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This study examines the prevalence of comorbid physical health conditions within a community sample of individuals with severe mental illness (SMI), compares them to a matched national sample without SMI, and identifies which comorbidities create the greatest disease burden for those with SMI. Self-reported health status, co-morbid medical conditions and perceived disease burden were collected from 203 adults with SMI. Prevalence of chronic health conditions was compared to a propensity-matched sample without SMI from the National Comorbidity Survey-Replication (NCS-R). Compared to NCS-R sample without SMI, our sample with SMI had a higher prevalence of seven out of nine categories of chronic health conditions. Chronic pain and headaches, as well as the number of chronic conditions, were associated with increased disease burden for individuals with SMI. Further investigation of possible interventions, including effective pain management, is needed to improve the health status of this population.
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Doença Crônica/epidemiologia , Efeitos Psicossociais da Doença , Transtornos Mentais/epidemiologia , Adulto , Comorbidade , Feminino , Nível de Saúde , Humanos , Masculino , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu's surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.
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OBJECTIVE: The authors' aim in this study was to determine, after adjustment for the effects of body mass index and sociodemographic measures, whether sex-specific weight control norms would have significant independent relationships with the weight control behavior of college women and men. PARTICIPANTS: The authors used an anonymous questionnaire to assess a sample of 470 college students, aged 18 to 26 years, attending either a 2- year community college or a 4-year public university. METHODS: To calculate body mass index, the authors objectively measured the height and weight of each participant. They conducted separate discriminant function analyses for women and men. RESULTS: The discriminant function analyses clearly indicated that weight control norms of same-sex, close friends were the best discriminators of involvement in weight control. CONCLUSIONS: The findings indicate that perceived peer norms may be important but overlooked risk factors for engaging in unhealthy weight control practices. The authors discuss the implications of these findings in the context of student health promotion.
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Índice de Massa Corporal , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Meio Social , Estudantes/psicologia , Universidades , Adolescente , Adulto , Feminino , Humanos , Masculino , Fatores de Risco , Fatores SexuaisRESUMO
Six different substitution mutations were identified in four different amino acid residues of antithrombin strand 1C and the polypeptide leading into strand 4B (F402S, F402C, F402L, A404T, N405K, and P407T), and are responsible for functional antithrombin deficiency in seven independently ascertained kindreds (Rosny, Torino, Maisons-Laffitte, Paris 3, La Rochelle, Budapest 5, and Oslo) affected by venous thromboembolic disease. In all seven families, variant antithrombins with heparin-binding abnormalities were detected by crossed immunoelectrophoresis, and in six of the kindreds there was a reduced antigen concentration of plasma antithrombin. Two of the variant antithrombins, Rosny and Torino, were purified by heparin-Sepharose and immunoaffinity chromatography, and shown to have greatly reduced heparin cofactor and progressive inhibitor activities in vitro. The defective interactions of these mutants with thrombin may result from proximity of s1C to the reactive site, while reduced circulating levels may be related to s1C proximity to highly conserved internal beta strands, which contain elements proposed to influence serpin turnover and intracellular degradation. In contrast, s1C is spatially distant to the positively charged surface which forms the heparin binding site of antithrombin; altered heparin binding properties of s1C variants may therefore reflect conformational linkage between the reactive site and heparin binding regions of the molecule. This work demonstrates that point mutations in and immediately adjacent to strand 1C have multiple, or pleiotropic, effects on this serpin, leading ultimately to failure of its regulatory function.
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Antitrombinas/genética , Trombose/genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Sequência Consenso , Heparina/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Oligodesoxirribonucleotídeos/química , Ovalbumina/química , Linhagem , Estrutura Terciária de Proteína , Inibidores da Tripsina/químicaRESUMO
Community-based participatory research (CBPR) is presented as an unrecognized and urgently needed approach for addressing the persistent public health concern of college student drinking in the United States. A major contention of this article is that the lack of progress in reducing alcohol-related harm among college students during the past several decades has been the research community's failure to effectively engage and collaborate with undergraduates on shared concerns. The challenges of addressing college student drinking are reviewed, distinctive features of CBPR are described, and suggestions are provided for adopting CBPR as a more viable approach than those offered by traditional campus strategies.
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Comportamento do Adolescente/psicologia , Consumo de Bebidas Alcoólicas/psicologia , Intoxicação Alcoólica/epidemiologia , Estudantes/psicologia , Universidades , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Intoxicação Alcoólica/psicologia , Pesquisa Comportamental , Humanos , Percepção , Características de Residência , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: The authors tested a prototype intervention designed to deter alcohol use in residence halls. PARTICIPANTS: Approximately 384 freshmen participated in the study over a 2-year period. METHODS: The authors devised a feedback method that assessed residents' blood alcohol concentration (BAC) at night and allowed the readings to be retrieved the next day via the Web. Residents in an intervention hall received their BAC readings as well as normative feedback. In a comparison hall, residents could retrieve only the BAC readings. RESULTS: The authors found statistically significant hall differences, but they were small in size and not meaningful. CONCLUSIONS: Qualitative findings suggest the intervention had an overall positive impact, but the actions of a subgroup of rebellious drinkers might have obscured the effect. Social norms interventions could provoke some episodes of excessive drinking in students who find these messages objectionable. More research is needed to evaluate delayed BAC feedback.
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Alcoolismo/prevenção & controle , Retroalimentação Psicológica , Internet , Avaliação de Resultados em Cuidados de Saúde , Conformidade Social , Estudantes/psicologia , Detecção do Abuso de Substâncias , Adolescente , Fatores Etários , Alcoolismo/diagnóstico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Entrevistas como Assunto , Masculino , Avaliação de Programas e Projetos de Saúde , Assunção de Riscos , Estados Unidos , UniversidadesRESUMO
OBJECTIVES: To create explanatory models of 3 undergraduate drinking practices based on sex-specific norms. METHODS: An electronic, student survey at one Mid-western university produced a representative sample of college students. RESULTS: Multivariate analyses indicated that close-friend norms were the best predictors of drinking frequency, quantity, and drunkenness. With one exception, typical student (or distal) norms had no significant relationship to drinking. Opposite-sex norms had associations with drinking above and beyond that explained by same-sex norms. CONCLUSIONS: The findings challenge the current application of the popular social norms approach that relies on distal drinking norms to provide normative feedback.
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Consumo de Bebidas Alcoólicas/psicologia , Atitude , Fatores Sexuais , Estudantes/psicologia , Adolescente , Adulto , Coleta de Dados , Feminino , Humanos , Masculino , Meio-Oeste dos Estados Unidos , Meio Social , UniversidadesRESUMO
OBJECTIVE: To establish and disseminate the position of the American Academy of Health Behavior (The Academy) on doctoral research training. METHODS: A collaborative process involving the Work Group on Doctoral Research Training with input from The Academy membership led to the development of the guidelines described herein. RESULTS: A set of guidelines is provided that describe the process of learning to be a scholar/researcher and the outcomes of learning the practice of health behavior research. CONCLUSIONS: The doctoral students who are to become the stewards of our field should be prepared to engage in scholarship that creates new knowledge, uses research to transform practice, and effectively communicates research findings.
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Pesquisa Comportamental/educação , Educação de Pós-Graduação/normas , Comportamentos Relacionados com a Saúde , Sociedades Científicas , Pesquisa Comportamental/ética , Pesquisa Comportamental/métodos , Pesquisa Comportamental/normas , Comportamento Cooperativo , Guias como Assunto , HumanosRESUMO
Antithrombin is the major proteinase inhibitor of thrombin and other blood coagulation proteinases. Antithrombin has two functional domains, a heparin binding site and a reactive centre (that complexes and inactivates the proteinase). Its deficiency results in an increased risk of venous thromboembolism. Appreciable progress has been made in recent years in understanding the structure and function of this protein, the genetic cause of inherited deficiency and its clinical consequence. The structure of antithrombin is now considered in terms of the models derived from X-ray crystallography, which have provided explanations for the function of its heparin interaction site and of its reactive loop. The structural organization of the antithrombin gene has been defined and numerous mutations have been identified that are responsible for antithrombin deficiency: these may reduce the level of the protein (Type I deficiency), alter the function of the protein (Type II deficiency, altering heparin binding or reactive sites), or even have multiple or 'pleiotropic effects' (Type II deficiency, altering both functional domains and the level of protein).
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Deficiência de Antitrombina III , Antitrombina III/química , Antitrombina III/genética , Cristalografia por Raios X , Humanos , Mutação , Polimorfismo GenéticoRESUMO
The molecular basis and functional properties of a variant antithrombin (AT) protein. AT Budapest 3, were studied. A single base substitution was identified in codon 99, CTC----TTC, altering the normal leucine to phenylalanine. The proband presented with a history of venous thrombotic disease and was found to be homozygous for the mutation. The variant protein demonstrated reduced heparin affinity and reduced antiproteinase activity in the presence of either unfractionated heparin or the AT-binding heparin pentasaccharide, when compared to normal AT. A small change in the isoelectric point was also identified. The substituted amino acid residue of AT Budapest 3 is located near to the proposed AT heparin binding site, and it is suggested that reduced heparin affinity of the variant protein may result from substitution-induced distortion of positive charge geometry in the binding site and/or changes in its position relative to the rest of the inhibitor molecule.
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Antitrombina III/genética , Proteínas de Transporte/genética , Heparina/genética , Leucina/genética , Mutação , Fenilalanina/genética , Sequência de Aminoácidos , Antitrombina III/química , Antitrombina III/isolamento & purificação , Sequência de Bases , Feminino , Variação Genética , Humanos , Dados de Sequência MolecularRESUMO
We report the identification of a new mutation resulting in type I antithrombin (AT) deficiency and the mechanism by which the deficiency arose. The single base substitution of G to A at nucleotide 2709 was identified in a proband with a family history of venous thrombosis. The mutation results in a substitution of 82 Ser by Asn, creating a new glycosylation site. Expression studies were then carried out, to confirm Asn-linked glycosylation occurred at this consensus site and that this resulted in the AT deficient phenotype. Cell-free translations using rabbit reticulocyte lysate in the presence of microsomes demonstrated that the 82 Asn variant was post-translationally processed efficiently. The 82 Asn variant protein was of a higher molecular weight than normal AT. consistent with the addition of a fifth glycan chain. Incubation of translation product with endoglycosidase H, confirmed that the higher molecular weight product had resulted from additional carbohydrate. Expression of the 82 Asn variant in COS-7 cells resulted in intracellular accumulation, with a low level of secretion of the protein into culture supernatant, consistent with type I AT deficiency. The addition of an extra carbohydrate side chain to residue 82 of antithrombin may block post-translational folding. trapping the variant intracellulary.
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Substituição de Aminoácidos , Deficiência de Antitrombina III/genética , Antitrombina III/genética , Mutação de Sentido Incorreto , Mutação Puntual , Processamento de Proteína Pós-Traducional , Trombofilia/genética , Trombose Venosa/etiologia , Adolescente , Adulto , Animais , Antitrombina III/biossíntese , Antitrombina III/metabolismo , Deficiência de Antitrombina III/classificação , Células COS , Sistema Livre de Células , Chlorocebus aethiops , Exocitose , Feminino , Glicosilação , Humanos , Masculino , Peso Molecular , Mutagênese Sítio-Dirigida , Linhagem , Dobramento de Proteína , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Especificidade por Substrato , Transfecção , Trombose Venosa/genéticaRESUMO
Elucidation of the molecular defects responsible for antithrombin III deficiency is proceeding rapidly. In order that a record is kept of the new and duplicated mutations that are found, we have compiled a database that we plan to update annually. In this, the first report of the database, we list 6 antithrombin III locus sequence polymorphisms and 94 recorded mutations causing functional deficiency of the protein, 38 of which are novel. As is the case with mutations affecting other protein genes, most mutations of antithrombin III involve a CG to TG or CA change.
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Antitrombina III/genética , Bases de Dados Factuais , Mapeamento Cromossômico , Humanos , Mutação/genética , Polimorfismo Genético/genéticaRESUMO
Inherited antithrombin deficiency is associated with an increased risk of thrombosis, primarily venous rather than arterial. Most affected individuals have inherited only a single copy of an abnormal antithrombin (AT) gene. Homozygously affected individuals, although rare, have a severe thrombotic history of early onset and often affecting the arteries. We report two new cases of type II HBS (heparin binding site) deficiency in which the propositi are homozygous for the previously reported mutation 99 Leu to Phe, and who have a severe thrombotic history. These cases are considered alongside existing homozygote and compound heterozygote cases.
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Antitrombinas/deficiência , Mutação Puntual , Trombose/genética , Antitrombinas/genética , Códon/genética , Feminino , Homozigoto , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Venous thrombosis represents a manifestation of disordered hemostatic balance. The classical presentation is of pain and swelling of the lower limb, although clinical history and examination are notoriously misleading in reaching a diagnosis. A number of acquired predispositions have been associated with a tendency to thrombosis, such as immobilisation, surgery, malignancy and certain types of oral contraception, but in at least half of the instances no predisposition can be identified. A variety of genetic risk factors have also been identified. Mutations within the genes for antithrombin, protein C and protein S are associated with a venous thromboembolic phenotype. The commonest thrombophilic predisposition however is a variant of coagulation factor V, factor V Leiden, which results from a single amino acid substitution rendering the factor V molecule resistant to activated protein C. Factor V Leiden is present in approximately 5% of individuals of European origin, and is found in up to 40% of those with confirmed venous thrombosis. Increasingly it is recognised that venous thrombosis should be considered a polygenic disorder, with interactions between the various single gene defects which predispose to thrombosis, as well as normal genetic variation between individuals in the levels of both procoagulant and anticoagulant proteins, all determining which individuals will express the phenotype of venous thrombosis.
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Tromboflebite/genética , Tromboflebite/fisiopatologia , Antitrombina III/genética , Antitrombina III/fisiologia , Coagulação Sanguínea/fisiologia , Fator V/genética , Fator V/fisiologia , Humanos , Mutação , Proteína C/genética , Proteína C/fisiologia , Proteína S/genética , Proteína S/fisiologia , Fatores de RiscoRESUMO
The blood rheology of EDTA-anticoagulated blood samples from blood donors and subjects considered to have myalgic encephalomyelitis was assessed by multiple shear rate viscometry and by multiple-pressure filterability. Although average viscosities of the two groups were different, the differences did not reach statistical significance. In contrast, the data from multiple-pressure filtration of whole blood showed significant differences between females at the lowest (2.5 cm of water) filtration pressure. It appears that the acute phase of the disorder is associated with changes in blood rheology which could impair microcirculatory blood flow. In contrast, the chronic state does not appear to be associated with rheological abnormalities.
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Viscosidade Sanguínea , Encefalomielite/sangue , Ácido Edético , Feminino , Filtração , Humanos , Masculino , Reologia , Viroses/sangue , Viroses/complicaçõesRESUMO
There is a high degree of genetic heterogeneity underlying antithrombin deficiency indicating that a number of genetic mechanisms are responsible for the disorder. We report the identification of a five nucleotide (CAGAA) deletion in exon 2 of the antithrombin gene that results in a shift in the frame of translation of the mRNA and introduces a premature STOP signal in codon 70. The deleted nucleotides represent one repeat of a duplicated sequence within codons 36-39. The deletion may have arisen by slippage and mispairing of the repeated sequences at the replication fork during DNA synthesis.
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Antitrombina III/genética , Deleção de Sequência , Adulto , Sequência de Aminoácidos , Deficiência de Antitrombina III , Sequência de Bases , Eletroforese em Gel de Poliacrilamida , Feminino , Mutação da Fase de Leitura , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Análise de Sequência de DNARESUMO
Blood rheology in multiple sclerosis (MS) was investigated in 15 subjects with varying degrees of locomotor difficulties who were members of the local MS Society. Control data were obtained from blood samples from 25 male and 25 female normal blood donors. Whole blood viscosity was measured and blood filterability was assessed. Six MS females provided blood samples for scanning electron microscopy. Erythrocyte membrane fatty acids and phospholipids were assayed. Whole blood viscosity in MS females was higher than controls at 3 of 4 shear rates (p less than 0.001) but in MS males blood viscosity was higher only at shear rate of 1.0 s-1 (p less than 0.05). MS erythrocyte filtration rates were significantly lower than controls (p less than 0.001). Leucocyte counts in MS were greater than controls both in males (p less than 0.01) and females (p less than 0.001). MS erythrocyte morphology was greatly different from controls (p less than 0.0001) and erythrocyte membranes contained less sphingomyelin than controls (p less than 0.01) but more phosphatidylinositol plus phosphatidylserine (p less than 0.02). We conclude that, because our findings indicate an identifiable and potentially correctable abnormality, it is possible to envisage an inhibition of the progressive nature of MS, with the hope of a better prognosis for patients.
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Eritrócitos/patologia , Esclerose Múltipla/sangue , Reologia , Adulto , Viscosidade Sanguínea , Membrana Eritrocítica/metabolismo , Eritrócitos/ultraestrutura , Ácidos Graxos/metabolismo , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Fosfolipídeos/metabolismo , UltrafiltraçãoRESUMO
Antithrombin is the most important physiological proteinase inhibitor of thrombin and other coagulation proteinases. It is a single chain glycoprotein of MW 58,200 which has sequence homology with alpha 1-antitrypsin and other members of the serpin superfamily of inhibitors. Two functional domains of importance have been identified, the reactive centre that interacts with the proteinase and a heparin binding domain. Failure to maintain an adequate level of functional antithrombin in plasma results in an increased risk of thromboembolism: deficiency can be inherited or acquired. There is still uncertainty regarding the prevalence of inherited deficiency and the prevalence of thrombosis in affected individuals. The production of antithrombin is under the control of a single gene which is localized on chromosome 1q 23-25. Characterization of the coding sequence, which is distributed over seven exons, has allowed the analysis of the molecular basis for inherited antithrombin deficiency. To date more than 100 cases have been successfully investigated at the gene and/or protein sequence level and 40 novel mutations have been identified. Mutations causing amino acid substitutions solely affecting the heparin binding site have thus far been located primarily at the N-terminal region of the molecule, residues 7-129; this region has been postulated to align as a positive groove in the molecule that forms the primary contact region for the essential antithrombin binding pentasaccharide of heparin. Not all the residues in which substitutions have been found are basic and some serve to maintain the conformation of nearby basic regions. Examples of this are provided by the Pro-41 to Leu mutation and a recently investigated mutant, Leu-99 to Phe. The reactive site defects are an interesting group, including those that alter P1, P1' and P12-P10 residues. Perhaps more remote mutations can also be included such as Pro-429 to Leu. The P1 and P1' mutations directly block interaction of the proteinase with anti-thrombin, while P12-P10 mutants (which have mutations affecting serpin strand s4A) enable the substrate reaction to proceed to completion, i.e. the antithrombin-thrombin complex is not stabilized and the mutant inhibitor is transformed into a substrate. The effect of the Pro-429 to Leu substitution is impairment of the reactive site and heparin binding, and the finding that this variant is not completely recognized by some MAbs implies a conformational change at the C terminus. Another group (nine cases) of interesting mutations is emerging, that has its primary defect in or near serpin strand 1C, amino acid sequence 402-407.(ABSTRACT TRUNCATED AT 400 WORDS)
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Antitrombinas/deficiência , Sequência de Aminoácidos , Antitrombinas/química , Antitrombinas/genética , Sítios de Ligação , Heparina/metabolismo , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Alinhamento de Sequência , alfa 1-Antitripsina/químicaRESUMO
Aims-(1) To undertake a pilot population study of the investigation of pharmacogenetic factors that may lead to adverse drug reactions (ADRs). (2) To investigate whether a population of patients taking fluoxetine, moclobemide or omeprazole reported to the New Zealand (NZ) Intensive Medicines Monitoring Programme (IMMP) with ADRs, have a higher frequency of CYP2D6 and CYP2C19 poor metabolizer (PM) genotypes than a reference population. (3) To determine the frequency of CYP2C19 alleles in the NZ Caucasian population.Methods-150 patients who had been notified to the NZ IMMP as experiencing an adverse event after being prescribed fluoxetine, moclobemide or omeprazole (50 on each) were approached by letter and asked if they would consent to take part. Of these, 31 patients and 56 subjects from a population of blood donors were genotyped for common CYP2D6 and CYP2C19 alleles.Results and conclusions-At either loci the distributions of genotypes were not significantly different in the IMMP patients compared with the reference population or with other reported studies. In this small study CYP2D6 or CYP2C19 PM genotypes are not overrepresented in selected patients with adverse reactions. Population studies involving sampling of blood for genotyping are feasible in the general population. Copyright (c) 2000 John Wiley & Sons, Ltd.
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OBJECTIVE: This field study of late-night college drinking sought to (1) test the ability of the 5+/4+ measure to screen for higher levels of intoxication and (2) examine the relation between estimated and actual blood alcohol concentration (BAC). METHOD: During a 15-week spring semester, college students returning to their residence halls between 10:00 PM and 3:00 AM on Wednesday through Saturday nights were anonymously interviewed to collect BAC and self-report data (n = 1,020). RESULTS: Although 70.9% had not been drinking on Wednesday nights, a majority of the intercepted students had been drinking on the other three nights. Mean BACs on these three nights were in a moderate range (48 to 51 mg/dl), but the 5+/4+ measure classified many students as heavy episodic drinkers at relatively low BACs. For example, 66.3% of those meeting the 5+/4+ criterion for the night had BACs < 100 mg/dl. Students with BACs ranging from 70 to 90 mg/dl exhibited the greatest accuracy in estimating their BAC; those with lower BACs tended to overestimate their level of intoxication; whereas those with higher BACs tended to underestimate it. CONCLUSIONS: Field assessment of student intoxication is an important tool for examining research questions in college drinking. The 5+/4+ measure classifies many college students as heavy episodic drinkers, even though their intoxication level is below conventional thresholds used to define drunkenness. In addition, there is a discernible pattern of BAC estimation in the field that corresponds to intoxication level.