Are multiple primary outcomes analysed appropriately in randomised controlled trials? A review

To review how multiple primary outcomes are currently considered in the analysis of randomised controlled trials. We briefly describe the methods available to safeguard the inferences and to raise awareness of the potential problems caused by multiple outcomes

Business intelligence and contribution of entrepreneurial information architecture

We are witnessing the need for a quick and intelligent reaction from organizations to the level and speed of change in business processes. The arising problems can be: from wrong lasting information; systems not fully used or explored; slow reaction to change; etc. This requires two main confluent action methods: people to synchronize their visions, ideas and strategies in the whole organization; and, in that context, select the information that strictly answers to the performance factors at the right moment. The proposed methodology turns to the potential of approach to the entrepreneurial architecture as well as to the potential of the information system in order to integrate the data and resources needed for that performance. The modeling of an information architecture of the company and its business helps in the identification of critical information, the one which is according to the mission, prospects and business success factors

Historical roots of Agile methods: where did “Agile thinking” come from?

The appearance of Agile methods has been the most noticeable change to software process thinking in the last fifteen years [16], but in fact many of the “Agile ideas” have been around since 70’s or even before. Many studies and reviews have been conducted about Agile methods which ascribe their emergence as a reaction against traditional methods. In this paper, we argue that although Agile methods are new as a whole, they have strong roots in the history of software engineering. In addition to the iterative and incremental approaches that have been in use since 1957 [21], people who criticised the traditional methods suggested alternative approaches which were actually Agile ideas such as the response to change, customer involvement, and working software over documentation. The authors of this paper believe that education about the history of Agile thinking will help to develop better understanding as well as promoting the use of Agile methods. We therefore present and discuss the reasons behind the development and introduction of Agile methods, as a reaction to traditional methods, as a result of people's experience, and in particular focusing on reusing ideas from histor

Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates

Trifluoroethylarenes are found in a variety of biologically active molecules, and strategies for accessing this substructure are important for developing therapeutic candidates and biological probes. Trifluoroethylarenes can be directly accessed via nucleophilic trifluoromethylation of benzylic electrophiles; however, current catalytic methods do not effectively transform electron-deficient substrates and heterocycles. To address this gap, we report a Cu-catalyzed decarboxylative trifluoromethylation of benzylic bromodifluoroacetates. To account for the tolerance of sensitive functional groups, we propose an inner-sphere mechanism of decarboxylation

Developing an algorithm to identify patients with intracerebral haemorrhage secondary to a macrovascular cause

Introduction: Determining the cause of spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is critical to guide treatment and prognosis. We investigated whether small vessel disease (SVD) in addition to clinical and other radiological findings on acute neuroimaging predicts a low risk of a macrovascular cause (e.g. an arterio-venous malformation, aneurysm or dural arteriovenous fistula). Patients and methods: We identified patients with acute spontaneous ICH who underwent acute non-contrast CT, CT angiography (CTA) and intra-arterial digital subtraction angiography (IADSA) at our institution from January 2010 to April 2014. Logistic regression including CTA result, SVD, age, pre-ICH hypertension and ICH location was used to derive a prediction model, validated using bootstrapping. Results: 173 patients (46% female, median age 49) of whom 78 had a macrovascular cause on IADSA were included. Predictors of a macrovascular cause were: abnormal CTA (OR 67.4; p < 0.001); absence of SVD (OR 5.0; p = 0.019); and absence of pre-ICH hypertension (OR 3.4; p = 0.05). In our internally derived prediction model, the combination of CTA, SVD and pre-ICH hypertension predicted the likelihood of an underlying macrovascular cause (optimism-adjusted ROC area 0.919). Patients with negative CTA, SVD and pre-ICH hypertension have a low likelihood of an underlying macrovascular cause (1.8%). Discussion and conclusion: A combination of CTA, SVD and pre-ICH hypertension predict the likelihood of finding a macrovascular cause in patients with acute spontaneous ICH, allowing informed decisions regarding the likely benefit and risk of IADSA

Epidermal Notch1 recruits RORγ+ group 3 innate lymphoid cells to orchestrate normal skin repair

Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ + ILC3s into wounded dermis; RORγ + ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ + ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data

Integration of DFDs into a UML - based model-driven engineering approach

The main aim of this article is to discuss how the functional and the object-oriented views can be inter-played to represent the various modeling perspectives of embedded systems.We discuss whether the object-oriented modeling paradigm, the predominant one to develop software at the present time, is also adequate for modeling embedded software and how it can be used with the functional paradigm.More specifically, we present how the main modeling tool of the traditional structured methods, data flow diagrams, can be integrated in an object-oriented development strategy based on the unified modeling language. The rationale behind the approach is that both views are important for modeling purposes in embedded systems environments, and thus a combined and integrated model is not only useful, but also fundamental for developing complex systems. The approach was integrated in amodel-driven engineering process, where tool support for the models used was provided. In addition, model transformations have been specified and implemented to automate the process.We exemplify the approach with an IPv6 router case study.FEDER -Fundação para a Ciência e a Tecnologia(HH-02-383