Educating...for what?: Engagement and Citizenry

Higgins School of the Humanities/Difficult Dialogues: Video Recording from 11/3/2011 event featuring Tom Hayden and Bob Ross "Engagement and Citizenry" Event Description: During their undergraduate years, students participate in a community that is a microcosm of society, and have the opportunity to learn about what it means to be a member of a society—a citizen—while they live it. How do we as educators (and humanists) best support and model this process? Where in our pedagogy can we enhance and develop the qualities of skillful empathy, effective analysis and motivated responsibility that good citizenship demands? Our guest for a conversation on engagement and citizenry is long-time activist Tom Hayden, who was the primary author of the Port Huron Statement of Students for a Democratic Society, which became known for its advocacy of “participatory democracy”. He is joined in conversation by Professor Bob Ross of Clark University, who participated with Hayden in the founding of SDS.

How to Create Posters

This morning Ms. Hayden will introduce you to a computer program designed to help you create a poster for presentation tomorrow.

Create Math Recital

Guest musicians: Heather Lingle and Mark Hayden

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

Life-threatening adverse events following therapeutic opioid administration in adults: Is pharmacogenetic analysis useful?

BACKGROUND Systemic approaches are needed to understand how variations in the genes associated with opioid pharmacokinetics and response can be used to predict patient outcome. The application of pharmacogenetic analysis to two cases of life-threatening opioid-induced respiratory depression is presented. The usefulness of genotyping in the context of these cases is discussed. METHODS A panel of 20 functional candidate polymorphisms in genes involved in the opioid biotransformation pathway (CYP2D6, UGT2B7, ABCB1, OPRM1, COMT) were genotyped in these two patients using commercially available genotyping assays. RESULTS In case 1, the patient experienced adverse outcomes when administered codeine and morphine, but not hydromorphone. Genetic test results suggested that this differential response may be due to an inherent propensity to generate active metabolites from both codeine and morphine. These active metabolites are not generated with hydromorphone. In case 2, the patient experienced severe respiratory depression during postoperative recovery following standard doses of morphine. The patient was found to carry genetic variations that result in decreased morphine efflux transporter activity at the blood-brain barrier and increased sensitivity to opioids. CONCLUSIONS Knowledge of the relative contribution of pharmacogenetic biomarkers and their influence on opioid response are continually evolving. Pharmacogenetic analysis, together with clinical history, has the potential to provide mechanistic insight into severe respiratory depressive events in patients who receive opioids at therapeutic doses.

VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children

BACKGROUND Despite substantial evidence supporting a pharmacogenetic approach to warfarin therapy in adults, evidence on the importance of genetics in warfarin therapy in children is limited, particularly for clinical outcomes. We assessed the contribution of CYP2C9/VKORC1/CYP4F2 genotypes and variation in other genes involved in vitamin K and coagulation pathways to warfarin dose and related clinical outcomes in children. PROCEDURE Clinical and genetic data for 93 children (age ≤ 18 years) who received warfarin therapy were obtained. DNA was genotyped for 93 selected single nucleotide polymorphisms using a custom assay. RESULTS With a median age of 4.8 years, our cohort included more young children than most previous studies. Overall, 76.3% of dose variability was explained by weight, indication, VKORC1-1639G/A and CYP2C9 *2/*3, with genotypes accounting for 21.1% of variability. There was a strong correlation (R(2) = 0.68; P < 0.001) between actual and predicted warfarin dose using a pediatric genotype-based dosing model. VKORC1 genotype had a significant impact on time to therapeutic international normalized ratio (INR) (P = 0.047) and time to over-anticoagulation (INR > 4; P = 0.024) during the initiation of therapy. CYP2C9*3 carriers were also at increased risk of major bleeding while receiving warfarin (adjusted OR = 11.28). An additional variant in CYP2C9 (rs7089580) was significantly associated with warfarin dose (P = 0.020) in a multivariate clinical and genetic model. CONCLUSIONS This study confirms the importance of VKORC1/CYP2C9 genotypes for warfarin dosing in a young pediatric cohort and demonstrates an impact of genetic factors on clinical outcomes in children. Furthermore, we identified an additional variant in CYP2C9 of potential relevance for warfarin dosing in children.

A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer

Anthracyclines are used in over 50% of childhood cancer treatment protocols, but their clinical usefulness is limited by anthracycline-induced cardiotoxicity (ACT) manifesting as asymptomatic cardiac dysfunction and congestive heart failure in up to 57% and 16% of patients, respectively. Candidate gene studies have reported genetic associations with ACT, but these studies have in general lacked robust patient numbers, independent replication or functional validation. Thus, the individual variability in ACT susceptibility remains largely unexplained. We performed a genome-wide association study in 280 patients of European ancestry treated for childhood cancer, with independent replication in similarly treated cohorts of 96 European and 80 non-European patients. We identified a nonsynonymous variant (rs2229774, p.Ser427Leu) in RARG highly associated with ACT (P = 5.9 × 10(-8), odds ratio (95% confidence interval) = 4.7 (2.7-8.3)). This variant alters RARG function, leading to derepression of the key ACT genetic determinant Top2b, and provides new insight into the pathophysiology of this severe adverse drug reaction.

Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children

AIM To identify novel variants associated with anthracycline-induced cardiotoxicity and to assess these in a genotype-guided risk prediction model. PATIENTS & METHODS Two cohorts treated for childhood cancer (n = 344 and 218, respectively) were genotyped for 4578 SNPs in drug ADME and toxicity genes. RESULTS Significant associations were identified in SLC22A17 (rs4982753; p = 0.0078) and SLC22A7 (rs4149178; p = 0.0034), with replication in the second cohort (p = 0.0071 and 0.047, respectively). Additional evidence was found for SULT2B1 and several genes related to oxidative stress. Adding the SLC22 variants to the prediction model improved its discriminative ability (AUC 0.78 vs 0.75 [p = 0.029]). CONCLUSION Two novel variants in SLC22A17 and SLC22A7 were significantly associated with anthracycline-induced cardiotoxicity and improved a genotype-guided risk prediction model, which could improve patient risk stratification.

Na 1 Nachlass Max Horkheimer, 4 - Korrespondenzen u.a. mit Richard Bach (p. I 2, 131-358)

24 Briefe zwischen Richard Bach und Max Horkheimer, 1938-1940; 2 Briefe zwischen Alfred Chalk und Max Horkheimer, 17.10.1939, 14.11.1939; 3 Briefe von Morduch Lexandrowitsch und der American Consulate General, 1939; 4 Briefe von der American Consulate General und Max Horkheimer, 1938-1939; 1 Brief von Max Horkheimer an das Amtstgericht Berlin, 15.03.1939; 1 Brief von Max Horkheimer an Stiedry, 05.12.1938; 1 Brief von Max Horkheimer an den Collector of Custom, 26.10.1938; 2 Briefe zwischen Josef Maier und Carson Alexandrowitsch, 28.06.1938, 29.06.1938; 1 Brief von Margarete Baruch an Alice Maier, 11.04.1938; 1 Brief von Emanuel List an Carson Alexandrowitsch, 23.02.1938; 1 Abschrift des Briefes von der Metropolitan Opera Association New York an Morduch Lexandrowitsch, 22.02.1938; 1 Brief von Jacques Barzun an Max Horkheimer, 09.07.1947; 4 Briefe zwischen K. Baschwitz und Max Horkheimer, 1938-1946; 2 Briefe zwischen E. Bauer und Max Horkheimer, 08.04.1935, 27.05.1935; 4 Briefe zwischen Fritz Bauer und Max Horkheimer, 1937-1938; 2 Briefe zwischen Lina Bauer und Max Horkheimer, 20.07.1942, 16,08,1942; 4 Briefe zwsichen Rudolf Bauer und Max Horkheimer, 1937; 15 Briefe zwischen Gertrud Bauer und Max Horkheimer, 1938-1941; 1 Brief von Max Horkheimer an den Collector of Customs, 15.03.1940; 2 Briefe zwischen I. Hannah Davidson vom Jewish Community Center San Francisco und Max Horkheimer, 19.09.1938, 29.09.1938; 2 Briefe zwsichen I. Bauer und Max Horkheimer, 25.09.1938, 29.09.1938; 1 Brief von Max Horkheimer an Klopfer, 27.09.1938; 3 Briefe zwischen Y.M.H.A. - Y.W.H.A The Jewish Center of Saint Louis und Max Horkheimer, 19.09.1938, 1938; 1 Brief von Max Horkheimer an Julius Rosenberg, 17.09.1938; 1 Brief von Max Horkheimer an das Jwish Center Salt Lake City, Utah, 07.09.1938; 1 Brief von Max Horkheimer an das Jewish Community Center San Fransisco, 07.09.1938; 3 Briefe zwischen dem New York Section of the National Council of Jewish Women und Max Horkheimer, 07.04.1938, 1938; 2 Briefe zwischen Baum und Max Horkheimer, 12.03.1946, 25.05.1946; 1 Brief von Max Horkheimer an Charles A. Beard , 12.12.1934; 1 Brief von Charles A. Beard an C. A. Beard; 5 Briefe von Friedrich Pollock an Charles A. Beard, 1940-1941; 5 Briefe zwischen Lilo Beck und Max Horkheimer, 1940-1941; 7 Briefe zwischen Maximilian Beck und Max Horkheimer, 1939-1940; 1 Brief von Paul Tillich an Max Horkheimer , 01.10.1940; 1 Brief von dem Emergency Committee in Aid of Displaced Foreign Scholars New York an Max Horkheimer, 19.04.1940; 5 Briefe zwischen Konrad Bekker und Max Horkheimer, 1936-1939; 2 Briefe von Max Horkheimer an Ludwig Bendix, 1921, 1937; 1 Brief von Peter Bendmann an Max Horkheimer; 1 Brief von Max Horkheimer an Ruth Benedict, 30.07.1937; 1 Brief von Eric Russel Bentley an Max Horkheimer, 30.01.1945; 1 Brief von George Berg an Max Horkheimer, 12.07.1945; 2 Briefe zwischen Egon Bergel und Max Horkheimer, 18.08.1938, 22.08.1938; 1 Brief von Marie Jahoda an Max Horkheimer, 14.07.1928; 1 Brief von Theodor W. Adorno an Kurt Bergel, 09.09.1939; 15 Briefe zwischen Klaus Berger und Max Horkheimer, 1936-1943; 1 Brief von Frederick Pollock an Philip M. Hayden von der Columbia University New York, 05.03.1942; 1 Brief von Hans Venedey an Max Horkheimer, 05.03.1938; 1 Brief von Max Horkheimer an Ida Berger-Chevant, 18.02.1939;

Aedes aegypti, Aedes albopictus, and Dengue virus in Harris county: An estimate of risk

Recent outbreaks of dengue fever (DF) along the United States/Mexico border, coupled with the high number of reported cases in Mexico suggest that there is the possibility for DF emergence in Houston, Texas1,2. To determine the presence of DF, populations of Aedes aegypti and Aedes albopictus were identified and tested for dengue virus. Maps were created to identify "hot spots" (Figure 1) based on historical data on Ae. aegypti and Ae. albopictus, demographic information, and locations of human cases of dengue fever. BG Sentinel Traps®, in conjunction with BG Lure® attractant, octanol and dry ice, were used to collect mosquitoes, which were then tested for presence of dengue virus using ELISA techniques. All samples tested were negative for dengue virus (DV). Survival of DV ultimately comes down to whether or not it will be vectored by a mosquito to a susceptible human host. The presence of infected humans and contact with the mosquito vectors are two critical factors necessary in the establishment of DF. Historical records indicate the presence of Ae. aegypti and Ae. albopictus in Harris County, which would support localized dengue transmission if infected individuals are present.^ (1) Brunkard JM, Robles-Lopez JL, Ramirez J, Cifuentes E, Rothenberg SJ, Hunsperger EA, Moore CG, Brussolo RM, Villarreal NA, Haddad BM, 2007. Dengue fever seroprevalence and risk factors, Texas-Mexico border, 2004. Emerg Infect Dis 13: 1477-1483. (2) Ramos MM, Mohammed H, Zielinski-Gutierrez E, Hayden MH, Lopez JL, Fournier M, Trujillo AR, Burton R, Brunkard JM, Anaya-Lopez L, Banicki AA, Morales PK, Smith B, Munoz JL, Waterman SH, 2008. Epidemic dengue and dengue hemorrhagic fever at the Texas-Mexico Border: results of a household-based seroepidemiologic survey, December 2005. Am J Trop Med Hyg 78: 364-369.^

Antonio Buero Vallejo y Rodolfo Usigli : Historiografía y dramaturgia

El artículo propone un análisis comparativo de las obras de teatro histórico del mexicano Rodolfo Usigli y del español Antonio Buero Vallejo bajo las ópticas críticas de Friedrich Nietzsche y Hayden White para indagar la validez del teatro iberoamericano como historiografía. A la vez, examina la relación entre historia, metáfora, sinécdoque y metonimia en la dramaturgia de estos autores

Respuestas culturales : Sexo y nación. A partir de Manuel Puig

El trabajo, apoyado en las consideraciones teóricas de Hayden White, reflexiona sobre un modo de réplica literaria y de posicionamiento político del escritor Manuel Puig respecto de los acontecimientos políticos vividos a partir de la primavera democrática de 1973. Tal operación se realiza a partir de la consideración de los manuscritos de su cuarta novela -El beso de la mujer araña- que empieza su génesis antes del exilio del escritor, en 1974 y de los manuscritos de un artículo que fue publicado en español sólo en forma póstuma y parcial bajo el título de 'El error gay' (los datos se indican en nota). El artículo -basándose en fundamentos de la crítica genética- pretende mostrar que por debajo de la historia de la literatura se oculta la historia de los textos que completan la respuesta cultural que la literatura consciente o inconscientemente conforma

Respuestas culturales : Sexo y nación. A partir de Manuel Puig

El trabajo, apoyado en las consideraciones teóricas de Hayden White, reflexiona sobre un modo de réplica literaria y de posicionamiento político del escritor Manuel Puig respecto de los acontecimientos políticos vividos a partir de la primavera democrática de 1973. Tal operación se realiza a partir de la consideración de los manuscritos de su cuarta novela -El beso de la mujer araña- que empieza su génesis antes del exilio del escritor, en 1974 y de los manuscritos de un artículo que fue publicado en español sólo en forma póstuma y parcial bajo el título de 'El error gay' (los datos se indican en nota). El artículo -basándose en fundamentos de la crítica genética- pretende mostrar que por debajo de la historia de la literatura se oculta la historia de los textos que completan la respuesta cultural que la literatura consciente o inconscientemente conforma

Antonio Buero Vallejo y Rodolfo Usigli : Historiografía y dramaturgia

El artículo propone un análisis comparativo de las obras de teatro histórico del mexicano Rodolfo Usigli y del español Antonio Buero Vallejo bajo las ópticas críticas de Friedrich Nietzsche y Hayden White para indagar la validez del teatro iberoamericano como historiografía. A la vez, examina la relación entre historia, metáfora, sinécdoque y metonimia en la dramaturgia de estos autores