Assuntos
Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética , Erros de Diagnóstico , Síndrome dos Cabelos Torcidos/diagnóstico , Síndrome dos Cabelos Torcidos/genética , Diagnóstico Pré-Natal , ATPases Transportadoras de Cobre , Éxons , Feminino , Duplicação Gênica , Testes Genéticos , Humanos , Achados Incidentais , Recém-Nascido , Masculino , GravidezRESUMO
Mental retardation (MR) occurs in approximately 3% of the population and therefore significantly impacts public health. Despite this relatively high prevalence, the specific causes of MR remain unknown in most cases, although both genetic and environmental factors are known to contribute. We describe a consanguineous family with autosomal recessive (AR) nonsyndromic MR (NSMR). Because the consanguinity of this family is complex, we explore alternative approaches for generating accurate estimates of the evidence for linkage in this family, and demonstrate evidence for linkage to chromosome 19p13 (lod score ranging from 1.2 to 3.5, depending on assumptions of allele frequencies). Fine mapping of the linked region defined a critical region of 3.6 Mb, which overlaps with a previously reported gene (CC2D1A) for MR. However, no mutations in the coding region of this gene are present in the family we describe. These results suggest that another gene causing autosomal recessive nonsyndromic MR (ARNSMR) is located within this genomic region.
Assuntos
Transtornos Cromossômicos/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 19/genética , Ligação Genética , Deficiência Intelectual/genética , Adulto , Consanguinidade , Proteínas de Ligação a DNA/genética , Feminino , Genoma Humano , Haplótipos , Humanos , Hibridização in Situ Fluorescente , Escore Lod , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Mutação , LinhagemRESUMO
BACKGROUND: In 2000, four community hospitals in the Cleveland Clinic Health System embarked on an electronic medical record (EMR) project to create an integrated information management environment and improve clinical decision making. METHODS: Executives and individuals from many departments and disciplines were organized into a project structure to launch the project, make decisions, and accomplish change management, which addressed communication, work-flow redesign, training, and support during transition to the new technology-enabled process. PROJECT: In 1999, a small group of regional information technology (IT) leaders for four community hospitals operated by the Cleveland Clinic Health System in the East Region developed a project for the implementation of computerized physician order management (CPOM). RESULTS: Huron Hospital, the first hospital selected for implementation, met its goals for a successful transition. After two pilots, implementation occurred on schedule and with a noticeable lack of major issues, both during rollout and thereafter. In addition, physician direct entry of orders reached the first-year goal of 40% physician entry in the first month and 75% within a year. CONCLUSIONS: Ensuring success required a systematic approach to the foundations of change management--work-flow redesign, communication, training, and support--during the transition.
Assuntos
Hospitais Comunitários/organização & administração , Sistemas de Registro de Ordens Médicas/organização & administração , Integração de Sistemas , Difusão de Inovações , Sistemas Multi-Institucionais , Ohio , Estudos de Casos Organizacionais , Inovação Organizacional , Recursos Humanos em Hospital/educaçãoRESUMO
BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.
Assuntos
Cromossomos Humanos Par 5/genética , Deleção de Genes , Transtornos do Crescimento/genética , Deficiências da Aprendizagem/genética , Anormalidades Múltiplas/genética , Alelos , Feminino , Frequência do Gene , Histona Metiltransferases , Histona-Lisina N-Metiltransferase , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Repetições de Microssatélites/genética , Proteínas Nucleares/genética , Fenótipo , Síndrome , Sequências Repetidas TerminaisRESUMO
De novo production of phosphatidic acid (PA) in tumor cells is required for phospholipid biosynthesis and growth of tumor cells. In addition, PA production by phospholipase D has been cited among the effects of certain oncogenes and growth factors. In this report, it has been demonstrated that enhanced phospholipid metabolism through PA in tumor cells can be exploited pharmacologically for development of anticancer agents, such as CT-2584, a cancer chemotherapeutic drug candidate currently in Phase II clinical trials. By inhibiting CTP:choline-phosphate cytidylyltransferase (CT), CT-2584 caused de novo phospholipid biosynthesis via PA to be shunted away from phosphatidylcholine (PC) and into phosphatidylinositol (PI), the latter of which was doubled in a variety of CT-2584-treated tumor cell lines. In contrast, cytotoxic concentrations of cisplatin did not induce accumulation of PI, indicating that PI elevation by CT-2584 was not a general consequence of chemotherapy-induced cell death. Consistent with this mechanism of action, propranolol, an inhibitor of PA phosphohydrolase and phosphatidylcholine biosynthesis, was also cytotoxic to tumor cell lines, induced PI accumulation, and potentiated the activity of CT-2584 in cytotoxicity assays. As expected from biophysical properties of anionic phospholipids on cellular membranes, CT-2584 cytotoxicity was associated with disruption and swelling of endoplasmic reticulum and mitochondria. We conclude that CT-2584 effects a novel mechanism of cytotoxicity to cancer cells, involving a specific modulation of phospholipid metabolism.
Assuntos
Antineoplásicos/toxicidade , Fosfatidilcolinas/biossíntese , Fosfatidilinositóis/metabolismo , Xantinas/toxicidade , Antagonistas Adrenérgicos beta/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Colina Quinase , Colina-Fosfato Citidililtransferase/metabolismo , Diglicerídeos de Citidina Difosfato/metabolismo , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Ácidos Fosfatídicos/biossíntese , Ácidos Fosfatídicos/metabolismo , Fosfatidilcolinas/antagonistas & inibidores , Fosfatidilinositóis/biossíntese , Propranolol/farmacologia , Especificidade por Substrato , Células Tumorais CultivadasRESUMO
This article describes the regulation of cell signaling by lipid phosphate phosphatases (LPPs) that control the conversion of bioactive lipid phosphates to their dephosphorylated counterparts. A structural model of the LPPs, that were previously called Type 2 phosphatidate phosphatases, is described. LPPs are characterized by having no Mg(2+) requirement and their insensitivity to inhibition by N-ethylmaleimide. The LPPs have six putative transmembrane domains and three highly conserved domains that define a phosphatase superfamily. The conserved domains are juxtaposed to the proposed membrane spanning domains such that they probably form the active sites of the phosphatases. It is predicted that the active sites of the LPPs are exposed at the cell surface or on the luminal surface of intracellular organelles, such as Golgi or the endoplasmic reticulum, depending where various LPPs are expressed. LPPs could attenuate cell activation by dephosphorylating bioactive lipid phosphate esters such as phosphatidate, lysophosphatidate, sphingosine 1-phosphate and ceramide 1-phosphate. In so doing, the LPPs could generate alternative signals from diacylglycerol, sphingosine and ceramide. The LPPs might help to modulate cell signaling by the phospholipase D pathway. For example, phosphatidate generated within the cell by phospholipase D could be converted by an LPP to diacylglycerol. This should change the relative balance of signaling by these two lipids. Another possible function of the LPPs relates to the secretion of lysophosphatidate and sphingosine 1-phosphate by activated platelets and other cells. These exogenous lipids activate phospholipid growth factor receptors on the surface of cells. LPP activities could attenuate cell activation by lysophosphatidate and sphingosine 1-phosphate through their respective receptors.
Assuntos
Sequência Conservada , Fosfatidato Fosfatase/metabolismo , Transdução de Sinais , Sequência de Aminoácidos , Animais , Bactérias , Ceramidas/metabolismo , Diglicerídeos/metabolismo , Regulação Enzimológica da Expressão Gênica , Humanos , Dados de Sequência Molecular , Fosfatidato Fosfatase/química , Fosfatidato Fosfatase/genética , Fosforilação , Alinhamento de Sequência , Esfingolipídeos/metabolismo , Especificidade por Substrato , Terminologia como Assunto , LevedurasRESUMO
The influence of strophanthidin, ouabain, and the removal of external sodium on the sodium efflux from frog sartorius muscle was measured. In freshly dissected muscles strophanthidin and ouabain in maximally effective concentrations reduced the efflux of sodium by about 50%. Of the sodium efflux which is strophanthidin-insensitive about 75% is inhibited after complete replacement of external sodium by lithium. In the absence of strophanthidin replacement of external sodium by lithium, calcium, or magnesium produces an initial rise in the sodium efflux, followed by a fall in the efflux as the exposure of the muscles to sodium-free media is continued. When the muscles are exposed for prolonged periods in sodium-free media, the fraction of internal sodium lost per minute is higher when returned to normal Ringer fluid than it was initially. The activation of sodium efflux by external sodium after long periods in sodium-free solutions is partly strophanthidin-sensitive and partly strophanthidin-insensitive. The internal sodium concentration is an important factor in these effects. The effects of temperature on the sodium efflux were also measured. Above 7 degrees C the Q(10) of both the strophanthidin-sensitive and strophanthidin-insensitive sodium efflux is about 2.0. Below 7 degrees C the strophanthidin-insensitive sodium efflux has a Q(10) of about 7.4.
Assuntos
Cardanolídeos/farmacologia , Músculos/metabolismo , Sódio/metabolismo , Animais , Anuros , Transporte Biológico Ativo/efeitos dos fármacos , Cálcio/farmacologia , Lítio/farmacologia , Magnésio/farmacologia , Músculos/efeitos dos fármacos , Ouabaína/farmacologia , Rana pipiens , Sódio/farmacologia , Temperatura , Fatores de TempoRESUMO
As a result of the increasing use of genome wide telomere screening, it has become evident that a significant proportion of people with idiopathic mental retardation have subtle abnormalities involving the telomeres of human chromosomes. However, during the course of these studies, there have also been telomeric imbalances identified in normal people that are not associated with any apparent phenotype. We have begun to scrutinize cases from both of these groups by determining the extent of the duplication or deletion associated with the imbalance. Five cases were examined where the telomere rearrangement resulted in trisomy for the 16p telomere. The size of the trisomic segment ranged from approximately 4-7 Mb and the phenotype included mental and growth retardation, brain malformations, heart defects, cleft palate, pancreatic insufficiency, genitourinary abnormalities, and dysmorphic features. Three cases with telomeric deletions without apparent phenotypic effects were also examined, one from 10q and two from 17p. All three deletions were inherited from a phenotypically normal parent carrying the same deletion, thus without apparent phenotypic effect. The largest deletion among these cases was approximately 600 kb on 17p. Similar studies are necessary for all telomeric regions to differentiate between those telomeric rearrangements that are pathogenic and those that are benign variants. Towards this goal, we are developing "molecular rulers" that incorporate multiple clones at each telomere that span the most distal 5 Mb region. While telomere screening has enabled the identification of telomere rearrangements, the use of molecular rulers will allow better phenotype prediction and prognosis related to these findings.
Assuntos
Telômero/genética , Calibragem , Criança , Deleção Cromossômica , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 17/genética , Evolução Fatal , Feminino , Amplificação de Genes/genética , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Fenótipo , Diagnóstico Pré-Natal , Trissomia/diagnóstico , Trissomia/genéticaRESUMO
The Cleveland Clinic Health System (CCHS) is committed to the enhancement of patient safety throughout the CCHS. This article describes the CCHS patient safety initiative, the development, objectives, strategies, goals, and activities.
Assuntos
Prestação Integrada de Cuidados de Saúde/normas , Hospitais de Prática de Grupo/normas , Erros Médicos/prevenção & controle , Modelos Organizacionais , Gestão da Segurança/organização & administração , Comunicação , Humanos , Ohio , Cultura Organizacional , Objetivos Organizacionais , Organizações sem Fins Lucrativos , Desenvolvimento de ProgramasRESUMO
Galactosemia is an inborn error of metabolism that causes life-threatening illness a few days after galactose-containing milk is fed to a newborn. Early treatment with a strict lactose-free diet results in rapid improvement, and, until recently, it was thought that the long-term prognosis in such infants was usually good. The speech characteristics of 24 patients treated for galactosemia were examined. Fifty-four percent had the specific speech disorder, verbal dyspraxia. This finding was not related to age at diagnosis, severity of symptoms in the newborn period, or to biochemical control. There may be, however, a relation between dyspraxia and diminished IQ scores observed in the group of patients with dyspraxia judged as "severe." The findings indicate the association of a specific and unusual speech defect with a specific and rare metabolic disorder.
Assuntos
Transtornos da Articulação/etiologia , Galactosemias/complicações , Adolescente , Transtornos da Articulação/epidemiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Galactosemias/dietoterapia , Galactosemias/psicologia , Humanos , Testes de Inteligência , Masculino , Fatores de Risco , Testes de Articulação da Fala , Inteligibilidade da FalaRESUMO
Individuals with neurofibromatosis 1 (NF1) develop both benign and malignant tumors at an increased frequency. One of the most common benign tumors in NF1 is the plexiform neurofibroma. These tumors cause significant morbidity and mortality on account of their propensity to grow and affect adjacent normal tissues. To determine the clinical profile of plexiform neurofibromas in NF1, we conducted a retrospective review of 68 NF1 patients with plexiform neurofibroma. In our series, 44% of tumors were detected by 5 years of age and most were located in the trunk and extremities. Only two patients developed malignant peripheral nerve sheath tumors in their preexisting plexiform neurofibromas. Lastly, we demonstrate that there were no specific clinical features of NF1 associated with the presence of plexiform neurofibroma. These results underscore the importance of careful serial examinations in the evaluation of patients with NF1.
Assuntos
Neurofibroma Plexiforme/patologia , Neurofibromatose 1/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prontuários Médicos , Neurofibroma Plexiforme/etiologia , Neurofibromatose 1/complicações , Estudos RetrospectivosRESUMO
Methylmalonic acidemia can be secondary to a deficiency of methylmalonyl CoA mutase or to a defect of cobalamin metabolism that is classified by complementation group. We report on a new patient with cblF complementation group that is associated with an elevation of both methylmalonic acid and homocysteine, and her outcome in response to routine therapy and a dietary restriction.
Assuntos
Ácido Metilmalônico/urina , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Feminino , Humanos , Propionatos/metabolismo , Vitamina B 12/metabolismoRESUMO
Chondrodysplasia punctata (CDP) is associated with a variety of genetic and nongenetic conditions. We report a girl with CDP, complex congenital cardiac disease, central nervous system (CNS) anomalies, and clinical findings that resemble those of the sibs described by Toriello et al. [1993, Am J Med Genet 47:797-799]. The cardiac defects and CNS abnormalities reported are unique in the context of CDP and may serve to expand the phenotypic spectrum of the unique form of CDP described by Toriello et al. [1993].
Assuntos
Coartação Aórtica/genética , Encéfalo/anormalidades , Condrodisplasia Punctata/genética , Coartação Aórtica/patologia , Calcinose/genética , Calcinose/patologia , Condrodisplasia Punctata/patologia , Feminino , Dedos/anormalidades , Humanos , Recém-Nascido , Fígado/anormalidades , Fígado/diagnóstico por imagem , Gravidez , Síndrome , UltrassonografiaRESUMO
The Nager syndrome is the most common form of acrofacial dysostosis. Although autosomal dominant and recessive forms of acrofacial dysostosis have been described the molecular etiology of these disorders is unknown. We report on a child with acrofacial dysostosis, critical aortic stenosis, and a deletion of chromosome 1q involving the heterochromatic block and adjacent euchromatin.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Disostose Craniofacial/genética , Estenose da Valva Aórtica/genética , Braço/anormalidades , Braço/diagnóstico por imagem , Cromatina/genética , Disostose Craniofacial/diagnóstico por imagem , Eucromatina , Deformidades Congênitas da Mão/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Masculino , RadiografiaRESUMO
We report on 3 patients with partial deletions of the long arm of chromosome 10-46,XY,del (10)(q26.2), 46,XX,del(10) (q25.3q26.3) or 46,XX,del(10)(q26.1), and 46,XX,del (10)(q26.1). They are compared with other known cases with interstitial or terminal deletions involving chromosome bands 10q25 or q26. Unique manifestations are identified, including scoliosis and a severe behavior disorder with attention deficit and hyperactivity in a 12-year-old boy as well as patchy alopecia in a 6-year-old patient.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 10/genética , Monossomia/genética , Anormalidades Múltiplas/genética , Criança , Quebra Cromossômica/genética , Feminino , Cardiopatias/congênito , Cardiopatias/genética , Humanos , Masculino , Fenótipo , Diferenciação Sexual/genéticaRESUMO
Mammalian lipid phosphate phosphatases (LPPs, or Type 2 phosphatidate phosphohydrolases) constitute a family of enzymes that belongs to a phosphatase superfamily. The LPPs dephosphorylate a variety of bioactive lipid phosphates including phosphatidate, lysophosphatidate, sphingosine 1-phosphate, and ceramide 1-phosphate. Mouse LPP-1 was stably expressed in rat2 fibroblasts to determine its structural and functional properties. Transduced cells showed increased dephosphorylation of exogenous lysophosphatidate. This result is compatible with mutational studies that show the active site of LPP-1 to be located on the external surface of the plasma membrane. Elevated LPP-1 activity attenuated the ability of lysophosphatidate to stimulate mitogen-activated protein kinase (ERK1 and 2) activities and DNA synthesis. It is concluded that one function of LPP-1 is to dephosphorylate exogenous lysophosphatidate, thereby attenuating cell signaling through endothelial cell differentiation gene (EDG) receptors.
Assuntos
Lisofosfolipídeos/metabolismo , Fosfatidato Fosfatase/metabolismo , Transdução de Sinais , Sequência de Aminoácidos , Animais , Sítios de Ligação , Linhagem Celular , Replicação do DNA , Ativação Enzimática , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Dados de Sequência Molecular , Fosfatidato Fosfatase/química , Fosforilação , RatosRESUMO
A Mg(2+)-independent and N-ethylmaleimide-insensitive phosphatidate phosphohydrolase (PAP-2) has been identified in the plasma membrane of cells and it has been purified. The enzyme is a multi-functional phosphohydrolase that can dephosphorylate phosphatidate, lysophosphatidate, sphingosine 1-phosphate and ceramide 1-phosphate and these substrates are competitive inhibitors of the reaction. The action of PAP-2 could terminate signalling by these bioactive lipids and at the same time generates compounds such as diacylglycerol, sphingosine and ceramide which are also potent signalling molecules. In relation to phosphatidate metabolism, sphingosine (or sphingosine 1-phosphate) stimulates phospholipase D and thus the formation of phosphatidate. At the same time sphingosine inhibits PAP-2 activity thus further increasing phosphatidate concentrations. By contrast, ceramides inhibit the activation of phospholipase D by a wide variety of agonists and increase the dephosphorylation of phosphatidate, lysophosphatidate, sphingosine 1-phosphate and ceramide 1-phosphate. These actions demonstrate "cross-talk' between the glycerolipid and sphingolipid signalling pathways and the involvement of PAP-2 in modifying the balance of the bioactive lipids generated by these pathways during cell activation.
Assuntos
Isoenzimas/fisiologia , Fosfatidato Fosfatase/fisiologia , Transdução de Sinais/fisiologia , Animais , HumanosRESUMO
Opiate systems in the brain are thought to play a major, though not exclusive, role in the regulation of intake. The rough correspondence of feeding and pineal activity rhythms in the rat offers the possibility that the pineal may also modulate ingestive behavior. In these studies we measured the possibility that pineal manipulations would influence feeding responses to opiate agonists and the antagonist naloxone. Male rats received one of four treatments (or a corresponding control treatment): pinealectomy, removal of the superior cervical ganglia (SCG), transection of the optic nerves or chronic melatonin treatment (1 mg/kg daily). Pinealectomy and melatonin treatment reduced intake during the first half of the dark period, and removal of the SCG reduced intake during the second half of the light period. The most striking effect was seen after optic nerve transection, which reduced nocturnal and increased diurnal intake. Pinealectomy, but no other manipulation, caused a slight decrease in sensitivity to the inhibitory effects of naloxone on intake. None of the treatments affected daytime feeding responses to morphine, ketocyclazocine, or butorphanol. These results suggest that the pineal gland has a minimal role in modulating the opioid regulation of food intake.
Assuntos
Endorfinas/fisiologia , Etilcetociclazocina/análogos & derivados , Comportamento Alimentar/fisiologia , Glândula Pineal/fisiologia , Animais , Butorfanol/farmacologia , Ciclazocina/análogos & derivados , Ciclazocina/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Masculino , Melatonina/farmacologia , Morfina/farmacologia , Naloxona/farmacologia , Ratos , Ratos Endogâmicos , Receptores Opioides/fisiologia , Receptores Opioides kappaRESUMO
Several quality measurement needs surfaced when the Cleveland Clinic Health System (CCHS) was formed, including a need for standardized measurement of clinical processes and outcomes, patient satisfaction, critical care, and patient safety. The Quality Institute (QI) facilitates system teams to address these issues, manages selection of measurement tools, collects and analyzes performance data, coordinates presentations, and presents team findings. The QI manages the CCHS performance improvement plan and coordinates activities designed to accomplish priority goals, in collaboration with multiple CCHS teams and the regional and hospital staffs. The most important outcome of the QI's operations is improved care, as demonstrated through objective measurement. Other outcomes include external recognition and funding; implementation of standardized measurement systems, data management activities, and production of quarterly reports; increased internal recognition; completion of several education programs; acceptance of data by payers and plans; and participation in attainment of Joint Commission on Accreditation of Healthcare Organizations network accreditation.
Assuntos
Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Cuidados Críticos/estatística & dados numéricos , Ohio , Objetivos Organizacionais , Satisfação do Paciente/estatística & dados numéricos , Indicadores de Qualidade em Assistência à SaúdeRESUMO
This article discusses key points that we believe are important as we consider how a professional society in Washington could address animal issues with a changing paradigm as expressed by the public. In summary, our professional perspectives need to change as much as or more than society does. We must understand the advocacy groups and where they are coming from. We have to provide relevant messages to the diverse audiences that play an important role in the public policy process. We have to be clear about our goals and objectives as professionals so as to be more effective as we participate with others in trying to achieve stated goals. We need to understand the broad view of the role of science that exists today, particularly focusing on accountability and relevance of our work to assure the public that their funds are well spent. We need to ensure that all the questions are addressed so that society will maintain trust and respect for the role of science in society.