Evidence that convergence rather than accommodation controls intermittent distance exotropia

Purpose. This study considered whether vergence drives accommodation or accommodation drives vergence during the control of distance exotropia for near fixation. High accommodative convergence to accommodation (AC/A) ratios are often used to explain this control, but the role of convergence to drive accommodation (the CA/C relationship) is rarely considered. Atypical CA/C characteristics could equally, or better, explain common clinical findings. Methods. 19 distance exotropes, aged 4-11 years, were compared while controlling their deviation with 27 non-exotropic controls aged 5-9 years. Simultaneous vergence and accommodation responses were measured to a range of targets incorporating different combinations of blur, disparity and looming cues at four fixation distances between 2m and 33cm. Stimulus and response AC/A and CA/C ratios were calculated. Results. Accommodation responses for near targets (p=0.017) response gains (p=0.026) were greater in the exotropes than the controls. Despite higher clinical stimulus AC/A ratios, the distance exotropes showed lower laboratory response AC/A ratios (p=0.02), but significantly higher CA/C ratios (p=0.02). All the exotropes, whether the angle changed most with lenses (“controlled by accommodation”) or on occlusion (“controlled by fusion”), used binocular disparity not blur as their main cue to target distance. Conclusions. Increased vergence demand to control intermittent distance exotropia for near also drives significantly more accommodation. Minus lens therapy is more likely to act by correcting over-accommodation driven by controlling convergence, rather than by inducing blur-driven vergence. The use of convergence as a major drive to accommodation explains many clinical characteristics of distance exotropia, including apparently high near stimulus AC/A ratios.

Wave trapping in a two-dimensional sound-soft or sound-hard acoustic waveguide of slowly-varying width

In this paper we derive novel approximations to trapped waves in a two-dimensional acoustic waveguide whose walls vary slowly along the guide, and at which either Dirichlet (sound-soft) or Neumann (sound-hard) conditions are imposed. The guide contains a single smoothly bulging region of arbitrary amplitude, but is otherwise straight, and the modes are trapped within this localised increase in width. Using a similar approach to that in Rienstra (2003), a WKBJ-type expansion yields an approximate expression for the modes which can be present, which display either propagating or evanescent behaviour; matched asymptotic expansions are then used to derive connection formulae which bridge the gap across the cut-off between propagating and evanescent solutions in a tapering waveguide. A uniform expansion is then determined, and it is shown that appropriate zeros of this expansion correspond to trapped mode wavenumbers; the trapped modes themselves are then approximated by the uniform expansion. Numerical results determined via a standard iterative method are then compared to results of the full linear problem calculated using a spectral method, and the two are shown to be in excellent agreement, even when $\epsilon$, the parameter characterising the slow variations of the guide’s walls, is relatively large.

UK planning controls and the market responsiveness of housing supply

There is growing international interest in the impact of regulatory controls on the supply of housing The UK has a particularly restrictive planning regime and a detailed and uncertain process of development control linked to it. This paper presents the findings of empirical research on the time taken to gain planning permission for selected recent major housing projects from a sample of local authorities in southern England. The scale of delay found was far greater than is indicated by average official data measuring the extent to which local authorities meet planning delay targets. Hedonic analysis indicated that there is considerable variation in time it takes local authorities to process planning applications, with the worst being four times slower than the best. Smaller builders and housing association developments are processed more quickly than those of large developers and small sites appear to be particularly time intensive. These results suggest that delays in development control may be a significant contributory factor to the low responsiveness of UK housing supply to upturns in market activity.

Planning delay and the responsiveness of English housing supply

There is growing international interest in the impact of regulatory controls on the supply of housing. Most research focuses on the supply impacts of prescribed limits on land use but housing supply may also be affected by the process of planning monitoring and approval but this is hard to measure in detail. The UK has a particularly restrictive planning regime and a detailed and uncertain process of development control linked to it, but does offer the opportunity of detailed site-based investigation of planning delay. This paper presents the findings of empirical research on the time taken to gain planning permission for selected recent major housing projects in southern England. The scale of delay found was far greater than is indicated by average official data measuring the extent to which local authorities meet planning delay targets. Hedonic modelling indicated that there is considerable variation in the time it takes local authorities to process planning applications. Housing association developments are processed more quickly than those of large developers and small sites appear to be particularly time-intensive. These results suggest that delays in development control may be a significant contributory factor to the low responsiveness of UK housing supply to upturns in market activity.

Acidity controls on dissolved organic carbon mobility in organic soils

Dissolved organic carbon (DOC) concentrations in surface waters have increased across much of Europe and North America, with implications for the terrestrial carbon balance, aquatic ecosystem functioning, water treatment costs and human health. Over the past decade, many hypotheses have been put forward to explain this phenomenon, from changing climate and land-management to eutrophication and acid deposition. Resolution of this debate has been hindered by a reliance on correlative analyses of time-series data, and a lack of robust experimental testing of proposed mechanisms. In a four-year, four-site replicated field experiment involving both acidifying and de-acidifying treatments, we tested the hypothesis that DOC leaching was previously suppressed by high levels of soil acidity in peat and organo-mineral soils, and therefore that observed DOC increases a consequence of decreasing soil acidity. We observed a consistent, positive relationship between DOC and acidity change at all sites. Responses were described by similar hyperbolic relationships between standardised changes in DOC and hydrogen ion concentrations at all sites, suggesting potentially general applicability. These relationships explained a substantial proportion of observed changes in peak DOC concentrations in nearby monitoring streams, and application to a UK-wide upland soil pH dataset suggests that recovery from acidification alone could have led to soil solution DOC increases in the range 46-126% by habitat type since 1978. Our findings raise the possibility that changing soil acidity may have wider impacts on ecosystem carbon balances. Decreasing sulphur deposition may be accelerating terrestrial carbon loss, and returning surface waters to a natural, high-DOC condition.

Allosteric mechanism controls traffic in the chaperone/usher pathway

Many virulence organelles of Gram-negative bacterial pathogens are assembled via the chaperone/ usher pathway. The chaperone transports organelle subunits across the periplasm to the outer membrane usher, where they are released and incorporated into growing fibers. Here, we elucidate the mechanism of the usher-targeting step in assembly of the Yersinia pestis F1 capsule at the atomic level. The usher interacts almost exclusively with the chaperone in the chaperone:subunit complex. In free chaperone, a pair of conserved proline residues at the beginning of the subunit-binding loop form a ‘‘proline lock’’ that occludes the usher-binding surface and blocks usher binding. Binding of the subunit to the chaperone rotates the proline lock away from the usher-binding surface, allowing the chaperone-subunit complex to bind to the usher. We show that the proline lock exists in other chaperone/usher systems and represents a general allosteric mechanism for selective targeting of chaperone:subunit complexes to the usher and for release and recycling of the free chaperone.

Empathy and emotion recognition in people with autism, first-degree relatives, and controls

Empathy is the lens through which we view others' emotion expressions, and respond to them. In this study, empathy and facial emotion recognition were investigated in adults with autism spectrum conditions (ASC; N=314), parents of a child with ASC (N=297) and IQ-matched controls (N=184). Participants completed a self-report measure of empathy (the Empathy Quotient [EQ]) and a modified version of the Karolinska Directed Emotional Faces Task (KDEF) using an online test interface. Results showed that mean scores on the EQ were significantly lower in fathers (p<0.05) but not mothers (p>0.05) of children with ASC compared to controls, whilst both males and females with ASC obtained significantly lower EQ scores (p<0.001) than controls. On the KDEF, statistical analyses revealed poorer overall performance by adults with ASC (p<0.001) compared to the control group. When the 6 distinct basic emotions were analysed separately, the ASC group showed impaired performance across five out of six expressions (happy, sad, angry, afraid and disgusted). Parents of a child with ASC were not significantly worse than controls at recognising any of the basic emotions, after controlling for age and non-verbal IQ (all p>0.05). Finally, results indicated significant differences between males and females with ASC for emotion recognition performance (p<0.05) but not for self-reported empathy (p>0.05). These findings suggest that self-reported empathy deficits in fathers of autistic probands are part of the 'broader autism phenotype'. This study also reports new findings of sex differences amongst people with ASC in emotion recognition, as well as replicating previous work demonstrating empathy difficulties in adults with ASC. The use of empathy measures as quantitative endophenotypes for ASC is discussed.

Mast cell tryptase controls paracellular permeability of the intestine: role of protease-activated receptor 2 and beta-arrestins

Tight junctions between intestinal epithelial cells prevent ingress of luminal macromolecules and bacteria and protect against inflammation and infection. During stress and inflammation, mast cells mediate increased mucosal permeability by unknown mechanisms. We hypothesized that mast cell tryptase cleaves protease-activated receptor 2 (PAR2) on colonocytes to increase paracellular permeability. Colonocytes expressed PAR2 mRNA and responded to PAR2 agonists with increased [Ca2+]i. Supernatant from degranulated mast cells increased [Ca2+]i in colonocytes, which was prevented by a tryptase inhibitor, and desensitized responses to PAR2 agonist, suggesting PAR2 cleavage. When applied to the basolateral surface of colonocytes, PAR2 agonists and mast cell supernatant decreased transepithelial resistance, increased transepithelial flux of macromolecules, and induced redistribution of tight junction ZO-1 and occludin and perijunctional F-actin. When mast cells were co-cultured with colonocytes, mast cell degranulation increased paracellular permeability of colonocytes. This was prevented by a tryptase inhibitor. We determined the role of ERK1/2 and of beta-arrestins, which recruit ERK1/2 to PAR2 in endosomes and retain ERK1/2 in the cytosol, on PAR2-mediated alterations in permeability. An ERK1/2 inhibitor abolished the effects of PAR2 agonist on permeability and redistribution of F-actin. Down-regulation of beta-arrestins with small interfering RNA inhibited PAR2-induced activation of ERK1/2 and suppressed PAR2-induced changes in permeability. Thus, mast cells signal to colonocytes in a paracrine manner by release of tryptase and activation of PAR2. PAR2 couples to beta-arrestin-dependent activation of ERK1/2, which regulates reorganization of perijunctional F-actin to increase epithelial permeability. These mechanisms may explain the increased epithelial permeability of the intestine during stress and inflammation.

Which words are hard for autistic children to learn?

Motivated by accounts of concept use in autistic spectrum disorder (ASD), and a computational model of weak central coherence (O’Loughlin & Thagard, 2000) we examined comprehension and production vocabulary in typically-developing children, and those with ASD and Down syndrome (DS). Controlling for frequency, familiarity, length, and imageability, Colorado Meaningfulness played a hitherto unremarked role in the vocabularies of children with ASD. High Colorado Meaningful words were underrepresented in the comprehension vocabularies of 2- to 12-year-olds with ASD. The Colorado Meaningfulness of a word is a measure of how many words can be associated with it. Situations in which high Colorado Meaningfulness words are encountered are typically highly variable, and words with High Colorado Meaningfulness often involve extensive use of context. Our data suggest that the number of contexts in which a particular word can appear has a role in determining vocabulary in ASD. This suggestion is consistent with the weak central coherence theory of autism.

Ever decreasing circles: speech production in semantic dementia

We explored the impact of a degraded semantic system on lexical, morphological and syntactic complexity in language production. We analysed transcripts from connected speech samples from eight patients with semantic dementia (SD) and eight age-matched healthy speakers. The frequency distributions of nouns and verbs were compared for hand-scored data and data extracted using text-analysis software. Lexical measures showed the predicted pattern for nouns and verbs in hand-scored data, and for nouns in software-extracted data, with fewer low frequency items in the speech of the patients relative to controls. The distribution of complex morpho-syntactic forms for the SD group showed a reduced range, with fewer constructions that required multiple auxiliaries and inflections. Finally, the distribution of syntactic constructions also differed between groups, with a pattern that reflects the patients’ characteristic anomia and constraints on morpho-syntactic complexity. The data are in line with previous findings of an absence of gross syntactic errors or violations in SD speech. Alterations in the distributions of morphology and syntax, however, support constraint satisfaction models of speech production in which there is no hard boundary between lexical retrieval and grammatical encoding.

Global biomass burning: a synthesis and review of Holocene paleofire records and their controls.

We synthesize existing sedimentary charcoal records to reconstruct Holocene fire history at regional, continental and global scales. The reconstructions are compared with the two potential controls of burning at these broad scales – changes in climate and human activities – to assess their relative importance on trends in biomass burning. Here we consider several hypotheses that have been advanced to explain the Holocene record of fire, including climate, human activities and synergies between the two. Our results suggest that 1) episodes of high fire activity were relatively common in the early Holocene and were consistent with climate changes despite low global temperatures and low levels of biomass burning globally; 2) there is little evidence from the paleofire record to support the Early Anthropocene Hypothesis of human modification of the global carbon cycle; 3) there was a nearly-global increase in fire activity from 3 to 2 ka that is difficult to explain with either climate or humans, but the widespread and synchronous nature of the increase suggests at least a partial climate forcing; and 4) burning during the past century generally decreased but was spatially variable; it declined sharply in many areas, but there were also large increases (e.g., Australia and parts of Europe). Our analysis does not exclude an important role for human activities on global biomass burning during the Holocene, but instead provides evidence for a pervasive influence of climate across multiple spatial and temporal scales.