Insights into language processing in aphasia from semantic priming and semantic judgement tasks

The nature of semantic impairment in people with aphasia (PWA) provides the background to the current study, which examines whether different methods of semantic assessment can account for such deficits. Cognitive ability, which has previously been linked to language ability in PWA, may impact on test performance and was therefore also examined. The aims of the current study were to compare performance of control participants and PWA on implicit and explicit assessment of semantics, and to relate it to performance on tests of cognition. The impact of semantically similar versus associative relationship types between test stimuli was also considered. Three experimental semantic tasks were developed, including one implicit measure of semantic processing (Semantic Priming) and two explicit measures (Word to Picture Verification and Word to Picture Matching). Test stimuli were matched in terms of key psycholinguistic variables of frequency, imageability and length, and other factors including visual similarity, semantic similarity, and association. Performance of 40 control participants and 20 PWA was investigated within and between participant groups. The relationship between semantic task performance and existing semantic and cognitive assessments was also explored in PWA. An important finding related to a subgroup of PWA who were impaired on the explicit experimental semantic tasks but demonstrated intact semantic processing via the implicit method. Within tasks some differences were found in the effects of semantically related or associated stimuli. No relationships were found between experimental semantic task performance and cognitive task accuracy. The research offers insights into the role of implicit language testing, the impact of stimuli relationship type, and the complex relationship between semantic processing and cognition. The findings underline the need for valid and accurate measures of semantic processing to be in place to enable accurate diagnosis for PWA, in order to direct appropriate intervention choice and facilitate successful rehabilitation

The Equine Learning Curve: Horses and mules in British Army transport services during the First World War

This article combines research methodologies from military history and animal studies to write equines into the history of the First World War. In doing so, it seeks to demonstrate how considering the animal perspective can advance our understanding of conflict at an individual and operational level. It proposes that the horses and mules used in British Army transport services were not just passive victims as they are often portrayed, but sentient beings who played an active role in operations

Bacterial fitness shapes the population dynamics of antibiotic-resistant and -susceptible bacteria in a model of combined antibiotic and anti-virulence treatment

Bacterial resistance to antibiotic treatment is a huge concern: introduction of any new antibiotic is shortly followed by the emergence of resistant bacterial isolates in the clinic. This issue is compounded by a severe lack of new antibiotics reaching the market. The significant rise in clinical resistance to antibiotics is especially problematic in nosocomial infections, where already vulnerable patients may fail to respond to treatment, causing even greater health concern. A recent focus has been on the development of anti-virulence drugs as a second line of defence in the treatment of antibiotic-resistant infections. This treatment, which weakens bacteria by reducing their virulence rather than killing them, should allow infections to be cleared through the body's natural defence mechanisms. In this way there should be little to no selective pressure exerted on the organism and, as such, a predominantly resistant population would be unlikely to emerge. However, much controversy surrounds this approach with many believing it would not be powerful enough to clear existing infections, restricting its potential application to prophylaxis. We have developed a mathematical model that provides a theoretical framework to reveal the circumstances under which anti-virulence drugs may or may not be successful. We demonstrate that by harnessing and combining the advantages of antibiotics with those provided by anti-virulence drugs, given infection-specific parameters, it is possible to identify treatment strategies that would efficiently clear bacterial infections, while preventing the emergence of resistant subpopulations. Our findings strongly support the continuation of research into anti-virulence drugs and demonstrate that their applicability may reach beyond infection prevention.Comment: Pre-review manuscript. Submitted to Journal of Theoretical Biology, July 21st 201

Novel matched stimuli for assessment of lexical semantics

Background: Diagnosis of semantic impairment in stroke and progressive neuro-cognitive conditions is typically facilitated using tests of word comprehension, such as word-picture matching. Many of these tests are not controlled for psycholinguistic variables or the semantic relationships between competitor stimuli and involve pictures which are not controlled for ease of access. Semantic assessment also demands additional cognitive resources, such as explicit decision-making and suppression of semantic competitors. These factors may all confound test performance and subsequent diagnosis. Aims: To develop novel semantic test stimuli for three new semantic processing assessments, which are controlled for psycholinguistic variables, semantic relationship between stimuli, and visual similarity between images presented simultaneously. An additional aim included matching stimuli for these variables across three tests: semantic priming, word-picture verification, and word-picture matching, to allow direct comparison of performance on tests that differ in terms of the additional cognitive demands involved, with priming entailing implicit semantic processing. Methods & Procedures: In phase one, novel stimuli were developed for the three semantic processing tests. Existing databases were searched for values to match stimuli psycholinguistic variables. In phase two, new data were collected from control participants regarding the semantic and visual similarity of stimuli presented simultaneously. Outcomes & Results: Data for three sets of target and distractor stimuli are presented, which are psycholinguistically matched within and between the three semantic tests for concreteness, imageability, age of acquisition, frequency, word length, and emotional valence. “Semantic” relationships between pairs of stimuli are differentiated by semantic similarity (dog-cat) or association (dog-lead). Visual similarity is controlled between images presented in an array. Conclusions: The data provided ensure that test performance across three semantic tasks, differing in additional cognitive demands, can be directly compared in people with potential semantic deficits. This is the first such study to provide control of stimuli within and across a range of semantic tests. Patterns of performance via test reaction time and accuracy data may reveal semantic deficit or competence, contributing to more accurate diagnosis and appropriate therapy choice

Understanding Spatial and Spectral Morphologies of Ultracompact H II Regions

The spatial morphology, spectral characteristics, and time variability of ultracompact H II regions provide strong constraints on the process of massive star formation. We have performed simulations of the gravitational collapse of rotating molecular cloud cores, including treatments of the propagation of ionizing and non-ionizing radiation. We here present synthetic radio continuum observations of H II regions from our collapse simulations, to investigate how well they agree with observation, and what we can learn about how massive star formation proceeds. We find that intermittent shielding by dense filaments in the gravitationally unstable accretion flow around the massive star leads to highly variable H II regions that do not grow monotonically, but rather flicker, growing and shrinking repeatedly. This behavior appears able to resolve the well-known lifetime problem. We find that multiple ionizing sources generally form, resulting in groups of ultracompact H II regions, consistent with observations. We confirm that our model reproduces the qualitative H II region morphologies found in surveys, with generally consistent relative frequencies. We also find that simulated spectral energy distributions (SEDs) from our model are consistent with the range of observed H II region SEDs, including both regions showing a normal transition from optically thick to optically thin emission, and those with intermediate spectral slopes. In our models, anomalous slopes are solely produced by inhomogeneities in the H II region, with no contribution from dust emission at millimeter or submillimeter wavelengths. We conclude that many observed characteristics of ultracompact H II regions appear consistent with massive star formation in fast, gravitationally unstable, accretion flows.Comment: ApJ in pres

The Relationship Between Apraxia of Speech and Oral Apraxia: Association or Dissociation?

Acquired apraxia of speech (AOS) is a motor speech disorder that affects the implementation of articulatory gestures and the fluency and intelligibility of speech. Oral apraxia (OA) is an impairment of nonspeech volitional movement. Although many speakers with AOS also display difficulties with volitional nonspeech oral movements, the relationship between the 2 conditions is unclear. This study explored the relationship between speech and volitional nonspeech oral movement impairment in a sample of 50 participants with AOS. We examined levels of association and dissociation between speech and OA using a battery of nonspeech oromotor, speech, and auditory/aphasia tasks. There was evidence of a moderate positive association between the 2 impairments across participants. However, individual profiles revealed patterns of dissociation between the 2 in a few cases, with evidence of double dissociation of speech and oral apraxic impairment. We discuss the implications of these relationships for models of oral motor and speech control

On the evolution of irradiated turbulent clouds: A comparative study between modes of triggered star-formation

Here we examine the evolution of irradiated clouds using the Smoothed Particle Hydrodynamics ({\small SPH}) algorithm coupled with a ray-tracing scheme that calculates the position of the ionisation-front at each timestep. We present results from simulations performed for three choices of {\small IR}-flux spanning the range of fluxes emitted by a typical {\small B}-type star to a cluster of {\small OB}-type stars. The extent of photo-ablation, of course, depends on the strength of the incident flux and a strong flux of {\small IR} severely ablates a {\small MC}. Consequently, the first star-formation sites appear in the dense shocked layer along the edges of the irradiated cloud. Radiation-induced turbulence readily generates dense filamentary structure within the photo-ablated cloud although several new star-forming sites also appear in some of the densest regions at the junctions of these filaments. Prevalent physical conditions within a {\small MC} play a crucial role in determining the mode, i.e., filamentary as compared to isolated pockets, of star-formation, the timescale on which stars form and the distribution of stellar masses. The probability density functions ({\small PDF}s) derived for irradiated clouds in this study are intriguing due to their resemblance with those presented in a recent census of irradiated {\small MC}s. Furthermore, irrespective of the nature of turbulence, the protostellar mass-functions({\small MF}s) derived in this study follow a power-law distribution. When turbulence within the cloud is driven by a relatively strong flux of {\small IR} such as that emitted by a massive {\small O}-type star or a cluster of such stars, the {\small MF} approaches the canonical form due to Salpeter, and even turns-over for protostellar masses smaller than $\sim$0.2 M$_{\odot}$.Comment: 13 pages, 19 figures, 3 tables. Rendered images of significantly lowered resolution have been deliberately submitted to stay within the maximum permissible limits of size. Also, the original abstract has been shortened. To be published by the Monthly Notices of the RA

Protein retention in the endoplasmic reticulum rescues Aβ toxicity in Drosophila

Amyloid β (Aβ) accumulation is a hallmark of Alzheimer's disease. In adult Drosophila brains, human Aβ overexpression harms climbing and lifespan. It's uncertain whether Aβ is intrinsically toxic or activates downstream neurodegeneration pathways. Our study uncovers a novel protective role against Aβ toxicity: intra-endoplasmic reticulum (ER) protein accumulation with a focus on laminin and collagen subunits. Despite high Aβ, laminin B1 (LanB1) overexpression robustly counters toxicity, suggesting a potential Aβ resistance mechanism. Other laminin subunits and collagen IV also alleviate Aβ toxicity; combining them with LanB1 augments the effect. Imaging reveals ER retention of LanB1 without altering Aβ secretion. LanB1's rescue function operates independently of the IRE1α/XBP1 ER stress response. ER-targeted GFP overexpression also mitigates Aβ toxicity, highlighting broader ER protein retention advantages. Proof-of-principle tests in murine hippocampal slices using mouse Lamb1 demonstrate ER retention in transduced cells, indicating a conserved mechanism. Though ER protein retention generally harms, it could paradoxically counter neuronal Aβ toxicity, offering a new therapeutic avenue for Alzheimer's disease

pRb Inactivation in Mammary Cells Reveals Common Mechanisms for Tumor Initiation and Progression in Divergent Epithelia

Retinoblastoma 1 (pRb) and the related pocket proteins, retinoblastoma-like 1 (p107) and retinoblastoma-like 2 (p130) (pRb(f), collectively), play a pivotal role in regulating eukaryotic cell cycle progression, apoptosis, and terminal differentiation. While aberrations in the pRb-signaling pathway are common in human cancers, the consequence of pRb(f) loss in the mammary gland has not been directly assayed in vivo. We reported previously that inactivating these critical cell cycle regulators in divergent cell types, either brain epithelium or astrocytes, abrogates the cell cycle restriction point, leading to increased cell proliferation and apoptosis, and predisposing to cancer. Here we report that mouse mammary epithelium is similar in its requirements for pRb(f) function; Rb(f) inactivation by T(121), a fragment of SV40 T antigen that binds to and inactivates pRb(f) proteins, increases proliferation and apoptosis. Mammary adenocarcinomas form within 16 mo. Most apoptosis is regulated by p53, which has no impact on proliferation, and heterozygosity for a p53 null allele significantly shortens tumor latency. Most tumors in p53 heterozygous mice undergo loss of the wild-type p53 allele. We show that the mechanism of p53 loss of heterozygosity is not simply the consequence of Chromosome 11 aneuploidy and further that chromosomal instability subsequent to p53 loss is minimal. The mechanisms for pRb and p53 tumor suppression in the epithelia of two distinct tissues, mammary gland and brain, are indistinguishable. Further, this study has produced a highly penetrant breast cancer model based on aberrations commonly observed in the human disease

Effects of syntactic cueing therapy on picture naming and connected speech in acquired aphasia

Language therapy for word-finding difficulties in aphasia usually involves picture naming of single words with the support of cues. Most studies have addressed nouns in isolation, even though in connected speech nouns are more frequently produced with determiners. We hypothesised that improved word finding in connected speech would be most likely if intervention treated nouns in usual syntactic contexts. Six speakers with aphasia underwent language therapy using a software program developed for the purpose, which provided lexical and syntactic (determiner) cues. Exposure to determiners with nouns would potentially lead to improved picture naming of both treated and untreated nouns, and increased production of determiner plus noun combinations in connected speech. After intervention, picture naming of treated words improved for five of the six speakers, but naming of untreated words was unchanged. The number of determiner plus noun combinations in connected speech increased for four speakers. These findings attest to the close relationship between frequently co-occurring content and function words, and indicate that intervention for word-finding deficits can profitably proceed beyond single word naming, to retrieval in appropriate syntactic contexts. We also examined the relationship between effects of therapy, and amount and intensity of therapy. We found no relationship between immediate effects and amount or intensity of therapy. However, those participants whose naming maintained at follow-up completed the therapy regime in fewer sessions, of relatively longer duration. We explore the relationship between therapy regime and outcomes, and propose future considerations for research