Abnormal rolls and regular arrays of disclinations in homeotropic electroconvection

We present the first quantitative verification of an amplitude description for systems with (nearly) spontaneously broken isotropy, in particular for the recently discovered abnormal-roll states. We also obtain a conclusive picture of the three-dimensional director configuration in a spatial period doubling phenomenon involving disclination loops. The first observation of two Lifshitz frequencies in electroconvection is reported.

Interhemispheric gradient of atmospheric radiocarbon reveals natural variability of Southern Ocean winds

Tree ring Delta C-14 data (Reimer et al., 2004; McCormac et al., 2004) indicate that atmospheric Delta C-14 varied on multi-decadal to centennial timescales, in both hemispheres, over the period between AD 950 and 1830. The Northern and Southern Hemispheric Delta C-14 records display similar variability, but from the data alone is it not clear whether these variations are driven by the production of C-14 in the stratosphere (Stuiver and Quay, 1980) or by perturbations to exchanges between carbon reservoirs (Siegenthaler et al., 1980). As the sea-air flux of (CO2)-C-14 has a clear maximum in the open ocean regions of the Southern Ocean, relatively modest perturbations to the winds over this region drive significant perturbations to the interhemispheric gradient. In this study, model simulations are used to show that Southern Ocean winds are likely a main driver of the observed variability in the interhemispheric gradient over AD 950-1830, and further, that this variability may be larger than the Southern Ocean wind trends that have been reported for recent decades (notably 1980-2004). This interpretation also implies that there may have been a significant weakening of the winds over the Southern Ocean within a few decades of AD 1375, associated with the transition between the Medieval Climate Anomaly and the Little Ice Age. The driving forces that could have produced such a shift in the winds at the Medieval Climate Anomaly to Little Ice Age transition remain unknown. Our process-focused suite of perturbation experiments with models raises the possibility that the current generation of coupled climate and earth system models may underestimate the natural background multi-decadal- to centennial-timescale variations in the winds over the Southern Ocean.

Palaeoenvironmental changes since the Last Glacial Maximum: Patterns, timing and dynamics throughout South America

The vast diversity of present vegetation and environments that occur throughout South America (12°N to 56°S) is the result of diverse processes that have been operating and interacting at different spatial and temporal scales. Global factors, such as the concentration of CO2 in the atmosphere, may have been significant for high altitude vegetation during times of lower abundance, while lower sea levels of glacial stages potentially opened areas of continental shelf for colonisation during a substantial portion of the Quaternary. Latitudinal variation in orbital forcing has operated on a regional scale. The pace of climate change in the tropics is dominated by precessional oscillations of c. 20 kyr, while the high latitudes of the south are dominated by obliquity oscillations of c. 40 kyr. In particular, seasonal insolation changes forced by precessional oscillations must have had important consequences for the distribution limits of species, with potentially different effects depending on the latitude. The availability of taxa, altitude and human impact, among other events, have locally influenced the environments. Disentangling the different forcing factors of environmental change that operate on different timescales, and understanding the underlying mechanisms leads to considerable challenges for palaeoecologists. The papers in this Special Issue present a selection of palaeoecological studies throughout South America on vegetation changes and other aspects of the environment, providing a window on the possible complexity of the nature of transitions and timings that are potentially available.

Laughter Induction Techniques Suitable for Generating Motion Capture Data of Laughter Associated Body Movements

Laughter is a frequently occurring social signal and an important part of human non-verbal communication. However it is often overlooked as a serious topic of scientific study. While the lack of research in this area is mostly due to laughter’s non-serious nature, it is also a particularly difficult social signal to produce on demand in a convincing manner; thus making it a difficult topic for study in laboratory settings. In this paper we provide some techniques and guidance for inducing both hilarious laughter and conversational laughter. These techniques were devised with the goal of capturing mo- tion information related to laughter while the person laughing was either standing or seated. Comments on the value of each of the techniques and general guidance as to the importance of atmosphere, environment and social setting are provided.

Laughter Type Recognition from Whole Body Motion

Despite the importance of laughter in social interactions it remains little studied in affective computing. Respiratory, auditory, and facial laughter signals have been investigated but laughter-related body movements have received almost no attention. The aim of this study is twofold: first an investigation into observers' perception of laughter states (hilarious, social, awkward, fake, and non-laughter) based on body movements alone, through their categorization of avatars animated with natural and acted motion capture data. Significant differences in torso and limb movements were found between animations perceived as containing laughter and those perceived as nonlaughter. Hilarious laughter also differed from social laughter in the amount of bending of the spine, the amount of shoulder rotation and the amount of hand movement. The body movement features indicative of laughter differed between sitting and standing avatar postures. Based on the positive findings in this perceptual study, the second aim is to investigate the possibility of automatically predicting the distributions of observer's ratings for the laughter states. The findings show that the automated laughter recognition rates approach human rating levels, with the Random Forest method yielding the best performance.

Gremlin1 preferentially binds to Bone Morphogenetic Protein-2 (BMP-2) and BMP-4 over BMP-7

Gremlin (Grem1) is a member of the DAN family of secreted bone morphogenetic protein (BMP) antagonists. Bone morphogenetic protein-7 (BMP-7) mediates protective effects during renal fibrosis-associated with diabetes and other renal diseases. The pathogenic mechanism of Grem1 during DN has been suggested to be binding and inhibition of BMP-7. However, the precise interactions between Grem1, BMP-7 and other BMPs have not been accurately defined. Here we show the affinity of Grem1 for BMP-7 is lower than that of BMP-2 and BMP-4, using a combination of surface plasmon resonance and cell culture techniques. Using kidney proximal tubule cells and HEK-293 cell Smad1/5/8 phosphorylation and BMP-dependent gene expression as readout, Grem1 consistently demonstrated a higher affinity for BMP-2>4>7. Cell-associated Grem1 did not inhibit BMP-2 or BMP-4 mediated signalling, suggesting that Grem1-BMP-2 binding occurred in solution, preventing BMP receptor activation. These data suggest that Grem1 preferentially binds to BMP-2 and this may be the dominant complex in a disease situation where levels of Grem1 and BMPs are elevated.

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.

Hirschsprung's disease prevalence in Europe: A register based study

Background: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. Methods: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. Results: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03–1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00–1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91–1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91–1.31; p = 0.355). Conclusion: This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age.

European Recommendations for Primary Prevention of Congenital Anomalies: A Joined Effort of EUROCAT and EUROPLAN Projects to Facilitate Inclusion of This Topic in the National Rare Disease Plans

Congenital anomalies (CA) are the paradigm example of rare diseases liable to primary prevention actions due to the multifactorial etiology of many of them, involving a number of environmental factors together with genetic predispositions. Yet despite the preventive potential, lack of attention to an integrated preventive strategy has led to the prevalence of CA remaining relatively stable in recent decades. The 2 European projects, EUROCAT and EUROPLAN, have joined efforts to provide the first science-based and comprehensive set of recommendations for the primary prevention of CA in the European Union. The resulting EUROCAT-EUROPLAN 'Recommendations on Policies to Be Considered for the Primary Prevention of Congenital Anomalies in National Plans and Strategies on Rare Diseases' were issued in 2012 and endorsed by EUCERD (European Union Committee of Experts on Rare Diseases) in 2013. The recommendations exploit interdisciplinary expertise encompassing drugs, diet, lifestyles, maternal health status, and the environment. The recommendations include evidence-based actions aimed at reducing risk factors and at increasing protective factors and behaviors at both individual and population level. Moreover, consideration is given to topics specifically related to CA (e.g. folate status, teratogens) as well as of broad public health impact (e.g. obesity, smoking) which call for specific attention to their relevance in the pre- and periconceptional period. The recommendations, reported entirely in this paper, are a comprehensive tool to implement primary prevention into national policies on rare diseases in Europe.

Perception and Automatic Recognition of Laughter from Whole-Body Motion: Continuous and Categorical Perspectives

Despite its importance in social interactions, laughter remains little studied in affective computing. Intelligent virtual agents are often blind to users’ laughter and unable to produce convincing laughter themselves. Respiratory, auditory, and facial laughter signals have been investigated but laughter-related body movements have received less attention. The aim of this study is threefold. First, to probe human laughter perception by analyzing patterns of categorisations of natural laughter animated on a minimal avatar. Results reveal that a low dimensional space can describe perception of laughter “types”. Second, to investigate observers’ perception of laughter (hilarious, social, awkward, fake, and non-laughter) based on animated avatars generated from natural and acted motion-capture data. Significant differences in torso and limb movements are found between animations perceived as laughter and those perceived as non-laughter. Hilarious laughter also differs from social laughter. Different body movement features were indicative of laughter in sitting and standing avatar postures. Third, to investigate automatic recognition of laughter to the same level of certainty as observers’ perceptions. Results show recognition rates of the Random Forest model approach human rating levels. Classification comparisons and feature importance analyses indicate an improvement in recognition of social laughter when localized features and nonlinear models are used.

Human Perception of Laughter from Context-free Whole Body Motion Dynamic Stimuli

Laughter is a ubiquitous social signal in human interactions yet it remains understudied from a scientific point of view. The need to understand laughter and its role in human interactions has become more pressing as the ability to create conversational agents capable of interacting with humans has come closer to a reality. This paper reports on three aspects of the human perception of laughter when context has been removed and only the body information from the laughter episode remains. We report on ability to categorise the laugh type and the sex of the laugher; the relationship between personality factors with laughter categorisation and perception; and finally the importance of intensity in the perception and categorisation of laughter.

Reva Siegel and the Role of Religion in Constructing the Meaning of ‘Human Dignity

The “religious understanding” of dignity is a topic of considerable complexity and is the subject of extensive scholarship. In this paper, I consider understandings of dignity that are currently under discussion in Roman Catholic circles, not least because Catholic discussions of dignity are often seen as influential in public policy and legal interpretation, directly and indirectly. I shall focus on one relatively neglected issue in legal scholarship: how scholars go about the task of identifying what a particular religion’s understanding of human dignity involves.
To illustrate the methodological problems that such an enterprise raises, I shall take one attempt by a scholar writing in the field of secular legal scholarship to describe Catholic understandings of dignity in the context of abortion and same-sex marriage. The discussion is that of Reva Siegel, an academic lawyer at Yale University; her recent analysis of differing understandings of dignity illustrates some of the issues that arise when the secular scholarly community addresses religious understandings of dignity.