Tackling self-selection into treatment and self-selection into the sample biases in VAA research

Self‐selection into treatment and self‐selection into the sample are major concerns of VAA research and need to be controlled for if the aim is to deduce causal effects from VAA use in observational data. This paper focuses on the methodological aspects of VAA research and outlines omnipresent endogeneity issues, partly imposed through unobserved factors that affect both whether individuals chose to use VAAs and their electoral behavior. We promote using Heckman selection models and apply various versions of the model to data from the Swiss electorate and smartvote users in order to see to what extent selection biases interfere with the estimated effects of interest.

Substantial deletion overlap among divergent Arabidopsis genomes revealed by intersection of short reads and tiling arrays.

ABSTRACT: Identification of small polymorphisms from next generation sequencing short read data is relatively easy, but detection of larger deletions is less straightforward. Here, we analyzed four divergent Arabidopsis accessions and found that intersection of absent short read coverage with weak tiling array hybridization signal reliably flags deletions. Interestingly, individual deletions were frequently observed in two or more of the accessions examined, suggesting that variation in gene content partly reflects a common history of deletion events.

A gating mutation in the internal pore of ASIC1a.

Using a substituted cysteine accessibility scan, we have investigated the structures that form the internal pore of the acid-sensing ion channel 1a. We have identified the amino acid residues Ala-22, Ile-33, and Phe-34 in the amino terminus and Arg-43 in the first transmembrane helix, which when mutated into cysteine, were modified by intracellular application of MTSET, resulting in channel inhibition. The inhibition of the R43C mutant by internal MTSET requires opening of the channel. In addition, binding of Cd2+ ions to R43C slows the channel inactivation. This indicates that the first transmembrane helix undergoes conformational changes during channel inactivation. The effect of Cd2+ on R43C can be obtained with Cd2+ applied at either the extracellular or the intracellular side, indicating that R43C is located in the channel pore. The block of the A22C, I33C, and F34C mutants by MTSET suggests that these residues in the amino terminus of the channel also participate to the internal pore.

Temporo-Parietal Junction encodes the Embodied Self: Neuro-Robotics, fMRI, and Lesion mapping.

Introduction: Neuroimaging of the self focused on high-level mechanisms such as language, memory or imagery of the self. Recent evidence suggests that low-level mechanisms of multisensory and sensorimotor integration may play a fundamental role in encoding self-location and the first-person perspective (Blanke and Metzinger, 2009). Neurological patients with out-of body experiences (OBE) suffer from abnormal self-location and the first-person perspective due to a damage in the temporo-parietal junction (Blanke et al., 2004). Although self-location and the first-person perspective can be studied experimentally (Lenggenhager et al., 2009), the neural underpinnings of self-location have yet to be investigated. To investigate the brain network involved in self-location and first-person perspective we used visuo-tactile multisensory conflict, magnetic resonance (MR)-compatible robotics, and fMRI in study 1, and lesion analysis in a sample of 9 patients with OBE due to focal brain damage in study 2. Methods: Twenty-two participants saw a video showing either a person's back or an empty room being stroked (visual stimuli) while the MR-compatible robotic device stroked their back (tactile stimulation). Direction and speed of the seen stroking could either correspond (synchronous) or not (asynchronous) to those of the seen stroking. Each run comprised the four conditions according to a 2x2 factorial design with Object (Body, No-Body) and Synchrony (Synchronous, Asynchronous) as main factors. Self-location was estimated using the mental ball dropping (MBD; Lenggenhager et al., 2009). After the fMRI session participants completed a 6-item adapted from the original questionnaire created by Botvinick and Cohen (1998) and based on questions and data obtained by Lenggenhager et al. (2007, 2009). They were also asked to complete a questionnaire to disclose the perspective they adopted during the illusion. Response times (RTs) for the MBD and fMRI data were analyzed with a 3-way mixed model ANOVA with the in-between factor Perspective (up, down) and the two with-in factors Object (body, no-body) and Stroking (synchronous, asynchronous). Quantitative lesion analysis was performed using MRIcron (Rorden et al., 2007). We compared the distributions of brain lesions confirmed by multimodality imaging (Knowlton, 2004) in patients with OBE with those showing complex visual hallucinations involving people or faces, but without any disturbance of self-location and first person perspective. Nine patients with OBE were investigated. The control group comprised 8 patients. Structural imaging data were available for normalization and co-registration in all the patients. Normalization of each patient's lesion into the common MNI (Montreal Neurological Institute) reference space permitted simple, voxel-wise, algebraic comparisons to be made. Results: Even if in the scanner all participants were lying on their back and were facing upwards, analysis of perspective showed that half of the participants had the impression to be looking down at the virtual human body below them, despite any cues about their body position (Down-group). The other participants had the impression to be looking up at the virtual body above them (Up-group). Analysis of Q3 ("How strong was the feeling that the body you saw was you?") indicated stronger self-identification with the virtual body during the synchronous stroking. RTs in the MBD task confirmed these subjective data (significant 3-way interaction between perspective, object and stroking). fMRI results showed eight cortical regions where the BOLD signal was significantly different during at least one of the conditions resulting from the combination of Object and Stroking, relative to baseline: right and left temporo-parietal junction, right EBA, left middle occipito-temporal gyrus, left postcentral gyrus, right medial parietal lobe, bilateral medial occipital lobe (Fig 1). The activation patterns in right and left temporo-parietal junction and right EBA reflected changes in self-location and perspective as revealed by statistical analysis that was performed on the percentage of BOLD change with respect to the baseline. Statistical lesion overlap comparison (using nonparametric voxel based lesion symptom mapping) with respect to the control group revealed the right temporo-parietal junction, centered at the angular gyrus (Talairach coordinates x = 54, y =-52, z = 26; p>0.05, FDR corrected). Conclusions: The present questionnaire and behavioural results show that - despite the noisy and constraining MR environment) our participants had predictable changes in self-location, self-identification, and first-person perspective when robotic tactile stroking was applied synchronously with the robotic visual stroking. fMRI data in healthy participants and lesion data in patients with abnormal self-location and first-person perspective jointly revealed that the temporo-parietal cortex especially in the right hemisphere encodes these conscious experiences. We argue that temporo-parietal activity reflects the experience of the conscious "I" as embodied and localized within bodily space.

Temporo-parietal cortex encodes location of the self: joining fMRI with neuroscience robotics to study bodily self-consciousness

Neuroimaging of the self has focused on high-level mechanisms such as language, memory or imagery of the self and implicated widely distributed brain networks. Yet recent evidence suggests that low-level mechanisms such as multisensory and sensorimotor integration may play a fundamental role in self-related processing. In the present study we used visuotactile multisensory conflict, robotics, virtual reality, and fMRI to study such low-level mechanisms by experimentally inducing changes in self-location. Participants saw a video of a person's back (body) or an empty room (no-body) being stroked while a MR-compatible robotic device stroked their back. The latter tactile input was synchronous or asynchronous with respect to the seen stroking. Self-location was estimated behaviorally confirming previous data that self-location only differed between the two body conditions. fMRI results showed a bilateral activation of the temporo-parietal cortex with a significantly higher BOLD signal increase in the synchronous/body condition with respect to the other conditions. Sensorimotor cortex and extrastriate-body-area were also activated. We argue that temporo-parietal activity reflects the experience of the conscious 'I' as embodied and localized within bodily space, compatible with clinical data in neurological patients with out-of-body experiences.

Self-potential investigations of a gravel bar in a restored river corridor

Self-potentials (SP) are sensitive to water fluxes and concentration gradients in both saturated and unsaturated geological media, but quantitative interpretations of SP field data may often be hindered by the superposition of different source contributions and time-varying electrode potentials. Self-potential mapping and close to two months of SP monitoring on a gravel bar were performed to investigate the origins of SP signals at a restored river section of the Thur River in northeastern Switzerland. The SP mapping and subsequent inversion of the data indicate that the SP sources are mainly located in the upper few meters in regions of soil cover rather than bare gravel. Wavelet analyses of the time-series indicate a strong, but non-linear influence of water table and water content variations, as well as rainfall intensity on the recorded SP signals. Modeling of the SP response with respect to an increase in the water table elevation and precipitation indicate that the distribution of soil properties in the vadose zone has a very strong influence. We conclude that the observed SP responses on the gravel bar are more complicated than previously proposed semi-empiric relationships between SP signals and hydraulic head or the thickness of the vadose zone. We suggest that future SP monitoring in restored river corridors should either focus on quantifying vadose zone processes by installing vertical profiles of closely spaced SP electrodes or by installing the electrodes within the river to avoid signals arising from vadose zone processes and time-varying electrochemical conditions in the vicinity of the electrodes.

Concise reviews: in vitro-produced pancreas organogenesis models in three dimensions: self-organization from few stem cells or progenitors.

Three-dimensional models of organ biogenesis have recently flourished. They promote a balance between stem/progenitor cell expansion and differentiation without the constraints of flat tissue culture vessels, allowing for autonomous self-organization of cells. Such models allow the formation of miniature organs in a dish and are emerging for the pancreas, starting from embryonic progenitors and adult cells. This review focuses on the currently available systems and how these allow new types of questions to be addressed. We discuss the expected advancements including their potential to study human pancreas development and function as well as to develop diabetes models and therapeutic cells.

Prise en charge des jeunes patients avec endocrinopathies pediatriques chroniques: les défis d'une transition souvent difficile [Caring for patients with pediatric endocrinopathies and diabetes into adulthood: challenges of an often difficult transition].

The success of therapies for a number of pediatric disorders has posed new challenges for the long-term follow-up of adolescents with chronic endocrinopathies. Unfortunately, too many patients are lost during the transfer from pediatric to adult clinics. The transition process should be well-organized and include the young person and family. Recognizing the special needs of these adolescents is an important step in developing patient-centered approaches to care that enable patients to develop autonomy and self care skills. Key elements in this process include structured policies and guidelines, communication and close collaboration between pediatric and adult clinics, and integrating nurse clinicians in the transition process to help close the gaps in care.

Direct detection of a BRAF mutation in total RNA from melanoma cells using cantilever arrays.

Malignant melanoma, the deadliest form of skin cancer, is characterized by a predominant mutation in the BRAF gene. Drugs that target tumours carrying this mutation have recently entered the clinic. Accordingly, patients are routinely screened for mutations in this gene to determine whether they can benefit from this type of treatment. The current gold standard for mutation screening uses real-time polymerase chain reaction and sequencing methods. Here we show that an assay based on microcantilever arrays can detect the mutation nanomechanically without amplification in total RNA samples isolated from melanoma cells. The assay is based on a BRAF-specific oligonucleotide probe. We detected mutant BRAF at a concentration of 500 pM in a 50-fold excess of the wild-type sequence. The method was able to distinguish melanoma cells carrying the mutation from wild-type cells using as little as 20 ng µl(-1) of RNA material, without prior PCR amplification and use of labels.