Factors affecting judgment accuracy when scoring children's responses to non-word repetition stimuli in real time

Background: Non-word repetition (NWR) tests are an important way speech and language therapists (SaLTs) assess language development. NWR tests are often scored whilst participants make their responses (i.e., in real time) in clinical and research reports (documented here via a secondary analysis of a published systematic review). / Aims: The main aim was to determine the extent to which real-time coding of NWR stimuli at the whole-item level (as correct/incorrect) was predicted by models that had varying levels of detail provided from phonemic transcriptions using several linear mixed method (LMM) models. / Methods & Procedures: Live scores and recordings of responses on the universal non-word repetition (UNWR) test were available for 146 children aged between 3 and 6 years where the sample included all children starting in five UK schools in one year or two consecutive years. Transcriptions were made of responses to two-syllable NWR stimuli for all children and these were checked for reliability within and between transcribers. Signal detection analysis showed that consonants were missed when judgments were made live. Statistical comparisons of the discrepancies between target stimuli and transcriptions of children's responses were then made and these were regressed against live score accuracy. Six LMM models (three normalized: 1a, 2a, 3a; and three non-normalized: 1b, 2b, 3b) were examined to identify which model(s) best captured the data variance. Errors on consonants for live scores were determined by comparison with the transcriptions in the following ways (the dependent variables for each pair of models): (1) consonants alone; (2) substitutions, deletions and insertions of consonants identified after automatic alignment of live and transcribed materials; and (3) as with (2) but where substitutions were coded further as place, manner and voicing errors. / Outcomes & Results: The normalized model that coded consonants in non-words as ‘incorrect’ at the level of substitutions, deletions and insertions (2b) provided the best fit to the real-time coding responses in terms of marginal R2, Akaike's information criterion (AIC) and Bayesian information criterion (BIC) statistics. / Conclusions & Implications: Errors that occur on consonants when non-word stimuli are scored in real time are characterized solely by the substitution, deletion and insertion measure. It is important to know that such errors arise when real-time judgments are made because NWR tasks are used to assess and diagnose several cognitive–linguistic impairments. One broader implication of the results is that future work could automate the analysis procedures to provide the required information objectively and quickly without having to transcribe data

Factors Affecting Judgment-Accuracy when Scoring Children’s Responses to Non-word Repetition Stimuli in Real Time

Data analyses for the paper: ``Factors Affecting Judgment-Accuracy when Scoring Children’s Responses to Non-word Repetition Stimuli in Real Time'

Identification of IMP Dehydrogenase as a Potential Target for Anti-Mpox Virus Agents

ABSTRACT Mpox virus (formerly monkeypox virus [MPXV]) is a neglected zoonotic pathogen that caused a worldwide outbreak in May 2022. Given the lack of an established therapy, the development of an anti-MPXV strategy is of vital importance. To identify drug targets for the development of anti-MPXV agents, we screened a chemical library using an MPXV infection cell assay and found that gemcitabine, trifluridine, and mycophenolic acid (MPA) inhibited MPXV propagation. These compounds showed broad-spectrum anti-orthopoxvirus activities and presented lower 90% inhibitory concentrations (0.026 to 0.89 μM) than brincidofovir, an approved anti-smallpox agent. These three compounds have been suggested to target the postentry step to reduce the intracellular production of virions. Knockdown of IMP dehydrogenase (IMPDH), the rate-limiting enzyme of guanosine biosynthesis and a target of MPA, dramatically reduced MPXV DNA production. Moreover, supplementation with guanosine recovered the anti-MPXV effect of MPA, suggesting that IMPDH and its guanosine biosynthetic pathway regulate MPXV replication. By targeting IMPDH, we identified a series of compounds with stronger anti-MPXV activity than MPA. This evidence shows that IMPDH is a potential target for the development of anti-MPXV agents. IMPORTANCE Mpox is a zoonotic disease caused by infection with the mpox virus, and a worldwide outbreak occurred in May 2022. The smallpox vaccine has recently been approved for clinical use against mpox in the United States. Although brincidofovir and tecovirimat are drugs approved for the treatment of smallpox by the U.S. Food and Drug Administration, their efficacy against mpox has not been established. Moreover, these drugs may present negative side effects. Therefore, new anti-mpox virus agents are needed. This study revealed that gemcitabine, trifluridine, and mycophenolic acid inhibited mpox virus propagation and exhibited broad-spectrum anti-orthopoxvirus activities. We also suggested IMP dehydrogenase as a potential target for the development of anti-mpox virus agents. By targeting this molecule, we identified a series of compounds with stronger anti-mpox virus activity than mycophenolic acid

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo