Bypass language en route to meaning at your peril.

The learning account of the puzzle of ideography cannot be dismissed as readily as Morin maintains, and is compatible with the standardization account. The reading difficulties of deaf and dyslexic individuals, who cannot easily form connections between written letter strings and spoken words, suggest limits to our ability to bypass speech and reliably access meaning directly from graphic symbols.

Braille literacy as a human right: A challenge to the "inefficiency" argument against braille instruction.

The United Nations Convention on the Rights of Persons with Disabilities (CRPD) affirms a right to education for disabled persons and aims to ensure braille instruction for blind individuals. However, there is evidence that braille instruction is often circumvented or abandoned early in CRPD nations because it is perceived as an inefficient learning medium for blind students. This perception persists despite insufficient empirical evidence and a lack of understanding of the efficiency of reading versus listening for learning in sighted individuals. We therefore investigated the efficiency of learning written versus spoken words in blind and sighted samples. Participants (23 blind, 20 sighted) studied the written definitions of 70 rare English words in successive rounds, presented in conjunction with written or spoken wordforms. Blind participants learned with equal efficiency across modalities, whereas sighted participants learned spoken words more efficiently. The findings indicate the inefficiency argument against teaching braille is groundless, both because braille word learning is not less efficient than auditory word learning for blind individuals, and because reading is valued in the education of sighted individuals despite its apparent inefficiency in that population.

Benchmarking challenging small variants with linked and long reads.

Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling and sequencing methods. Here we use accurate linked and long reads to expand benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are challenging for short reads. These benchmarks add more than 300,000 SNVs and 50,000 insertions or deletions (indels) and include 16% more exonic variants, many in challenging, clinically relevant genes not covered previously, such as PMS2. For HG002, we include 92% of the autosomal GRCh38 assembly while excluding regions problematic for benchmarking small variants, such as copy number variants, that should not have been in the previous version, which included 85% of GRCh38. It identifies eight times more false negatives in a short read variant call set relative to our previous benchmark. We demonstrate that this benchmark reliably identifies false positives and false negatives across technologies, enabling ongoing methods development.

Culture is not destiny, for reading: highlighting variable routes to literacy within writing systems.

Cross-writing system research in psychology and cognitive neuroscience has yielded important findings regarding how a writing system's structure can influence the cognitive challenges of learning to read and the neural underpinnings of literacy. The current paper reviews these differences and extends the findings to demonstrate diversity in how skilled reading is accomplished within a single writing system, English. We argue that broad clusters of behavioral and neural patterns found across writing systems can also be found within subpopulations who display atypical routes to skilled English reading, subpopulations including Chinese-English bilinguals, deaf native signers, compensated readers, and distortion-sensitive readers. The patterns of interest include a tradeoff between the degree of reliance on phonological and morphological processing for skilled reading, a shift in attentional focus from smaller to larger orthographic units, and enhanced bilaterality of neural processing during word reading. Lastly, we consider how understanding atypical routes to reading may apply to other writing systems.

The role of word knowledge in error detection: a challenge to the broken error monitor account of dyslexia.

Dyslexic children often fail to correct errors while reading aloud, and dyslexic adolescents and adults exhibit lower amplitudes of the error-related negativity (ERN)-the neural response to errors-than typical readers during silent reading. Past researchers therefore suggested that dyslexia may arise from a faulty error detection mechanism that interferes with orthographic learning and text comprehension. An alternative possibility is that comprehension difficulty in dyslexics is primarily a downstream effect of low-quality lexical representations-that is, poor word knowledge. On this view, the attenuated ERN in dyslexics is a byproduct, rather than a source, of underdeveloped orthographic knowledge. Because the second view implies a direct association of the error response with comprehension skill in populations of all ability levels, the present study evaluates these alternatives through a reanalysis of behavioral and neural data from 31 typical adult readers. If it is true that faulty error processing can manifest as dyslexia, a model in which error monitoring contributes directly to comprehension should outperform a model in which it does not. ERNs recorded during spelling judgments were used as a measure of error detection aptitude in path analyses of reading comprehension. The data were better fit by a model in which error detection aptitude was a consequence of word knowledge than a model in which it contributed directly to comprehension. The findings challenge the notion that comprehension difficulty in dyslexics is attributable to error processing deficits and are consistent with the hypothesis that comprehension difficulty in dyslexics is partially attributable to low-quality word knowledge.

Curated variation benchmarks for challenging medically relevant autosomal genes.

The repetitive nature and complexity of some medically relevant genes poses a challenge for their accurate analysis in a clinical setting. The Genome in a Bottle Consortium has provided variant benchmark sets, but these exclude nearly 400 medically relevant genes due to their repetitiveness or polymorphic complexity. Here, we characterize 273 of these 395 challenging autosomal genes using a haplotype-resolved whole-genome assembly. This curated benchmark reports over 17,000 single-nucleotide variations, 3,600 insertions and deletions and 200 structural variations each for human genome reference GRCh37 and GRCh38 across HG002. We show that false duplications in either GRCh37 or GRCh38 result in reference-specific, missed variants for short- and long-read technologies in medically relevant genes, including CBS, CRYAA and KCNE1. When masking these false duplications, variant recall can improve from 8% to 100%. Forming benchmarks from a haplotype-resolved whole-genome assembly may become a prototype for future benchmarks covering the whole genome.

Corticosteroids in Community-Acquired Pneumonia: A Review of Current Literature.

Objective: To review the evidence and recommendations for the use of adjunctive corticosteroid therapy in community-acquired pneumonia (CAP). Data Sources: A literature search was conducted using PubMed (1993 to November 2020) using the search terms corticosteroids AND community-acquired pneumonia. Study Selection and Data Extraction: Pertinent randomized controlled trials, systematic reviews, and meta-analyses assessing the efficacy and safety of adjunctive corticosteroids in patients with pneumonia were evaluated for inclusion. Data Synthesis: Studies suggest that corticosteroids reduce time to clinical stability and length of hospital stay, but data regarding other important clinical outcomes, such as mortality, are limited. The greatest margin of benefit appears to be in patients with severe CAP. Evidence consistently demonstrates hyperglycemia as the most common adverse effect of corticosteroid therapy in CAP. Safety concerns regarding the potential impact of corticosteroids on the rate of CAP-related rehospitalizations require further investigation. Relevance to Patient Care and Clinical Practice: This review summarizes literature evaluating the efficacy and safety of adjunctive corticosteroids in patients with CAP. It also includes a discussion on current guideline recommendations, patient selection, corticosteroid regimens, adverse effect considerations, limitations, and future directions in this area of research. Conclusions: Studies reviewed suggest that corticosteroids are relatively beneficial and safe in patients with CAP, with the greatest benefit in severe CAP. Currently, the routine use of corticosteroids is not recommended by clinical practice guidelines with the exception of CAP and refractory septic shock. Further research is needed to better define the ideal role of corticosteroids in CAP.

Reference standards for accurate validation and optimization of assays that determine integrated lentiviral vector copy number in transduced cells.

Lentiviral vectors (LV) have emerged as a robust technology for therapeutic gene delivery into human cells as advanced medicinal products. As these products are increasingly commercialized, there are concomitant demands for their characterization to ensure safety, efficacy and consistency. Standards are essential for accurately measuring parameters for such product characterization. A critical parameter is the vector copy number (VCN) which measures the genetic dose of a transgene present in gene-modified cells. Here we describe a set of clonal Jurkat cell lines with defined copy numbers of a reference lentiviral vector integrated into their genomes. Genomic DNA was characterized for copy number, genomic integrity and integration coordinates and showed uniform performance across independent quantitative PCR assays. Stability studies during continuous long-term culture demonstrated sustained renewability of the reference standard source material. DNA from the Jurkat VCN standards would be useful for control of quantitative PCR assays for VCN determination in LV gene-modified cellular products and clinical samples.

Performance of non-laboratory staff for diagnostic testing and specimen collection in HIV programs: A systematic review and meta-analysis.

BACKGROUND: In most high HIV burden countries, many HIV patients do not have reliable access to required diagnostic laboratory tests. Task shifting of clinical tasks to lower cadres of health care workers and lay counselors has been successful in scaling up treatment for HIV and may also be an effective strategy in expanding access to essential diagnostic testing. METHODS: We screened major electronic databases between 1 January 2005 to 26 August 2018 to identify studies assessing ease of use and accuracy of task shifting of HIV-related diagnostic testing and/or specimen collection to non-laboratory health staff. Two independent reviewers screened all titles and abstracts for studies that analyzed diagnostic accuracy, patient impact, ease-of-use, or cost-effectiveness. Studies were assessed for quality, bias, and applicability following the QUADAS-2 framework. We generated summary estimates using random-effects meta-analyses. RESULTS: We identified 42 relevant studies. Overall, point-of-care CD4 testing performed by non-laboratory staff had a mean bias of -54.44 (95% CI: -72.40 --36.48) compared to conventional laboratory-based. Though studies were limited, the diagnostic accuracy of point-of-care alanine transaminase enzyme (ALT) and hemoglobin testing performed by non-laboratory staff was comparable to conventional laboratory-based testing by laboratory professionals. Point-of-care testing and/or specimen collection were generally found to be acceptable and easy to use for non-laboratory staff. CONCLUSIONS: Task shifting of testing using point-of-care technologies to non-laboratory staff was comparable to laboratory professionals operating the same technology in the laboratory. Some variability was observed comparing the performance of point-of-care CD4 testing by non-laboratory staff to conventional laboratory-based technologies by laboratory professionals indicating potential lower performance was likely technological rather than operator caused. The benefits of task shifting of testing may outweigh any possible harms as task shifting allows for increased decentralization, access of specific diagnostics, and faster result delivery.

Impact of SMS/GPRS Printers in Reducing Time to Early Infant Diagnosis Compared With Routine Result Reporting: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite significant gains made toward improving access, early infant diagnosis (EID) testing programs suffer from long test turnaround times that result in substantial loss to follow-up and mortality associated with delays in antiretroviral therapy initiation. These delays in treatment initiation are particularly impactful because of significant HIV-related infant mortality observed by 2-3 months of age. Short message service (SMS) and general packet radio service (GPRS) printers allow test results to be transmitted immediately to health care facilities on completion of testing in the laboratory. METHODS: We conducted a systematic review and meta-analysis to assess the benefit of using SMS/GPRS printers to increase the efficiency of EID test result delivery compared with traditional courier paper-based results delivery methods. RESULTS: We identified 11 studies contributing data for over 16,000 patients from East and Southern Africa. The test turnaround time from specimen collection to result received at the health care facility with courier paper-based methods was 68.0 days (n = 6835), whereas the test turnaround time with SMS/GPRS printers was 51.1 days (n = 6711), resulting in a 2.5-week (25%) reduction in the turnaround time. CONCLUSIONS: Courier paper-based EID test result delivery methods are estimated to add 2.5 weeks to EID test turnaround times in low resource settings and increase the risk that infants receive test results during or after the early peak of infant mortality. SMS/GPRS result delivery to health care facility printers significantly reduced test turnaround time and may reduce this risk. SMS/GPRS printers should be considered for expedited delivery of EID and other centralized laboratory test results.