Spatial relational learning and memory abilities do not differ between men and women in a real-world, open-field environment

This study assesses gender differences in spatial and non-spatial relational learning and memory in adult humans behaving freely in a real-world, open-field environment. In Experiment 1, we tested the use of proximal landmarks as conditional cues allowing subjects to predict the location of rewards hidden in one of two sets of three distinct locations. Subjects were tested in two different conditions: (1) when local visual cues marked the potentially-rewarded locations, and (2) when no local visual cues marked the potentially-rewarded locations. We found that only 17 of 20 adults (8 males, 9 females) used the proximal landmarks to predict the locations of the rewards. Although females exhibited higher exploratory behavior at the beginning of testing, males and females discriminated the potentially-rewarded locations similarly when local visual cues were present. Interestingly, when the spatial and local information conflicted in predicting the reward locations, males considered both spatial and local information, whereas females ignored the spatial information. However, in the absence of local visual cues females discriminated the potentially-rewarded locations as well as males. In Experiment 2, subjects (9 males, 9 females) were tested with three asymmetrically-arranged rewarded locations, which were marked by local cues on alternate trials. Again, females discriminated the rewarded locations as well as males in the presence or absence of local cues. In sum, although particular aspects of task performance might differ between genders, we found no evidence that women have poorer allocentric spatial relational learning and memory abilities than men in a real-world, open-field environment.

The efficacy of a protective cream in a real-world apprentice hairdresser environment.

The object of this study was to compare the protective action of a new barrier cream (Excipial Protect, Spirig Pharma AG, Egerkingen, Switzerland) to its vehicle in the context of hand irritation of apprentice hairdressers caused by repeated shampooing and exposure to hair-care products. This was a double-blind cross-over comparing Excipial Protect (containing aluminium chlorohydrate 5% as active ingredient) against its vehicle alone. The efficacy of the creams was evaluated taking into account: (1) clinical scores by researchers, (2) biometric measurements, (3) subjective opinions of the subjects. An analysis of variance was performed considering order of application, degree of atopy, and reported number of shampoos. We observed very little difference in efficacy between the protective cream and its vehicle. The presence, however, of aluminium chlorhydrate in the protective cream was shown to have a positive effect against work-related irritation. The cosmetic qualities of the creams seemed, to the participants, to be as important as their real protective and hydrating properties, an important factor in compliance issues.

Duration of anticoagulation after venous thromboembolism in real world clinical practice.

INTRODUCTION: Venous thromboembolism (VTE) carries a considerable risk of recurrence and anticoagulants should be administered for a minimum of three months. Since little is known about real life management of VTE, we aimed to describe current practice in the secondary prevention of VTE. MATERIALS AND METHODS: Using the database of an international, prospective registry on patients treated for VTE, RIETE, information was collected on risk factors for VTE and bleeding, anticoagulant treatment, and clinical outcomes during follow up. Multivariate analysis using logistic regression was performed to identify predictors of treatment duration. RESULTS: Of 6944 patients with a first episode of VTE 41.1% had unprovoked VTE, 31.8% had transient risk factors, 27.1% had cancer. After the exclusion of patients who died during the first year of observation, the rate of patients treated for >12 months was 55.1%, 41.9%, and 43.2%, respectively (p<0.001). Pulmonary embolism at presentation, recurrence while on treatment, chronic heart failure and age >65 years were independently associated with treatment for >12 months. Body weight <75 kg, anemia, cancer, and the presence of transient risk factors were associated with treatment for 12 months or less. Major bleeding occurred more frequently than recurrent VTE in patients with VTE secondary to transient risk factors and cancer; fatal bleeding was more frequent than fatal recurrent PE in all subgroups. CONCLUSIONS: We observed heterogeneous duration of anticoagulant treatment for the secondary prevention of VTE. A substantial proportion of patients, in particular those with VTE secondary to transient risk factors, may be exposed to a possibly unnecessary risk of bleeding.

As the world turns: short-term human spatial memory in egocentric and allocentric coordinates

We aimed to determine whether human subjects' reliance on different sources of spatial information encoded in different frames of reference (i.e., egocentric versus allocentric) affects their performance, decision time and memory capacity in a short-term spatial memory task performed in the real world. Subjects were asked to play the Memory game (a.k.a. the Concentration game) without an opponent, in four different conditions that controlled for the subjects' reliance on egocentric and/or allocentric frames of reference for the elaboration of a spatial representation of the image locations enabling maximal efficiency. We report experimental data from young adult men and women, and describe a mathematical model to estimate human short-term spatial memory capacity. We found that short-term spatial memory capacity was greatest when an egocentric spatial frame of reference enabled subjects to encode and remember the image locations. However, when egocentric information was not reliable, short-term spatial memory capacity was greater and decision time shorter when an allocentric representation of the image locations with respect to distant objects in the surrounding environment was available, as compared to when only a spatial representation encoding the relationships between the individual images, independent of the surrounding environment, was available. Our findings thus further demonstrate that changes in viewpoint produced by the movement of images placed in front of a stationary subject is not equivalent to the movement of the subject around stationary images. We discuss possible limitations of classical neuropsychological and virtual reality experiments of spatial memory, which typically restrict the sensory information normally available to human subjects in the real world.

Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study.

BACKGROUND/AIMS: Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. METHODS: IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres. RESULTS: A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. CONCLUSION: The subset of IMPROVE data presented gives a present-day, real-life overview of the OMT landscape in Switzerland. It represents a valuable resource for policy makers, key opinion leaders and drug addiction researchers and will be a useful basis for improving the current Swiss OMT model.

Source wavelet estimation for waveform inversion of crosshole georadar data

AbstractFor a wide range of environmental, hydrological, and engineering applications there is a fast growing need for high-resolution imaging. In this context, waveform tomographic imaging of crosshole georadar data is a powerful method able to provide images of pertinent electrical properties in near-surface environments with unprecedented spatial resolution. In contrast, conventional ray-based tomographic methods, which consider only a very limited part of the recorded signal (first-arrival traveltimes and maximum first-cycle amplitudes), suffer from inherent limitations in resolution and may prove to be inadequate in complex environments. For a typical crosshole georadar survey the potential improvement in resolution when using waveform-based approaches instead of ray-based approaches is in the range of one order-of- magnitude. Moreover, the spatial resolution of waveform-based inversions is comparable to that of common logging methods. While in exploration seismology waveform tomographic imaging has become well established over the past two decades, it is comparably still underdeveloped in the georadar domain despite corresponding needs. Recently, different groups have presented finite-difference time-domain waveform inversion schemes for crosshole georadar data, which are adaptations and extensions of Tarantola's seminal nonlinear generalized least-squares approach developed for the seismic case. First applications of these new crosshole georadar waveform inversion schemes on synthetic and field data have shown promising results. However, there is little known about the limits and performance of such schemes in complex environments. To this end, the general motivation of my thesis is the evaluation of the robustness and limitations of waveform inversion algorithms for crosshole georadar data in order to apply such schemes to a wide range of real world problems.One crucial issue to making applicable and effective any waveform scheme to real-world crosshole georadar problems is the accurate estimation of the source wavelet, which is unknown in reality. Waveform inversion schemes for crosshole georadar data require forward simulations of the wavefield in order to iteratively solve the inverse problem. Therefore, accurate knowledge of the source wavelet is critically important for successful application of such schemes. Relatively small differences in the estimated source wavelet shape can lead to large differences in the resulting tomograms. In the first part of my thesis, I explore the viability and robustness of a relatively simple iterative deconvolution technique that incorporates the estimation of the source wavelet into the waveform inversion procedure rather than adding additional model parameters into the inversion problem. Extensive tests indicate that this source wavelet estimation technique is simple yet effective, and is able to provide remarkably accurate and robust estimates of the source wavelet in the presence of strong heterogeneity in both the dielectric permittivity and electrical conductivity as well as significant ambient noise in the recorded data. Furthermore, our tests also indicate that the approach is insensitive to the phase characteristics of the starting wavelet, which is not the case when directly incorporating the wavelet estimation into the inverse problem.Another critical issue with crosshole georadar waveform inversion schemes which clearly needs to be investigated is the consequence of the common assumption of frequency- independent electromagnetic constitutive parameters. This is crucial since in reality, these parameters are known to be frequency-dependent and complex and thus recorded georadar data may show significant dispersive behaviour. In particular, in the presence of water, there is a wide body of evidence showing that the dielectric permittivity can be significantly frequency dependent over the GPR frequency range, due to a variety of relaxation processes. The second part of my thesis is therefore dedicated to the evaluation of the reconstruction limits of a non-dispersive crosshole georadar waveform inversion scheme in the presence of varying degrees of dielectric dispersion. I show that the inversion algorithm, combined with the iterative deconvolution-based source wavelet estimation procedure that is partially able to account for the frequency-dependent effects through an "effective" wavelet, performs remarkably well in weakly to moderately dispersive environments and has the ability to provide adequate tomographic reconstructions.

Large-scale clustering through functional embedding

We present a new framework for large-scale data clustering. The main idea is to modify functional dimensionality reduction techniques to directly optimize over discrete labels using stochastic gradient descent. Compared to methods like spectral clustering our approach solves a single optimization problem, rather than an ad-hoc two-stage optimization approach, does not require a matrix inversion, can easily encode prior knowledge in the set of implementable functions, and does not have an ?out-of-sample? problem. Experimental results on both artificial and real-world datasets show the usefulness of our approach.

Quality control and conduct of genome-wide association meta-analyses.

Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.

Binding under Conflict Conditions: State-Space Analysis of Multivariate EEG Synchronization.

Real-world objects are often endowed with features that violate Gestalt principles. In our experiment, we examined the neural correlates of binding under conflict conditions in terms of the binding-by-synchronization hypothesis. We presented an ambiguous stimulus ("diamond illusion") to 12 observers. The display consisted of four oblique gratings drifting within circular apertures. Its interpretation fluctuates between bound ("diamond") and unbound (component gratings) percepts. To model a situation in which Gestalt-driven analysis contradicts the perceptually explicit bound interpretation, we modified the original diamond (OD) stimulus by speeding up one grating. Using OD and modified diamond (MD) stimuli, we managed to dissociate the neural correlates of Gestalt-related (OD vs. MD) and perception-related (bound vs. unbound) factors. Their interaction was expected to reveal the neural networks synchronized specifically in the conflict situation. The synchronization topography of EEG was analyzed with the multivariate S-estimator technique. We found that good Gestalt (OD vs. MD) was associated with a higher posterior synchronization in the beta-gamma band. The effect of perception manifested itself as reciprocal modulations over the posterior and anterior regions (theta/beta-gamma bands). Specifically, higher posterior and lower anterior synchronization supported the bound percept, and the opposite was true for the unbound percept. The interaction showed that binding under challenging perceptual conditions is sustained by enhanced parietal synchronization. We argue that this distributed pattern of synchronization relates to the processes of multistage integration ranging from early grouping operations in the visual areas to maintaining representations in the frontal networks of sensory memory.

The de facto independence of regulatory agencies and its consequences for policy making and regulatory outcomes

This dissertation focuses on the practice of regulatory governance, throughout the study of the functioning of formally independent regulatory agencies (IRAs), with special attention to their de facto independence. The research goals are grounded on a "neo-positivist" (or "reconstructed positivist") position (Hawkesworth 1992; Radaelli 2000b; Sabatier 2000). This perspective starts from the ontological assumption that even if subjective perceptions are constitutive elements of political phenomena, a real world exists beyond any social construction and can, however imperfectly, become the object of scientific inquiry. Epistemologically, it follows that hypothetical-deductive theories with explanatory aims can be tested by employing a proper methodology and set of analytical techniques. It is thus possible to make scientific inferences and general conclusions to a certain extent, according to a Bayesian conception of knowledge, in order to update the prior scientific beliefs in the truth of the related hypotheses (Howson 1998), while acknowledging the fact that the conditions of truth are at least partially subjective and historically determined (Foucault 1988; Kuhn 1970). At the same time, a sceptical position is adopted towards the supposed disjunction between facts and values and the possibility of discovering abstract universal laws in social science. It has been observed that the current version of capitalism corresponds to the golden age of regulation, and that since the 1980s no government activity in OECD countries has grown faster than regulatory functions (Jacobs 1999). Following an apparent paradox, the ongoing dynamics of liberalisation, privatisation, decartelisation, internationalisation, and regional integration hardly led to the crumbling of the state, but instead promoted a wave of regulatory growth in the face of new risks and new opportunities (Vogel 1996). Accordingly, a new order of regulatory capitalism is rising, implying a new division of labour between state and society and entailing the expansion and intensification of regulation (Levi-Faur 2005). The previous order, relying on public ownership and public intervention and/or on sectoral self-regulation by private actors, is being replaced by a more formalised, expert-based, open, and independently regulated model of governance. Independent regulation agencies (IRAs), that is, formally independent administrative agencies with regulatory powers that benefit from public authority delegated from political decision makers, represent the main institutional feature of regulatory governance (Gilardi 2008). IRAs constitute a relatively new technology of regulation in western Europe, at least for certain domains, but they are increasingly widespread across countries and sectors. For instance, independent regulators have been set up for regulating very diverse issues, such as general competition, banking and finance, telecommunications, civil aviation, railway services, food safety, the pharmaceutical industry, electricity, environmental protection, and personal data privacy. Two attributes of IRAs deserve a special mention. On the one hand, they are formally separated from democratic institutions and elected politicians, thus raising normative and empirical concerns about their accountability and legitimacy. On the other hand, some hard questions about their role as political actors are still unaddressed, though, together with regulatory competencies, IRAs often accumulate executive, (quasi-)legislative, and adjudicatory functions, as well as about their performance.

Development of allocentric spatial memory abilities in children from 18 months to 5 years of age.

Episodic memories for autobiographical events that happen in unique spatiotemporal contexts are central to defining who we are. Yet, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. Here, we studied the development of allocentric spatial memory, a fundamental component of episodic memory, in two versions of a real-world memory task requiring 18 month- to 5-year-old children to search for rewards hidden beneath cups distributed in an open-field arena. Whereas children 25-42-months-old were not capable of discriminating three reward locations among 18 possible locations in absence of local cues marking these locations, children older than 43 months found the reward locations reliably. These results support previous findings suggesting that allocentric spatial memory, if present, is only rudimentary in children under 3.5 years of age. However, when tested with only one reward location among four possible locations, children 25-39-months-old found the reward reliably in absence of local cues, whereas 18-23-month-olds did not. Our findings thus show that the ability to form a basic allocentric representation of the environment is present by 2 years of age, and its emergence coincides temporally with the offset of infantile amnesia. However, the ability of children to distinguish and remember closely related spatial locations improves from 2 to 3.5 years of age, a developmental period marked by persistent deficits in long-term episodic memory known as childhood amnesia. These findings support the hypothesis that the differential maturation of distinct hippocampal circuits contributes to the emergence of specific memory processes during early childhood.

A system to test the toxicity of brake wear particles

Fine particulate matter from traffic increases mortality and morbidity. An important source of traffic particles is brake wear. American studies reported cars to emit break wear particles at a rate of about 11mg/km to 20mg/km of driven distance. A German study estimated that break wear contributes about 12.5% to 21% of the total traffic particle emissions. The goal of this study was to build a system that allows the study of brake wear particle emissions during different braking behaviours of different car and brake types. The particles should be characterize in terms of size, number, metal, and elemental and organic carbon composition. In addition, the influence of different deceleration schemes on the particle composition and size distribution should be studied. Finally, this system should allow exposing human cell cultures to these particles. An exposure-box (0.25 cubic-m volume) was built that can be mounted around a car's braking system. This allows exposing cells to fresh brake wear particles. Concentrations of particle numbers, mass and surface, metals, and carbon compounds were quantified. Tests were conducted with A549 lung epithelial cells. Five different cars and two typical braking behaviours (full stop and normal deceleration) were tested. Particle number and size distribution was analysed for the first six minutes. In this time, two braking events occurred. Full stop produced significantly higher particle concentrations than normal deceleration (average of 23'000 vs. 10'400 #/cm3, p= 0.016). The particle number distribution was bi-modal with one peak at 60 to 100 nm (depending on the tested car and braking behaviour) and a second peak at 200 to 400 nm. Metal concentrations varied depending on the tested car type. Iron (range of 163 to 15'600 μg/m3) and Manganese (range of 0.9 to 135 μg/m3) were present in all samples, while Copper was absent in some samples (<6 to 1220 μg/m3). The overall "fleet" metal ratio was Fe:Cu:Mn = 128:14:1. Temperature and humidity varied little. A549-cells were successfully exposed in the various experimental settings and retained their viability. Culture supernatant was stored and cell culture samples were fixated to test for inflammatory response. Analysis of these samples is ongoing. The established system allowed testing brake wear particle emissions from real-world cars. The large variability of chemical composition and emitted amounts of brake wear particles between car models seems to be related to differences between brake pad compositions of different producers. Initial results suggest that the conditions inside the exposure box allow exposing human lung epithelial cells to freshly produced brake wear particles.

Selective integration of auditory-visual looming cues by humans.

An object's motion relative to an observer can confer ethologically meaningful information. Approaching or looming stimuli can signal threats/collisions to be avoided or prey to be confronted, whereas receding stimuli can signal successful escape or failed pursuit. Using movement detection and subjective ratings, we investigated the multisensory integration of looming and receding auditory and visual information by humans. While prior research has demonstrated a perceptual bias for unisensory and more recently multisensory looming stimuli, none has investigated whether there is integration of looming signals between modalities. Our findings reveal selective integration of multisensory looming stimuli. Performance was significantly enhanced for looming stimuli over all other multisensory conditions. Contrasts with static multisensory conditions indicate that only multisensory looming stimuli resulted in facilitation beyond that induced by the sheer presence of auditory-visual stimuli. Controlling for variation in physical energy replicated the advantage for multisensory looming stimuli. Finally, only looming stimuli exhibited a negative linear relationship between enhancement indices for detection speed and for subjective ratings. Maximal detection speed was attained when motion perception was already robust under unisensory conditions. The preferential integration of multisensory looming stimuli highlights that complex ethologically salient stimuli likely require synergistic cooperation between existing principles of multisensory integration. A new conceptualization of the neurophysiologic mechanisms mediating real-world multisensory perceptions and action is therefore supported.