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The Sphere Model of Consciousness (SMC) delineates a sphere-shaped matrix that aims to describe subjective experiences using geometric coordinates, in accordance with a neurophenomenological perspective. According to the SMC, an experience of overcoming the habitual self and the conditioning of memories could be placed at the center of the matrix, which can then be called the Place of Pre-Existence (PPE). The PPE is causally associated with self-determination. In this context, we suggest that silence could be considered an intentional inner environment enabling self-perception to focus on the “here and now,” which in turn improves perception of one’s own body in space. To investigate the hypotheses grounded in the model, the current preliminary study examined the Place of Pre-Existence Technique (PPEt), in which practitioners are guided to focus on a self-defined aim, reach a state of detachment from the habitual self, and envision the future. Four-hundred eighty-one volunteer PPEt practitioners completed self-report questionnaires before and after an intensive 3-day meditative training. We analyzed potential relationships between subjective experiences related to physical, emotional, mental, temporal, and spatial components, as well as self-determination and silence, before and after training. The results indicated a transition from a prevailing influence of mental dimension on the other aspects of experience, to a prevailing influence of the spatial dimension. Silence was reported more often following the training and was predominantly related to mental and emotional experiences. The results are discussed in the framework of the SMC, as compared to other models, and in relation to the shift from Narrative to Minimal Self and to increased balance among the considered dimensions.

Endometriosis is a common gynecological condition which affects 5–10% of women of reproductive age and up to 50% of women with pelvic pain and infertility. The most commonly affected areas are the pelvic peritoneum, ovaries and rectovaginal septum. Isolated endometriosis of the sciatic nerve is very rare. Our patient suffered from worsening right hip and buttock pain with severe exacerbation during menstruation. Several different imaging modalities (ultrasound of her pelvis and right hip, as well as X-rays and computed tomography scans of her right hip and lumbosacral spine) failed to identify any pathology. Magnetic resonance imaging scans of her pelvis revealed a 3.5 cm endometriotic lesion over the pelvic segment of her right sciatic nerve. Following a multidisciplinary discussion, the patient underwent laparoscopic excision of endometriosis. The patient recovered well from her surgery. She successfully conceived with in vitro fertilization 3 years after her surgery, following a failed course of Clomid (Clomiphene citrate) for ovulatory dysfunction.

Previous studies demonstrated exercise-induced modulation of neurotrophins, such as Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Yet, no study that we are aware of has examined their change as a function of different training paradigms. In addition, the understanding of the possible training-induced relationship between NGF and BDNF change is still lacking. Consequently, in the current study we examined the effect of a Walking Training (WT) and of Quadrato Motor Training (QMT) on NGF and BDNF precursors (proNGF and proBDNF). QMT is a specifically structured sensorimotor training that involves sequences of movements based on verbal commands, that was previously reported to improve spatial cognition, reflectivity, creativity as well as emotion regulation and general self-efficacy. In addition, QMT was reported to induce electrophysiological and morphological changes, suggesting stimulation of neuroplasticity processes. In two previous independent studies we reported QMT-induced changes in the salivary proNGF and proBDNF levels. Our present results demonstrate that following 12 weeks of daily QMT practice, proNGF level increases while proBDNF showed no significant change. More importantly, while no correlation between the two neurotrophins prior to training was detectable, there was a significant correlation between change in proNGF and proBDNF levels. Taken together the current results suggest that the two neurotrophins undergo a complex modulation, likely related to the different pathways by which they are produced and regulated. Since variations of these neurotrophins have been previously linked to depression, stress and anxiety, the current study may have practical implications and aid in understanding the possible physiological mechanisms that mediate improved well-being, and the dynamic change of neurotrophins as a result of training.

We herein describe the operative approach of a postmenopausal woman with a history of surgically corrected congenital bladder exstrophy-epispadias who presented with long-standing complete procidentia. The patient was initially treated by laparoscopic sacral colpopexy in conjunction with a modified Elevate mesh kit anterior vaginal repair with and posterior vaginal wall repair in the form of native tissue suture plication repair. Her prolapse recurred 8 months' later due to a detachment of the mesh at the level of the promontorium. During the second-look laparoscopy, a resuspension of this mesh was deemed unsatisfactory; therefore, with patients' consent, a successful colpocleisis was performed. This case report emphasizes the complexity of pelvic organ prolapse (POP) in the context of a bladder exstrophy-epispadias complex. These women are more likely to fail the more conventional current surgical treatments for POP, coercing to revert to colpocleisis.

Diffusion tensor imaging (DTI) is an important way to characterize white matter (WM) microstructural changes. While several cross-sectional DTI studies investigated possible links between mindfulness practices and WM, only few longitudinal investigations focused on the effects of these practices on WM architecture, behavioral change, and the relationship between them. To this aim, in the current study, we chose to conduct an unbiased tract-based spatial statistics (TBSS) analysis (n = 35 healthy participants) to identify longitudinal changes in WM diffusion parameters following 6 and 12 weeks of daily Quadrato Motor Training (QMT), a whole-body mindful movement practice aimed at improving well-being by enhancing attention, coordination, and creativity. We also investigated the possible relationship between training-induced WM changes and concomitant changes in creativity, self-efficacy, and motivation. Our results indicate that following 6 weeks of daily QMT, there was a bilateral increase of fractional anisotropy (FA) in tracts related to sensorimotor and cognitive functions, including the corticospinal tracts, anterior thalamic radiations, and uncinate fasciculi, as well as in the left inferior fronto-occipital, superior and inferior longitudinal fasciculi. Interestingly, significant FA increments were still present after 12 weeks of QMT in most of the above WM tracts, but only in the left hemisphere. FA increase was accompanied by a significant decrease of radial diffusivity (RD), supporting the leading role of myelination processes in training-related FA changes. Finally, significant correlations were found between training-induced diffusion changes and increased self-efficacy as well as creativity. Together, these findings suggest that QMT can improve WM integrity and support the existence of possible relationships between training-related WM microstructural changes and behavioral change.

The notion that exposure to a monotonous sensory environment could elicit reports indicating aberrant subjective experience and altered time perception is the impetus for the present report. Research has looked at the influence of exposure to such environments on time perception, reporting that the greater the environmental variation, the shorter is the time estimation obtained by the method of production. Most conditions for creating an altered sensory environment, however, have not facilitated an immersive experience, one that directly impacts both time perception and subjective experience. In this study, we invited our participants to enter a whole-body altered sensory environment for a 20-min session, wherein they were asked to relax without falling asleep. The session included white-colored illumination of the chamber with eyes closed (5 min), followed by 10 min of illuminating the room with color, after which a short report of subjective experience was collected using a brief questionnaire; this was followed by an additional 5 min of immersion in white light with closed eyes. The participants were then interviewed regarding their subjective experience, including their experience of time within the chamber. Prior to entering the chamber, the participants completed a time-production (TP) task. One group of participants then repeated the task within the chamber, at the end of the session; a second group of participants repeated the task after exiting the chamber. We shall report on changes in TP, and present data indicating that when produced time is plotted as a function of target duration, using a log–log plot, the major influence of sensory environment is on the intercept of the psychophysical function. We shall further present data indicating that for those participants reporting a marked change in time experience, such as “the sensation of time disappeared,” their TP data could not be linearized using a log–log plot, hence indicating that for these individuals there might be a “break” in the psychophysical function.

Quadrato Motor Training (QMT) is a new training paradigm, which was found to increase cognitive flexibility, creativity and spatial cognition. In addition, QMT was reported to enhance inter- and intra-hemispheric alpha coherence as well as Fractional Anisotropy (FA) in a number of white matter pathways including corpus callosum. Taken together, these results seem to suggest that electrophysiological and structural changes induced by QMT may be due to an enhanced interplay and communication of the different brain areas within and between the right and the left hemisphere. In order to test this hypothesis using the exact low-resolution brain electromagnetic tomography (eLORETA), we estimated the current neural density and lagged linear connectivity (LLC) of the alpha band in the resting state electroencephalography (rsEEG) recorded with open (OE) and closed eyes (CE) at three different time points, following 6 and 12 weeks of daily QMT. Significant changes were observed for the functional connectivity. In particular, we found that limbic and fronto-temporal alpha connectivity in the OE condition increased after 6 weeks, while it enhanced at the CE condition in occipital network following 12-weeks of daily training. These findings seem to show that the QMT may have dissociable long-term effects on the functional connectivity depending on the different ways of recording rsEEG. OE recording pointed out a faster onset of Linear Lag Connectivity modulations that tend to decay as quickly, while CE recording showed sensible effect only after the complete 3-months training.

We present imaging and spectroscopy of a hydrogen-poor superluminous supernova (SLSN) discovered by the intermediate Palomar Transient Factory, iPTF 13ajg. At a redshift of z = 0.7403, derived from narrow absorption lines, iPTF 13ajg peaked at an absolute magnitude of M u, AB = -22.5, one of the most luminous supernovae to date. The observed bolometric peak luminosity of iPTF 13ajg is 3.2 × 1044 erg s-1, while the estimated total radiated energy is 1.3 × 1051 erg. We detect narrow absorption lines of Mg I, Mg II, and Fe II, associated with the cold interstellar medium in the host galaxy, at two different epochs with X-shooter at the Very Large Telescope. From Voigt profile fitting, we derive the column densities log N(Mg I) =11.94 ± 0.06, log N(Mg II) =14.7 ± 0.3, and log N(Fe II) =14.25 ± 0.10. These column densities, as well as the Mg I and Mg II equivalent widths of a sample of hydrogen-poor SLSNe taken from the literature, are at the low end of those derived for gamma-ray bursts (GRBs) whose progenitors are also thought to be massive stars. This suggests that the environments of hydrogen-poor SLSNe and GRBs are different. From the nondetection of Fe II fine-structure absorption lines, we derive a lower limit on the distance between the supernova and the narrow-line absorbing gas of 50 pc. The neutral gas responsible for the absorption in iPTF 13ajg exhibits a single narrow component with a low velocity width, ΔV = 76 km s-1, indicating a low-mass host galaxy. No host galaxy emission lines are detected, leading to an upper limit on the unobscured star formation rate (SFR) of SFR. Late-time imaging shows the iPTF 13ajg host galaxy to be faint, with g AB 27.0 and R AB ≥ 26.0 mag, corresponding to M B, Vega ≳ -17.7 mag.

We present the results of a Palomar Transient Factory (PTF) archival search for blue transients that lie in the magnitude range between "normal" core-collapse and superluminous supernovae (i.e., with -21 ≤ MR(peak)≤-19). Of the six events found after excluding all interacting Type IIn and Ia-CSM supernovae, three (PTF09ge, 09axc, and 09djl) are coincident with the centers of their hosts, one (10iam) is offset from the center, and a precise offset cannot be determined for two (10nuj and 11glr). All the central events have similar rise times to the He-rich tidal disruption candidate PS1-10jh, and the event with the best-sampled light curve also has similar colors and power-law decay. Spectroscopically, PTF09ge is He-rich, while PTF09axc and 09djl display broad hydrogen features around peak magnitude. All three central events are in low star formation hosts, two of which are E+A galaxies. Our spectrum of the host of PS1-10jh displays similar properties. PTF10iam, the one offset event, is different photometrically and spectroscopically from the central events, and its host displays a higher star formation rate. Finding no obvious evidence for ongoing galactic nuclei activity or recent star formation, we conclude that the three central transients likely arise from the tidal disruption of a star by a supermassive black hole. We compare the spectra of these events to tidal disruption candidates from the literature and find that all of these objects can be unified on a continuous scale of spectral properties. The accumulated evidence of this expanded sample strongly supports a tidal disruption origin for this class of nuclear transients.

There is a growing number of Type IIn supernovae (SNe) which present an outburst prior to their presumably final explosion. These precursors may affect the SN display, and are likely related to poorly charted phenomena in the final stages of stellar evolution. By coadding Palomar Transient Factory (PTF) images taken prior to the explosion, here we present a search for precursors in a sample of 16 Type IIn SNe. We find five SNe IIn that likely have at least one possible precursor event (PTF 10bjb, SN 2010mc, PTF 10weh, SN 2011ht, and PTF 12cxj), three of which are reported here for the first time. For each SN we calculate the control time. We find that precursor events among SNe IIn are common: at the one-sided 99% confidence level, >50% of SNe IIn have at least one pre-explosion outburst that is brighter than 3 × 107 L ⊙ taking place up to 1/3 yr prior to the SN explosion. The average rate of such precursor events during the year prior to the SN explosion is likely ≳ 1 yr-1, and fainter precursors are possibly even more common. Ignoring the two weakest precursors in our sample, the precursors rate we find is still on the order of one per year. We also find possible correlations between the integrated luminosity of the precursor and the SN total radiated energy, peak luminosity, and rise time. These correlations are expected if the precursors are mass-ejection events, and the early-time light curve of these SNe is powered by interaction of the SN shock and ejecta with optically thick circumstellar material. © 2014. The American Astronomical Society. All rights reserved.

Interaction of supernova (SN) ejecta with the optically thick circumstellar medium (CSM) of a progenitor star can result in a bright, long-lived shock-breakout event. Candidates for such SNe include Type IIn and superluminous SNe. If some of these SNe are powered by interaction, then there should be a specific relation between their peak luminosity, bolometric light-curve rise time, and shock-breakout velocity. Given that the shock velocity during shock breakout is not measured, we expect a correlation, with a significant spread, between the rise time and the peak luminosity of these SNe. Here, we present a sample of 15 SNe IIn for which we have good constraints on their rise time and peak luminosity from observations obtained using the Palomar Transient Factory. We report on a possible correlation between the R-band rise time and peak luminosity of these SNe, with a false-alarm probability of 3%. Assuming that these SNe are powered by interaction, combining these observables and theory allows us to deduce lower limits on the shock-breakout velocity. The lower limits on the shock velocity we find are consistent with what is expected for SNe (i.e., ∼104 km s-1). This supports the suggestion that the early-time light curves of SNe IIn are caused by shock breakout in a dense CSM. We note that such a correlation can arise from other physical mechanisms. Performing such a test on other classes of SNe (e.g., superluminous SNe) can be used to rule out the interaction model for a class of events. © 2014. The American Astronomical Society. All rights reserved..

The explosive fate of massive Wolf-Rayet stars (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections. Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 10(12) centimetres, as expected for some WRSs. The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions.

We present optical photometric and spectroscopic observations of the Type Ibn (SN 2006jclike) supernova (SN) iPTF13beo. Detected by the intermediate Palomar Transient Factory~3 h after the estimated first light, iPTF13beo is the youngest and the most distant (~430 Mpc) Type Ibn event ever observed. The iPTF13beo light curve is consistent with light curves of other Type Ibn SNe and with light curves of fast Type Ic events, but with a slightly faster rise-time of two days. In addition, the iPTF13beo R-band light curve exhibits a double-peak structure separated by ~9 d, not observed before in any Type Ibn SN. A low-resolution spectrum taken during the iPTF13beo rising stage is featureless, while a late-time spectrum obtained during the declining stage exhibits narrow and intermediate-width He I and Si II features with full width at half-maximum ≈2000-5000 km s-1 and is remarkably similar to the prototypical SN Ibn 2006jc spectrum. We suggest that our observations support a model of a massive star exploding in a dense He-rich circumstellar medium (CSM). A shock breakout in a CSM model requires an eruption releasing a total mass of ~0.1 M⊙ over a time-scale of couple of weeks prior to the SN explosion. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

The Type Ia supernova (SN Ia) SN 2000cx was one of the most peculiar transients ever discovered, with a rise to maximum brightness typical of a SN Ia, but a slower decline and a higher photospheric temperature. 13 yr later SN 2013bh (also known as iPTF13abc), a near identical twin, was discovered and we obtained optical and near-infrared photometry and low-resolution optical spectroscopy from discovery until about 1 month past r-band maximum brightness. The spectra of both objects show iron-group elements [Co II, Ni II, FeII, Fe III and high-velocity features (HVFs) of Ti II], intermediate-mass elements (Si II, Si III and S II) and separate normal velocity features (~12 000 km s-1) and HVFs (~24 000 km s-1) of Ca II. Persistent absorption from Fe III and Si III, along with the colour evolution, implies high blackbody temperatures for SNe 2013bh and 2000cx (~12 000 K). Both objects lack narrow Na I D absorption and exploded in the outskirts of their hosts, indicating that the SN environments were relatively free of interstellar or circumstellar material and may imply that the progenitors came from a relatively old and low-metallicity stellar population. Models of SN 2000cx, seemingly applicable to SN 2013bh, imply the production of up to 1 M of 56Ni and (4.3-5.5) × 10-3 M⊙ of fast-moving Ca ejecta. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Abstract Bacterial pathogens carrying multidrug resistance (MDR) plasmids are a major threat to human health. The acquisition of antibiotic resistance genes (ARGs) in plasmids is often facilitated by mobile genetic elements that copy or translocate ARGs between DNA molecules. The agglomeration of mobile elements in plasmids generates resistance islands comprising multiple ARGs. However, whether the emergence of resistance islands is restricted to specific MDR plasmid lineages remains understudied. Here we show that the agglomeration of ARGs in resistance islands is biased towards specific large plasmid lineages. Analyzing 6784 plasmids in 2441 Escherichia, Salmonella, and Klebsiella isolates, we quantify that 84% of the ARGs in MDR plasmids are found in resistance islands. We furthermore observe rapid evolution of ARG combinations in resistance islands. Most regions identified as resistance islands are shared among closely related plasmids but rarely among distantly related plasmids. Our results suggest the presence of barriers for the dissemination of ARGs between plasmid lineages, which are related to plasmid genetic properties, host range and the plasmid evolutionary history. The agglomeration of ARGs in plasmids is attributed to the workings of mobile genetic elements that operate within the framework of existing plasmid lineages.

Abstract Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.

Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are not without their own drawbacks; namely, these hydrogels are rapidly degraded in vivo, and cells delivered via microtissues are quickly expelled from the area of action. Here, we report the development of an easily customized protocol for creating a protective, biocompatible hydrogel barrier around microtissues. We show that calcium carbonate nanoparticles embedded within an ECM-based microtissue diffuse outwards and, when then exposed to a solution of alginate, can be used to generate a coated layer around the tissue. We further show that this technique can be fine-tuned by adjusting numerous parameters, granting us full control over the thickness of the hydrogel coating layer. The microtissues’ protective hydrogel functioned as hypothesized in both in vitro and in vivo testing by preventing the cells inside the tissue from escaping and protecting the microdroplets against external degradation. This technology may provide microtissues with customized properties for use as sources of regenerative therapies.

Summary: Biofilm formation, a major concern for healthcare systems, is initiated when bacteria adhere to surfaces. Escherichia coli adhesion is mediated by appendages, including type-1 fimbriae and curli amyloid fibers. Antifouling surfaces prevent the adhesion of bacteria to combat biofilm formation. Here, we used single-cell force-spectroscopy to study the interaction between E. coli and glass or two antifouling surfaces: the tripeptide DOPA-Phe(4F)-Phe(4F)-OMe and poly(ethylene glycol) polymer-brush. Our results indicate that both antifoulants significantly deter E. coli initial adhesion. By using two mutant strains expressing no type-1 fimbriae or curli amyloids, we studied the adhesion mechanism. Our results suggest that the bacteria adhere to different antifoulants via separate mechanisms. Finally, we show that some bacteria adhere much better than others, illustrating how the variability of bacterial cultures affects biofilm formation. Our results emphasize how additional study at the single-cell level can enhance our understanding of bacterial adhesion, thus leading to novel antifouling technologies.

Tissue engineering is considered a promising approach to treating advanced degenerative maculopathies such as nonexudative age-related macular degeneration (AMD), the leading cause of blindness worldwide. The retina consists of several hierarchical tissue layers, each of which is supported by a layer underneath. Each of these layers has a different morphology and requires distinct conditions for proper assembly. In fact, a prerequisite step for the assembly of each of these layers is the organization of the layer underneath. Advanced retinal degeneration includes degeneration of the other retina layers, including the choroid, the retinal pigmented epithelium (RPE), and the photoreceptors. Here, we report a step-by-step fabrication process of a three-layer retina-like structure. The process included the 3D printing of a choroid-like structure in an extracellular matrix (ECM) hydrogel, followed by deposition of the RPE monolayer. After the formation of the blood vessel–RPE interface, the photoreceptor cells were deposited to interact with the RPE layer. At the end of the fabrication process, each layer was characterized for its morphology and expression of specific markers, and the integration of the three-layer retina was evaluated. We envision that such a retina-like structure may be able to attenuate the deterioration of a degenerated retina and improve engraftment and regeneration. This retinal implant may potentially be suitable for a spectrum of macular degenerative diseases for which there are currently no cures and may save millions from complete blindness.