as reported by parents for children at 3 and 5 years of age for comparison children but not for children in EHS center-based programs. However, moderation impacts were not observed for objective ratings of child negativity to parent in semistructured interactions. Practice or Policy: These findings may suggest that attending lesser quality child care and living in a family characterized by conflict is associated with heightened aggressiv...

Families/caregivers of children with ASD experience problems and disparities in healthcare and service delivery first hand. As a result, they can provide valuable input in the development of a system that best meets the needs of these children. Results from an informal, open response survey completed by participants of the 2011 Autism Speaks Walk in Little Rock most commonly identified the need for better quality educational/interventional services and the need to develop or transform community assets to be more knowledgeable and supportive of individuals with autism as major gaps in the system of care for their children.

In 2002, the Arkansas Autism and Developmental Disabilities Monitoring (AR ADDM) project collected data on the number and characteristics of resident children aged 8 years using a retrospective record review standardized methodology. This paper provides a first-look epidemiology of ASDs among 8 year old Arkansas children using data from the 2002 study year. Overall prevalence estimates, demographic distribution and a temporal lag from concerns identified to diagnosis of ASDs among 8 year olds in Arkansas were similar to that in other sites. Dissemination of information that promotes timely resolution of developmental concerns and improving educational services will benefit children with autism in Arkansas.

Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism.

PURPOSE. Some healthcare concerns have been found to be commonly associated with Autism Spectrum Disorders (ASD). Identification and treatment of these medical issues can improve the functioning of the child with ASD. This article will offer practical suggestions for the school nurse. CONCLUSIONS. As a “front-line” medical professional in the schools, the school nurse is positioned to provide guidance on implementing interventions for the student with ASD. PRACTICE IMPLICATIONS. By being knowledgeable about current research and treatment options for the various associated medical conditions, the school nurse can help the student achieve academic success in the school setting.

Uma das causas mais expressivas no fracasso do desenvolvimento de produtos novos é a falta de integração entre P&D e marketing. A presente pesquisa estuda a integração de marketing e P&D no processo de desenvolvimento de novos produtos. A falta de integração estudada, é caracterizada como a ausência total ou a sua insuficiência de relacionamentos, entre os integrantes dessas áreas em torno de das atividades que pudessem garantir o sucesso do produto no mercado. A integração P&D e marketing é uma tarefa que demanda esforços na compatibilização de duas funções, com visões diferentes, à busca de um objetivo em comum. No processo de integração, problemas decorrentes das diferenças de percepções de cada função, acabam por ocorrer, principalmente aqueles relacionados a adoção de diferentes atitudes que acabam por se traduzirem em fatores inibidores e/ou facilitadores do sucesso no desenvolvimento do produto. A pesquisa identifica do ponto de vista do gerenciamento das inovações, os elementos relevantes à integração das atividades de P&D e marketing, em torno do processo de desenvolvimento de novos produtos. One of the more important causes for product development failure is the lack of integration between marketing and R&D. This dissertation examines marketing-R&D integration in the product development process. The lack of integration studied has been characterized as the absence or insufficiency of relationships between the activities responsible for product success. Marketing - R&D integration is a very difficult task, which demands effort to assure compatibility of two differents functions, both oriented to a common objective. Problems related to the different perceptions and points of view of the various functions may occur. Differences of perspective may become either inhibitors or facilitators of project development success. This study identifies from the innovation management point of view, the more relevant elements for marketing - R&D integration in the product development process.

Yerba mate extracts are naturally enriched with several antioxidant compounds. Therefore, this natural product constitutes a fertile field of research directed to test its antioxidant and therapeutic properties in the Central Nervous System. We tested the ability of yerba mate to prevent the chemically-induced reactive oxygen species (ROS) formation, lipid peroxidation, glutathione balance (GSH:GSSG) disruption and mitochondrial dysfunction in vitro in rat brain synaptosomal/mitochondrial fractions, and compared these effects with those of its most abundant compound chlorogenic acid (CGA). Yerba mate prevented glutathione depletion and mitochondrial dysfunction, and these effects were correlated with its ability to prevent ROS formation. CGA prevented oxidative damage and mitochondrial dysfunction, but its effects were less intense than those of the extract. Our results suggest that the protective properties exhibited by yerba mate cannot be merely attributable to its main component CGA. (C) 2017 Elsevier Ltd. All rights reserved.