Memory, learning and language in autism spectrum disorder

Background and aims: The ‘dual-systems’ model of language acquisition has been used by Ullman and colleagues to explain patterns of strength and weakness in the language of higher-functioning people with autism spectrum disorder (ASD). Specifically, intact declarative/explicit learning is argued to compensate for a deficit in non-declarative/implicit procedural learning, constituting an example of the so-called ‘see-saw’ effect. Ullman and Pullman (2015) extended their argument concerning a see-saw effect on language in ASD to cover other perceived anomalies of behaviour, including impaired acquisition of social skills. The aim of this paper is to present a critique of Ullman and colleagues’ claims, and to propose an alternative model of links between memory systems and language in ASD. Main contribution: We argue that a 4-systems model of learning, in which intact semantic and procedural memory are used to compensate for weaknesses in episodic memory and perceptual learning, can better explain patterns of language ability across the autistic spectrum. We also argue that attempts to generalise the ‘impaired implicit learning/spared declarative learning’ theory to other behaviours in ASD are unsustainable. Conclusions: Clinically significant language impairments in ASD are under-researched, despite their impact on everyday functioning and quality of life. The relative paucity of research findings in this area lays it open to speculative interpretation which may be misleading. Implications: More research is need into links between memory/learning systems and language impairments across the spectrum. Improved understanding should inform therapeutic intervention, and contribute to investigation of the causes of language impairment in ASD with potential implications for prevention

Inferring the Origin Locations of Tweets with Quantitative Confidence

Social Internet content plays an increasingly critical role in many domains, including public health, disaster management, and politics. However, its utility is limited by missing geographic information; for example, fewer than 1.6% of Twitter messages (tweets) contain a geotag. We propose a scalable, content-based approach to estimate the location of tweets using a novel yet simple variant of gaussian mixture models. Further, because real-world applications depend on quantified uncertainty for such estimates, we propose novel metrics of accuracy, precision, and calibration, and we evaluate our approach accordingly. Experiments on 13 million global, comprehensively multi-lingual tweets show that our approach yields reliable, well-calibrated results competitive with previous computationally intensive methods. We also show that a relatively small number of training data are required for good estimates (roughly 30,000 tweets) and models are quite time-invariant (effective on tweets many weeks newer than the training set). Finally, we show that toponyms and languages with small geographic footprint provide the most useful location signals.Comment: 14 pages, 6 figures. Version 2: Move mathematics to appendix, 2 new references, various other presentation improvements. Version 3: Various presentation improvements, accepted at ACM CSCW 201

Binary-state speciation and extinction method is conditionally robust to realistic violations of its assumptions

Phylogenetic comparative methods allow us to test evolutionary hypotheses without the benefit of an extensive fossil record. These methods, however, make simplifying assumptions, among them that clades are always increasing or stable in diversity, an assumption we know to be false. This study simulates hypothetical clades to test whether the Binary State Speciation and Extinction (BiSSE) method can be used to correctly detect relative differences in diversification rate between ancestral and derived character states even as net diversification rates are declining overall. We simulate clades with declining but positive diversification rates, as well those in which speciation rates decline below extinction rates so that they are losing richness for part of their history. We run these analyses both with simulated symmetric and asymmetric speciation rates to test whether BiSSE can be used to detect them correctly. For simulations with a neutral character, the fit for a BiSSE model with a neutral character is better than alternative models so long as net diversification rates remain positive. Once net diversification rates become negative, the BiSSE model with the greatest likelihood often has a non-neutral character, even though there is no such character in the simulation. BiSSE’s usefulness in detecting real asymmetry in speciation rates improves with clade age, even well after net diversification rates have become negative. BiSSE is most useful in analyzing clades of intermediate age, before they have reached peak diversity and gone into decline. After this point, users of BiSSE risk incorrectly inferring differential evolutionary rates when none exist. Fortunately, most studies using BiSSE and similar models focus on rapid, recent diversifications, and are less likely to encounter the biases BiSSE models are subject to for older clades. For extant groups that were once more diverse than now, however, caution should be taken in inferring past diversification patterns without fossil data

A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly

Copyright © 2003 Massachusetts Medical Society. All rights reserved.Background Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin–angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting–enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents. Methods We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models. Results At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group). Conclusions Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure.Lindon M.H. Wing, Christopher M. Reid, Philip Ryan, Lawrence J. Beilin, Mark A. Brown, Garry L.R. Jennings, Colin I. Johnston, John J. McNeil, Graham J. Macdonald, John E. Marley, Trefor O. Morgan, and Malcolm J. West, for the Second Australian National Blood Pressure Study Grou

A behavioral comparison of male and female adults with high functioning autism spectrum conditions

Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males

STU Black Holes and String Triality

We find double-extreme black holes associated with the special geometry of the Calabi-Yau moduli space with the prepotential F=STU. The area formula is STU-moduli independent and has ${[SL(2,Z)]}^3$ symmetry in space of charges. The dual version of this theory without prepotential treats the dilaton S asymmetric versus T,U-moduli. We display the dual relation between new (STU) black holes and stringy (S|TU) black holes using particular Sp(8, Z) transformation. The area formula of one theory equals that of the dual theory when expressed in terms of dual charges. We analyse the relation between (STU) black holes to string triality of black holes: (S|TU), (T|US), (U|ST) solutions. In the democratic STU-symmetric version we find that all three S and T and U duality symmetries are non-perturbative and mix electric and magnetic charges.Comment: 12 pages, 2 Postscript figures, ref.added, minor corrections, version to appear in Phys. Rev.

Mechanism of Ad5 Vaccine Immunity and Toxicity: Fiber Shaft Targeting of Dendritic Cells

Recombinant adenoviral (rAd) vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5) vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs) was independent of the coxsackievirus and adenovirus receptor (CAR), its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines

Shapes of leading tunnelling trajectories for single-electron molecular ionization

Based on the geometrical approach to tunnelling by P.D. Hislop and I.M. Sigal [Memoir. AMS 78, No. 399 (1989)], we introduce the concept of a leading tunnelling trajectory. It is then proven that leading tunnelling trajectories for single-active-electron models of molecular tunnelling ionization (i.e., theories where a molecular potential is modelled by a single-electron multi-centre potential) are linear in the case of short range interactions and "almost" linear in the case of long range interactions. The results are presented on both the formal and physically intuitive levels. Physical implications of the obtained results are discussed.Comment: 14 pages, 5 figure

Identification of guinea pig remains in the Pucará de Tilcara (Jujuy, Argentina): Evidence in favour of the presence of the Andean breed in the Quebrada de Humahuaca

In this article, we identified rodent remains found in the Pucará de Tilcara, an archaeological site from the Argentine Northwest that was occupied by humans from 1,100 ad until the Spanish conquest. The zooarchaeological analyses were carried out using anatomical descriptions and geometric morphometric analyses of the dorsal and ventral views of mandibular remains. The results and the archaeological context discussed showed that all the rodent remains could correspond to the Andean breed of domestic guinea pigs. The combination of the methods used here gave us a strong support to the taxonomical assignment. The presence of domestic guinea pigs in archaeological sites of the northwestern Argentina was never proposed. This approach allowed us to increase knowledge about the distribution of caviines in the region, and their relationship to anthropic processes.Fil: Lopez Geronazzo, Lautaro Nahuel. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Otero, Clarisa. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras; ArgentinaFil: Alvarez, Alicia. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; Argentina. Universidad Nacional de Jujuy. Instituto de Geología Minera; ArgentinaFil: Ercoli, Marcos Darío. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; Argentina. Universidad Nacional de Jujuy. Instituto de Geología Minera; ArgentinaFil: Cortés Delgado, Natalia. University of Illinois; Estados Unido

Evaluating Lifeworld as an emancipatory methodology

Disability research is conducted within a highly politicised ‘hotbed’ of competing paradigms and principles. New researchers, who want to work within the social model, are soon faced with complex and challenging methodological and philosophical dilemmas. The social model advocates research agendas that are focused on the emancipation and empowerment of disabled people but, in reality, these are rarely achieved. To be successful researchers need to engage with innovative and creative methodologies and to share their experiences of these within environments that welcome challenge and debate. This paper focuses on Lifeworld and assesses its value as a tool for emancipatory research. Using examples from a study with parents, whose children were in the process of being labelled as having autism, the paper illustrates how the principles that ‘underpin’ the methodology offered a supportive framework for a novice researcher