Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

Objectives: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. Setting: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. Intervention: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. Main outcome measures: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. Results: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. Trial registrations: NCT00092521 and NCT00092534.

16/6-idiotype expressing antibodies induce brain inflammation and cognitive impairment in mice: the mosaic of central nervous system involvement in lupus

Background: The 16/6-idiotype (16/6-Id) of the human anti-DNA antibody was found to induce experimental lupus in naive mice, manifested by production of autoantibodies, leukopenia and elevated inflammatory markers, as well as kidney and brain involvement. We assessed behavior and brain pathology of naive mice injected intracerebra-ventricularly (ICV) with the 16/6-Id antibody. Methods: C3H female mice were injected ICV to the right hemisphere with the human 16/6-Id antibody or commercial human IgG antibodies (control). The mice were tested for depression by the forced swimming test (FST), locomotor and explorative activity by the staircase test, and cognitive functions were examined by the novel object recognition and Y-maze tests. Brain slices were stained for inflammatory processes. Results: 16/6-Id injected mice were cognitively impaired as shown by significant differences in the preference for a new object in the novel object recognition test compared to controls (P = 0.012). Similarly, the preference for spatial novelty in the Y-maze test was significantly higher in the control group compared to the 16/6-Id-injected mice (42% vs. 9%, respectively, P = 0.065). Depression-like behavior and locomotor activity were not significantly different between the16/6-Id-injected and the control mice. Immunohistochemistry analysis revealed an increase in astrocytes and microglial activation in the hippocampus and amygdala, in the 16/6-Id injected group compared to the control. Conclusions: Passive transfer of 16/6-Id antibodies directly into mice brain resulted in cognitive impairments and histological evidence for brain inflammation. These findings shed additional light on the diverse mosaic pathophysiology of neuropsychiatric lupus.

La evolución de la delincuencia de menores en Francia: entre criminalización, judicialización y guetización

Este texto pretende proporcionar a la vez el estado de los conocimientos empíricos y un marco de análisis global para reflexionar sobre la evolución de la delincuencia de menores en Francia desde los años setenta. Lejos de los estereotipos moralizadores del debate mediático-político y de los enfoques comportamentalistas, lo que aquí se propone es demostrar que el análisis de la evolución de la delincuencia de menores es inseparable de la del derecho penal, del funcionamiento de las instituciones penales, de los procesos de remisiones al sistema penal y de las evoluciones económicas, sociales y políticas que favorecen o no la integración social de los jóvenes. Este marco de análisis global articula así los tres conceptos de criminalización, judicialización y guetización.

Factores pronósticos al desarrollo de mutaciones relacionadas con resistencia antiretroviral secundaria en pacientes colombianos viviendo con VIH

Las mutaciones secundarias de resistencia al manejo antiretroviral es una realidad, y determina el éxito o fracaso del manejo del VIH. En Colombia, los casos de resistencia asociadas a mutaciones han aumentado. Para determinar esta condición en nuestra población, se realiza un estudio de tipo casos y controles, en pacientes VIH manejados en una IPS especializada en manejo y seguimiento de la enfermedad. Toman 71 pacientes con fracaso terapéutico por resistencia antiretroviral, y se documentaron las mutaciones confirmadas con Genotipo, pacientes que han manejado los diferentes esquemas antirretrovirales, y se comparan con pacientes controles que no desarrollaron resistencia a pesar de haber recibido un manejo antiretroviral similar e iniciado al mismo tiempo. Se busca evidenciar factores predictivos para controlar presencia de estas mutaciones a futuro. El estudio encontró que en ambos grupos, no existen diferencias significativas en cuanto a género, preferencia sexual, uso de psicoactivos, nivel social y las etapas de la enfermedad clasificadas según CDC. Observando que los pacientes con resistencia al tratamiento, eran más jóvenes que los controles (OR: 0,891; p> 0,001), y con una menor carga viral al momento del diagnóstico. La adecuada adherencia al tratamiento, se mostró como un factor protector al desarrollo de resistencia (OR: 0,030, p< 0,000). Se evidencia que existe mayor riesgo de generación de mutaciones en pacientes jóvenes. Respecto a los tipos de mutaciones evidenciadas por genotipos, se describen múltiples mutaciones, observando mutaciones para inhibidores de la transcriptasa reversa nucleosidos (33 mutaciones) y no nucleosidos (32 mutaciones), principalmente M184V en INTR (81%) y K103N en INNTR (40%), mutaciones para inhibidores de proteasa (57 mutaciones), principalmente L24I (40%); esta prevalencia de mutaciones son similares a estudios realizados y descritos en la literatura médica (1)

Risk, ambiguity, and diversification

Attitudes toward risk influence the decision to diversify among uncertain options. Yet, because in most situations the options are ambiguous, attitudes toward ambiguity may also play an important role. I conduct a laboratory experiment to investigate the effect of ambiguity on the decision to diversify. I find that diversification is more prevalent and more persistent under ambiguity than under risk. Moreover, excess diversification under ambiguity is driven by participants who stick with a status quo gamble when diversification among gambles is not feasible. This behavioral pattern cannot be accommodated by major theories of choice under ambiguity.