What underlies the neuropsychological pattern of irregular>regular past-tense verb production?

The disadvantage in producing the past tense of regular relative to irregular verbs shown by some patients with non-fluent aphasia has been alternatively attributed (a) to the failure of a specific rule-based morphological mechanism, or (b) to a more generalised phonological impairment that penalises regular verbs more than irregular owing to the on-average greater phonological complexity of regular past-tense forms. Guided by the second of these two accounts, the current study was designed to identify more specific aspects of phonological deficit that might be associated with the pattern of irregular > regular past-tense production. Non-fluent aphasic patients (N = 8) were tested on past-tense verb production tasks and assessed with regard to the impact of three main manipulations in other word-production tasks: (i) insertion of a delay between stimulus and response in repetition; (ii) presence/ number of consonant clusters in a target word in repetition; (iii) position of stress within a bi-syllabic word in repetition and picture naming. The performance of all patients deteriorated in delayed repetition; but the patients with the largest discrepancy between regular and irregular past-tense production showed greater sensitivity to the other two manipulations. The phonological nature of the factors that correlated with verb-inflection performance emphasises the role of a phonological deficit in the observed pattern of irregular > regular

The relationship between phonological and morphological deficits in Broca's aphasia: further evidence from errors in verb inflection

A previous study of 10 patients with Broca’s aphasia demonstrated that the advantage for producing the past tense of irregular over regular verbs exhibited by these patients was eliminated when the two sets of past-tense forms were matched for phonological complexity (Bird, Lambon Ralph, Seidenberg, McClelland, & Patterson, 2003). The interpretation given was that a generalised phonological impairment was central to the patients’ language deficits, including their poor performance on regular past tense verbs. The current paper provides further evidence in favour of this hypothesis, on the basis of a detailed analysis of the errors produced by these same 10 patients in reading, repetition, and sentence completion for a large number of regular, irregular, and nonce verbs. The patients’ predominant error types in all tasks and for all verb types were close and distant phonologically related responses. The balance between close and distant errors varied along three continua: the severity of the patient (more distant errors produced by the more severely impaired patients); the difficulty of the task (more distant errors in sentence completion > reading > repetition); the difficulty of the item (more distant errors for novel word forms than real verbs). A position analysis for these phonologically related errors revealed that vowels were most likely to be preserved and that consonant onsets and offsets were equally likely to be incorrect. Critically, the patients’ errors exhibited a strong tendency to simplify the phonological form of the target. These results are consistent with the notion that the patients’ relatively greater difficulty with regular past tenses reflects a phonological impairment that is sensitive to the complexity of spoken forms

Endovascular aneurysm sealing for the treatment of ruptured abdominal aortic aneurysms.

PURPOSE: To assess the feasibility and report preliminary results of ruptured abdominal aortic aneurysm (rAAA) repair with endovascular aneurysm sealing (EVAS), a novel therapeutic alternative whose feasibility has not been established in rAAAs due to the unknown effects of the rupture site on the ability to achieve sealing. CASE REPORT: Between December 2013 and April 2014, 5 patients (median age 71 years, range 57-90; 3 men) with rAAAs were treated with the Nellix EVAS system at a single institution. Median aneurysm diameter was 70 mm (range 67-91). Aneurysm morphology in 4 of the 5 patients was noncompliant with instructions for use (IFU) for both EVAS and standard stent-grafts; the remaining patient was outside the IFU for standard stent-grafts but treated with EVAS under standard IFU for the Nellix system. Median Hardman index was 2 (range 0-3). Two patients died of multiorgan failure after re-laparotomy and intraoperative cardiac arrest, respectively. Among survivors, all devices were patent with no signs of endoleak or failed aneurysm sac sealing at 6 months (median follow-up 9.2 months). CONCLUSION: EVAS for the management of infrarenal rAAAs appears feasible. The use of EVAS in emergency repairs may broaden the selection criteria of the current endovascular strategy to include patients with more complex aneurysm morphology

Filoviruses utilize glycosaminoglycans for their attachment to target cells

Filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. The envelope glycoprotein (GP), responsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to interact with multiple molecules in order to enhance entry into host cells. Here we have demonstrated that filoviruses utilize glycosaminoglycans, and more specifically heparan sulfate proteoglycans, for their attachment to host cells. This interaction is mediated by GP and does not require the presence of the mucin domain. Both the degree of sulfation and the structure of the carbohydrate backbone play a role in the interaction with filovirus GPs. This new step of filovirus interaction with host cells can potentially be a new target for antiviral strategies. As such, we were able to inhibit filovirus GP-mediated infection using carrageenan, a broad-spectrum microbicide that mimics heparin, and also using the antiviral dendrimeric peptide SB105-A10, which interacts with heparan sulfate, antagonizing the binding of the virus to cells

Connectionist perspectives on language learning, representation and processing.

The field of formal linguistics was founded on the premise that language is mentally represented as a deterministic symbolic grammar. While this approach has captured many important characteristics of the world\u27s languages, it has also led to a tendency to focus theoretical questions on the correct formalization of grammatical rules while also de-emphasizing the role of learning and statistics in language development and processing. In this review we present a different approach to language research that has emerged from the parallel distributed processing or \u27connectionist\u27 enterprise. In the connectionist framework, mental operations are studied by simulating learning and processing within networks of artificial neurons. With that in mind, we discuss recent progress in connectionist models of auditory word recognition, reading, morphology, and syntactic processing. We argue that connectionist models can capture many important characteristics of how language is learned, represented, and processed, as well as providing new insights about the source of these behavioral patterns. Just as importantly, the networks naturally capture irregular (non-rule-like) patterns that are common within languages, something that has been difficult to reconcile with rule-based accounts of language without positing separate mechanisms for rules and exceptions

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose

Hamlet and the fall of the Berlin wall : the myth of interventionist Shakespeare performance

The critical reception of Heiner Müller’s 1990 Hamlet/Maschine at the Deutsches Theater in East Berlin epitomizes a trend of crediting GDR Shakespeare performance with political influence. Drawing on rehearsal notes and reviews, Oliver challenges the interventionist Shakespeare myth, contrasting the Deutsches Theater’s political involvement with the impact of its Hamlet production on events surrounding the fall of the Berlin Wall. Shakespeare’s capacity for political intervention at this point was limited by theater practitioners’ reliance on public funding, their close relationships with governmental authority, and an underlying distrust of the masses. Ultimately, GDR artists proved useful to the 1989 protest movement because they occupied a unique position at the interface of dissidence and power