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A highly productive derivational process, diminutive suffixation in Spanish (e.g., gatito ~ gatiko/gatico ‘little/well-known/beloved/awful cat’ < gato ‘cat’) has received much attention in the morphology–phonology interface literature. The present study contributes a novel comparative analysis of a dissimilatory alternation between diminutive suffix allomorphs -ito/a and -ico/a (-iko/a) across three Hispano-Romance varieties. In Judeo-Spanish, the voiceless dorsal stop [k] of default -iko/a dissimilates to coronal [t] after any dorsal segment [k, ɡ, ɡʷ, x, w] in the base-final syllable. In Colombian Spanish, the voiceless coronal stop [t] of default -ito/a dissimilates to dorsal [k] after only an identical [t] in the base-final syllable. By contrast, Castilian Spanish -ito/a does not dissimilate, thereby providing a baseline for comparison. All three varieties allow for optional iteration of the suffix, which conveys greater smallness or endearment than the simple diminutive, e.g., Castilian Spanish gatitito ‘little/beloved kitty’, without dissimilation. Iterated diminutives in Colombian Spanish show two patterns of dissimilation, which have not been fully acknowledged in the previous literature. For example, either (i) [it] and [ik] alternate to avoid adjacent identical syllable onsets, e.g., gat[ikitíko], or (ii) [it] is iterated until alternating with word-final [ik], e.g., gat[ititíko]. In all three Hispano-Romance varieties, base-final unstressed vowels are deleted before a vowel-initial diminutive suffix, followed by unstressed -o/a, and stress (indicated by an acute accent) is shifted rightward onto the penultimate syllable of the diminutive word. Vowel deletion and stress shift apply recursively in iterated diminutives. We propose an Optimality Theory analysis of these alternations in terms of suffix allomorphy that is phonologically conditioned by consonantal place dissimilation. The analysis is formalized as an interaction among constraints that enforce prosodic unmarkedness, output–output correspondence, allomorph preference, and similarity avoidance. We consider theoretical alternatives and compare our analysis to other recent proposals.

This article analyzes the writing development of heritage speakers (hs) of Spanish in an intermediate level composition course at the University of California, Davis. The data comprised 480 essays written by 80 students from two groups: one who received face-to-face peer tutoring before the covid-19 pandemic (Fall 2019), and one who received online tutoring during the pandemic (Fall 2020). These data were analyzed in terms of lexical richness as measured by (a) lexical density, (b) lexical sophistication, and (c) lexical variation in both in-person and online settings. Findings revealed that lexical density and lexical sophistication were similar in both groups. However, the online group had higher levels of lexical variation throughout their essays. We conclude that online tutoring is an effective alternative to face-to-face tutoring, showing no disadvantages in terms of students’ lexical richness and offering a significant advantage with respect to lexical variation. Finally, we offer suggestions for hs tutor training in an online setting.

This article traces the development of voiced prepalatal obstruents /dʒ⌢/ and /ʒ/ in Judeo-Spanish, the language spoken by the Sephardic Jews since before their expulsion from late-15th century Spain. Using Medieval Spanish as a comparative starting point, we examine diachronic innovations in the phonological status and distribution of affricate /dʒ⌢/ and fricative /ʒ/ in Judeo-Spanish during the diaspora, focusing in particular on the effects of lexical borrowing from Turkish and French in territories of the former Ottoman Empire. In contemporary Sephardic communities that are in contact with non-Sephardic varieties of Mainstream Spanish, some speakers occasionally replace syllable-initial /∫/, /dʒ⌢/, and /ʒ/ in certain Judeo-Spanish words by a voiceless velar /x/ in efforts to accommodate the pronunciation of the corresponding Mainstream Spanish cognate form. We provide a novel analysis of Judeo-Spanish voiced prepalatal obstruents, including their diachronic and synchronic variation under language contact. The analysis combines a constraint-based approach to phonological alternations, as formalized in Optimality Theory, with a usage-based representation of the mental lexicon, as proposed in Exemplar Theory, to account for speaker- and word-specific variability. A hybrid theoretical model provides a more nuanced understanding of the relationship between lexicon and grammar in Judeo-Spanish phonology than is available in previous structuralist descriptions.

This dissertation examines the process of lenition, or spirantization, of intervocalic voiced stops /b, d, ɡ/ in heritage Spanish. While spirantization is one of the more extensively studied phonetic and phonological phenomena in Spanish, this study introduces methodological and theoretical advances for the study of heritage phonology. The data come from an understudied variety of U.S. Spanish spoken by heritage speakers of Colombian descent in New Jersey and Florida across three generations. Previous studies have analyzed linguistic factors such as phoneme, stress, word position, and task type, that mediate voiced stop lenition in monolingual varieties of Spanish (Broś et al., 2021; Carrasco, 2008; Carrasco et al., 2012; Colatoni & Marinescu, 2010; Eddington, 2011; Figueroa, 2016), heritage Spanish (Amengual, 2019; Blair & Lease, 2021; Rao, 2014, 2015), and L2 Spanish (Cabrelli Amaro, 2017; Zampini, 1997, 1998). The present study builds on this research by expanding the variable of word position beyond the binary medial vs. initial distinction to include three prosodic domains: syllable-initial within the word, initial in the minimal prosodic word, and initial in the maximal prosodic word. The results from a reading task and conversation dyad confirm that the linguistic variables of phoneme, stress, prosodic domain, and task type mediate categorical acoustic measures of lenition in heritage Spanish in a way that replicates previous studies’ findings for other varieties. Social factors such as generation, order of language acquisition, and speech community are not found to be significant predictors of voiced stop lenition in the corpus of data analyzed here. Based on the results of the experimental tasks and previous studies on other varieties of Spanish, this dissertation offers a formal analysis in phonetically based Optimality Theory that accounts for domain-medial spirantization as continuity lenition, which, in conjunction with fortition at domain edges, helps demarcate prosodic constituents for the listener’s benefit (Katz, 2016). The analysis makes testable predictions about possible patterns of variation both in and beyond Colombian heritage Spanish. In sum, this dissertation contributes to a growing body of work (Broś et al., 2021; Harper, 2014; Katz, 2016; Katz & Fricke, 2018; Katz & Moore, 2021; Keating, 2006; Kingston, 2008) seeking to flip the traditional narrative that consonantal weakening is primarily a speaker-based phenomenon driven by effort minimization.

Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady-state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) Tlr2, Dectin-1, and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardii CNCM I-745 ( Sb ) in vivo reduced bone loss in ovariectomized but not sham mice by reducing inflammatory osteoclastogenesis. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of Tlr2, Dectin-1, and Mincle specifically inhibited directly the differentiation of inflammatory but not steady-state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.

Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm(3) or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.

Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE‐SAFETY randomized, double‐blind, placebo‐controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta‐oxidation pathways. An ACLF‐specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady-state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) Tlr2, Dectin-1, and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardii CNCM I-745 ( Sb ) in vivo reduced bone loss in ovariectomized but not sham mice by reducing inflammatory osteoclastogenesis. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of Tlr2, Dectin-1, and Mincle specifically inhibited directly the differentiation of inflammatory but not steady-state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.

Bone destruction is a hallmark of chronic inflammation, and bone-resorbing osteoclasts arising under such a condition differ from steady-state ones. However, osteoclast diversity remains poorly explored. Here, we combined transcriptomic profiling, differentiation assays and in vivo analysis in mouse to decipher specific traits for inflammatory and steady state osteoclasts. We identified and validated the pattern-recognition receptors (PRR) TLR2, Dectin-1 and Mincle, all involved in yeast recognition as major regulators of inflammatory osteoclasts. We showed that administration of the yeast probiotic Saccharomyces boulardi CNCM I-745 (Sb) in vivo reduced bone loss in OVX but not sham mice by reducing inflammatory osteoclasts. This beneficial impact of Sb is mediated by the regulation of the inflammatory environment required for the generation of inflammatory osteoclasts. We also showed that Sb derivatives as well as agonists of TLR2, Dectin-1 and Mincle specifically inhibited directly the differentiation of inflammatory but not steady state osteoclasts in vitro. These findings demonstrate a preferential use of the PRR-associated costimulatory differentiation pathway by inflammatory osteoclasts, thus enabling their specific inhibition, which opens new therapeutic perspectives for inflammatory bone loss.