Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples

Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample procedure for TDM. TDM was found to be an important component of clinical care for many (but not all) pulmonary infections. For gentamicin, linezolid, voriconazole and posaconazole dried blood spot methods and their use in TDM were already evident in literature. For glycopeptides, beta-lactam antibiotics and fluoroquinolones it was determined that development of a dried blood spot (DBS) method could be useful. This review identifies specific antibiotics for which development of DBS methods could support the optimization of treatment of pulmonary infections

Valuing local perspectives on invasive species management: Moving beyond the ecosystem service-disservice dichotomy

This paper uses the concept of ecosystem disservices to explore and understand how rapid environmental change associated with an invasive plant species is framed and understood by different stakeholders. Through a focus on narratives, the paper explores how socially-differentiated populations understand the causes and consequences of a plant invasion and express preferences for often contrasting management interventions. The research design uses a workshop format to instigate a series of conversations with socially-differentiated groups of people to explore how people perceive and respond to the impact of Prosopis juliflora (a species of mesquite) in the drylands of Ethiopia. The results show that preferences for interventions differs by age, gender, location and livelihood and also by primary and secondary stakeholder. Different sets of values underpin people’s views and these contribute to the variation in the preference for different management interventions. To understand complex issues associated with alien invasive species, we find that the dichotomy between ecosystem services and disservices is artificial and call for a more dynamic and graduated view of ecosystem outputs. More practically, our research shows that P. juliflora management options need wider consideration of socially-differentiated implications and trade-offs and this requires greater efforts to engage with primary stakeholders

Chemosignalling effects of human tears revisited:Does exposure to female tears decrease males' perception of female sexual attractiveness?

Gelstein et al. reported the results of three experiments suggesting a dampening influence of inhalation of female emotional tears on males' arousal and perception of female sexual attractiveness, specifically in non-sexual situations. This prompted the hypothesis that crying exerts its influence on others not only via the auditory and visual mode but also via chemosignals. In three studies, we attempted to replicate and extend Gelstein et al.'s findings by including an additional condition with irritant tears, by using pictures of sexually attractive women, and by testing related hypotheses on the pro-social effects of exposure to tears. All three studies, separately or combined in a meta-analysis, failed to replicate the original inhibitory effects of tears. In addition, sniffing tears did not affect measures of connectedness, aggression and pro-social behaviour. It is concluded that the effects of female tears on male arousal and perception of female sexual attractiveness, if any, are very weak at best. Rather, it seems that crying exerts its strong inter-personal effects through the visual and auditory sensory channels

Cardiac motion estimation using multi-scale feature points

Heart illnesses influence the functioning of the cardiac muscle and are the major causes of death inthe world. Optic flow methods are essential tools to assess and quantify the contraction of the cardiacwalls, but are hampered by the aperture problem. Harmonic phase (HARP) techniques measure thephase in magnetic resonance (MR) tagged images. Due to the regular geometry, patterns generated bya combination of HARPs and sine HARPs represent a suitable framework to extract landmark features.In this paper we introduce a new aperture-problem free method to study the cardiac motion by trackingmulti-scale features such as maxima, minima, saddles and corners, on HARP and sine HARP taggedimages

Publication bias examined in meta-analyses from psychology and medicine: A meta-meta-analysis

<div><p>Publication bias is a substantial problem for the credibility of research in general and of meta-analyses in particular, as it yields overestimated effects and may suggest the existence of non-existing effects. Although there is consensus that publication bias exists, how strongly it affects different scientific literatures is currently less well-known. We examined evidence of publication bias in a large-scale data set of primary studies that were included in 83 meta-analyses published in Psychological Bulletin (representing meta-analyses from psychology) and 499 systematic reviews from the Cochrane Database of Systematic Reviews (CDSR; representing meta-analyses from medicine). Publication bias was assessed on all homogeneous subsets (3.8% of all subsets of meta-analyses published in Psychological Bulletin) of primary studies included in meta-analyses, because publication bias methods do not have good statistical properties if the true effect size is heterogeneous. Publication bias tests did not reveal evidence for bias in the homogeneous subsets. Overestimation was minimal but statistically significant, providing evidence of publication bias that appeared to be similar in both fields. However, a Monte-Carlo simulation study revealed that the creation of homogeneous subsets resulted in challenging conditions for publication bias methods since the number of effect sizes in a subset was rather small (median number of effect sizes equaled 6). Our findings are in line with, in its most extreme case, publication bias ranging from no bias until only 5% statistically nonsignificant effect sizes being published. These and other findings, in combination with the small percentages of statistically significant primary effect sizes (28.9% and 18.9% for subsets published in Psychological Bulletin and CDSR), led to the conclusion that evidence for publication bias in the studied homogeneous subsets is weak, but suggestive of mild publication bias in both psychology and medicine.</p></div

Associations between lifestyle factors and multidimensional frailty:A cross-sectional study among community-dwelling older people

BACKGROUND: Multidimensional frailty, including physical, psychological, and social components, is associated to disability, lower quality of life, increased healthcare utilization, and mortality. In order to prevent or delay frailty, more knowledge of its determinants is necessary; one of these determinants is lifestyle. The aim of this study is to determine the association between lifestyle factors smoking, alcohol use, nutrition, physical activity, and multidimensional frailty. METHODS: This cross-sectional study was conducted in two samples comprising in total 45,336 Dutch community-dwelling individuals aged 65 years or older. These samples completed a questionnaire including questions about smoking, alcohol use, physical activity, sociodemographic factors (both samples), and nutrition (one sample). Multidimensional frailty was assessed with the Tilburg Frailty Indicator (TFI). RESULTS: Higher alcohol consumption, physical activity, healthy nutrition, and less smoking were associated with less total, physical, psychological and social frailty after controlling for effects of other lifestyle factors and sociodemographic characteristics of the participants (age, gender, marital status, education, income). Effects of physical activity on total and physical frailty were up to considerable, whereas the effects of other lifestyle factors on frailty were small. CONCLUSIONS: The four lifestyle factors were not only associated with physical frailty but also with psychological and social frailty. The different associations of frailty domains with lifestyle factors emphasize the importance of assessing frailty broadly and thus to pay attention to the multidimensional nature of this concept. The findings offer healthcare professionals starting points for interventions with the purpose to prevent or delay the onset of frailty, so community-dwelling older people have the possibility to aging in place accompanied by a good quality of life

eIF1A/eIF5B Interaction Network and its Functions in Translation Initiation Complex Assembly and Remodeling

Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments

Postprint "Who believes in the storybook image of the scientist?" accepted for publication in Accountability in Research

Do lay people and scientists themselves recognize that scientists are human and therefore prone to human fallibilities such as error, bias, and even dishonesty? In a series of three experimental studies and one correlational study (total N = 3,278) we found that the ‘storybook image of the scientist’ is pervasive: American lay people and scientists from over 60 countries attributed considerably more objectivity, rationality, open-mindedness, intelligence, integrity, and communality to scientists than other highly-educated people. Moreover, scientists perceived even larger differences than lay people did. Some groups of scientists also differentiated between different categories of scientists: established scientists attributed higher levels of the scientific traits to established scientists than to early-career scientists and PhD students, and higher levels to PhD students than to early-career scientists. Female scientists attributed considerably higher levels of the scientific traits to female scientists than to male scientists. A strong belief in the storybook image and the (human) tendency to attribute higher levels of desirable traits to people in one’s own group than to people in other groups may decrease scientists’ willingness to adopt recently proposed practices to reduce error, bias and dishonesty in science

Cardiac motion estimation using covariant derivatives and Helmholtz decomposition

The investigation and quantification of cardiac movement is important for assessment of cardiac abnormalities and treatment effectiveness. Therefore we consider new aperture problem-free methods to track cardiac motion from 2-dimensional MR tagged images and corresponding sine-phase images. Tracking is achieved by following the movement of scale-space maxima, yielding a sparse set of linear features of the unknown optic flow vector field. Interpolation/reconstruction of the velocity field is then carried out by minimizing an energy functional which is a Sobolev-norm expressed in covariant derivatives (rather than standard derivatives). These covariant derivatives are used to express prior knowledge about the velocity field in the variational framework employed. They are defined on a fiber bundle where sections coincide with vector fields. Furthermore, the optic flow vector field is decomposed in a divergence free and a rotation free part, using our multi-scale Helmholtz decomposition algorithm that combines diffusion and Helmholtz decomposition in a single non-singular analytic kernel operator. Finally, we combine this multi-scale Helmholtz decomposition with vector field reconstruction (based on covariant derivatives) in a single algorithm and present some experiments of cardiac motion estimation. Further experiments on phantom data with ground truth show that both the inclusion of covariant derivatives and the inclusion of the multi-scale Helmholtz decomposition improves the optic flow reconstruction