The Challenge of Quantification: An Interdisciplinary Reading.

The present work looks at what we call "the multiverse of quantification", where visible and invisible numbers permeate all aspects and venues of life. We review the contributions of different authors who focus on the roles of quantification in society, with the aim of capturing different and sometimes separate voices. Several scholars, including economists, jurists, philosophers, sociologists, communication and data scientists, express concerns or identify critical areas of our relationship with new technologies of 'numericization'. While mindful of the important specificities of the different families of quantification, we use our broad and holistic canvas to explore possible spaces for a more systematic investigation of incumbent and novel quantifications, as to increase communication among disciplinary communities, and among these and society, in the pursuit a democratic agency and self-defence.

Effect of single and repeat doses of casopitant on the pharmacokinetics of CYP450 3A4 substrates midazolam and nifedipine.

AIM: To evaluate the impact of single and repeated doses casopitant on the pharmacokinetics of single dose midazolam and nifedipine (CYP3A substrates) in healthy subjects. The effect on debrisoquine metabolism (CYP2D6 substrate) was also assessed. METHODS: Three open-label studies were conducted in healthy subjects. In the first study subjects received single dose 50 or 100 mg oral casopitant, single dose 5 mg oral midazolam and single dose 10 mg oral debrisoquine. In the other two studies subjects received repeated doses of 10 mg (study 2), 30, or 120 mg oral casopitant and single doses of 5 mg oral midazolam (study 2) and single doses of 10 mg oral nifedipine (study 3). Plasma concentration-time data were analyzed using standard non-compartmental methods. The effect of casopitant on all probes was assessed using geometric means ratios and corresponding 90% confidence intervals (CIs). RESULTS: The AUC(0,∞) of midazolam was increased 1.44-fold (90% CI 1.35, 1.54) and 1.52-fold (90% CI 1.41, 1.65) after co-administration with a single dose of 50 or 100 mg casopitant, respectively. Debrisoquine metabolism was unchanged. After 3 days of casopitant administration, midazolam AUC(0,∞) was increased 1.45- (90% CI 1.32, 1.59), 2.02- (90% CI 1.75, 2.32), and 2.67-fold (90% CI 2.18, 3.27) after co-administration with 10, 30 or 120 mg casopitant, respectively. After 14 days of casopitant administration, midazolam AUC(0,∞) was increased 1.51- (90% CI 1.40, 1.63) to 3.49-fold (90% CI 2.98, 4.08). After 3 days of casopitant administration, nifedipine AUC(0,∞) was increased 1.56- (90% CI 1.37, 1.78) and 1.77-fold (90% CI 1.54, 2.04) after co-administration with 30 or 120 mg casopitant, respectively. Similar increases in nifedipine exposure were observed after 14 days of casopitant administration. CONCLUSIONS: Casopitant is a dose- and duration-dependent weak to moderate inhibitor of CYP3A.

Single nucleotide polymorphisms detection based on DNA microarray technology: HLA as a model.

The significance of DNA variations among individuals, including single nucleotide polymorphisms (SNPs) and/or genome nucleotide mutations as well as to their detection by using new technology, will improve and facilitate the knowledge of each gene sequence. Microarray may provide information about thousands of gene simultaneously, leading to a more rapid and accurate genotyping. In this view, we developed a new methodology as an example for the detection of SNPs based on DNA microarray, using a panel of HLA alleles representative of loci A, B, DRB1. A panel of 180 oligonucleotide probes was selected to identify polymorphic positions located in exons 2 and 3 of HLA-A and B, and in exon 2 of HLA-DRB1 locus. Each oligonucleotide sequence was designed with a nucleotide mismatch located in the same position as the center of the hybridization sequence. Hybridization experiments were carried out with genomic probes constructed with an asymmetric PCR strategy. The amplified DNAs were obtained from bone marrow cells of donors previously typed for transplant. The results obtained were showing that the method was reliable thus providing a feasible technique both for HLA typing and for the investigation of other regions of genetic and clinical interest including polymorphisms correlated with different autoimmune diseases.

Combined NK1 antagonism and serotonin reuptake inhibition: effects on emotional processing in humans.

BACKGROUND: Synergistic effects of NK1 receptor antagonism combined with serotonin reuptake inhibition have been reported in preclinical models. GSK424887 is a selective competitive antagonist of the human NK1 receptor and inhibitor of the serotonin transporter. However, its actions in human models of depression have not been assessed. METHODS: This study explored the effects of acute administration of GSK424887 compared to placebo in healthy male volunteers. The selective serotonin reuptake inhibitor (SSRI) citalopram was used as a positive control. A battery of emotional processing tasks was given at the peak time of drug effect. RESULTS: GSK424887 enhanced attentional vigilance in the dot-probe task to both positive and negative stimuli. By contrast, citalopram enhanced perception of angry, sad and happy facial expressions and increased positive bias in the facial expression recognition task. Neither drug significantly affected emotion potentiated startle responses or emotional memory. CONCLUSIONS: These results suggest that acute administration of GSK424887 modulated some aspects of emotional processing but these effects were not similar to those seen previously with antidepressant agents. This was the first use of the battery of emotional processing tasks in a Phase 1 study. Repeated administration of the test and active control drugs may be needed to reliably characterise their effects.

Características dos pacientes em serviço privado de cardiologia pediátrica: análise de sete anos / Characteristics of patients in private pediatric cardiology unit: seven-year analysis

Fundamentos: Apesar dos avanços no diagnóstico etratamento das cardiopatias na infância, as cardiopatias congênitas figuram como fator de destaque namorbimortalidade neonatal. Cardiopatias adquiridas,como a febre reumática, também têm alto impacto nasaúde pública. Logo, o conhecimento do perfil dessescardiopatas é importante para focalizar recursos eotimizar resultados. Objetivo: Descrever os principais achados clínicos ediagnósticos de pacientes atendidos em clínica privadade cardiologia pediátrica por faixa etária. Métodos: Analisados 17873 prontuários de pacientesatendidos nos últimos sete anos, com ênfase em: sexo, idade, motivo do encaminhamento, principais achadosna história da doença atual, achados ao exame físico,exames complementares realizados e principais diagnósticos ao ecocardiograma. Resultados: Houve predomínio do sexo masculino(53,7 %). A média de idade foi 63,5 meses, compacientes abaixo de 2 anos representando aproximadamente 25,0 % da amostra. O motivoprincipal do encaminhamento foi o parecer cardiológicoem pacientes acima de 2 anos, e suspeita de cardiopatianas faixas etárias menores. Ao exame físico, 59,8 %apresentavam anormalidades, com sopro presente em35,8%. O ecocardiograma foi realizado em 96,93% daamostra. Dentre as cardiopatias detectadas ao ecocardiograma, as mais frequentes foram as de shuntE-D (62,75%). Conclusão: A maioria das cardiopatias ocorreu empacientes de menor faixa etária no momento doencaminhamento. A diferença entre as faixas etáriasfoi essencial na diferenciação das cardiopatias e dosachados clínicos.

Background: Despite advances in the diagnosis andtreatment of heart diseases during childhood, congenital heart defects remain a prominent factor in neonatal morbidity and mortality. Acquired heart diseases, such as rheumatic fever, also have high impact on public health. Knowledge of these cardiac patient profiles is thus important for focus ingresources and optimizing results. Objective: To describe the main diagnostic and clinical findings for patients seen at a private pediatric cardiology center, by age bracket. Methods: We analyzed 17,873 records for patients seen during the past seven years, emphasizing: gender, age, reason for referral, the main findings in the history of the current disease, main findings from physical examinations, supplementary tests and the main diagnoses through echocardiograms. Results: There was a predominance of males (53.7%), with an average age of 63.5 months, with some 25% of the sample younger than two years of age. The main reasons for referral were cardiological reports for patients more than two years old, and suspected CHD for younger children. On physical examination, 59.8% presented anomalies, with murmurs found in 35.8%. Echocardiography was performed for 96.93% of the sample. The most frequent CHDs detected by echocardiography were left-to-right shunt lesions (62.75%).Conclusion: Most CHDS were found in younger children, on referral. The difference between the age brackets was essential for distinguishing CHDs and clinical findings.