Archaeological silence and ecorefuges: arid events in the Puna of Atacama during the Middle Holocene

This paper briefly summarizes presearch concerning the mid-Holocene in the western slope of the puna de Atacama (20–25°S). Proxy data and dates from palynological, limnological, geomorphological archives were compared with data recovered from the archaeological sites in high altitude basins, intermediate ravines and piemontane paleowetlands. Due to exceptionally favorable conditions, numerous Early Holocene archaeological sites were found. In contrast, the lack of occupations in previously populated areas suggests a decline in human activity during the arid mid-Holocene. In this context, two key concepts are introduced: ecorefuge or ecological refuge, and archaeological silence (silencio arqueológico). The first refers to the particular favorable locations occupied by human groups during the mid-Holocene. The second provides a better understanding about the impact of the arid interval during this period on human adaptations in the most barren territories of the New World.

Law and science: risk assessment and risk management in the WTO agreement on the application of sanitary and phytosanitary measures

Assessing and managing risks relating to the consumption of food stuffs for humans and to the environment has been one of the most complex legal issues in WTO law, ever since the Agreement on Sanitary and Phytosanitary Measures was adopted at the end of the Uruguay Round and entered into force in 1995. The problem was expounded in a number of cases. Panels and the Appellate Body adopted different philosophies in interpreting the agreement and the basic concept of risk assessment as defined in Annex A para. 4 of the Agreement. Risk assessment entails fundamental question on law and science. Different interpretations reflect different underlying perceptions of science and its relationship to the law. The present thesis supported by the Swiss National Research Foundation undertakes an in-depth analysis of these underlying perceptions. The author expounds the essence and differences of positivism and relativism in philosophy and natural sciences. He clarifies the relationship of fundamental concepts such as risk, hazards and probability. This investigation is a remarkable effort on the part of lawyer keen to learn more about the fundamentals based upon which the law – often unconsciously – is operated by the legal profession and the trade community. Based upon these insights, he turns to a critical assessment of jurisprudence both of panels and the Appellate Body. Extensively referring and discussing the literature, he deconstructs findings and decisions in light of implied and assumed underlying philosophies and perceptions as to the relationship of law and science, in particular in the field of food standards. Finding that both positivism and relativism does not provide adequate answers, the author turns critical rationalism and applies the methodologies of falsification developed by Karl R. Popper. Critical rationalism allows combining discourse in science and law and helps preparing the ground for a new approach to risk assessment and risk management. Linking the problem to the doctrine of multilevel governance the author develops a theory allocating risk assessment to international for a while leaving the matter of risk management to national and democratically accountable government. While the author throughout the thesis questions the possibility of separating risk assessment and risk management, the thesis offers new avenues which may assist in structuring a complex and difficult problem

Polymorphisms in MIR27A Associated with Early-Onset Toxicity in Fluoropyrimidine-Based Chemotherapy

PURPOSE The microRNA miR-27a was recently shown to directly regulate dihydropyrimidine dehydrogenase (DPD), the key enzyme in fluoropyrimidine catabolism. A common polymorphism (rs895819A>G) in the miR-27a genomic region (MIR27A) was associated with reduced DPD activity in healthy volunteers, but the clinical relevance of this effect is still unknown. Here, we assessed the association of MIR27A germline variants with early-onset fluoropyrimidine toxicity. EXPERIMENTAL DESIGN MIR27A was sequenced in 514 patients with cancer receiving fluoropyrimidine-based chemotherapy. Associations of MIR27A polymorphisms with early-onset (cycles 1-2) fluoropyrimidine toxicity were assessed in the context of known risk variants in the DPD gene (DPYD) and additional covariates associated with toxicity. RESULTS The association of rs895819A>G with early-onset fluoropyrimidine toxicity was strongly dependent on DPYD risk variant carrier status (Pinteraction = 0.0025). In patients carrying DPYD risk variants, rs895819G was associated with a strongly increased toxicity risk [OR, 7.6; 95% confidence interval (CI), 1.7-34.7; P = 0.0085]. Overall, 71% (12/17) of patients who carried both rs895819G and a DPYD risk variant experienced severe toxicity. In patients without DPYD risk variants, rs895819G was associated with a modest decrease in toxicity risk (OR, 0.62; 95% CI, 0.43-0.9; P = 0.012). CONCLUSIONS These results indicate that miR-27a and rs895819A>G may be clinically relevant for further toxicity risk stratification in carriers of DPYD risk variants. Our data suggest that direct suppression of DPD by miR-27a is primarily relevant in the context of fluoropyrimidine toxicity in patients with reduced DPD activity. However, miR-27a regulation of additional targets may outweigh its effect on DPD in patients without DPYD risk variants.

Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning

Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes’ theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment.

Beyond belief : Strategic taboos and organizational identity in strategic agenda setting

A comprehensive strategic agenda matters for fundamental strategic change. Our study seeks to explore and theorize how organizational identity beliefs influence the judgment of strategic actors when setting an organization's strategic agenda. We offer the notion of "strategic taboo" as those strategic options initially disqualified and deemed inconsistent with the organizational identity beliefs of strategic actors. Our study is concerned with how strategic actors confront strategic taboos in the process of setting an organization's strategic agenda. Based on a revelatory inductive case study, we find that strategic actors engage in assessing the concordance of the strategic taboos with organizational identity beliefs and, more specifically, that they focus on key identity elements (philosophy; priorities; practices) when doing so. We develop a typology of three reinterpretation practices that are each concerned with a key identity element. While contextualizing assesses the potential concordance of a strategic taboo with an organization's overall philosophy and purpose, instrumentalizing assesses such concordance with respect to what actors deem an organization's priorities to be. Finally, normalizing explores concordance with respect to compatibility and fit with the organization's practices. We suggest that assessing concordance of a strategic taboo with identity elements consists in reinterpreting collective identity beliefs in ways that make them consistent with what organizational actors deem the right course of action. This article discusses the implications for theory and research on strategic agenda setting, strategic change, a practice-based perspective on strategy, and on organizational identity.

Anticipating intended users - Prospective sensemaking in technology development

How do developers and designers of a new technology make sense of intended users? The critical groundwork for user-centred technology development begins not by involving actual users' exposure to the technological artefact but much earlier, with designers' and developers' vision of future users. Thus, anticipating intended users is critical to technology uptake. We conceptualise the anticipation of intended users as a form of prospective sensemaking in technology development. Employing a narrative analytical approach and drawing on four key communities in the development of Grid computing, we reconstruct how each community anticipated the intended Grid user. Based on our findings, we conceptualise user anticipation in Terms of two key dimensions, namely the intended possibility to inscribe user needs into the technological artefact as well as the intended scope of the application domain. In turn, these dimensions allow us to develop an initial typology of intended user concepts that in turn might provide a key building block towards a generic typology of intended users.

On the Edge of the Primeval Forest. Accounts and reflections of a medical Doctor in French Equatorial Africa

Reading for 4th-year students