From protein sequences to 3D-structures and beyond: the example of the UniProt knowledgebase.

With the dramatic increase in the volume of experimental results in every domain of life sciences, assembling pertinent data and combining information from different fields has become a challenge. Information is dispersed over numerous specialized databases and is presented in many different formats. Rapid access to experiment-based information about well-characterized proteins helps predict the function of uncharacterized proteins identified by large-scale sequencing. In this context, universal knowledgebases play essential roles in providing access to data from complementary types of experiments and serving as hubs with cross-references to many specialized databases. This review outlines how the value of experimental data is optimized by combining high-quality protein sequences with complementary experimental results, including information derived from protein 3D-structures, using as an example the UniProt knowledgebase (UniProtKB) and the tools and links provided on its website ( http://www.uniprot.org/ ). It also evokes precautions that are necessary for successful predictions and extrapolations.

The evolution of information suppression in communicating robots with conflicting interests.

Reliable information is a crucial factor influencing decision-making and, thus, fitness in all animals. A common source of information comes from inadvertent cues produced by the behavior of conspecifics. Here we use a system of experimental evolution with robots foraging in an arena containing a food source to study how communication strategies can evolve to regulate information provided by such cues. The robots could produce information by emitting blue light, which the other robots could perceive with their cameras. Over the first few generations, the robots quickly evolved to successfully locate the food, while emitting light randomly. This behavior resulted in a high intensity of light near food, which provided social information allowing other robots to more rapidly find the food. Because robots were competing for food, they were quickly selected to conceal this information. However, they never completely ceased to produce information. Detailed analyses revealed that this somewhat surprising result was due to the strength of selection on suppressing information declining concomitantly with the reduction in information content. Accordingly, a stable equilibrium with low information and considerable variation in communicative behaviors was attained by mutation selection. Because a similar coevolutionary process should be common in natural systems, this may explain why communicative strategies are so variable in many animal species.

The impact of information on decision-making in palliative care

Résumé Ce travail vise à clarifier les résultats contradictoires de la littérature concernant les besoins des patients d'être informés et de participer à la prise de décision. La littérature insiste sur le contenu de l'information comme base de la prise de décision, bien qu'il existe des preuves que d'autres contenus sont importants pour les patients. La thèse essaie en outre d'identifier des possibilités de mieux répondre aux préférences d'information et de participation des patients. Les travaux ont porté en particulier sur les soins palliatifs. Une analyse de la littérature donne un aperçu sur les soins palliatifs, sur l'information des patients et sur leur participation à la prise de décisions thérapeutiques. Cette analyse résume les résultats d'études précédentes et propose un: modèle théorique d'information, de prise de décision et de relation entre ces deux domaines. Dans le cadre de ce travail, deux études empiriques ont utilisé des questionnaires écrits adressés à des personnes privées et à des professionnels de la santé, couvrant la Suisse et le Royaume Uni, pour identifier d'éventuelles différences entre ces deux pays. Les enquêtes ont été focalisées sur des patients souffrant de cancer du poumon. Les instruments utilisés pour ces études proviennent de la littérature afin de les rendre comparables. Le taux de réponse aux questionnaires était de 30-40%. La majorité des participants aux enquêtes estime que les patients devraient: - collaborer à la prise de décision quant à leur traitement - recevoir autant d'information que possible, positive aussi bien que négative - recevoir toutes les informations mentionnées dans le questionnaire (concernant la maladie, le diagnostic et les traitements), tenant compte de la diversité des priorités des patients - être soutenus par des professionnels de la santé, leur famille, leurs amis et/ou les personnes souffrant de la même maladie En plus, les participants aux enquêtes ont identifié divers contenus de l'information aux patients souffrant d'une maladie grave. Ces contenus comprennent entre autres: - L'aide à la prise de décision concernant le traitement - la possibilité de maintenir le contrôle de la situation - la construction d'une relation entre le patient et le soignant - l'encouragement à faire des projets d'avenir - l'influence de l'état émotionnel - l'aide à la compréhension de la maladie et de son impact - les sources potentielles d'états confusionnels et d'états anxieux La plupart des contenus proposés sont positifs. Les résultats suggèrent la coexistence possible de différents contenus à un moment donné ainsi que leur changement au cours du temps. Un modèle est ensuite développé et commenté pour présenter le diagnostic d'une maladie grave. Ce modèle est basé sur la littérature et intègre les résultats des études empiriques réalisées dans le cadre de ce travail. Ce travail analyse également les sources préférées d'information et de soutien, facteurs qui peuvent influencer ou faire obstacle aux préférences d'information et de participation. Les deux groupes de participants considèrent les médecins spécialistes comme la meilleure source d'information. En ce qui concerne le soutien, les points de vue divergent entre les personnes privées et les professionnels de la santé: généralement, les rôles de soutien semblent peu définis parmi les professionnels. Les barrières à l'information adéquate du patient apparaissent fréquemment liées aux caractéristiques des professionnels et aux problèmes d'organisation. Des progrès dans ce domaine contribueraient à améliorer les soins fournis aux patients. Finalement, les limites des études empiriques sont discutées. Celles-ci comprennent, entre autres, la représentativité restreinte des participants et les objections de certains groupes de participants à quelques détails des questionnaires. Summary The present thesis follows a call from the current body of literature to better understand patient needs for information and for participation in decision-making, as previous research findings had been contradictory. Information so far seems to have been considered essentially as a means to making treatment decisions, despite certain evidence that it may have a number of other values to patients. Furthermore, the thesis aims to identify ways to optimise meeting patient preferences for information and participation in treatment decisions. The current field of interest is palliative care. An extensive literature review depicts the background of current concepts of palliative care, patient information and patient involvement into treatment decisions. It also draws together results from previous studies and develops a theoretical model of information, decision-making, and the relationship between them. This is followed by two empirical studies collecting data from members of the general public and health care professionals by means of postal questionnaires. The professional study covers both Switzerland and the United Kingdom in order to identify possible differences between countries. Both studies focus on newly diagnosed lung cancer patients. The instruments used were taken from the literature to make them comparable. The response rate in both surveys was 30-40%, as expected -sufficient to allow stastical tests to be performed. A third study, addressed to lung cancer patients themselves, turned out to require too much time within the frame available. A majority of both study populations thought that patients should: - have a collaborative role in treatment-related decision-making -receive as much information as possible, good or bad - receive all types of information mentioned in the questionnaire (about illness, tests, and treatment), although priorities varied across the study populations - be supported by health professionals, family members, friends and/or others with the same illness Furthermore they identified various 'meanings' information may have to patients with a serious illness. These included: - being an aid in treatment-related decision-making - allowing control to be maintained over the situation - helping the patient-professional relationship to be constructed - allowing plans to be made - being positive for the patient's emotional state - helping the illness and its impact to be understood - being a source of anxiety - being a potential source of confusion to the patient Meanings were mostly positive. It was suggested that different meanings could co-exist at a given time and that they might change over time. A model of coping with the disclosure of a serious diagnosis is then developped. This model is based on existing models of coping with threatening events, as takeñ from the literature [ref. 77, 78], and integrates findings from the empirical studies. The thesis then analyses the remaining aspects apparent from the two surveys. These range from the identification of preferred information and support providers to factors influencing or impeding information and participation preferences. Specialist doctors were identified by both study populations as the best information providers whilst with regard to support provision views differed between the general public and health professionals. A need for better definition of supportive roles among health care workers seemed apparent. Barriers to information provision often seem related to health professional characteristics or organisational difficulties, and improvements in the latter field could well help optimising patient care. Finally, limitations of the studies are discussed, including questions of representativness of certain results and difficulties with or objections against questionnaire details by some groups of respondents.

A step beyond--the relevance of depressed mood and mastery in the interplay between the number of social roles and alcohol use.

OBJECTIVES: The present study examines whether depressed mood and external control mediate or moderate the relationship between the number of social roles and alcohol use. PARTICIPANTS: The analysis was based on a national representative sample of 25- to 45-year-old male and female drinkers in Switzerland. METHOD: The influence of depressed mood and external control on the relationship between the number of social roles (parenthood, partnership, employment) and alcohol use was examined in linear structural equation models (mediation) and in multiple regressions (moderation) stratified by gender. All analyses were adjusted for age and education level. RESULTS: Holding more roles was associated with lower alcohol use, lower external control and lower depressed mood. The study did not find evidence of depressed mood or external control mediating the social roles-alcohol relationship. A moderation effect was identified among women only, whereby a protective effect of having more roles could not be found among those who scored high on external control. In general, a stronger link was observed between roles and alcohol use, while depressed mood and external control acted independently on drinking. With the exception of women with high external control, the study found no link between a higher number of social roles and greater alcohol use. CONCLUSION: Our results indicate that drinking behaviours are more strongly linked to external control and depressed mood than they are to the number of social roles. The study also demonstrates that in any effective alcohol prevention policy, societal actions that enable individuals to combine more social roles play a central role.

The impact of information on patient preferences in different delivery patterns: a contingent valuation study of prescription versus OTC drugs.

OBJECTIVES: Our analysis assessed the impact of information on patients' preferences in prescription versus over-the-counter (OTC) delivery systems. METHODS: A contingent valuation (CV) study was implemented, randomly assigning 534 lay people into the receipt of limited or extended information concerning new influenza drugs. In each information arm, people answered two questions: the first asked about willingness to pay (WTP) for the new prescription drug; the second asked about WTP for the same drug sold OTC. RESULTS: We show that WTP is higher for the OTC scenario and that the level of information plays a significant role in the evaluation of the OTC scenario, with more information being associated with an increase in the WTP. In contrast, the level of information provided has no impact on WTP for prescription medicine. Thus, for the kind of drug considered here (i.e. safe, not requiring medical supervision), a switch to OTC status can be expected to be all the more beneficial, as the patient is provided with more information concerning the capability of the drug. CONCLUSIONS: Our results shed light on one of the most challenging issues that health policy makers are currently faced with, namely the threat of a bird flu pandemic. Drug delivery is a critical component of pandemic influenza preparedness. Furthermore, the congruence of our results with the agency and demand theories provides an important test of the validity of using WTP based on CV methods.

In vivo assessment of use-dependent brain plasticity--beyond the "one trick pony" imaging strategy.

This article has been written as a comment to Dr Thomas and Dr Baker's article "Teaching an adult brain new tricks: A critical review of evidence for training-dependent structural plasticity in humans". We deliberately expand on the key question about the biological substrates underlying use-dependent brain plasticity rather than reiterating the authors' main points of criticism already addressed in more general way by previous publications in the field. The focus here is on the following main issues: i) controversial brain plasticity findings in voxel-based morphometry studies are partially due to the strong dependency of the widely used T1-weighted imaging protocol on varying magnetic resonance contrast contributions; ii) novel concepts in statistical analysis allow one to directly infer topological specificity of structural brain changes associated with plasticity. We conclude that iii) voxel-based quantification of relaxometry derived parameter maps could provide a new perspective on use-dependent plasticity by characterisation of brain tissue property changes beyond the estimation of volume and cortical thickness changes. In the relevant sections we respond to the concerns raised by Dr Thomas and Dr Baker from the perspective of the proposed data acquisition and analysis strategy.

Beyond the 'dyad': a qualitative re-evaluation of the changing clinical consultation.

OBJECTIVE: To identify characteristics of consultations that do not conform to the traditionally understood communication 'dyad', in order to highlight implications for medical education and develop a reflective 'toolkit' for use by medical practitioners and educators in the analysis of consultations. DESIGN: A series of interdisciplinary research workshops spanning 12 months explored the social impact of globalisation and computerisation on the clinical consultation, focusing specifically on contemporary challenges to the clinician-patient dyad. Researchers presented detailed case studies of consultations, taken from their recent research projects. Drawing on concepts from applied sociolinguistics, further analysis of selected case studies prompted the identification of key emergent themes. SETTING: University departments in the UK and Switzerland. PARTICIPANTS: Six researchers with backgrounds in medicine, applied linguistics, sociolinguistics and medical education. One workshop was also attended by PhD students conducting research on healthcare interactions. RESULTS: The contemporary consultation is characterised by a multiplicity of voices. Incorporation of additional voices in the consultation creates new forms of order (and disorder) in the interaction. The roles 'clinician' and 'patient' are blurred as they become increasingly distributed between different participants. These new consultation arrangements make new demands on clinicians, which lie beyond the scope of most educational programmes for clinical communication. CONCLUSIONS: The consultation is changing. Traditional consultation models that assume a 'dyadic' consultation do not adequately incorporate the realities of many contemporary consultations. A paradox emerges between the need to manage consultations in a 'super-diverse' multilingual society, while also attending to increasing requirements for standardised protocol-driven approaches to care prompted by computer use. The tension between standardisation and flexibility requires addressing in educational contexts. Drawing on concepts from applied sociolinguistics and the findings of these research observations, the authors offer a reflective 'toolkit' of questions to ask of the consultation in the context of enquiry-based learning.

New perspectives in the use of ink evidence in forensic science: Part I. Development of a quality assurance process for forensic ink analysis by HPTLC

The level of information provided by ink evidence to the criminal and civil justice system is limited. The limitations arise from the weakness of the interpretative framework currently used, as proposed in the ASTM 1422-05 and 1789-04 on ink analysis. It is proposed to use the likelihood ratio from the Bayes theorem to interpret ink evidence. Unfortunately, when considering the analytical practices, as defined in the ASTM standards on ink analysis, it appears that current ink analytical practices do not allow for the level of reproducibility and accuracy required by a probabilistic framework. Such framework relies on the evaluation of the statistics of the ink characteristics using an ink reference database and the objective measurement of similarities between ink samples. A complete research programme was designed to (a) develop a standard methodology for analysing ink samples in a more reproducible way, (b) comparing automatically and objectively ink samples and (c) evaluate the proposed methodology in a forensic context. This report focuses on the first of the three stages. A calibration process, based on a standard dye ladder, is proposed to improve the reproducibility of ink analysis by HPTLC, when these inks are analysed at different times and/or by different examiners. The impact of this process on the variability between the repetitive analyses of ink samples in various conditions is studied. The results show significant improvements in the reproducibility of ink analysis compared to traditional calibration methods.

Renal protection with calcium antagonists: the role of lercanidipine.

Abstract Background: Clinical research in the field of hypertension is now increasingly focusing on the potential effects of antihypertensive treatments that may go beyond the reduction of blood pressure (BP). In particular, renal protection appears as a desirable goal, especially considering that hypertension is associated with an increased risk of developing kidney damage, which may eventually lead to end-stage renal disease and a higher mortality. Dihydropyridine calcium channel blockers (CCBs) are widely used in the field of hypertension therapy but the different renal effects of the various CCBs have been poorly explored to date. Scope: This review will discuss available evidence on the renal effects of two calcium channel blockers: amlodipine and lercanidipine, on the basis of clinical data. Methods: MEDLINE and EMBASE were searched for inclusion of relevant studies. No limitations in time were considered. Results: Results from preclinical and clinical studies suggest that amlodipine is overall less effective in terms of renal protection when compared with other antihypertensive tested agents. Its beneficial effect in retarding the progression of renal disease is achievable only when combined with a blocker of the renin-angiotensin system. Conversely lercanidipine seems to provide renal protection in a similar way to ACE inhibitors, probably thanks to its mechanism of action which acts directly on the afferent and efferent renal arterioles. Conclusions: Treatment of hypertension with CCBs should take into consideration the special effects of each single agent at different levels; lercanidipine for example may play a useful role in the management not only of hypertension but also in renal protection of hypertensive patients.