Spoken Discourse Assessment and Analysis in Aphasia: An International Survey of Current Practices.

Purpose Spoken discourse analysis is commonly employed in the assessment and treatment of people living with aphasia, yet there is no standardization in assessment, analysis, or reporting procedures, thereby precluding comparison/meta-analyses of data and hindering replication of findings. An important first step is to identify current practices in collecting and analyzing spoken discourse in aphasia. Thus, this study surveyed current practices, with the goal of working toward standardizing spoken discourse assessment first in research settings with subsequent implementation into clinical settings. Method A mixed-methods (quantitative and qualitative) survey was publicized to researchers and clinicians around the globe who have collected and/or analyzed spoken discourse data in aphasia. The survey data were collected between September and November 2019. Results Of the 201 individuals who consented to participate, 189 completed all mandatory questions in the survey (with fewer completing nonmandatory response questions). The majority of respondents reported barriers to utilizing discourse including transcription, coding, and analysis. The most common barrier was time (e.g., lack of time). Respondents also indicated that there was a lack of, and a need for, psychometric properties and normative data for spoken discourse use in the assessment and treatment of persons with aphasia. Quantitative and qualitative results are described in detail. Conclusions The current survey study evaluated spoken discourse methods in aphasia across research and clinical settings. Findings from this study will be used to guide development of process standardization in spoken discourse and for the creation of a psychometric and normative property database. Supplemental Material https://doi.org/10.23641/asha.166395100

Discourse or dialogue? Habermas, the Bakhtin Circle, and the question of concrete utterances

This is the author's accepted manuscript. The final publication is available at Springer via the link below.This article argues that the Bakhtin Circle presents a more realistic theory of concrete dialogue than the theory of discourse elaborated by Habermas. The Bakhtin Circle places speech within the “concrete whole utterance” and by this phrase they mean that the study of everyday language should be analyzed through the mediations of historical social systems such as capitalism. These mediations are also characterized by a determinate set of contradictions—the capital-labor contradiction in capitalism, for example—that are reproduced in unique ways in more concrete forms of life (the state, education, religion, culture, and so on). Utterances always dialectically refract these processes and as such are internal concrete moments, or concrete social forms, of them. Moreover, new and unrepeatable dialogic events arise in these concrete social forms in order to overcome and understand the constant dialectical flux of social life. But this theory of dialogue is different from that expounded by Habermas, who tends to explore speech acts by reproducing a dualism between repeatable and universal “abstract” discursive processes (commonly known as the ideal speech situation) and empirical uses of discourse. These critical points against Habermas are developed by focusing on six main areas: sentences and utterances; the lifeworld and background language; active versus passive understandings of language; validity claims; obligation and relevance in language; and dialectical universalism

Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity.

BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa. RESULTS: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). CONCLUSIONS: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission

Clinical outcome and prognostic factors for patients treated within the context of a phase I study: the Royal Marsden Hospital experience

The main aim of phase I trials is to evaluate the tolerability and pharmacology of a new compound. However, investigating the potential for clinical benefit is also a key objective. Our phase I trial portfolio incorporates a range of new drugs, including molecular targeted agents, sometimes given together with cytotoxic agents. We performed this analysis of response rate, progression-free (PFS) and overall survival (OS) to assess the extent of clinical benefit rate (CBR: partial response (PR)+stable disease (SD)) derived from current trials. We analysed 212 consecutive patients who were treated in 29 phase I studies, from January 2005 to June 2006. All patients had progression of disease prior to study entry. The median age was 58 years (range: 18–86) with a male/female ratio of 2 : 1. A total of 148 patients (70%) were treated in ‘first in human trials' involving biological agents (132 patients) or new cytotoxic compounds (16 patients) alone, and 64 patients (30%) received chemotherapy-based regimens with or without biological agents. After a median follow-up time of 34 weeks, the median PFS and OS were 11 and 43 weeks, respectively. The CBR was 53% (9% PR and 44% SD) after the first tumour evaluation after two cycles (between weeks 6 and 8) and has been maintained at 36 and 26% at 3 and 6 months, respectively. Treatment related deaths occurred in 0.47% of our patients and treatment had to be withdrawn in 11.8% of patients due to toxicity. A multivariate analysis (MVA) of 13 factors indicated that low albumin (<35 g l−1), lactate dehydrogenase>upper normal limit and >2 sites of metastasis were independent negative prognostic factors for OS. A risk score based on the MVA revealed that patients with a score of 2–3 had a significantly shorter OS compared to patients with a score of 0–1 (24.9 weeks, 95% CI 19.5–30.2 vs 74.1 weeks, 95% CI 53.2–96.2). This analysis shows that a significant number of patients who develop disease progression while receiving standard therapy derived benefit from participation in phase I trials. Risk scoring based on objective clinical parameters indicated that patients with a high score had a significantly shorter OS, and this may help in the process of patient selection for phase I trial entry

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

Efficacy of EGFR Inhibition Is Modulated by Model, Sex, Genetic Background and Diet: Implications for Preclinical Cancer Prevention and Therapy Trials

Molecule-targeted therapies are being widely developed and deployed, but they are frequently less effective in clinical trials than predicted based upon preclinical studies. Frequently, only a single model or genetic background is utilized using diets that are not relevant to that consumed by most cancer patients, which may contribute to the lack of predictability of many preclinical therapeutic studies. Inhibition of epidermal growth factor receptor (EGFR) in colorectal cancer was used to investigate potential causes for low predictive values of many preclinical studies. The efficacy of the small molecule EGFR inhibitor AG1478 was evaluated using two mouse models, ApcMin/+ and azoxymethane (AOM), both sexes on three genetic backgrounds, C57BL/6J (B6) and A/J (A) inbred strains and AB6F1 hybrids, and two diets, standard chow (STD) or Western-style diet (WD). AG1478 has significant anti-tumor activity in the B6-ApcMin/+ model with STD but only moderately on the WD and in the AOM model on an A background with a WD but not STD. On the F1 hybrid background AG1478 is effective in the ApcMin/+ model with either STD or WD, but has only moderate efficacy in the AOM model with either diet. Sex differences were also observed. Unexpectedly, the level of liver EGFR phosphorylation inhibition by AG1478 was not positively correlated with inhibition of tumor growth in the AOM model. Model-dependent interactions between genetic background and diet can dramatically impact preclinical results, and indicate that low predictive values of preclinical studies can be attributed to study designs that do not account for the heterogeneous patient population or the diets they consume. Better-designed preclinical studies should lead to more accurate predictions of therapeutic response in the clinic

Gender differences in the association between adiposity and probable major depression: a cross-sectional study of 140,564 UK Biobank participants

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Previous studies on the association between adiposity and mood disorder have produced contradictory results, and few have used measurements other than body mass index (BMI). We examined the association between probable major depression and several measurements of adiposity: BMI, waist circumference (WC), waist-hip-ratio (WHR), and body fat percentage (BF%).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; We conducted a cross-sectional study using baseline data on the sub-group of UK Biobank participants who were assessed for mood disorder. Multivariate logistic regression models were used, adjusting for potential confounders including: demographic and life-style factors, comorbidity and psychotropic medication.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Of the 140,564 eligible participants, evidence of probable major depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR) for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and 1.18 (95% CI 1.12, 1.25) using BF% (all p &#60;0.001). There was a significant interaction between adiposity and gender (p = 0.001). Overweight women were at increased risk of depression with a dose response relationship across the overweight (25.0-29.9 kg/m2), obese I (30.0-34.9 kg/m2), II (35.0-39.9 kg/m2) and III (≥40.0 kg/m2) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48, respectively (all p &#60; 0.001). In contrast, only obese III men had significantly increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Adiposity was associated with probable major depression, irrespective of the measurement used. The association was stronger in women than men. Physicians managing overweight and obese women should be alert to this increased risk