The unexplained nature of reading.

The effects of properties of words on their reading aloud response times (RTs) are 1 major source of evidence about the reading process. The precision with which such RTs could potentially be predicted by word properties is critical to evaluate our understanding of reading but is often underestimated due to contamination from individual differences. We estimated this precision without such contamination individually for 4 people who each read 2,820 words 50 times each. These estimates were compared to the precision achieved by a 31-variable regression model that outperforms current cognitive models on variance-explained criteria. Most (around 2/3) of the meaningful (non-first-phoneme, non-noise) word-level variance remained unexplained by this model. Considerable empirical and theoretical-computational effort has been expended on this area of psychology, but the high level of systematic variance remaining unexplained suggests doubts regarding contemporary accounts of the details of the mechanisms of reading at the level of the word. Future assessment of models can take advantage of the availability of our precise participant-level database

PSYCHOSOCIAL FACTORS AND MOBILE HEALTH INTERVENTION: IMPACT ON LONG-TERM OUTCOMES AFTER LUNG TRANSPLANTATION

Identifying and intervening on modifiable risk factors may improve outcomes in lung transplantation (LTx), which, despite recent improvements, remain suboptimal. Evidence suggests that two modifiable risk factors, psychiatric disorders and nonadherence, may improve LTx outcomes in the short-term; however, neither has been explored in the long-term. Therefore, the overarching goal of this dissertation was to determine the long-term impact of these modifiable risk factors and intervention to attenuate them. First, we examined the relationship of pre- and early post-transplant psychiatric disorders on LTx-related morbidity and mortality for up to 15 years post-LTx. Our sample included 155 1-year LTx survivors enrolled in a prospective study of mental health post- LTx. We found that depression during the first year post-LTx increased risk of BOS, mortality and graft loss by nearly twofold, and that pre-transplant depression and pre- and post-transplant anxiety were not associated with clinical outcomes. Next, we examined the impact of a mobile health intervention designed to promote adherence to the post-LTx regimen, PocketPATH, on long-term LTx-related morbidity, mortality and nonadherence. We conducted two follow-up studies to the original yearlong randomized controlled trial in which participants assigned to PocketPATH showed improved adherence to the regimen, relative to usual care. Among the 182 LTx recipients (LTxRs) who survived the original trial, we found that PocketPATH had a protective indirect effect on mortality by promoting LTxRs’ communication with the LTx team during the first year. Among the 104 LTxRs who completed the follow-up assessment, we found that PocketPATH’s adherence benefits over the first year were not sustained into the long-term, although LTxRs assigned to PocketPATH were more likely than LTxRs assigned to usual care to perform the home self-care tasks of the regimen at follow-up. Median time since LTx for participants in both follow-up studies was 4.2 years (range, 2.8-5.7 years). This dissertation presents an important first step toward identifying and intervening on modifiable risk factors to improve long-term LTx outcomes. Mobile health technologies offer limitless potential to target these risk factors and others. More work is needed to determine specific features and long-term patient engagement strategies that will optimize and sustain intervention effectiveness

Impact of sociodemographic characteristics of applicants in multiple mini-interviews

Background: Multiple mini-interviews (MMI) are commonly used for medical school admission. This study aimed to assess if sociodemographic characteristics are associated with MMI performance, and how they may act as barriers or enablers to communication in MMI.Methods: This mixed-method study combined data from a sociodemographic questionnaire, MMI scores, semi-structured interviews and focus groups with applicants and assessors. Quantitative and qualitative data were analyzed using multiple linear regression and a thematic framework analysis.Results: 1099 applicants responded to the questionnaire. A regression model (R(2 )=( )0.086) demonstrated that being age 25-29 (β = 0.11, p = 0.001), female and a French-speaker (β = 0.22, p = 0.003) were associated with better MMI scores. Having an Asian-born parent was associated with a lower score (β = -0.12, p &lt; 0.001). Candidates reporting a higher family income had higher MMI scores. In the qualitative data, participants discussed how maturity and financial support improved life experiences, how language could act as a barrier, and how ethnocultural differences could lead to misunderstandings.Conclusion: Age, gender, ethnicity, socioeconomic status and language seem to be associated with applicants' MMI scores because of perceived differences in communications skills and life experiences. Monitoring this association may provide guidance to improve fairness of MMI stations.</p

Thalamic pathology and memory loss in early Alzheimer’s disease: moving the focus from the medial temporal lobe to Papez circuit

It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer’s disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer’s disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer’s disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer’s disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer’s disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer’s disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer’s disease

Enhanced multiplex genome engineering through co-operative oligonucleotide co-selection

Genome-scale engineering of living organisms requires precise and economical methods to efficiently modify many loci within chromosomes. One such example is the directed integration of chemically synthesized single-stranded deoxyribonucleic acid (oligonucleotides) into the chromosome of Escherichia coli during replication. Herein, we present a general co-selection strategy in multiplex genome engineering that yields highly modified cells. We demonstrate that disparate sites throughout the genome can be easily modified simultaneously by leveraging selectable markers within 500 kb of the target sites. We apply this technique to the modification of 80 sites in the E. coli genome.United States. Dept. of Energy. Genomes To Life (DE-FG02-03ER6344)National Science Foundation (U.S.). Genes and Genomes Systems Cluster (0719344)National Science Foundation (U.S.). Center for Bits and Atoms (0122419)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (0540879

Patterns of pre-registration and publication of trials in Cochrane systematic reviews of interventions

Objectives It is widely recognized that selective reporting clinical trial results based on their outcomes, in the forms of publication bias, outcome reporting bias, or p-hacking, has detrimental effects on the scientific literature and on evidence synthesis. This can be recognized and perhaps ameliorated with comprehensive trial registration. However, previous investigations of clinical trial registration focused on study-level examinations rather than the number of trial participants, which is often more relevant to meta-analysis. Our objective was to investigate the risk of bias from selective reporting considering both trials but also the number of included participants. Methods We took a random sample of 50 Cochrane systematic reviews (SRs) of interventions which included randomized controlled trials, forming a retrospective cohort. Focusing on the primary outcome in the SR we used the review, published trial information, and public trial registration documents to collect information about the reviews themselves, as well as information about “included,” “ongoing,” and studies “awaiting classification”. Results In all 50 selected reviews, there were 423 “included” trials which examined the primary outcome, of which 109 (25.7%) were preregistered. There was substantial variability in proportions of preregistration of included trials among reviews, with a median of 16.0% (interquartile range 0%−79.6%). Registered trials covered 60.1% of all participants, suggesting larger studies were more likely to be preregistered. The proportion of participants in registered trials which were published was high (98.2%), but the proportion of registered trials which were published also varied substantially between reviews. Conclusion We found that in Cochrane reviews, there remains a low rate of preregistration among included studies and evidence for a substantial rate of trial nonreporting of registered trials. However, preregistered trials contributed proportionally more patients to reviews, and findings remain unpublished for only a small proportion of participants in registered trials

Letters in words are read simultaneously, not in left-to-right sequence

The identification of individual letters is necessary for reading words in alphabetic script (Pelli, Farell, & Moore, 2003). Sequential models of letter processing (Whitney, 2001) in reading words posit an initial left-to-right sequence of letter processing (in left-to-right languages, such as English), each letter taking 10–25 ms to process before the next is processed. In contrast, simultaneous models of letter processing (e.g., Tydgat & Grainger, 2009) in reading words posit that information about the identity of each letter starts to be extracted at the same time point, regardless of horizontal position. Here we show that people reading four-letter words do not extract identity information for any letter from an 18 ms display of the word, but some information about all four letters is available from 24 ms of display. Our results indicate that a left-to-right sequence of attention across letters is not used in establishing the cognitive representation of words. Instead, all letters are processed simultaneously