Are autistic traits measured equivalently in individuals with and without an Autism Spectrum Disorder?:An invariance analysis of the Autism Spectrum Quotient Short Form

It is common to administer measures of autistic traits to those without autism spectrum disorders (ASDs) with, for example, the aim of understanding autistic personality characteristics in non-autistic individuals. Little research has examined the extent to which measures of autistic traits actually measure the same traits in the same way across those with and without an ASD. We addressed this question using a multi-group confirmatory factor invariance analysis of the Autism Quotient Short Form (AQ-S: Hoekstra et al. in J Autism Dev Disord 41(5):589-596, 2011) across those with (n = 148) and without (n = 168) ASD. Metric variance (equality of factor loadings), but not scalar invariance (equality of thresholds), held suggesting that the AQ-S measures the same latent traits in both groups, but with a bias in the manner in which trait levels are estimated. We, therefore, argue that the AQ-S can be used to investigate possible causes and consequences of autistic traits in both groups separately, but caution is due when combining or comparing levels of autistic traits across the two group

I Did Not Accept That: Demonstrating Consent in Online Collection of Personal Data

Privacy in online collection of personal data is currently a much debated topic considering, amongst other reasons, the incidents with well known digital organisations, such as social networks and, in Europe, the recent EU/GDPR regulation. Among other required practices, explicit and simply worded consent from individuals must be obtained before collecting and using personal information. Further, individuals must also be given detailed information about what, how and what for data is collected. Consent is typically obtained at the collection point and, at a single point in time (ignoring updates), associated with Privacy Policies or End-User Agreements. At any moment, both the user and the organization should be able to produce evidence of this consent. This proof should not be disputable which leads us to strong cryptographic properties. The problem we discuss is how to robustly demonstrate such consent was given. We adapt fair-exchange protocols to this particular problem and, upon an exchange of personal data, we are able to produce a cryptographic receipt of acceptance that any party can use to prove consent and elicit non-repudiation. We discuss two broad strategies: a pure peerto-peer scheme and the use of a Trusted Third Party

Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT

Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFß-dependent biological outputs such as epithelial–mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isoforms (N-terminal, WWP2-N; C-terminal WWP2-C), as novel Smad-binding partners. We show that WWP2-FL interacts exclusively with Smad2, Smad3 and Smad7 in the TGFß pathway. Interestingly, the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7. In addition, WWP2-FL and WWP2-C have a preference for Smad7 based on protein turnover and ubiquitination studies. Unexpectedly, we also find that WWP2-N, which lacks the HECT ubiquitin ligase domain, can also interact with WWP2-FL in a TGFß-regulated manner and activate endogenous WWP2 ubiquitin ligase activity causing degradation of unstimulated Smad2 and Smad3. Consistent with our protein interaction data, overexpression and knockdown approaches reveal that WWP2 isoforms differentially modulate TGFß-dependent transcription and EMT. Finally, we show that selective disruption of WWP2 interactions with inhibitory Smad7 can stabilise Smad7 protein levels and prevent TGFß-induced EMT. Collectively, our data suggest that WWP2-N can stimulate WWP2-FL leading to increased activity against unstimulated Smad2 and Smad3, and that Smad7 is a preferred substrate for WWP2-FL and WWP2-C following prolonged TGFß stimulation. Significantly, this is the first report of an interdependent biological role for distinct HECT E3 ubiquitin ligase isoforms, and highlights an entirely novel regulatory paradigm that selectively limits the level of inhibitory and activating Smads

Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop

This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressure–velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously

Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

&lt;p&gt;Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.&lt;/p&gt; &lt;p&gt;Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).&lt;/p&gt; &lt;p&gt;Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.&lt;/p&gt

Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe

Spatial Dimensions of Dengue Virus Transmission across Interepidemic and Epidemic Periods in Iquitos, Peru (1999–2003)

To target prevention and control strategies for dengue fever, it is essential to understand how the virus travels through the city. We report spatial analyses of dengue infections from a study monitoring school children and adult family members for dengue infection at six-month intervals from 1999–2003, in the Amazonian city of Iquitos, Peru. At the beginning of the study, only DENV serotypes 1 and 2 were circulating. Clusters of infections of these two viruses were concentrated in the northern region of the city, where mosquito indices and previous DENV infection were both high. In 2002, DENV-3 invaded the city, replacing DENV-1 and -2 as the dominant strain. During the invasion process, the virus spread rapidly across the city, at low levels. After this initial phase, clusters of infection appeared first in the northern region of the city, where clusters of DENV-1 and DENV-2 had occurred in prior years. Most of the clusters we identified had radii >100 meters, indicating that targeted or reactive treatment of these high-risk areas might be an effective proactive intervention strategy. Our results also help explain why vector control within 100 m of a dengue case is often not successful for large-scale disease prevention

Effectiveness of an Ultrasound Training Module for Internal Medicine Residents

<p>Abstract</p> <p>Background</p> <p>Few internal medicine residency programs provide formal ultrasound training. This study sought to assess the feasibility of simulation based ultrasound training among first year internal medicine residents and measure their comfort at effectively using ultrasound to perform invasive procedures before and after this innovative model of ultrasound training.</p> <p>Methods</p> <p>A simulation based ultrasound training module was implemented during intern orientation that incorporated didactic and practical experiences in a simulation and cadaver laboratory. Participants completed anonymous pre and post surveys in which they reported their level of confidence in the use of ultrasound technology and their comfort in identifying anatomic structures including: lung, pleural effusion, bowel, peritoneal cavity, ascites, thyroid, and internal jugular vein. Survey items were structured on a 5-point Likert scales (1 = extremely unconfident, 5 = extremely confident).</p> <p>Results</p> <p>Seventy-five out of seventy-six interns completed the pre-intervention survey and 55 completed the post-survey. The mean confidence score (SD) increased to 4.00 (0.47) (p < 0.0001). The mean (SD) comfort ranged from 3.61 (0.84) for peritoneal cavity to 4.48 (0.62) for internal jugular vein. Confidence in identifying all anatomic structures showed an increase over the pre-intervention means (p < 0.002).</p> <p>Conclusion</p> <p>A simulation based ultrasound learning module can improve the self-reported confidence with which residents identify structures important in performing invasive ultrasound guided procedures. Incorporating an ultrasound module into residents' education may address perceived need for ultrasound training, improve procedural skills, and enhance patient safety.</p

Geographical ecology of dry forest tree communities in the West Indies

© 2018 The Authors. Journal of Biogeography Published by John Wiley & Sons Ltd Aim: Seasonally dry tropical forest (SDTF) of the Caribbean Islands (primarily West Indies) is floristically distinct from Neotropical SDTF in Central and South America. We evaluate whether tree species composition was associated with climatic gradients or geographical distance. Turnover (dissimilarity) in species composition of different islands or among more distant sites would suggest communities structured by speciation and dispersal limitations. A nested pattern would be consistent with a steep resource gradient. Correlation of species composition with climatic variation would suggest communities structured by broad-scale environmental filtering. Location: The West Indies (The Bahamas, Cuba, Hispaniola, Jamaica, Puerto Rico, US Virgin Islands, Guadeloupe, Martinique, St. Lucia), Providencia (Colombia), south Florida (USA) and Florida Keys (USA). Taxon: Seed plants—woody taxa (primarily trees). Methods: We compiled 572 plots from 23 surveys conducted between 1969 and 2016. Hierarchical clustering of species in plots, and indicator species analysis for the resulting groups of sites, identified geographical patterns of turnover in species composition. Nonparametric analysis of variance, applied to principal components of bioclimatic variables, determined the degree of covariation in climate with location. Nestedness versus turnover in species composition was evaluated using beta diversity partitioning. Generalized dissimilarity modelling partitioned the effect of climate versus geographical distance on species composition. Results: Despite a set of commonly occurring species, SDTF tree community composition was distinct among islands and was characterized by spatial turnover on climatic gradients that covaried with geographical gradients. Greater Antillean islands were characterized by endemic indicator species. Northern subtropical areas supported distinct, rather than nested, SDTF communities in spite of low levels of endemism. Main conclusions: The SDTF species composition was correlated with climatic variation. SDTF on large Greater Antillean islands (Hispaniola, Jamaica and Cuba) was characterized by endemic species, consistent with their geological history and the biogeography of plant lineages. These results suggest that both environmental filtering and speciation shape Caribbean SDTF tree communities

Comparative Population Genetics of the Immunity Gene, Relish: Is Adaptive Evolution Idiosyncratic?

The frequency of adaptive evolution acting on common loci in distant lineages remains an outstanding question in evolutionary biology. We asked whether the immunity factor, Relish, a gene with a history of directional selection in Drosophila simulans, shows evidence of a similar selective history in other Drosophila species. We found only weak evidence of recurrent adaptive protein evolution at the Relish locus in three sister species pairs, suggesting that this key component of the insect immune system has an idiosyncratic evolutionary history in Drosophila