Bioluminescent sensor proteins for point-of-care therapeutic drug monitoring.

For many drugs, finding the balance between efficacy and toxicity requires monitoring their concentrations in the patient's blood. Quantifying drug levels at the bedside or at home would have advantages in terms of therapeutic outcome and convenience, but current techniques require the setting of a diagnostic laboratory. We have developed semisynthetic bioluminescent sensors that permit precise measurements of drug concentrations in patient samples by spotting minimal volumes on paper and recording the signal using a simple point-and-shoot camera. Our sensors have a modular design consisting of a protein-based and a synthetic part and can be engineered to selectively recognize a wide range of drugs, including immunosuppressants, antiepileptics, anticancer agents and antiarrhythmics. This low-cost point-of-care method could make therapies safer, increase the convenience of doctors and patients and make therapeutic drug monitoring available in regions with poor infrastructure.

Addressing the net balances problem as a prerequisite for EU budget reform: a proposal

Conflict among member states regarding the distribution of net financial burdens has been allowed to contaminate the entire design of the EU budget with very negative consequences in terms of equity, efficiency and transparency. To get around this problem and pave the way for a substantive budget reform, we propose to decouple distributional negotiations from the rest of the budget process by linking member state net balances in a rigid manner to relative prosperity. This would be achieved through the introduction of a system of compensating horizontal transfers that would take to its logical conclusion the Commission's proposal for a generalized compensation mechanism. We discuss the impact of the proposed scheme on member states? incentives and illustrate its financial implications using revenue and expenditure projections for 2013 that are based on the current Financial Perspectives and Own Resources Decision.

Orbit decidability and the conjugacy problem for some extensions of groups

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Empirical studies in industrial location: an assessment of their methods and results

This paper surveys recent evidence on the determinants of (national and/or foreign) industrial location. We find that the basic analytical framework has remained essentially unaltered since the early contributions of the early 1980's while, in contrast, there have been significant advances in the quality of the data and, to a lesser extent, the econometric modelling. We also identify certain determinants (neoclassical and institutional factors) that tend to provide largely consistent results across the reviewed studies. In light of this evidence, we finally suggest future lines of research.

The generic Hanna Neumann conjecture and post correspondence problem

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Structure du temps de travail des infirmières de santé publique: effets de l'âge des patients, de la nature des prestations fournies et du lieu du contact. [Structure of work times of public health nurses: effect of the age of patients, nature of care given and location of contact].

In the framework of health services research sponsored by the Swiss National Science Foundation, a research was undertaken of the activity of the large majority of the public health nurses working in the Swiss cantons of Vaud and Fribourg (total population 700,000). During one week, 130 nurses gathered, with a specially devised instrument, data on 4165 patient visits. Studying the duration of the contacts, one has distinguished contact duration per se (DC), duration of the travel time preceding the contact (DD), and total duration in relation with the contact (DTC-addition of the first two). It was noted that the three durations increased significantly with patient age (as regard travel time, this is explained by the higher proportion of home visits in higher age groups, as compared with visits at a health center). Examined according to location of the visit, contact duration per se (without travel) is higher for visits at home and in nursing homes than for those taking place at a health center. Looked at in respect to the care given (technical care, or basic nursing care, or both simultaneously), our data show that the provision of basic nursing care (alone or with technical care) doubles contact duration (from 20 to 42-45'). The analyses according to patient age shows that, at an advanced age (beyond 80 years particularly), there is an important increase of the visits where both types of care are given. However, contact duration per se shows a significant raise with age only for the group "technical care only"; it can be demonstrated that this is due to the fact that older patients require more complex technical acts (e.g., bladder care, as compared with simpler acts such as injection). A model of the relationships between patient age and contact duration is proposed: it is because of the increase in the proportions of home visits, of visits including basic nursing care, and of more complex technical acts that older persons require more of the working time of public health nurses.

Tax differentials and agglomeration economies in intraregional firm location

This paper analyses empirically how differences in local taxes affect the intraregional location of new manufacturing plants. These effects are examined within the random profit maximization framework while accounting for the presence of different types of agglomeration economies (localization/ urbanization/ Jacobs’ economies) at the municipal level. We look at the location decision of more than 10,000 establishments locating between 1996 and 2003 across more than 400 municipalities in Catalonia, a Spanish region. It is necessary to restrict the choice set to the local labor market and, above all, to control for agglomeration economies so as to identify the effects of taxes on the location of new establishments.

Estudio de sincronización cooperativa en redes de sensores

En este informe se estudia cómo es posible utilizar redes de sensores inalámbricos (WSN), para la localización de determinados eventos. Se hace un estudio previo de cómo una red de sensores puede llegar a estar sincronizada de una manera cooperativa, interactuando todos los sensores de la red entre sí. Primero se realiza el estudio para la sincronización de dos sensores con frecuencias diferentes, viéndose los parámetros que intervienen para que esta sincronización se realice con éxito, y también los efectos que en ella se produce al añadirle ruido. Seguidamente, se realiza el estudio para la sincronización de redes de N sensores, de manera que interactúen entre ellos de forma cooperativa. Se observan las características de la sincronización cuando todos los sensores llegan a consenso y, después, se busca la forma para que el consenso tienda hacia un valor determinado por mutuo acuerdo de los sensores. Finalmente, a partir de las características obtenidas en el consenso de N sensores, se realiza una aplicación práctica para la localización de eventos por medio del consenso de estas redes de sensores inalámbricos.

Market Familiarity and the Location of South and North MNEs

We use a systematic empirical analysis of the determinants of South-South (SS) and North-South (NS) foreign direct investment (FDI) as a canvas to explore how multinational enterprises’ (MNEs) location decisions are shaped by better acquaintance with a foreign market resulting from bilateral ties, experience of international expansion, and knowledge of how to deal with poor governance. We find that these various aspects of market familiarity, which can interact together, are important to explain and differentiate the location behaviours of South MNEs (S-MNEs) and North MNEs (N-MNEs) in developing countries.

Employment Protection, Flexibility and Firms’ Strategic Location Decisions under Uncertainty

We construct a model in which oligopolistic firms decide between locating in a country where employment protection implies costly output adjustments and in one without employment protection. Using a two-period three-stage game with uncertainty, we demonstrate that location is influenced by both flexibility and strategic concerns. The strategic effects under Cournot work towards domestic anchorage in the country with employment protection while those under Bertrand do not. Strategic agglomeration can occur in the inflexible country under Cournot and even under Bertrand, provided uncertainty and foreign direct investment costs are low.

The simultaneous conjugacy problem in groups of piecewise linear functions

Guba and Sapir asked, in their joint paper [8], if the simultaneous conjugacy problem was solvable in Diagram Groups or, at least, for Thompson's group F. We give an elementary proof for the solution of the latter question. This relies purely on the description of F as the group of piecewise linear orientation-preserving homeomorphisms of the unit. The techniques we develop allow us also to solve the ordinary conjugacy problem as well, and we can compute roots and centralizers. Moreover, these techniques can be generalized to solve the same questions in larger groups of piecewise-linear homeomorphisms.

Accuracy of a new transmittance-reflectance pulse oximetry sensor in critically ill neonates.

OBJECTIVE: To test the accuracy of a new pulse oximeter sensor based on transmittance and reflectance. This sensor makes transillumination of tissue unnecessary and allows measurements on the hand, forearm, foot, and lower limb. DESIGN: Prospective, open, nonrandomized criterion standard study. SETTING: Neonatal intensive care unit, tertiary care center. PATIENTS: Sequential sample of 54 critically ill neonates (gestational age 27 to 42 wks; postnatal age 1 to 28 days) with arterial catheters in place. MEASUREMENTS AND MAIN RESULTS: A total of 99 comparisons between pulse oximetry and arterial saturation were obtained. Comparison of femoral or umbilical arterial blood with transcutaneous measurements on the lower limb (n = 66) demonstrated an excellent correlation (r2 = .96). The mean difference was +1.44% +/- 3.51 (SD) % (range -11% to +8%). Comparison of the transcutaneous values with the radial artery saturation from the corresponding upper limb (n = 33) revealed a correlation coefficient of 0.94 with a mean error of +0.66% +/- 3.34% (range -6% to +7%). The mean difference between noninvasive and invasive measurements was least with the test sensor on the hand, intermediate on the calf and arm, and greatest on the foot. The mean error and its standard deviation were slightly larger for arterial saturation values < 90% than for values > or = 90%. CONCLUSION: Accurate pulse oximetry saturation can be acquired from the hand, forearm, foot, and calf of critically ill newborns using this new sensor.

An Empirical Examination of the R&D Boundaries of the Firm - A Problem-Solving Perspective

We consider, both theoretically and empirically, how different organization modes are aligned to govern the efficient solving of technological problems. The data set is a sample from the Chinese consumer electronics industry. Following mainly the problem solving perspective (PSP) within the knowledge based view (KBV), we develop and test several PSP and KBV hypotheses, in conjunction with competing transaction cost economics (TCE) alternatives, in an examination of the determinants of the R&D organization mode. The results show that a firm’s existing knowledge base is the single most important explanatory variable. Problem complexity and decomposability are also found to be important, consistent with the theoretical predictions of the PSP, but it is suggested that these two dimensions need to be treated as separate variables. TCE hypotheses also receive some support, but the estimation results seem more supportive of the PSP and the KBV than the TCE.

Symmetry for a Dirichlet-Neumann problem arising in water waves

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