Buildout and integration of an automated high-throughput CLIA laboratory for SARS-CoV-2 testing on a large urban campus.

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.

Assessment of a COVID-19 Control Plan on an Urban University Campus During a Second Wave of the Pandemic.

Importance: The COVID-19 pandemic has severely disrupted US educational institutions. Given potential adverse financial and psychosocial effects of campus closures, many institutions developed strategies to reopen campuses in the fall 2020 semester despite the ongoing threat of COVID-19. However, many institutions opted to have limited campus reopening to minimize potential risk of spread of SARS-CoV-2. Objective: To analyze how Boston University (BU) fully reopened its campus in the fall of 2020 and controlled COVID-19 transmission despite worsening transmission in Boston, Massachusetts. Design, Setting, and Participants: This multifaceted intervention case series was conducted at a large urban university campus in Boston, Massachusetts, during the fall 2020 semester. The BU response included a high-throughput SARS-CoV-2 polymerase chain reaction testing facility with capacity to deliver results in less than 24 hours; routine asymptomatic screening for COVID-19; daily health attestations; adherence monitoring and feedback; robust contact tracing, quarantine, and isolation in on-campus facilities; face mask use; enhanced hand hygiene; social distancing recommendations; dedensification of classrooms and public places; and enhancement of all building air systems. Data were analyzed from December 20, 2020, to January 31, 2021. Main Outcomes and Measures: SARS-CoV-2 diagnosis confirmed by reverse transcription-polymerase chain reaction of anterior nares specimens and sources of transmission, as determined through contact tracing. Results: Between August and December 2020, BU conducted more than 500 000 COVID-19 tests and identified 719 individuals with COVID-19, including 496 students (69.0%), 11 faculty (1.5%), and 212 staff (29.5%). Overall, 718 individuals, or 1.8% of the BU community, had test results positive for SARS-CoV-2. Of 837 close contacts traced, 86 individuals (10.3%) had test results positive for COVID-19. BU contact tracers identified a source of transmission for 370 individuals (51.5%), with 206 individuals (55.7%) identifying a non-BU source. Among 5 faculty and 84 staff with SARS-CoV-2 with a known source of infection, most reported a transmission source outside of BU (all 5 faculty members [100%] and 67 staff members [79.8%]). A BU source was identified by 108 of 183 undergraduate students with SARS-CoV-2 (59.0%) and 39 of 98 graduate students with SARS-CoV-2 (39.8%); notably, no transmission was traced to a classroom setting. Conclusions and Relevance: In this case series of COVID-19 transmission, BU used a coordinated strategy of testing, contact tracing, isolation, and quarantine, with robust management and oversight, to control COVID-19 transmission in an urban university setting.

Catalyzing Interdisciplinary Research and Training: Initial Outcomes and Evolution of the Affinity Research Collaboratives Model.

Team science has been recognized as critical to solving increasingly complex biomedical problems and advancing discoveries in the prevention, diagnosis, and treatment of human disease. In 2009, the Evans Center for Interdisciplinary Biomedical Research (ECIBR) was established in the Department of Medicine at Boston University School of Medicine as a new organizational paradigm to promote interdisciplinary team science. The ECIBR is made up of affinity research collaboratives (ARCs), consisting of investigators from different departments and disciplines who come together to study biomedical problems that are relevant to human disease and not under interdisciplinary investigation at the university. Importantly, research areas are identified by investigators according to their shared interests. ARC proposals are evaluated by a peer review process, and collaboratives are funded annually for up to three years.Initial outcomes of the first 12 ARCs show the value of this model in fostering successful biomedical collaborations that lead to publications, extramural grants, research networking, and training. The most successful ARCs have been developed into more sustainable organizational entities, including centers, research cores, translational research projects, and training programs.To further expand team science at Boston University, the Interdisciplinary Biomedical Research Office was established in 2015 to more fully engage the entire university, not just the medical campus, in interdisciplinary research using the ARC mechanism. This approach to promoting team science may be useful to other academic organizations seeking to expand interdisciplinary research at their institutions.

Communication and quality of life outcomes from an interprofessional intensive, comprehensive, aphasia program (ICAP).

BACKGROUND: Intensive Comprehensive Aphasia Programs (ICAPs) have developed in response to a growing need for treatments which produce changes in language function in people with aphasia, especially in the chronic phase of recovery. ICAPs are growing in number and several papers have presented preliminary results of their use, but little data exist about their efficacy or effectiveness. OBJECTIVE: This paper explores the communication effects of an ICAP program that incorporated evidenced-based individual and group treatment in an interprofessional program. METHOD: Twenty-seven individuals with chronic aphasia were provided with 30 h of interprofessional treatment a week for a four-week period in both individual and group formats. A delayed treatment, within-participant research protocol was used. Language measures were taken at two intervals pre- and two intervals post treatment. Functional, narrative, and quality of life measures were taken once pre and once post treatment. RESULTS: Significant change was observed on targeted language functions post treatment. Significant treatment effects were also observed on functional and quality of life measures as well as on all impairment-based language measures for the group. CONCLUSION: The results provide evidence of linguistic and quality of life change in individuals with chronic aphasia who were treated in an interprofessional ICAP.

Working memory and the revision of syntactic and discourse ambiguities.

Two hundred participants, 50 in each of 4 age ranges (19-29 years, 30-49 years, 50-69 years, 70-90 years) were tested for short-term working memory, speed of processing, and online processing of 3 types of sentences in which an initially assigned syntactic structure and/or semantic interpretation had to be revised. Self-paced reading times were longer for the segments that signaled the need for revision; there also were interactions of age and sentence type and speed of processing and sentence type, but not of working memory and sentence type on reading times for these segments. The results provide evidence that working memory does not support the processes that revise the structure and interpretation of sentences and discourse.

Memory mechanisms supporting syntactic comprehension.

Efforts to characterize the memory system that supports sentence comprehension have historically drawn extensively on short-term memory as a source of mechanisms that might apply to sentences. The focus of these efforts has changed significantly in the past decade. As a result of changes in models of short-term working memory (ST-WM) and developments in models of sentence comprehension, the effort to relate entire components of an ST-WM system, such as those in the model developed by Baddeley (Nature Reviews Neuroscience 4: 829-839, 2003) to sentence comprehension has largely been replaced by an effort to relate more specific mechanisms found in modern models of ST-WM to memory processes that support one aspect of sentence comprehension--the assignment of syntactic structure (parsing) and its use in determining sentence meaning (interpretation) during sentence comprehension. In this article, we present the historical background to recent studies of the memory mechanisms that support parsing and interpretation and review recent research into this relation. We argue that the results of this research do not converge on a set of mechanisms derived from ST-WM that apply to parsing and interpretation. We argue that the memory mechanisms supporting parsing and interpretation have features that characterize another memory system that has been postulated to account for skilled performance-long-term working memory. We propose a model of the relation of different aspects of parsing and interpretation to ST-WM and long-term working memory.

Effects of syntactic complexity, semantic reversibility, and explicitness on discourse comprehension in persons with aphasia and in healthy controls.

PURPOSE: Prior studies of discourse comprehension have concluded that the deficits of persons with aphasia (PWA) in syntactically based comprehension of sentences in isolation are not predictive of deficits in comprehension of sentences in discourse (Brookshire & Nicholas, 1984; Caplan & Evans, 1990). However, these studies used semantically constrained sentences in discourse, which do not require syntactic analysis to be understood. A discourse task was developed to assess the effect of syntactic complexity, among other factors, on discourse comprehension in PWA. METHOD: Thirty-eight PWA and 30 neurologically healthy control participants were presented with passages that contained 2-3 semantically reversible sentences that were either syntactically simple or syntactically complex. The passages were presented auditorily, and comprehension was assessed with the auditory and written presentation of 4 multiple-choice questions immediately following each passage. RESULTS: Passages with syntactically simple sentences were better understood than passages with syntactically complex sentences. Moreover, semantically constrained sentences were more likely to be accurately interpreted than semantically reversible sentences. Comprehension accuracy on our test correlated positively with comprehension accuracy on an existing test. CONCLUSION: The presence of semantically reversible, syntactically complex sentences in a passage affects comprehension of the passage in both PWA and neurologically healthy individuals.

Slave systems in verbal short-term memory.

BACKGROUND: The model of performance in short-term memory (STM) tasks that has been most influential in cognitive neuropsychological work on deficits of STM is the "working memory" model mainly associated with the work of Alan Baddeley and his colleagues. AIM: This paper reviews the model. We examine the development of this theory in studies that account for STM performances in normal (non-brain-damaged) individuals, and then review the application of this theory to neuropsychological cases and specifications, modifications, and extensions of the theory that have been suggested on the basis of these cases. Our approach is to identify the major phenomena that have been discussed and to examine selected papers dealing with those phenomena in some detail. MAIN CONTRIBUTION: The main contribution is a review of the WM model that includes both normative and neuropsychological data. CONCLUSIONS: We conclude that the WM model has many inconsistencies and empirical inadequacies, and that cognitive neuropsychologists might benefit from considering other models when they attempt to describe and explain patients' performances on STM tasks.

Effects of concurrent arithmetical and syntactic complexity on self-paced reaction times and eye fixations.

Two dual-task experiments (replications of Experiments 1 and 2 in Fedorenko, Gibson, & Rohde, Journal of Memory and Language, 56, 246-269 2007) were conducted to determine whether syntactic and arithmetical operations share working memory resources. Subjects read object- or subject-extracted relative clause sentences phrase by phrase in a self-paced task while simultaneously adding or subtracting numbers. Experiment 2 measured eye fixations as well as self-paced reaction times. In both experiments, there were main effects of syntax and of mathematical operation on self-paced reading times, but no interaction of the two. In the Experiment 2 eye-tracking results, there were main effects of syntax on first-pass reading time and total reading time and an interaction between syntax and math in total reading time on the noun phrase within the relative clause. The findings point to differences in the ways individuals process sentences under these dual-task conditions, as compared with viewing sentences during "normal" reading conditions, and do not support the view that arithmetical and syntactic integration operations share a working memory system.

Effects of age, speed of processing, and working memory on comprehension of sentences with relative clauses.

Two hundred participants, 50 in each of four age ranges (19-29, 30-49, 50-69, 70-90) were tested for working memory, speed of processing, and the processing of sentences with relative clauses. In Experiment 1, participants read four sentence types (cleft subject, cleft object, subject-subject, subject-object) in a word-by-word, non-cumulative, self-paced reading task and made speeded plausibility judgments about them. In Experiment 2, participants read two types of sentences, one of which contained a doubly center embedded relative clause. Older participants' comprehension was less accurate and there was age-related slowing of online processing times in all but the simplest sentences, which increased in syntactically complex sentences in Experiment 1. This pattern suggests an age-related decrease in the efficiency of parsing and interpretation. Slower speed of processing and lower working memory were associated with longer online processing times only in Experiment 2, suggesting that task-related operations are related to general speed of processing and working memory. Lower working memory was not associated with longer reading times in more complex sentences, consistent with the view that general working memory is not critically involved in online syntactic processing. Longer online processing at the most demanding point in the most demanding sentence was associated with better comprehension, indicating that it reflects effective processing under some certain circumstances. However, the poorer comprehension performance of older individuals indicates that their slower online processing reflects inefficient processing even at these points.

Task-dependent and task-independent neurovascular responses to syntactic processing.

The neural basis for syntactic processing was studied using event-related fMRI to determine the locations of BOLD signal increases in the contrast of syntactically complex sentences with center-embedded, object-extracted relative clauses and syntactically simple sentences with right-branching, subject-extracted relative clauses in a group of 15 participants in three tasks. In a sentence verification task, participants saw a target sentence in one of these two syntactic forms, followed by a probe in a simple active form, and determined whether the probe expressed a proposition in the target. In a plausibility judgment task, participants determined whether a sentence in one of these two syntactic forms was plausible or implausible. Finally, in a non-word detection task, participants determined whether a sentence in one of these two syntactic forms contained only real words or a non-word. BOLD signal associated with the syntactic contrast increased in the left posterior inferior frontal gyrus in non-word detection and in a widespread set of areas in the other two tasks. We conclude that the BOLD activity in the left posterior inferior frontal gyrus reflects syntactic processing independent of concurrent cognitive operations and the more widespread areas of activation reflect the use of strategies and the use of the products of syntactic processing to accomplish tasks.

Syntactic and thematic constraint effects on blood oxygenation level dependent signal correlates of comprehension of relative clauses.

The effects of plausibility of thematic role assignment and syntactic structure on blood oxygenation level dependent (BOLD) signal were studied using event-related functional magnetic resonance imaging by orthogonally varying syntactic structure (subject-vs. object-extracted relative clauses) and the plausibility of nouns playing thematic roles (constrained vs. unconstrained sentences) in a plausibility judgment task. In plausible sentences, BOLD signal increased for object-compared to subject-extracted clauses in unconstrained sentences in left middle temporal and left inferior frontal areas, for this contrast in constrained sentences in left middle temporal but not left inferior frontal areas, and for constrained subject-extracted sentences compared to unconstrained subject-extracted sentences in the left inferior frontal gyrus and the left dorsolateral prefrontal cortex. We relate these areas of activation to the assignment of the syntactic structure of object-compared to subject-extracted structures and the process of checking which thematic roles activated in the course of processing a sentence are licensed by the syntactic structure of the sentence.

A study of syntactic processing in aphasia II: neurological aspects.

This paper presents the results of a study of the effects of left hemisphere strokes on syntactically-based comprehension in aphasic patients. We studied 42 patients with aphasia secondary to left hemisphere strokes and 25 control subjects for the ability to assign and interpret three syntactic structures (passives, object extracted relative clauses, and reflexive pronouns) in enactment, sentence-picture matching and grammaticality judgment tasks. We measured accuracy, RT and self-paced listening times in SPM and GJ. We obtained magnetic resonance (MR) and 5-deoxyglucose positron emission tomography (FDG PET) data on 31 patients and 12 controls. The percent of selected regions of interest (ROIs) that was lesioned on MR and the mean normalized PET counts per voxel in ROIs were calculated. In regression analyses, lesion measures in both perisylvian and non-perisylvian ROIs predicted performance. Patients who performed at similar levels behaviorally had lesions of very different sizes, and patients with equivalent lesion sizes varied greatly in their level of performance. The data are consistent with a model in which the neural tissue that is responsible for the operations underlying sentence comprehension and syntactic processing is localized in different neural regions in different individuals.

A study of syntactic processing in aphasia I: behavioral (psycholinguistic) aspects.

This paper presents the results of a study of syntactically based comprehension in aphasic patients. We studied 42 patients with aphasia secondary to left hemisphere strokes and 25 control participants. We measured off-line, end-of-sentence, performance (accuracy and reaction time) in two tasks that require comprehension--enactment and sentence-picture matching--and in grammaticality judgment, with whole sentence auditory presentation. We also used sentence-picture matching and grammaticality judgment as tasks in two self-paced listening studies with the same patients to measure on-line performance. In each task and presentation format, we presented sentences that tested the ability to assign and interpret three structural contrasts chosen to examine different basic syntactic operations: actives and passives, subject and object extracted relative clauses, and reflexive pronouns and matched sentences without these elements. We examined these behavioral data to determine patterns of impairment in individual patients and in groups of patients, using correlational analyses, factor analyses, and analyses of variance. The results showed that almost no individual patients had stable deficits referable to the ability to interpret individual syntactic structures, that a variety of structural features contributed to sentence processing complexity both on-line and off-line, that correct responses were associated with normal on-line and errors with abnormal performance, and that the major determinant of performance is a factor that affected performance on all sentence types. The results indicate that the major cause of aphasic impairments of syntactically based comprehension are intermittent reductions in the processing capacity available for syntactic, interpretive, and task-related operations.

Determinants of bold signal correlates of processing object-extracted relative clauses.

Event-related functional magnetic resonance imaging (fMRI) was used to investigate the determinants of blood oxygenation level-dependent (BOLD) signal correlates of processing relative clauses. Matched pairs of sentences that differed in their processing demands were compared. One member of the pair consisted of a syntactically simpler object-subject (OS) sentence, containing a subject-relativized clause attached to the object noun phrase. The second member of the pair consisted of a syntactically more complex subject-object (SO) sentence, containing an object-relativized clause attached to the subject noun phrase. Participants made plausibility judgments about the sentences in whole sentence visual presentation. Voxel-wise statistical activation maps showed increased BOLD signal in multiple cortical regions for complex compared to simple syntactic structures. This pattern was found for plausible sentences only and, within the set of plausible sentences, for SO sentences in which the head noun of the relative clause was animate and the subject noun of the relative clause was inanimate. These results require a re-interpretation of previous results with the same materials using positron emission tomography.

The relationship between age, processing speed, working memory capacity, and language comprehension.

A total of 50 elderly individuals and 48 college students were tested on several measures of processing speed and of working memory capacity. Language processing was tested with an on-line measure of sentence processing efficiency, an end-of-sentence acceptability judgement task, and a paragraph comprehension test. Elderly individuals performed more poorly than college students on the speed of processing and working memory measures and had longer listening times overall on the sentence processing measures. Elderly individuals did not, however, have overall longer listening times at the most capacity-demanding regions of the harder sentence types. Correlational analyses failed to establish a relationship between the increase in syntactic processing load at the capacity-demanding region of the harder sentence type and the measures of working memory capacity, but did establish a relationship between paragraph comprehension and working memory capacity. The data are argued to provide evidence that the WM system used to structure sentences syntactically is separate from that used in other aspects of language comprehension.

The relationship between age, verbal working memory, and language comprehension.

A structural modeling approach was used to examine the relationships between age, verbal working memory (vWM), and 3 types of language measures: online syntactic processing, sentence comprehension, and text comprehension. The best-fit model for the online-processing measure revealed a direct effect of age on online sentence processing, but no effect mediated through vWM. The best-fit models for sentence and text comprehension included an effect of age mediated through vWM and no direct effect of age. These results indicate that the relationship among age, vWM, and comprehension differs depending on the measure of language processing and support the view that individual differences in vWM do not affect individuals' online syntactic processing.

Verbal working memory and on-line syntactic processing: evidence from self-paced listening.

Two experiments investigated the relationship between performance on standard tests of verbal working-memory and the on-line construction of syntactic form. In Experiment 1, working-memory was measured in 100 college students on a version of the Daneman and Carpenter (1980) reading-span task, and online syntactic processing was assessed using a self-paced listening task with four sentence types. In Experiment 2, working-memory was measured in 48 college students on two versions of the reading-span task and two other tests of verbal working-memory, and on-line syntactic processing was assessed using the self-paced listening task with an additional sentence type. In both experiments, there was no relationship between working-memory capacity and the increase in processing time seen for the on-line construction of syntactic form for either syntactically more complex or syntactically simpler sentences. The results indicate that the capacity of the working-memory system that is measured by standard working-memory tests does not determine the efficiency of on-line syntactic processing. They are consistent with the view that the working-memory system used for parsing is at least partially separate from that measured by traditional measures of working-memory capacity.

Individual differences in rCBF correlates of syntactic processing in sentence comprehension: effects of working memory and speed of processing.

Positron emission tomography (PET) was used to determine the effect of working memory and speed of sentence processing on regional cerebral blood flow (rCBF) during syntactic processing in sentence comprehension. PET activity associated with making plausibility judgments about syntactically more complex subject-object (SO) sentences (e.g., The juice that the child spilled stained the rug) was compared to that associated with making judgments about synonymous syntactically simpler object-subject (OS) sentences (e.g., The child spilled the juice that stained the rug). Two groups of nine subjects differing in working memory and matched for speed of sentence processing both showed increases in rCBF in lateral posteroinferior frontal lobe bilaterally. The subjects were reclassified to form two groups of eight subjects who were matched for working memory but who differed in speed of sentence processing. Fast-performing subjects activated lateral posteroinferior frontal lobe bilaterally and slow-performing subjects showed activation of left superior temporal lobe. The results indicate that rCBF responses to syntactic comprehension tasks vary as a function of speed of sentence processing but not as a function of working memory.

On-line syntactic processing under concurrent memory load.

Thirty-six university students were tested in a plausibility judgment task using a self-paced listening paradigm under no-interference and two-digit load conditions. Listening times were longer at syntactically more complex portions of syntactically more complex sentences, and greater loads led to increased listening times. However, listening times at syntactically more complex positions in syntactically more complex sentences did not increase more than listening times at comparable positions in syntactically simple sentences under digit load conditions. The results indicate that a concurrent memory load does not reduce the availability of working memory resources used for on-line syntactic processing and, thus, provide evidence that the working memory system used for assigning syntactic structure is separate from that measured by standard working memory tasks.