Mapping visual symbols onto spoken language along the ventral visual stream.

Reading involves transforming arbitrary visual symbols into sounds and meanings. This study interrogated the neural representations in ventral occipitotemporal cortex (vOT) that support this transformation process. Twenty-four adults learned to read 2 sets of 24 novel words that shared phonemes and semantic categories but were written in different artificial orthographies. Following 2 wk of training, participants read the trained words while neural activity was measured with functional MRI. Representational similarity analysis on item pairs from the same orthography revealed that right vOT and posterior regions of left vOT were sensitive to basic visual similarity. Left vOT encoded letter identity and representations became more invariant to position along a posterior-to-anterior hierarchy. Item pairs that shared sounds or meanings, but were written in different orthographies with no letters in common, evoked similar neural patterns in anterior left vOT. These results reveal a hierarchical, posterior-to-anterior gradient in vOT, in which representations of letters become increasingly invariant to position and are transformed to convey spoken language information.

The Dramatic Impact of Explicit Instruction on Learning to Read in a New Writing System.

There is profound and long-standing debate over the role of explicit instruction in reading acquisition. In this research, we investigated the impact of teaching regularities in the writing system explicitly rather than relying on learners to discover these regularities through text experience alone. Over 10 days, 48 adults learned to read novel words printed in two artificial writing systems. One group learned spelling-to-sound and spelling-to-meaning regularities solely through experience with the novel words, whereas the other group received a brief session of explicit instruction on these regularities before training commenced. Results showed that virtually all participants who received instruction performed at ceiling on tests that probed generalization of underlying regularities. In contrast, despite up to 18 hr of training on the novel words, less than 25% of discovery learners performed on par with those who received instruction. These findings illustrate the dramatic impact of teaching method on outcomes during reading acquisition.

Hand eczema in children referred for patch testing: North American Contact Dermatitis Group Data, 2000-2016.

BACKGROUND: Little is known about the aetiologies and relevant allergens in paediatric patients with hand eczema (HE). OBJECTIVES: To characterize the aetiologies and determine the proportion of positive and currently relevant allergens in children/adolescents (age < 18 years) with HE referred for patch testing. METHODS: A retrospective analysis (2000-2016) of North American Contact Dermatitis Group data was performed. RESULTS: Of 1634 paediatric patients, 237 (14·5%) had involvement of the hands. Final physician diagnoses included allergic contact dermatitis (49·4%), atopic dermatitis (37·1%) and irritant contact dermatitis (16·9%). In multivariable logistic regression models, employment was the only association with increased odds of any HE or primary HE. Children with HE vs. those without HE had similar proportions of positive patch tests (56·1% vs. 61·7%; χ2 -test, P = 0·11). The five most common currently relevant allergens were nickel, methylisothiazolinone, propylene glycol, decyl glucoside and lanolin. In multivariable logistic regression models of the top 20 relevant allergens, HE was associated with significantly higher odds of currently relevant reactions to lanolin, quaternium-15, Compositae mix, thiuram mix, 2-mercaptobenzathiazole and colophony. The allergens with the highest mean significance-prevalence index number were methylisothiazolinone, carba mix, thiuram mix, nickel and methylchloroisothiazolinone/methylisothiazolinone. CONCLUSIONS: Children with HE who were referred for patch testing had a high proportion of positive patch tests, which was similar to the proportion found in children without HE. Children with HE had a distinct and fairly narrow profile of currently relevant allergens.

The relationships between oral language and reading instruction: Evidence from a computational model of reading.

Reading acquisition involves learning to associate visual symbols with spoken language. Multiple lines of evidence indicate that instruction on the relationship between spellings and sounds may be particularly important.However, it is unclear whether the effectiveness of this form of instruction depends on pre-existing oral language knowledge.To investigate this issue, we developed a series of computational models of reading incorporating orthographic, phonological and semantic processing to simulate bothartificialand natural orthographic learning conditions in adults and children. We exposed the models to instruction focused on spelling-sound or spelling-meaning relationships, and tested the influence of the models' oral language proficiency on the effectiveness of these training regimes. Overall, the simulations indicated thatoral language proficiency is a vital foundation for reading acquisition, and may modulate the effectiveness of reading instruction. These results provide a computational basis for the Simple View of Reading,and emphasise the importance of both oral language knowledge and spelling-sound instructionin the initial stages of learning to read.

Evaluating cognitive models of visual word recognition using fMRI: Effects of lexical and sublexical variables.

In this study predictions of the dual-route cascaded (DRC) model of word reading were tested using fMRI. Specifically, patterns of co-localization were investigated: (a) between pseudoword length effects and a pseudowords vs. fixation contrast, to reveal the sublexical grapho-phonemic conversion (GPC) system; and (b) between word frequency effects and a words vs. pseudowords contrast, to reveal the orthographic and phonological lexicon. Forty four native speakers of Greek were scanned at 3T in an event-related lexical decision task with three event types: (a) 150 words in which frequency, length, bigram and syllable frequency, neighborhood, and orthographic consistency were decorrelated; (b) 150 matched pseudowords; and (c) fixation. Whole-brain analysis failed to reveal the predicted co-localizations. Further analysis with participant-specific regions of interest defined within masks from the group contrasts revealed length effects in left inferior parietal cortex and frequency effects in the left middle temporal gyrus. These findings could be interpreted as partially consistent with the existence of the GPC system and phonological lexicon of the model, respectively. However, there was no evidence in support of an orthographic lexicon, weakening overall support for the model. The results are discussed with respect to the prospect of using neuroimaging in cognitive model evaluation.

Distinct neural specializations for learning to read words and name objects.

Understanding the neural systems that underpin reading acquisition is key if neuroscientific findings are to inform educational practice. We provide a unique window into these systems by teaching 19 adults to read 24 novel words written in unfamiliar letters and to name 24 novel objects while in an MRI scanner. Behavioral performance on trained items was equivalent for the two stimulus types. However, componential letter-sound associations were extracted when learning to read, as shown by correct reading of untrained words, whereas object-name associations were holistic and arbitrary. Activity in bilateral anterior fusiform gyri was greater during object name learning than learning to read, and ROI analyses indicated that left mid-fusiform activity was predictive of success in object name learning but not in learning to read. In contrast, activity in bilateral parietal cortices was predictive of success for both stimulus types but was greater during learning and recall of written word pronunciations relative to object names. We argue that mid-to-anterior fusiform gyri preferentially process whole items and contribute to learning their spoken form associations, processes that are required for skilled reading. In contrast, parietal cortices preferentially process componential visual-verbal mappings, a process that is crucial for early reading development.

Interpreting response time effects in functional imaging studies.

It has been suggested that differential neural activity in imaging studies is most informative if it is independent of response time (RT) differences. However, others view RT as a behavioural index of key cognitive processes, which is likely linked to underlying neural activity. Here, we reconcile these views using the effort and engagement framework developed by Taylor, Rastle, and Davis (2013) and data from the domain of reading aloud. We propose that differences in neural engagement should be independent of RT, whereas, differences in neural effort should co-vary with RT. We illustrate these different mechanisms using data from an fMRI study of neural activity during reading aloud of regular words, irregular words, and pseudowords. In line with our proposals, activation revealed by contrasts designed to tap differences in neural engagement (e.g., words are meaningful and therefore engage semantic representations more than pseudowords) survived correction for RT, whereas activation for contrasts designed to tap differences in neural effort (e.g., it is more difficult to generate the pronunciation of pseudowords than words) correlated with RT. However, even for contrasts designed to tap neural effort, activity remained after factoring out the RT-BOLD response correlation. This may reveal unpredicted differences in neural engagement (e.g., learning phonological forms for pseudowords>words) that could further the development of cognitive models of reading aloud. Our framework provides a theoretically well-grounded and easily implemented method for analysing and interpreting RT effects in neuroimaging studies of cognitive processes.

Clinical outcomes of patients with adenocarcinoma in situ of the cervix treated by conization.

OBJECTIVE: To describe the clinical outcomes of histologically confirmed adenocarcinoma in situ (AIS) of the cervix treated with cervical conization. MATERIALS AND METHODS: A retrospective chart review of patients with histologically confirmed AIS from July 1998 to February 2011 included 52 patients. The rates of residual disease in subsequent excisions, the clinical recurrence rate, the average disease-free interval, and risk of progression to adenocarcinoma were described. The clinical outcomes of patients treated with cold knife cone (CKC) and loop electrosurgical excisional procedure (LEEP) were compared. RESULTS: Fifteen LEEPs and 37 CKC procedures were performed as initial treatment and 26 patients (50%) had positive margins. There was no significant difference in rate of positive margins between LEEP and CKC (40% vs. 54%, respectively. p = 0.55). LEEPs and CKCs resulted in similar volumes of cervical tissue resected (4.98 cm3 vs. 5.04 cm3, p = 0.40). Of patients with positive margins, ten underwent immediate hysterectomy, six underwent a second cone biopsy, seven were managed expectantly, and four were lost to follow up. Residual AIS was found in 47% (eight of 17) of repeat cone biopsy and hysterectomy specimens performed for positive cone margins. Of the 26 patients with negative cone margins, no residual or recurrent disease was found after an average follow-up of 32 months. CONCLUSIONS: A positive surgical margin was associated with residual disease in 47% of patients with AIS treated with conization. No patient with negative cone margins had recurrent or progressive disease. Cervical conization with negative margins appears to be a safe treatment option for patients with AIS but requires further investigation. CKC and LEEP were equally efficacious treatments in our study population.

Flexible letter-position coding in Chinese-English L2 bilinguals: Evidence from eye movements.

Theories suggest that efficient recognition of English words depends on flexible letter-position coding, demonstrated by the fact that transposed-letter primes (e.g., JUGDE-judge) facilitate written word recognition more than substituted-letter primes (e.g., JUFBE-judge). The multiple route model predicts that reading experience should drive more flexible letter-position coding as readers transition from decoding words letter-by-letter to recognising words as wholes. This study therefore examined whether letter-position is coded flexibly in second-language English sentence reading for native Chinese speakers, and if this is influenced by English proficiency. Eye movements were measured while 54 adult native Chinese speakers read English sentences including either a real word (e.g., cheaply), a transposed-letter nonword (e.g., "chepaly"), or a substituted-letter nonword (e.g., "chegely"). Flexible letter-position coding was observed in initial and later processing stages-reading times were longer for substituted-letter than transposed-letter nonwords. In addition, reading times were longer in both initial and later processing stages for transposed-letter nonwords than real words, indicating that, despite encoding letter-position flexibly, readers processed letter-position. Although pre-registered frequentist analyses suggested that English proficiency did not predict overall reading times, Bayes Factors indicated that there was evidence for such a relationship. It is therefore likely that this proficiency analysis suffered from low power. Finally, neither frequentist nor Bayes Factor analyses suggested that English proficiency influenced the difference in reading times between different target word types, i.e., the nature of letter-position coding. Overall, these results suggest that highly proficient L2 learners code letter-position flexibly.

Relationship Between Resting State Functional Connectivity and Reading-Related Behavioural Measures in 69 Adults.

In computational models of reading, written words can be read using print-to-sound and/or print-to-meaning pathways. Neuroimaging data associate dorsal stream regions (left posterior occipitotemporal cortex, intraparietal cortex, dorsal inferior frontal gyrus [dIFG]) with the print-to-sound pathway and ventral stream regions (left anterior fusiform gyrus, middle temporal gyrus) with the print-to-meaning pathway. In 69 typical adults, we investigated whether resting state functional connectivity (RSFC) between the visual word form area (VWFA) and dorsal and ventral regions correlated with phonological (nonword reading, nonword repetition, spoonerisms), lexical-semantic (vocabulary, sensitivity to morpheme units in reading), and general literacy (word reading, spelling) skills. VWFA activity was temporally correlated with activity in both dorsal and ventral reading regions. In pre-registered whole-brain analyses, spoonerisms performance was positively correlated with RSFC between the VWFA and left dorsal regions (dIFG, superior parietal and intraparietal cortex). In exploratory region-of-interest analyses, VWFA-dIFG connectivity was also positively correlated with nonword repetition, spelling, and vocabulary. Connectivity between the VWFA and ventral stream regions was not associated with performance on any behavioural measure, either in whole-brain or region-of-interest analyses. Our results suggest that tasks such as spoonerisms and spellings, which are both complex (i.e., involve multiple subprocesses) and have high between-subject variability, provide greater opportunity for observing resting-state brain-behaviour associations. However, the complexity of these tasks limits the conclusions we can draw about the specific mechanisms that drive these associations. Future research would benefit from constructing latent variables from multiple tasks tapping the same reading subprocess.

White matter associations with spelling performance.

Multiple neurocognitive processes are involved in the highly complex task of producing written words. Yet, little is known about the neural pathways that support spelling in healthy adults. We assessed the associations between performance on a difficult spelling-to-dictation task and microstructural properties of language-related white matter pathways, in a sample of 73 native English-speaking neurotypical adults. Participants completed a diffusion magnetic resonance imaging scan and a cognitive assessment battery. Using constrained spherical deconvolution modeling and probabilistic tractography, we reconstructed dorsal and ventral white matter tracts of interest, bilaterally, in individual participants. Spelling associations were found in both dorsal and ventral stream pathways. In high-performing spellers, spelling scores significantly correlated with fractional anisotropy (FA) within the left inferior longitudinal fasciculus, a ventral stream pathway. In low-performing spellers, spelling scores significantly correlated with FA within the third branch of the right superior longitudinal fasciculus, a dorsal pathway. An automated analysis of spelling errors revealed that high- and low- performing spellers also differed in their error patterns, diverging primarily in terms of the orthographic distance between their errors and the correct spelling, compared to the phonological plausibility of their spelling responses. The results demonstrate the complexity of the neurocognitive architecture of spelling. The distinct white matter associations and error patterns detected in low- and high- performing spellers suggest that they rely on different cognitive processes, such that high-performing spellers rely more on lexical-orthographic representations, while low-performing spellers rely more on phoneme-to-grapheme conversion.

Inhibitory control predicts growth in irregular word reading: Evidence from a large-scale longitudinal study.

Irregular words cannot be read correctly by decoding letters into sounds using the most common letter-sound mapping relations. They are difficult to read and learn. Cognitive models of word reading and development as well as empirical data suggest that inhibitory control might be important for irregular word reading and its development. The current study tested this in a U.K. population-based cohort (N = 529, 52.74% male, 90.17% White) in which children were assessed longitudinally at ages 5-6, 7-8, and 10-11 years. Results showed that inhibitory control did not predict concurrent irregular word reading after controlling for the covariates of decoding and vocabulary. However, inhibitory control made a small but significant contribution to growth in irregular word reading across time points, over and above vocabulary (decoding did not predict growth). Therefore, children might need to inhibit the predisposition to overgeneralize the most common relations between letters and sounds when learning to read irregular words. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Contextual diversity during word learning through reading benefits generalisation of learned meanings to new contexts.

From mid-childhood onwards, most new words are learned through reading. The precise meaning of many words depends upon the linguistic context in which they are encountered, which readers use to infer the appropriate interpretation. However, it is unclear what features of these linguistic contexts best support learning of new word meanings. We investigated whether learning words in contextually diverse sentences benefits word form and meaning learning in adults (n = 239). Participants learned meanings for 8 pseudowords through reading 10 sentences about each. Four pseudowords were learned in a diverse condition (10 sentences on different topics) and four were learned in a non-diverse condition (10 sentences on the same topic). An old-new decision post-test indicated that diversity did not influence word form learning. In a second post-test, participants chose which trained pseudoword completed a sentence from either an unfamiliar, untrained context, or a familiar, trained context. For familiar contexts, accuracy was higher for pseudowords learned in the non-diverse condition, but for unfamiliar contexts, accuracy was higher for pseudowords learned in the diverse condition. These results suggest that diverse contexts may promote development of flexible, decontextualised meaning representations that are easier to generalise to new contexts. Conversely, non-diverse contexts may favour extraction of context-bound representations that are more easily used in the same context.

Percutaneous nephrostomy catheter-related infections in patients with gynaecological cancers: a multidisciplinary algorithmic approach.

BACKGROUND: Percutaneous nephrostomy catheters (PCNs) are commonly utilized in patients with gynaecological cancers due to intrinsic or extrinsic urinary obstruction. Unfortunately, these foreign medical devices may be associated with several infectious complications, including: pyelonephritis, renal abscess, and bacteraemia, which may lead to further delay of life-saving cancer therapy. AIM: To evaluate the performance of our multidisciplinary algorithm for diagnosis and treatment of PCN-related infections (PCNIs) and identify risk factors for recurrent urinary device-related infections. METHODS: Patients with gynaecological cancers having PCNIs were prospectively evaluated at our institution from July 2019 to September 2021. All patients were managed by our standardized algorithm and followed-up until reinfection or routine PCN exchange. FINDINGS: Of 100 consecutive patients with PCNIs, 74 had adequate follow-up, and were analysed in three groups according to clinical outcome: reinfection with the same organism (26%), reinfection with a different organism (23%), and no reinfection (51%). Their median age was 54 years, and the most common cancers were cervical (65%), and ovarian (19%) with 53% being metastatic. The most frequently recovered micro-organisms were Pseudomonas (32%), Enterococcus (27%), and Escherichia (24%) species. The main risk factors for recurrent PCNI with the same organism were pelvic radiation therapy (P=0.032), pelvic fistulas (P=0.014), and a PCNI with the same pathogen within the previous year (P = 0.012). CONCLUSIONS: Our algorithm has allowed for accurate diagnosis, staging, and treatment of and identification of several key risk factors for recurrent PCNIs. These results may lead to further preventive measures for these infections.

Learning new words through reading: do robust spelling-sound mappings boost learning of word forms and meanings?

High-quality lexical representations depend on robust representations of written form (orthography), spoken form (phonology) and meaning (semantics), and strong bonds between them. Quality of lexical representations may be affected by amount of print exposure and the form of individual words. Words that are harder to decode (print-to-sound) may lead to fuzzy representations of the orthographic and phonological forms, potentially creating less stable foundations for semantic knowledge. These factors are difficult to disentangle in natural language research; in this registered report, we experimentally manipulated decoding ease and exposure at the item level. Adults read paragraphs describing invented meanings of pseudowords. Pseudowords appeared two or six times in a paragraph, and had easy (e.g. bamper) or hard (e.g. uzide) to decode spelling-sound mappings. Post-tests assessed word-form knowledge, orthography-semantic mappings and semantic-phonology mappings. Results showed that greater decoding ease improved learning of word forms and consequently also impacted on word meanings. Higher exposure frequency improved learning of word forms but not meanings. Exposure frequency also modulated the effect of decoding ease on word-form learning, with a stronger effect of decoding ease for fewer exposures. Disentangling effects of decoding ease from print exposure has important implications for understanding potential barriers to vocabulary learning.

Pragmatic approach to the clinical work-up of patients with putative allergic disease to metallic orthopaedic implants before and after surgery.

Allergic complications following insertion of metallic orthopaedic implants include allergic dermatitis reactions but also extracutaneous complications. As metal-allergic patients and/or surgeons may ask dermatologists and allergologists for advice prior to planned orthopaedic implant surgery, and as surgeons may refer patients with complications following total joint arthroplasty for diagnostic work-up, there is a continuous need for updated guidelines. This review presents published evidence for patch testing prior to surgery and proposes tentative diagnostic criteria which clinicians can rely on in the work-up of patients with putative allergic complications following surgery. Few studies have investigated whether subjects with metal contact allergy have increased risk of developing complications following orthopaedic implant insertion. Metal allergy might in a minority increase the risk of complications caused by a delayed-type hypersensitivity reaction. At present, we do not know how to identify the subgroups of metal contact allergic patients with a potentially increased risk of complications following insertion of a metal implant. We recommend that clinicians should refrain from routine patch testing prior to surgery unless the patient has already had implant surgery with complications suspected to be allergic or has a history of clinical metal intolerance of sufficient magnitude to be of concern to the patient or a health provider. The clinical work-up of a patient suspected of having an allergic reaction to a metal implant should include patch testing and possibly in vitro testing. We propose diagnostic criteria for allergic dermatitis reactions as well as noneczematous complications caused by metal implants.

Estrogenic pyrethroid pesticides regulate expression of estrogen receptor transcripts in mouse Sertoli cells differently from 17beta-estradiol.

Studies suggested that exposure to agricultural pesticides may affect male fertility. Pyrethroids are widely used pesticides due to their insecticidal potency and low mammalian toxicity. A recombinant yeast assay system incorporating the human alpha-estrogen receptor was used to analyze the estrogenicity of a range of readily available pyrethroid pesticides. The commercial product Ripcord Plus showed estrogenic activity by this assay. To determine whether pyrethroid compounds might exert an effect on male fertility, mouse Sertoli cells were exposed in vitro to the endogenous estrogen, 17beta-estradiol, and selected estrogenic pyrethroids. Following exposure, transcript levels of the alpha- and beta-estrogen receptors were assessed. Exposure of Sertoli cells to the pyrethroid compounds, both at high and at low published serum concentrations, affected the expression of the two estrogen receptors; however, the influence on estrogen receptor gene expression was different from the effect from exposure to 17beta-estradiol. These results from our model systems suggest that (1) estrogenic pyrethroid pesticides affect the estrogen receptors, and therefore potentially the endocrine system, in a different manner from that of endogenous estrogen, and (2) should cells in the male testes be exposed to pyrethroid pesticides, male fertility may be affected through molecular mechanisms involving estrogen receptors.

pH homeostasis in human lymphocytes: modulation by ions and mitogen.

Quiescent human peripheral blood lymphocytes have been shown to maintain a relatively constant intracellular pH of 7.0-7.2 over an extracellular pH range of 6.9-7.4. Two methods of measuring intracellular pH were used in these studies, 19F nuclear magnetic resonance and [14C]5,5-dimethyloxazolidine-2,4-dione (DMO) equilibrium distributions. When ATP levels were decreased in these cells, actively maintained pH regulation was abolished and cells exhibited a constant pH gradient of 0.2 pH unit (acid inside relative to outside). Possible mechanisms for pH regulation are discussed. The effects of the Na+ and K+ composition of the medium on pH regulation showed no correlation with their effects on mitogen-induced proliferative response, which we have previously determined (Deutsch, C., and M. Price, 1982, J. Cell. Physiol., 111:73-79). In low-Na+ mannitol medium, pH regulation was similar to that observed for lymphocytes in normal medium, whereas mitogen-induced proliferation was severely inhibited in low-Na+ mannitol. In contrast, high-K+, low Na+ medium caused loss of pH homeostasis, whereas it restored the proliferative response. Loss of pH homeostasis was also observed on prolonged exposure of lymphocytes to mitogen (greater than 6 h in culture). However, mitogen stimulation led to little or no change in intracellular pH in the first few hours of cell culture. Therefore, a shift in intracellular pH is not a necessary or general event in mitogen-stimulated proliferation of lymphocytes.

Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan.

In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by thermally degraded polychlorinated biphenyls. Because these chemicals persist in human tissue, children born to female patients after the outbreak were exposed in utero. In 1985, 117 children born to affected women and 108 unexposed controls were examined and evaluated. The exposed children were shorter and lighter than controls; they had abnormalities of gingiva, skin, nails, teeth, and lungs more frequently than did controls. The exposed children showed delay of developmental milestones, deficits on formal developmental testing, and abnormalities on behavioral assessment. These findings are most consistent with a generalized disorder of ectodermal tissue. This syndrome is one of very few documented to result from transplacental exposure to pollutant chemicals.

Structural properties of the ventral reading pathways are associated with morphological processing in adult English readers.

Morphological processing, the ability to extract information about word structure, is an essential component of reading. Functional MRI studies have identified several cortical regions involved in morphological processing, but the white matter pathways that support this skill remain unknown. Here, we examine the relationship between behavioral measures of morphological processing and microstructural properties of white matter pathways. Using diffusion MRI (dMRI), we identified the major ventral and dorsal reading pathways in a group of 45 adult English readers. The same participants completed a behavioral battery that included a morphological task and measures of phonological and orthographic processing. We found significant correlations between morphological processing skill and microstructural properties of the ventral, but not dorsal, pathways. These correlations were detected primarily in the left hemisphere, and remained significant after controlling for phonological or orthographic measures, suggesting some level of cognitive specificity. Morphological processing of written words thus appears to rely on ventral pathways, primarily in the left hemisphere. This finding supports the contribution of morphological processing to lexical access and comprehension of complex English words.