Recent misconceptions about the "database search problem": a probabilistic analysis using Bayesian networks

This paper analyses and discusses arguments that emerge from a recent discussion about the proper assessment of the evidential value of correspondences observed between the characteristics of a crime stain and those of a sample from a suspect when (i) this latter individual is found as a result of a database search and (ii) remaining database members are excluded as potential sources (because of different analytical characteristics). Using a graphical probability approach (i.e., Bayesian networks), the paper here intends to clarify that there is no need to (i) introduce a correction factor equal to the size of the searched database (i.e., to reduce a likelihood ratio), nor to (ii) adopt a propositional level not directly related to the suspect matching the crime stain (i.e., a proposition of the kind 'some person in (outside) the database is the source of the crime stain' rather than 'the suspect (some other person) is the source of the crime stain'). The present research thus confirms existing literature on the topic that has repeatedly demonstrated that the latter two requirements (i) and (ii) should not be a cause of concern.

Hyperpolarized lithium-6 as a sensor of nanomolar contrast agents.

Lithium is widely used in psychotherapy. The (6)Li isotope has a long intrinsic longitudinal relaxation time T(1) on the order of minutes, making it an ideal candidate for hyperpolarization experiments. In the present study we demonstrated that lithium-6 can be readily hyperpolarized within 30 min, while retaining a long polarization decay time on the order of a minute. We used the intrinsically long relaxation time for the detection of 500 nM contrast agent in vitro. Hyperpolarized lithium-6 was administered to the rat and its signal retained a decay time on the order of 70 sec in vivo. Localization experiments imply that the lithium signal originated from within the brain and that it was detectable up to 5 min after administration. We conclude that the detection of submicromolar contrast agents using hyperpolarized NMR nuclei such as (6)Li may provide a novel avenue for molecular imaging.

Taking "Galton's problem" Seriously : Towards a Theory of Policy Diffusion

This article builds on the recent policy diffusion literature and attempts to overcome one of its major problems, namely the lack of a coherent theoretical framework. The literature defines policy diffusion as a process where policy choices are interdependent, and identifies several diffusion mechanisms that specify the link between the policy choices of the various actors. As these mechanisms are grounded in different theories, theoretical accounts of diffusion currently have little internal coherence. In this article we put forward an expected-utility model of policy change that is able to subsume all the diffusion mechanisms. We argue that the expected utility of a policy depends on both its effectiveness and the payoffs it yields, and we show that the various diffusion mechanisms operate by altering these two parameters. Each mechanism affects one of the two parameters, and does so in distinct ways. To account for aggregate patterns of diffusion, we embed our model in a simple threshold model of diffusion. Given the high complexity of the process that results, strong analytical conclusions on aggregate patterns cannot be drawn without more extensive analysis which is beyond the scope of this article. However, preliminary considerations indicate that a wide range of diffusion processes may exist and that convergence is only one possible outcome.

A new type of internal hernia after laparoscopic Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGBP) is currently the most common bariatric procedure. One of its late complications is the development of internal hernia, which can lead to acute intestinal obstruction or recurrent colicky abdominal pain. The aim of this paper is to present a new, unusual, and so far not reported type of internal hernia. A common computerized database is maintained for all patients undergoing bariatric surgery in our departments. The charts of patients with the diagnosis of internal hernia were reviewed. Three patients were identified who developed acute intestinal obstruction due to an internal hernia located between the jejunojejunostomy and the end of the biliopancreatic limb, directly between two jejunal limbs with no mesentery involved. Another seven patients with intermittent colicky abdominal pain, re-explored for the suspicion of internal hernia, were found to also have an open window of the same location apart from a hernia at one of the typical hernia sites. Since this gap is systematically closed during RYGBP, no other patient has been observed with this problem. Even very small defects can lead to the development of internal hernias after RYGBP. Patients with suggestive symptoms must be explored. Closure of the jejunojejunal defect with nonabsorbable sutures prevents the development of an internal hernia between the jejunal loops at the jejunojejunostomy.

Do Agglomeration Economies Reduce the Sensitivity of Firm Location to Tax Differentials?

Recent theoretical work in economic geography has shown that agglomeration forces can mitigate 'race-to-the-bottom' tax competition, by partly or fully offsetting firms' sensitivity to tax differentials. We test this proposition using data on firm births across Swiss municipalities. We find that corporate taxes deter firm births less in more spatially concentrated sectors. Firms in sectors with an agglomeration intensity in the top quintile are less than half as responsive to differences in corporate tax burdens as firms in sectors with an agglomeration intensity in the bottom quintile. Hence, agglomeration economies do appear to attenuate the impact of tax differentials on firms' location choices.

Modular support for developing mobile ad hoc applications

Abstract This PhD thesis addresses the issue of alleviating the burden of developing ad hoc applications. Such applications have the particularity of running on mobile devices, communicating in a peer-to-peer manner and implement some proximity-based semantics. A typical example of such application can be a radar application where users see their avatar as well as the avatars of their friends on a map on their mobile phone. Such application become increasingly popular with the advent of the latest generation of mobile smart phones with their impressive computational power, their peer-to-peer communication capabilities and their location detection technology. Unfortunately, the existing programming support for such applications is limited, hence the need to address this issue in order to alleviate their development burden. This thesis specifically tackles this problem by providing several tools for application development support. First, it provides the location-based publish/subscribe service (LPSS), a communication abstraction, which elegantly captures recurrent communication issues and thus allows to dramatically reduce the code complexity. LPSS is implemented in a modular manner in order to be able to target two different network architectures. One pragmatic implementation is aimed at mainstream infrastructure-based mobile networks, where mobile devices can communicate through fixed antennas. The other fully decentralized implementation targets emerging mobile ad hoc networks (MANETs), where no fixed infrastructure is available and communication can only occur in a peer-to-peer fashion. For each of these architectures, various implementation strategies tailored for different application scenarios that can be parametrized at deployment time. Second, this thesis provides two location-based message diffusion protocols, namely 6Shot broadcast and 6Shot multicast, specifically aimed at MANETs and fine tuned to be used as building blocks for LPSS. Finally this thesis proposes Phomo, a phone motion testing tool that allows to test proximity semantics of ad hoc applications without having to move around with mobile devices. These different developing support tools have been packaged in a coherent middleware framework called Pervaho.

Accurate memory for object location by individuals with intellectual disability: Absolute spatial tagging instead of configural processing?

Using head-mounted eye tracker material, we assessed spatial recognition abilities (e.g., reaction to object permutation, removal or replacement with a new object) in participants with intellectual disabilities. The "Intellectual Disabilities (ID)" group (n=40) obtained a score totalling a 93.7% success rate, whereas the "Normal Control" group (n=40) scored 55.6% and took longer to fix their attention on the displaced object. The participants with an intellectual disability thus had a more accurate perception of spatial changes than controls. Interestingly, the ID participants were more reactive to object displacement than to removal of the object. In the specific test of novelty detection, however, the scores were similar, the two groups approaching 100% detection. Analysis of the strategies expressed by the ID group revealed that they engaged in more systematic object checking and were more sensitive than the control group to changes in the structure of the environment. Indeed, during the familiarisation phase, the "ID" group explored the collection of objects more slowly, and fixed their gaze for a longer time upon a significantly lower number of fixation points during visual sweeping.

An Adeno-Associated Virus-Based Intracellular Sensor of Pathological Nuclear Factor-κB Activation for Disease-Inducible Gene Transfer.

Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.

Alcohol consumption in late adolescence and early adulthood - where is the problem?

Risky single-occasion drinking (RSOD) is more common in late adolescence and early adulthood (approximately between the ages of 16 and 30) than in any other period in life. This is also the age when young people in Switzerland and many other European countries are legally allowed to buy and drink alcohol, but they usually do not yet have adult responsibilities. This paper reviews evidence from the international literature and provides examples of studies conducted in Switzerland demonstrating that (a) RSOD is by far most prevalent on Saturday evenings followed by Friday evenings, usually because young people go out and do not have any work or study responsibilities the next day; (b) RSOD results from drinking in private before going out ("predrinking") and accelerating the pace of drinking (i.e. increasing the number of drinks consumed per hour); (c) RSOD is often not accidental but purposeful,. to seek excitement, to have fun and to feel the effects of alcohol; (d) RSOD occurs predominantly outside the home, mostly in bars, pubs, discos or at special events and festivals; (e) RSOD often results in intended and unintended injuries and other acute consequences, which are leading risk factors for mortality and morbidity in this age group. Effective prevention strategies should include attempts to reduce opportunities to engage in heavy drinking as well as strategies to reduce its harmful consequences.