A tale of two lexica: Investigating computational pressures on word representation with neural networks

IntroductionThe notion of a single localized store of word representations has become increasingly less plausible as evidence has accumulated for the widely distributed neural representation of wordform grounded in motor, perceptual, and conceptual processes. Here, we attempt to combine machine learning methods and neurobiological frameworks to propose a computational model of brain systems potentially responsible for wordform representation. We tested the hypothesis that the functional specialization of word representation in the brain is driven partly by computational optimization. This hypothesis directly addresses the unique problem of mapping sound and articulation vs. mapping sound and meaning.ResultsWe found that artificial neural networks trained on the mapping between sound and articulation performed poorly in recognizing the mapping between sound and meaning and vice versa. Moreover, a network trained on both tasks simultaneously could not discover the features required for efficient mapping between sound and higher-level cognitive states compared to the other two models. Furthermore, these networks developed internal representations reflecting specialized task-optimized functions without explicit training.DiscussionTogether, these findings demonstrate that different task-directed representations lead to more focused responses and better performance of a machine or algorithm and, hypothetically, the brain. Thus, we imply that the functional specialization of word representation mirrors a computational optimization strategy given the nature of the tasks that the human brain faces

Rules from Words: A Dynamic Neural Basis for a Lawful Linguistic Process

Listeners show a reliable bias towards interpreting speech sounds in a way that conforms to linguistic restrictions (phonotactic constraints) on the permissible patterning of speech sounds in a language. This perceptual bias may enforce and strengthen the systematicity that is the hallmark of phonological representation. Using Granger causality analysis of magnetic resonance imaging (MRI)- constrained magnetoencephalography (MEG) and electroencephalography (EEG) data, we tested the differential predictions of rule-based, frequency–based, and top-down lexical influence-driven explanations of processes that produce phonotactic biases in phoneme categorization. Consistent with the top-down lexical influence account, brain regions associated with the representation of words had a stronger influence on acoustic-phonetic regions in trials that led to the identification of phonotactically legal (versus illegal) word-initial consonant clusters. Regions associated with the application of linguistic rules had no such effect. Similarly, high frequency phoneme clusters failed to produce stronger feedforward influences by acoustic-phonetic regions on areas associated with higher linguistic representation. These results suggest that top-down lexical influences contribute to the systematicity of phonological representation

Trained immunity or tolerance : opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors

Article Accepted Date: 29 January 2014. ACKNOWLEDGMENTS D.C.I. received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-2010-260338 (“Fungi in the setting of inflammation, allergy and autoimmune diseases: translating basic science into clinical practices” [ALLFUN]) (awarded to M.G.N.). M.G.N. and J.Q. were supported by a Vici grant of the Netherlands Organization of Scientific Research (awarded to M.G.N.). This work was supported, in part, by National Institutes of Health grant GM53522 to D.L.W. N.A.R.G. was supported by the Wellcome Trust.Peer reviewedPublisher PD

Trained immunity or tolerance : opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors

Article Accepted Date: 29 January 2014. ACKNOWLEDGMENTS D.C.I. received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-2010-260338 (“Fungi in the setting of inflammation, allergy and autoimmune diseases: translating basic science into clinical practices” [ALLFUN]) (awarded to M.G.N.). M.G.N. and J.Q. were supported by a Vici grant of the Netherlands Organization of Scientific Research (awarded to M.G.N.). This work was supported, in part, by National Institutes of Health grant GM53522 to D.L.W. N.A.R.G. was supported by the Wellcome Trust.Peer reviewedPublisher PD

Development and validation of the Gender-Equity Model for Liver Allocation (GEMA) to prioritise candidates for liver transplantation: a cohort study

BACKGROUND: The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. METHODS: In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010-20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998-2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessed by Harrell's concordance statistic. FINDINGS: 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell's concordance statistic 0·752 [95% CI 0·700-0·804] vs 0·712 [0·656-0·769]; p=0·001 in the internal validation group and 0·761 [0·703-0·819] vs 0·739 [0·682-0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715-0·818] vs 0·742 [0·686-0·797]; p=0·0058 in the internal validation group and 0·774 [0·720-0·827] vs 0·745 [0·690-0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716-0·888]) and external validation cohorts (0·796 [0·698-0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. INTERPRETATION: GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation. FUNDING: Junta de Andalucía and EDRF

Association Between a Type 2 Inflammatory Disease Burden Score and Outcomes Among Patients with Asthma

Funding This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Acknowledgments At the time of development of this manuscript, Fen Ye was an employee of Sanofi and Yufang Lu was an employee of Regeneron Pharmaceuticals.Medical writing support was provided by Abby Armitt, MSc, and Gauri Saal, MA Economics, of Prime, Knutsford, UK, and funded by Sanofi and Regeneron Pharmaceuticals, Inc.Peer reviewedPublisher PD

The structure of blocks with a Klein four defect group

We prove Erdmann’s conjecture [16] stating that every block with a Klein four defect group has a simple module with trivial source, and deduce from this that Puig’s finiteness conjecture holds for source algebras of blocks with a Klein four defect group. The proof uses the classification of finite simple groups

Characterising the impact of sex on severe asthma (SA) in the UK Severe Asthma Registry (UKSAR)

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Itraconazole associated quadriparesis and edema: a case report

<p>Abstract</p> <p>Introduction</p> <p>Itraconazole is an anti-fungal agent widely used to treat various forms of mycosis. It is particularly useful in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Side effects are uncommon and usually mild. Mild neuropathy is noted to occur very rarely. We present an unusual and, to the best of our knowledge, as yet unreported case of severe neuropathy and peripheral edema due to itraconazole in the absence of a concomitant risk factor.</p> <p>Case presentation</p> <p>A 72-year-old Caucasian man was started on itraconazole following diagnosis of severe asthma with fungal sensitization. One month later he presented with severe bilateral ankle edema with an elevated serum itraconazole level. The itraconazole dose was reduced but his ankle edema persisted and he developed weakness of all four limbs. Itraconazole was completely stopped leading to improvement in his leg edema but he became bed bound due to weakness. He gradually improved with supportive care and neurorehabilitation. On review at six months, our patient was able to mobilize with the aid of two elbow crutches and power had returned to 5/5 in distal extremities and 4+/5 in proximal extremities. The diagnosis was established based on the classical presentation of drug-induced neuropathy and negative investigatory findings for any alternative diagnoses.</p> <p>Conclusion</p> <p>We report the case of a patient presenting with an unusual complication of severe neuropathy and peripheral edema due to itraconazole. Clinicians should be alert to this association when encountered with neuropathy and/or edema in an itraconazole therapy recipient.</p

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

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