Modulating Complex Sentence Processing in Aphasia Through Attention and Semantic Networks.

PURPOSE: Lexical processing impairments such as delayed and reduced activation of lexical-semantic information have been linked to syntactic processing disruptions and sentence comprehension deficits in individuals with aphasia (IWAs). Lexical-level deficits can also preclude successful lexical encoding during sentence processing and amplify the processing costs of similarity-based interference during syntactic retrieval. We investigate whether two manipulations to engage attention and pre-activate semantic features of a target (to-be-retrieved) noun will (a) boost lexical activation during initial lexical encoding and (b) facilitate syntactic dependency linking through improved resolution of interference in IWAs and neurologically unimpaired age-matched controls (AMCs). METHOD: Eye-tracking-while-listening with a visual world paradigm was used to investigate whether semantic and attentional manipulations modulated initial lexical processing and downstream syntactic retrieval of the direct-object noun in object-relative sentences. RESULTS: In the attention and semantic manipulations, the AMC group showed no changes in initial lexical access levels; however, gaze patterns revealed clear facilitations in dependency linking and interference resolution. In the IWA group, the attentional cue increased and maintained activation of N1 with modest facilitations in dependency linking. In the semantic condition, IWA results showed a greater degree of facilitation during dependency linking. CONCLUSIONS: The results suggest that attention and semantic activation are parameters that may be manipulated to strengthen encoding of lexical representations to facilitate retrieval (i.e., dependency linking) and mitigate similarity-based interference. In IWAs, these manipulations may help to reduce lexical processing deficits that can preclude successful encoding.

The effect of time on lexical and syntactic processing in aphasia.

Processing deficits at the lexical level, such as delayed and reduced lexical activation, have been theorized as the source of breakdowns in syntactic operations and thus contribute to sentence comprehension deficits in individuals with aphasia (IWA). In the current study, we investigate the relationship between lexical and syntactic processing in object-relative sentences using eye-tracking while listening in IWA. We explore whether manipulating the time available to process a critical lexical item (the direct-object noun) when it is initially heard in a sentence has an immediate effect on lexical access as well as a downstream effect on syntactic processing. To achieve this aim, we use novel temporal manipulations to provide additional time for lexical processing to occur. In addition to exploring these temporal effects in IWA, we also seek to understand the effect that additional time has on sentence processing in neurotypical age-matched adults (AMC). We predict that the temporal manipulations designed to provide increased processing time for critical lexical items will 1) enhance lexical processing of the target noun, 2) facilitate syntactic integration, and 3) improve sentence comprehension for both IWA and AMC. We demonstrate that strengthening lexical processing via the addition of time can affect lexical processing and facilitate syntactic retrieval of the target noun and lead to enhanced interference resolution in both unimpaired and impaired systems. In aphasia, additional time can mitigate impairments in spreading activation thereby improving lexical access and reducing interference during downstream dependency linking. However, individuals with aphasia may require longer additions of time to fully realize these benefits.

Effect of Lexical-Semantic Cues during Real-Time Sentence Processing in Aphasia.

Using a visual world eye-tracking paradigm, we investigated the real-time auditory sentence processing of neurologically unimpaired listeners and individuals with aphasia. We examined whether lexical-semantic cues provided as adjectives of a target noun modulate the encoding and retrieval dynamics of a noun phrase during the processing of complex, non-canonical sentences. We hypothesized that the real-time processing pattern of sentences containing a semantically biased lexical cue (e.g., the venomous snake) would be different than sentences containing unbiased adjectives (e.g., the voracious snake). More specifically, we predicted that the presence of a biased lexical cue would facilitate (1) lexical encoding (i.e., boosted lexical access) of the target noun, snake, and (2) on-time syntactic retrieval or dependency linking (i.e., increasing the probability of on-time lexical retrieval at post-verb gap site) for both groups. For unimpaired listeners, results revealed a difference in the time course of gaze trajectories to the target noun (snake) during lexical encoding and syntactic retrieval in the biased compared to the unbiased condition. In contrast, for the aphasia group, the presence of biased adjectives did not affect the time course of processing the target noun. Yet, at the post-verb gap site, the presence of a semantically biased adjective influenced syntactic re-activation. Our results extend the cue-based parsing model by offering new and valuable insights into the processes underlying sentence comprehension of individuals with aphasia.

It's about time! Time as a parameter for lexical and syntactic processing: an eye-tracking-while-listening investigation.

We examined the time-course of lexical activation, deactivation, and the syntactic operation of dependency linking during the online processing of object-relative sentence constructions using eye-tracking-while-listening. We explored how manipulating temporal aspects of the language input affects the tight lexical and syntactic temporal constraints found in sentence processing. The three temporal manipulations were (1) increasing the duration of the direct object noun, (2) adding the disfluency uh after the noun, and (3) replacing the disfluency with a silent pause. The findings from this experiment revealed that the disfluent and silence temporal manipulations enhanced the processing of subject and object noun phrases by modulating activation and deactivation. The manipulations also changed the time-course of dependency linking (increased reactivation of the direct object). The modulated activation dynamics of these lexical items are thought to play a role in mitigating interference and suggest that deactivation plays a beneficial role in complex sentence processing.

Defining Hypoperfusion in Chronic Aphasia: An Individualized Thresholding Approach.

Within the aphasia literature, it is common to link location of lesioned brain tissue to specific patterns of language impairment. This has provided valuable insight into the relationship between brain structure and function, but it does not capture important underlying alterations in function of regions that remain structurally intact. Research has demonstrated that in the chronic stage of aphasia, variable patterns of reduced cerebral blood flow (CBF; hypoperfusion) in structurally intact regions of the brain contribute to persisting language impairments. However, one consistent issue in this literature is a lack of clear consensus on how to define hypoperfusion, which may lead to over- or underestimation of tissue functionality. In the current study, we conducted an exploratory analysis in six individuals with chronic aphasia (>1 year post-onset) using perfusion imaging to (1) suggest a new, individualized metric for defining hypoperfusion; (2) identify the extent of hypoperfused tissue in perilesional bands; and (3) explore the relationship between hypoperfusion and language impairment. Results indicated that our individualized metric for defining hypoperfusion provided greater precision when identifying functionally impaired tissue and its effects on language function in chronic aphasia. These results have important implications for intervention approaches that target intact (or impaired) brain tissue.

The time course of priming in aphasia: An exploration of learning along a continuum of linguistic processing demands.

This study investigates learning in aphasia as manifested through automatic priming effects. There is growing evidence that people with aphasia have impairments beyond language processing that could affect their response to treatment. Therefore, better understanding these mechanisms would be beneficial for improving methods of rehabilitation. This study assesses semantic and repetition priming effects at varied interstimulus intervals, using stimuli that are both non-linguistic and linguistic in tasks that range from requiring nearly no linguistic processing to requiring both lexical and semantic processing. Results indicate that people with aphasia maintain typical patterns of learning across both linguistic and non-linguistic tasks as long as the implicit prime-target relationship does not depend on deep levels of linguistic processing. As linguistic processing demands increase, those with agrammatic aphasia may require more time to take advantage of learning through implicit prime-target relationships, and people with both agrammatic and non-agrammatic aphasia are more susceptible to breakdown of the semantic networks as processing demands on that system increase.

Lack of effectiveness of the 23-valent polysaccharide pneumococcal vaccine in reducing all-cause pneumonias among healthy young military recruits: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Streptococcus pneumoniae infections have periodically caused significant morbidity and outbreaks among military personnel, especially trainees. This study evaluated the effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in reducing pneumonia in healthy military trainees. METHODS: From 2000-2003, 152723 military trainees from 5 US training camps were enrolled in a double-blind, placebo-controlled trial of PPV23. Participants were closely monitored during basic training for radiographically confirmed pneumonia etiology and loss-of-training days. Participants were also followed using electronic medical encounter data until 1 June 2007 for three additional outcomes: any-cause pneumonia, any acute respiratory disease, and meningitis. RESULTS: Comparison of demographic data by study arm suggested the randomization procedures were sound. During basic training, 371 study participants developed radiographically confirmed pneumonia. None had evidence of S. pneumoniae infection, but other etiologies included adenovirus (38%), Chlamydophila pneumoniae (9%), and Mycoplasma pneumoniae (8%). During the follow-up period, many study participants, in both the vaccine and placebo groups, had clinical encounters for the medical outcomes of interest. However, Cox's proportional hazard modeling revealed no evidence of a protective vaccine effect during recruit training (radiographically confirmed pneumonia) or up to 6.7 years after enrollment (any-cause pneumonia, any acute respiratory disease, or meningitis). CONCLUSIONS: Data from this large, double-blind, placebo controlled trial do not support routine use of PPV23 among healthy new military trainees. This clinical trial was registered at clinicaltrials.gov (registration number NCT02079701, http://www.clinicaltrials.gov/ct2/show/NCT02079701?term=NCT02079701&rank=1).

Creating sustained improvements in patient access and flow: experiences from three Ontario healthcare institutions.

Ensuring that patients receive timely, high-quality healthcare is the highest priority of Ontario's hospitals, physicians and nurses. Given that the emergency department (ED) is often the "front door" to our healthcare system, developing approaches to improve access and flow in the ED is important - made more challenging by rising patient demand and acuity. Long-standing efforts to improve the ED system have outlined promising approaches and pushed access and flow up the priority list. Recently, in partnership with the Ministry of Health and Long-Term Care (MOHLTC), several Ontario hospitals participated in an intensive and sustained effort to improve access and flow, with promising results. Participants in these efforts described the initiatives as transformational, and the results have been promising and sustained. This article chronicles the efforts of three hospitals to enable other hospitals, physicians and nurses to learn from these experiences and gain confidence that a similar impact can be achieved in their facilities. Specifically, it discusses the following: The three pillars of sustainable transformation. Hospital case studies. St. Joseph's Health Centre (SJHC), Toronto. London Health Sciences Centre (LHSC) - University Hospital. University Health Network (UHN) - Toronto General and Toronto Western. Advice for other hospitals

Fatal meningitis in a previously healthy young adult caused by Streptococcus pneumoniae serotype 38: an emerging serotype?

BACKGROUND: In December 2001, a fatal case of pneumococcal meningitis in a Marine Corps recruit was identified. As pneumococcal vaccine usage in recruit populations is being considered, an investigation was initiated into the causative serotype. CASE PRESENTATION: Traditional and molecular methods were utilized to determine the serotype of the infecting pneumococcus. The pneumococcal isolate was identified as serotype 38 (PS38), a serotype not covered by current vaccine formulations. The global significance of this serotype was explored in the medical literature, and found to be a rare but recognized cause of carriage and invasive disease. CONCLUSION: The potential of PS38 to cause severe disease is documented in this report. Current literature does not support the hypothesis that this serotype is increasing in incidence. However, as we monitor the changing epidemiology of pneumococcal illness in the US in this conjugate era, PS38 might find a more prominent and concerning niche as a replacement serotype.

Functional behavior of primary rat liver cells in a three-dimensional perfused microarray bioreactor.

We have previously described the design and operation of a microfabricated bioreactor that supports perfused 3D culture of liver cells and facilitates evolution of tissue-like morphological structures. Here, we describe the functional viability of cells maintained in this microarray bioreactor and examine the influence of different seeding protocols on the evolution of structure and function in comparison with static culture. Primary rat hepatocytes were seeded into the perfusion reactors either as single-cell suspensions immediately after isolation or as spheroidal aggregates formed over a 2- to 3-day period. Initial studies in which cells were cultured for 7 days postisolation revealed significantly greater functional activity and morphological stability of cells that were preaggregated for up to 3 days before seeding in the reactor, compared with direct seeding of single cells. Total albumin secretion and urea genesis rates in single-cell reactor cultures declined significantly during this initial culture period while remaining constant in preaggregated reactor cultures. Longer term studies indicate that rates of albumin secretion and urea genesis are maintained at constant levels through 15 days postisolation. These metabolic rates are an order of magnitude higher than observed for the same preaggregated structures cultured statically with comparable medium ratio and exchange conditions. The metabolic function data are supported by light microscopy images showing viable tissue structures, and electron microscopy images that reveal tight junctions, glycogen storage, and bile canaliculi.