CNS safety at 48-week of switching to ATV/r plus 3TC or two nucleos(t)ides in HIV-suppressed patients on stable ART: the SALT neurocognitive sub-study.

INTRODUCTION Due to their low CNS penetrance, there are concerns about the capacity of non-conventional PI-based ART (monotherapy and dual therapies) to preserve neurocognitive performance (NP). METHODS We evaluated the NP change of aviremic participants of the SALT clinical trial (1) switching therapy to dual therapy (DT: ATV/r+3TC) or triple therapy (TT: ATV/r+2NRTI) who agreed to perform an NP assessment (NPZ-5) at baseline and W48. Neurocognitive impairment and NP were assessed using AAN-2007 criteria (2) and global deficit scores (GDS) (3). Neurocognitive change (GDS change: W48 - baseline) and the effect of DT on NP evolution crude and adjusted by significant confounders were determined using ANCOVA. RESULTS A total of 158 patients were included (Table 1). They had shorter times because HIV diagnosis, ART initiation and HIV-suppression and their virologic outcome at W48 by snapshot was higher (79.1% vs 72.7%; p=0.04) compared to the 128 patients not included in the sub-study. By AAN-2007 criteria, 51 patients in each ART group (68% vs 63%) were neurocognitively impaired at baseline (p=0.61). Forty-seven patients were not reassessed at W48: 30 lost of follow-up (16 DT-14 TT) and 17 had non-evaluable data (6 DT-11 TT). Patients retested were more likely to be men (78.9% vs 61.4%) and had neurological cofounders (9.6% vs 0%) than patients non-retested. At W48, 3 out of 16 (5.7%) patients on DT and 6 out of 21 (10.5%) on TT who were non-impaired at baseline became impaired (p=0.49) while 10 out of 37 (18.9%) on DT and 7 out of 36 (12.3%) on TT who were neurocognitively impaired at baseline became non-impaired (p=0.44). Mean GDS changes (95% CI) were: Overall -0.2 (-0.3 to -0.04): DT -0.26 (-0.4 to -0.07) and TT -0.08 (-0.2 to 0.07). NP was similar between DT and TT (0.15). This absence of differences was also observed in all cognitive tests. Effect of DT: -0.16 [-0.38 to 0.06]) (r(2)=0.16) on NP evolution was similar to TT (reference), even after adjusting (DT: -0.11 [-0.33 to 0.1], TT: reference) by significant confounders (geographical origin, previous ATV use and CD4 cell count) (r(2)=0.25). CONCLUSIONS NP stability was observed after 48 weeks of follow up in the majority of patients whether DT or TT was used to maintain HIV-suppression. Incidence rates of NP impairment or NP impairment recovery were also similar between DT and TT.

The European Union in North Korea: Current Realities and Paths for Future Engagement – A Qualitative and Quantitative Study

Malgrat la rellevància estratègica i el paper desestabilitzador de Corea del Nord a la regió econòmicament més dinàmica del món, la UE no compta amb cap estratègia clara per involucrar-se amb aquest país. Combinant tècniques d’anàlisi qualitatives i quantitatives, aquest treball pretén descobrir possibles contradiccions internes que impedeixin la definició d'una política exterior europea coherent i efectiva amb respecte a Corea del Nord, així com discrepàncies entre les percepcions d’actors interns de la UE i les d’actors externs. S'han detectat importants diferències d’expectatives i mancances en termes de coherència, tant entre les visions expressades pels actors interns com entre les opinions d’aquests actors i les dels futurs líders sudcoreans enquestats – diferències que fins i tot afecten la promoció dels drets humans

Lipid changes in HIV-patients switching to the coformulated single tablet FTC/RPV/TDF (Eviplera®). Efficacy and safety analysis. GeSida Study 8114.

INTRODUCTION Rilpivirine (RPV) has a better lipid profile than efavirenz (EFV) in naïve patients (1). Switching to RPV may be convenient for many patients, while maintaining a good immunovirological control (2). The aim of this study was to analyze lipid changes in HIV-patients at 24 weeks after switching to Eviplera® (emtricitabine/RPV/tenofovir disoproxil fumarate [FTC/RPV/TDF]). MATERIALS AND METHODS Retrospective, multicentre study of a cohort of asymptomatic HIV-patients who switched from a regimen based on 2 nucleoside reverse transcriptase inhibitors (NRTI)+protease inhibitor (PI)/non nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir boosted PI monotherapy to Eviplera® during February-December, 2013; all had undetectable HIV viral load for ≥3 months prior to switching. Patients with previous failures on antiretroviral therapy (ART) including TDF and/or FTC/3TC, with genotype tests showing resistance to components of Eviplera®, or who had changed the third drug of the ART during the study period were excluded. Changes in lipid profile and cardiovascular risk (CVR), and efficacy and safety at 24 weeks were analyzed. RESULTS Among 305 patients included in the study, 298 were analyzed (7 cases were excluded due to lack of data). Men 81.2%, mean age 44.5 years, 75.8% of HIV sexually transmitted. 233 (78.2%) patients switched from a regimen based on 2 NRTI+NNRTI (90.5% EFV/FTC/TDF). The most frequent reasons for switching were central nervous system (CNS) adverse events (31.0%), convenience (27.6%) and metabolic disorders (23.2%). At this time, 293 patients have reached 24 weeks: 281 (95.9%) have continued Eviplera®, 6 stopped it (3 adverse events, 2 virologic failures, 1 discontinuation) and 6 have been lost to follow up. Lipid profiles of 283 cases were available at 24 weeks and mean (mg/dL) baseline vs 24 weeks are: total cholesterol (193 vs 169; p=0.0001), HDL-c (49 vs 45; p=0.0001), LDL-c (114 vs 103; p=0.001), tryglycerides (158 vs 115; p=0.0001), total cholesterol to HDL-c ratio (4.2 vs 4.1; p=0.3). CVR decreased (8.7 vs 7.5%; p= 0.0001). CD4 counts were similar to baseline (653 vs 674 cells/µL; p=0.08), and 274 (96.8%) patients maintained viral suppression. CONCLUSIONS At 24 weeks after switching to Eviplera®, lipid profile and CVR improved while maintaining a good immunovirological control. Most subjects switched to Eviplera® from a regimen based on NNRTI, mainly EFV/FTC/TDF. CNS adverse events, convenience and metabolic disorders were the most frequent reasons for switching.

Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery.

The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era.

Efficacy of prescribed injectable diacetylmorphine in the Andalusian trial: Bayesian analysis of responders and non-responders according to a multi domain outcome index.

BACKGROUND The objective of this research was to evaluate data from a randomized clinical trial that tested injectable diacetylmorphine (DAM) and oral methadone (MMT) for substitution treatment, using a multi-domain dichotomous index, with a Bayesian approach. METHODS Sixty two long-term, socially-excluded heroin injectors, not benefiting from available treatments were randomized to receive either DAM or MMT for 9 months in Granada, Spain. Completers were 44 and data at the end of the study period was obtained for 50. Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration, used in a previous trial. Data was analyzed with Bayesian methods, using information from a similar study conducted in The Netherlands to select a priori distributions. On adding the data from the present study to update the a priori information, the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations. RESULTS In the experimental group (n = 27), the rate of responders to treatment was 70.4% (95% CI 53.287.6), and in the control group (n = 23), it was 34.8% (95% CI 15.354.3). The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis. Almost the whole distribution of the rates difference (the one for diacetylmorphine minus methadone) was located to the right of the zero, indicating the superiority of the experimental treatment. CONCLUSION The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments. TRIAL REGISTRATION Current Controlled Trials ISRCTN52023186.

Possible solution of some essential zero problems in compositional data analysis

One of the tantalising remaining problems in compositional data analysis lies in how to deal with data sets in which there are components which are essential zeros. By anessential zero we mean a component which is truly zero, not something recorded as zero simply because the experimental design or the measuring instrument has not been sufficiently sensitive to detect a trace of the part. Such essential zeros occur inmany compositional situations, such as household budget patterns, time budgets,palaeontological zonation studies, ecological abundance studies. Devices such as nonzero replacement and amalgamation are almost invariably ad hoc and unsuccessful insuch situations. From consideration of such examples it seems sensible to build up amodel in two stages, the first determining where the zeros will occur and the secondhow the unit available is distributed among the non-zero parts. In this paper we suggest two such models, an independent binomial conditional logistic normal model and a hierarchical dependent binomial conditional logistic normal model. The compositional data in such modelling consist of an incidence matrix and a conditional compositional matrix. Interesting statistical problems arise, such as the question of estimability of parameters, the nature of the computational process for the estimation of both the incidence and compositional parameters caused by the complexity of the subcompositional structure, the formation of meaningful hypotheses, and the devising of suitable testing methodology within a lattice of such essential zero-compositional hypotheses. The methodology is illustrated by application to both simulated and real compositional data

Transmission delays in residual computation

The design of control, estimation or diagnosis algorithms most often assumes that all available process variables represent the system state at the same instant of time. However, this is never true in current network systems, because of the unknown deterministic or stochastic transmission delays introduced by the communication network. During the diagnosing stage, this will often generate false alarms. Under nominal operation, the different transmission delays associated with the variables that appear in the computation form produce discrepancies of the residuals from zero. A technique aiming at the minimisation of the resulting false alarms rate, that is based on the explicit modelling of communication delays and on their best-case estimation is proposed

When zero doesn't mean it and other geomathematical mischief

There is almost not a case in exploration geology, where the studied data doesn’tincludes below detection limits and/or zero values, and since most of the geological dataresponds to lognormal distributions, these “zero data” represent a mathematicalchallenge for the interpretation.We need to start by recognizing that there are zero values in geology. For example theamount of quartz in a foyaite (nepheline syenite) is zero, since quartz cannot co-existswith nepheline. Another common essential zero is a North azimuth, however we canalways change that zero for the value of 360°. These are known as “Essential zeros”, butwhat can we do with “Rounded zeros” that are the result of below the detection limit ofthe equipment?Amalgamation, e.g. adding Na2O and K2O, as total alkalis is a solution, but sometimeswe need to differentiate between a sodic and a potassic alteration. Pre-classification intogroups requires a good knowledge of the distribution of the data and the geochemicalcharacteristics of the groups which is not always available. Considering the zero valuesequal to the limit of detection of the used equipment will generate spuriousdistributions, especially in ternary diagrams. Same situation will occur if we replace thezero values by a small amount using non-parametric or parametric techniques(imputation).The method that we are proposing takes into consideration the well known relationshipsbetween some elements. For example, in copper porphyry deposits, there is always agood direct correlation between the copper values and the molybdenum ones, but whilecopper will always be above the limit of detection, many of the molybdenum values willbe “rounded zeros”. So, we will take the lower quartile of the real molybdenum valuesand establish a regression equation with copper, and then we will estimate the“rounded” zero values of molybdenum by their corresponding copper values.The method could be applied to any type of data, provided we establish first theircorrelation dependency.One of the main advantages of this method is that we do not obtain a fixed value for the“rounded zeros”, but one that depends on the value of the other variable.Key words: compositional data analysis, treatment of zeros, essential zeros, roundedzeros, correlation dependency

Postmortem angiography: review of former and current methods.

OBJECTIVE: Postmortem investigations are becoming more and more sophisticated. CT and MRI are already being used in pathology and forensic medicine. In this context, the impact of postmortem angiography increases because of the rapid evaluation of organ-specific vascular patterns, vascular alteration under pathologic and physiologic conditions, and tissue changes induced by artificial and unnatural causes. CONCLUSION: In this article, the advantages and disadvantages of former and current techniques and contrast agents are reviewed.

La Gestió policial als esdeveniments públics en espais urbans a l'Àfrica: situació actual i perspectives = Policing public events in urban spaces in Africa : an analysis of the current situation and a perspective on follow-up action

L’informe que es presenta en aquest llibre és el resultat d’un nou acord de col·laboració entre el Programa de les Nacions Unides per als Assentaments Humans (ONU-Habitat) i l’Institut de Seguretat Pública de Catalunya, impulsat amb l’objectiu de millorar la seguretat en esdeveniments públics en els espais urbans a l’Àfrica. La fase pilot es va dur a terme el 2010, durant els dos seminaris de formació realitzats a Mollet del Vallès (Barcelona) com a part de la Plataforma Policia per al Desenvolupament Urbà (PPUD). En aquest informe es descriuen els orígens i l’estat de la iniciativa i resumeix els resultats. També s’inclouen algunes recomanacions per a millorar la seguretat d’esdeveniments públics. Font d'informació: http://www.onuhabitat.org.

Personnes âgées aux urgences: défis actuels et futurs [Older patients at the emergency department: current and future challenges].

Emergency departments are and will be at the front line to face the forthcoming increased use of the health care system by the aging baby boomers cohort. Emergency department services will need to adjust on a quantitative as well as on a qualitative basis to manage the impact of these demographic changes. Various models of care have been developed to improve the care of older geriatric patients in the Emergency department that resulted in favorable results on functional, health, as well as health services utilization outcomes. Key components of these successful models have been identified that require a high level of integration between geriatric and emergency teams.

Iowa Airport Directory, 2003 ***NOTE*** This document is for historical viewing, the internal information is no longer current or accurate! ***NOTE*** Current information can be found at http://www.iowadot.gov/aviation/aircraftregistration/registration.aspx ***NOTE***

Iowa has 8 commercial service airports and 105 general aviation airports, of which three serve as reliever airports. ***NOTE*** This document is for historical viewing, the internal information is no longer current or accurate! ***NOTE*** Current information can be found at http://www.iowadot.gov/aviation/aircraftregistration/registration.aspx ***NOTE***