Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Background Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. Methods Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA <400 copies/ml throughout the study period. Results From January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01–0.99; LPV/r: OR 0.29, 95% CI: 0.09–0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62–18.75; LPV/r: OR 5.65, 95% CI: 1.82–17.56). Conclusions The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

The role of self-monitoring of blood glucose in glucagon-like Peptide-1-based treatment approaches: a European expert recommendation

The role of glucagon-like peptide (GLP)-1-based treatment approaches for type 2 diabetes mellitus (T2DM) is increasing. Although self-monitoring of blood glucose (SMBG) has been performed in numerous studies on GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, the potential role of SMBG in GLP-1-based treatment strategies has not been elaborated. The expert recommendation suggests individualized SMBG strategies in GLP-1-based treatment approaches and suggests simple and clinically applicable SMBG schemes. Potential benefits of SMBG in GLP-1-based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and diabetes education. Its length and frequency should depend on the clinical setting and the quality of metabolic control. It is considered to play an important role for the optimization of diabetes management in T2DM patients treated with GLP-1-based approaches.

Retrospective adjustment of self-assessed medical competencies - noteworthy in the evaluation of postgraduate practical training courses

The efficacy of postgraduate practical training courses is frequently evaluated by self-assessment instruments. The present study analyses the effect of a basic course in laparoscopic surgery on self-assessed medical competencies.

Representations of the Human/ Nonhuman Primate Divide: the Influence of Science, Fiction, and Science-Fiction on the Concept of 'Being Human'

For as far back as human history can be traced, mankind has questioned what it means to be human. One of the most common approaches throughout Western culture's intellectual tradition in attempts to answering this question has been to compare humans with or against other animals. I argue that it was not until Charles Darwin's publication of The Descent of Man and Selection in Relation to Sex (1871) that Western culture was forced to seriously consider human identity in relation to the human/ nonhuman primate line. Since no thinker prior to Charles Darwin had caused such an identity crisis in Western thought, this interdisciplinary analysis of the history of how the human/ nonhuman primate line has been understood focuses on the reciprocal relationship of popular culture and scientific representations from 1871 to the Human Genome Consortium in 2000. Focusing on the concept coined as the "Darwin-Müller debate," representations of the human/ nonhuman primate line are traced through themes of language, intelligence, and claims of variation throughout the popular texts: Descent of Man, The Jungle Books (1894), Tarzan of the Apes (1914), and Planet of the Apes (1963). Additional themes such as the nature versus nurture debate and other comparative phenotypic attributes commonly used for comparison between man and apes are also analyzed. Such popular culture representations are compared with related or influential scientific research during the respective time period of each text to shed light on the reciprocal nature of Western intellectual tradition, popular notions of the human/ nonhuman primate line, and the development of the field of primatology. Ultimately this thesis shows that the Darwin-Müller debate is indeterminable, and such a lack of resolution makes man uncomfortable. Man's unsettled response and desire for self-knowledge further facilitates a continued search for answers to human identity. As the Human Genome Project has led to the rise of new debates, and primate research has become less anthropocentric over time, the mysteries of man's future have become more concerning than the questions of our past. The human/ nonhuman primate line is reduced to a 1% difference, and new debates have begun to overshadow the Darwin-Müller debate. In conclusion, I argue that human identity is best represented through the metaphor of evolution: both have an unknown beginning, both have an indeterminable future with no definite end, and like a species under the influence of evolution, what it means to be human is a constant, indeterminable process of change.

How scientific is the science in ethnopharmacology? Historical perspectives and epistemological problems

This commentary is based on a general concern regarding the low level of self-criticism (-evaluation) in the interpretation of molecular pharmacological data published in ethnopharmacology-related journals. Reports on potentially new lead structures or pharmacological effects of medicinal plant extracts are mushrooming. At the same time, nonsense in bioassays is an increasing phenomenon in herbal medicine research. Only because a dataset is reproducible does not imply that it is meaningful. Currently, there are thousands of claims of pharmacological effects of medicinal plants and natural products. It is argued that claims to knowledge in ethnopharmacology, as in the exact sciences, should be rationally criticized if they have empirical content as it is the case with biochemical and pharmacological analyses. Here the major problem is the misemployment of the concentration-effect paradigm and the overinterpretation of data obtained in vitro. Given the almost exponential increase of scientific papers published it may be the moment to adapt to a falsificationist methodology.

Electrochemical characterization of self-assembled Ferrocene-terminated alkanethiol monolayers on low-index gold single crystal electrodes

We present a voltammetric and in situ STM study of 11-ferrocenyl-1-undecanethiol (FcC11) assembled on low-index single crystal and polycrystalline gold electrodes. The influence of electrode surface structure as well as of structure defects in the self-assembled FcC11 monolayers on the electrochemical response during the oxidation and reduction of the terminal ferrocene group is explored. The nature of the redox peaks is discussed in detail. We identified the coexistence of disordered FcC11 regions with 2D patches of “locally ordered” FcC11 species. We demonstrate that close-packed domains are preferentially formed at atomically flat terraces. Increasing the defect density of the substrate surface leads to a decreasing amount of locally ordered FcC11 molecules.

Ferrocene-terminated alkanethiol self-assembled monolayers: An electrochemical and in situ surface-enhanced infra-red absorption spectroscopy study

The effect of anions on the redox behavior and structure of 11-ferrocenyl-1-undecanethiol (FcC11) monolayers (SAM) on Au(1 1 1) single crystal and Au(1 1 1-25 nm) thin film electrodes was investigated in 0.1 M solutions of HPF6, HClO4, HBF4, HNO3, and H2SO4 by cyclic voltammetry (CV) and in situ surface-enhanced infrared reflection-absorption spectroscopy (SEIRAS). We demonstrate that the FcC11 redox peaks shift toward positive potentials and broaden with increasing hydrophilicity of the anions. In situ surface-enhanced IR-spectroscopy (SEIRAS) provided direct access for the incorporation of anions into the oxidized adlayer. The coadsorption of anions is accompanied by the penetration of water molecules. The latter effect is particularly pronounced in aqueous HNO3 and H2SO4 electrolytes. The adlayer permeability increases with increasing hydrophilicity of the anions. We also found that even the neutral (reduced) FcC11 SAM is permeable for water molecules. Based on the property of interfacial water to reorient upon charge inversion, we propose a spectroscopic approach for estimating the potential of zero total charge of the FcC11-modified Au(1 1 1) electrodes in aqueous electrolytes.

Self-dual continuous processes

The important application of semi-static hedging in financial markets naturally leads to the notion of conditionally quasi self-dual processes which is, for continuous semimartingales, related to conditional symmetry properties of both their ordinary as well as their stochastic logarithms. We provide a structure result for continuous conditionally quasi self-dual processes. Our main result is to give a characterization of continuous Ocone martingales via a strong version of self-duality.

Actor and partner effects of self-esteem on relationship satisfaction and the mediating role of secure attachment between the partners

We examined actor and partner effects of self-esteem on relationship satisfaction, using the actor-partner interdependence model and data from five independent samples of couples. The results indicated that self-esteem predicted the individual’s own relationship satisfaction (i.e., an actor effect) and the relationship satisfaction of his or her partner (i.e., a partner effect), controlling for the effect of the partner’s selfesteem. Gender, age, and length of relationship did not moderate the effect sizes. Moreover, using one of the samples, we tested whether secure attachment to the current partner (assessed as low attachment-related anxiety and avoidance) mediated the effects. The results showed that attachment-related anxiety and avoidance independently mediated both the actor and the partner effect of self-esteem on relationship satisfaction.

Software Engineering for Self-Adaptive Systems: A Second Research Roadmap

The goal of this roadmap paper is to summarize the state-of-the-art and identify research challenges when developing, deploying and managing self-adaptive software systems. Instead of dealing with a wide range of topics associated with the field, we focus on four essential topics of self-adaptation: design space for self-adaptive solutions, software engineering processes for self-adaptive systems, from centralized to decentralized control, and practical run-time verification & validation for self-adaptive systems. For each topic, we present an overview, suggest future directions, and focus on selected challenges. This paper complements and extends a previous roadmap on software engineering for self-adaptive systems published in 2009 covering a different set of topics, and reflecting in part on the previous paper. This roadmap is one of the many results of the Dagstuhl Seminar 10431 on Software Engineering for Self-Adaptive Systems, which took place in October 2010.