Failure of humeral shaft fixation: construct characteristics.

PURPOSE: Fixation failure following open reduction and internal fixation (ORIF) of humeral shaft fractures can be a challenging complication. We aimed to identify the modes of failure and characteristics of failed fixation constructs. METHODS: We queried our institutional database for patients > 18 years old with fixation failure after ORIF with single plate and screw constructs of humeral shaft fractures from 2006 to 2017. Demographics, fracture characteristics, fixation construct design and mode of failure were recorded. RESULTS: Twenty-three failures were identified. Mean age was 55.9 years (SD 19.2 years) with 15 (65%) women. Twelve patients (52%) had midshaft fractures; the remainder had distal-third shaft (8 pts, 35%) or proximal-third shaft (3 pts, 13%) fractures. Midshaft fractures were most commonly fixed through an anterolateral approach with plates and all non-locking screws (83%), while distal-third shaft fractures were fixed with a combination of locking and non-locking screws from a posterior approach. Distal-third shaft fractures failed by plate breakage (63%) or screw pullout (38%) and all midshaft failures occurred by screw pullout proximal (92%) or distal (8%) to the fracture. Resultant varus deformity occurred in 20 (87%) fractures. CONCLUSION: Screw pullout in midshaft fractures suggests that fixation to bone was insufficient or biomechanically disadvantageous. Varus moments contribute significantly to the failure of humeral shaft fracture ORIF. Plate breakage in distal fractures suggests high concentrations of stress over a narrow working length of constructs with inadequate plate strength. Recognizing how these constructs fail can aid proper implant selection and application for humeral shaft fracture. LEVEL OF EVIDENCE: Treatment level IV.

Louise Eisenhardt (1891-1967): World Renowned Neuropathologist, Brain Tumor Registry Director, First Editor-In-Chief of Journal of Neurosurgery, and President of Harvey Cushing Society.

BACKGROUND: This historical account reviews the course and lasting impact of Dr. Louise Eisenhardt (1891-1967) in neurosurgery. METHOD: The writing of this project was sparked by the discovery of original scientific and bibliographical information about Eisenhardt, testimony on personal relationships, and viewpoints after comprehensive compilation of information. It is a thorough review of literature on Eisenhardt and reflects the scope and depth of these prior works. RESULTS: It begins with the decisive influence of Harvey Cushing's mentorship and academic; follows Eisenhardt's impact on the development of modern neuropathology; discusses the Eisenhardt-Percival-Bailey-Cushing collaboration on gross brain specimens and histological classification of brain tumors; recounts Cushing's creation of a neuropathologist team for the Brain Tumor Registry working asynchronously with the Pathology Department at Peter Bent Brigham Hospital; Eisenhardt's aid in the development of intraoperative analysis of brain tumors; her career as a neuropathologist; her contributions as Editor-in-Chief of the Journal of Neurosurgery; and her preservation of the Brain Tumor Registry at Yale University School of Medicine estimated the largest and most valuable databank of information in the history of medicine. Eisenhardt served as President, Historian, and Secretary-Treasurer of the Harvey Cushing Society, the professional organization now known as the American Association of Neurological Surgeons, and was senior lecturer for members of the Congress of Neurological Surgeons, constituents of NEUROSURGERY Publications. CONCLUSIONS: Our article provides glimpses into the personality of Dr. Louise Eisenhardt and her marked impact on neurosurgery and allied neurosciences.

Observational cohort study of perinatal outcomes of women with COVID-19.

BACKGROUND: Understanding the impact of SARS-CoV-2 infection on pregnancy outcomes and of pregnancy on COVID-19 outcomes is critical for ensuring proper prenatal and antenatal care. No similar studies have been published in Saudi Arabia. METHODS: We performed a prospective cohort study of pregnant women with confirmed SARS-CoV-2 infection who presented at King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Kingdom of Saudi Arabia. COVID-19 staging was performed, pregnancy-related complications were assessed, and neonatal infection was evaluated. RESULTS: We enrolled 81 patients (mean age 31.75 years, SD 5.25) of which there were 17 cases in the first trimester, 20 in the second trimester, and 34 in the third trimester. The distribution of COVID-19 severity was 40 patients with Stage A, 36 with Stage B, 4 with Stage C, and 1 with Stage D. Complications were pregnancy loss in 2 patients (one in each first and second trimester) and 1 fetal death after 20 weeks of pregnancy, 7 patients with fetal growth restriction, and 8 with pre-term delivery. CONCLUSIONS: We did not observe an unusual frequency of pregnancy-related complications due to SARS-CoV-2 infection in this high-risk obstetric population and there was no evidence of vertical transmission in newborns from women who delivered while positive for the virus.

Amphotericin B-Loaded Plant-Inspired Polyphenol Nanoparticles Enhance Its Antifungal Activity and Biocompatibility.

Amphotericin B (AmB) is one of the first-line treatments for systemic fungal infections, yet it suffers from dose-limiting systemic toxicity and high cost of less toxic lipid-based formulations. Here, we report on a facile approach to synthesize an AmB-loaded nanomedicine by leveraging plant-inspired oxidative self-polymerization of the ubiquitous polyphenol quercetin (QCT). Polymerized QCT nanoparticles (pQCT NPs) were formed, loaded with AmB, and functionalized with poly(ethylene glycol) (PEG) to impart steric stability in a simple procedure that relied on mixing followed by dialysis. The AmB-loaded NPs (AmB@pQCT-PEG NPs) were characterized by a drug loading efficiency of more than 90%, a particle size of around 160 nm, a polydispersity index of 0.07, and a partially negative surface charge. AmB release from the NPs was sustained over several days and followed the Korsmeyer-Peppas model with a release exponent (n) value >0.85, denoting drug release by polymer relaxation and swelling. A hemolysis assay revealed the NPs to be highly biocompatible, with negligible hemolytic activity and 30-60% hemolysis after 1 and 24 h of incubation with erythrocytes, respectively, across a wide concentration range (6.25-100.00 µg/mL). Conversely, equivalent concentrations of free AmB caused 90-100% hemolysis within the same timeframe. Importantly, AmB@pQCT-PEG NPs outperformed free AmB in microbial susceptibility assays on Candida albicans, achieving a minimum inhibitory concentration of 62.5 ng/mL after 48 h of incubation, which was 2-fold lower than the free drug. Our results demonstrate that pQCT NPs may serve as a viable AmB delivery platform for the treatment of fungal infections and potentially other AmB-susceptible pathogens.

Omentum-on-a-chip: A multicellular, vascularized microfluidic model of the human peritoneum for the study of ovarian cancer metastases.

Epithelial ovarian cancer has the highest mortality rate of any gynecologic malignancy and most frequently metastasizes to the peritoneal cavity. Intraperitoneal metastases are highly associated with ascites, the pathologic accumulation of peritoneal fluid due to impaired drainage, increased peritoneal permeability, and tumor and stromal cytokine secretion. However, the relationship between ascites, vascular and mesothelial permeability, and ovarian cancer intraperitoneal metastases remains poorly understood. In this study, a vascularized in vitro model of the human peritoneal omentum and ovarian tumor microenvironment (TME) was employed to study stromal cell effects on tumor cell (TC) attachment and growth, as well as TC effects on vascular and mesothelial permeability in models of both early- and late-stage metastases. Control over the number of TCs seeded in the vascularized peritoneum revealed a critical cell density requirement for tumor growth, which was further enhanced by stromal adipocytes and endothelial cells found in the peritoneal omentum. This tumor growth resulted in both a physically-mediated decrease and cytokine-mediated increase in microvascular permeability, emphasizing the important and potentially opposing roles of tumor cells in ascites formation. This system provides a robust platform to elucidate TC-stromal cell interactions during intraperitoneal metastasis of ovarian cancer and presents the first in vitro vascularized model of the human peritoneum and ovarian cancer TME.

The minimally conscious state: an analysis of current clinical trials registered in ClinicalTrials.gov.

The minimally conscious state (MCS) is a disorder of consciousness described in recent years for patients who have behavioral responses to stimuli that do not meet the classification of chronic vegetative state (CVS) or coma. This distinction is valuable in clinical practice, as minimally conscious patients may require different treatments and may have different long-term outcomes when compared to vegetative states or coma. In this report, we analyzed the ClinicalTrials.gov database to systematically assess all clinical trials regarding MCS. The database was queried using the term "minimally conscious state" in the "condition or disease" search parameter. Of the studies identified, those that had suspended, terminated, or otherwise unknown statuses were excluded. In total, 41 studies were analyzed. The included studies were initiated between 2008 and 2020, with the majority (63%) beginning in 2015 or later. Of the primary intervention modalities included, 15 (37%) evaluated stimulation modalities such as transcranial magnetic stimulation, transcranial direct current stimulation, implantable neurostimulation, vagus nerve stimulation, focused ultrasound and median nerve stimulation. Additionally, 5 (12%) used some form of behavioral therapy. A total of 4 (10%) studies involved pharmaceutical intervention, including dopamine agonists, analgesics and sedatives. Finally, 4 (10%) studies sought to determine the validity of current diagnostic methods and systems used to assess the status of patients in MCSs. Since the definition and criteria for CVS and MCS have been established, these two conditions remain closely associated despite evidence of different patient outcomes and treatment options. Many clinical trials are underway assessing interventions with stimulation. However, the trials are lacking with respect to diagnostic methods and pharmaceutical treatment.

A robust vasculogenic microfluidic model using human immortalized endothelial cells and Thy1 positive fibroblasts.

Human umbilical vein endothelial cells (HUVECs) and stromal cells, such as human lung fibroblasts (FBs), have been widely used to generate functional microvascular networks (µVNs) in vitro. However, primary cells derived from different donors have batch-to-batch variations and limited lifespans when cultured in vitro, which hampers the reproducibility of µVN formation. Here, we immortalize HUVECs and FBs by exogenously expressing human telomerase reverse transcriptase (hTERT) to obtain stable endothelial cell and FB sources for µVN formation in vitro. Interestingly, we find that immortalized HUVECs can only form functional µVNs with immortalized FBs from earlier passages but not from later passages. Mechanistically, we show that Thy1 expression decreases in FBs from later passages. Compared to Thy1 negative FBs, Thy1 positive FBs express higher IGFBP2, IGFBP7, and SPARC, which are important for angiogenesis and lumen formation during vasculogenesis in 3D. Moreover, Thy1 negative FBs physically block microvessel openings, reducing the perfusability of µVNs. Finally, by culturing immortalized FBs on gelatin-coated surfaces in serum-free medium, we are able to maintain the majority of Thy1 positive immortalized FBs to support perfusable µVN formation. Overall, we establish stable cell sources for µVN formation and characterize the functions of Thy1 positive and negative FBs in vasculogenesis in vitro.

Early detection of SARS-CoV-2 and other infections in solid organ transplant recipients and household members using wearable devices.

The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.

Coffee Bean Polyphenols Can Form Biocompatible Template-free Antioxidant Nanoparticles with Various Sizes and Distinct Colors.

Plant polyphenols have attracted attention in recent years due to their ability to undergo oxidative coupling reactions enabled by the presence of multiple phenolic hydroxyl groups, forming chemically versatile coatings and biocompatible nanoparticles (NPs) for various applications. The aim of this study was to investigate whether coffee bean aqueous extracts, which are known to be rich in polyphenols, could serve as a natural source of NP building blocks. Extracts were prepared by heating ground Arabica beans of varying roasting degrees in water with or without the addition of sodium metaperiodate or copper sulfate as an oxidizing agent, followed by filtration. NP formation was verified by dynamic light scattering and transmission electron microscopy, which revealed the presence of nano-sized particles with varying sizes and polydispersities as a function of the coffee type and oxidizing agent used. NP colors ranged from light to medium to dark brown, and particle sizes were between 44 and 250 nm with relatively low polydispersity indices. In vitro antioxidant assays showed that oxidizing agent-treated coffee NPs had lower antioxidant potency compared to air-oxidized NPs, but the free-radical scavenging activity was still retained. Coffee NPs exhibited no antimicrobial activity against common bacterial and fungal strains. Cell viability assays demonstrated that the NPs were biocompatible in human dermal fibroblasts, while exhibiting antiproliferative activity against MCF7 breast cancer cells, particularly copper sulfate-oxidized NPs. This study presents a facile and economical method to produce template-free antioxidant NPs that may be explored for various applications such as drug delivery and cosmetics.

The cancer glycocalyx mediates intravascular adhesion and extravasation during metastatic dissemination.

The glycocalyx on tumor cells has been recently identified as an important driver for cancer progression, possibly providing critical opportunities for treatment. Metastasis, in particular, is often the limiting step in the survival to cancer, yet our understanding of how tumor cells escape the vascular system to initiate metastatic sites remains limited. Using an in vitro model of the human microvasculature, we assess here the importance of the tumor and vascular glycocalyces during tumor cell extravasation. Through selective manipulation of individual components of the glycocalyx, we reveal a mechanism whereby tumor cells prepare an adhesive vascular niche by depositing components of the glycocalyx along the endothelium. Accumulated hyaluronic acid shed by tumor cells subsequently mediates adhesion to the endothelium via the glycoprotein CD44. Trans-endothelial migration and invasion into the stroma occurs through binding of the isoform CD44v to components of the sub-endothelial extra-cellular matrix. Targeting of the hyaluronic acid-CD44 glycocalyx complex results in significant reduction in the extravasation of tumor cells. These studies provide evidence of tumor cells repurposing the glycocalyx to promote adhesive interactions leading to cancer progression. Such glycocalyx-mediated mechanisms may be therapeutically targeted to hinder metastasis and improve patient survival.

Immobilization of glucose oxidase on bioinspired polyphenol coatings as a high-throughput glucose assay platform.

Glucose oxidase (GOx) is an enzyme with important industrial and biochemical applications, particularly in glucose detection. Here we leveraged the oxidative self-polymerization phenomenon of simple polyphenols (pyrogallol or catechol) in the presence of polyethylenimine (PEI) to form adhesive coatings that enabled GOx immobilization on conventional multi-well plates. Immobilization was verified and optimized by directly measuring GOx activity inside the coated wells. Our results showed that incorporating PEI in polyphenol coatings enhanced their enzyme immobilization efficiency, with pyrogallol (PG)-based coatings displaying the greatest enzyme activity. The immobilized enzyme maintained similar affinity to glucose compared to the free enzyme. GOx-immobilized PG/PEI-coated wells exhibited intermediate recycling ability but excellent resistance to urea as a denaturing agent compared to the free enzyme. GOx-immobilized 96-well plates allowed the construction of a linear glucose calibration curve upon adding glucose standards, with a detection limit of 0.4-112.6 mg dL-1, which was comparable to commercially available enzymatic glucose assay kits. The assay platform was also capable of effectively detecting glucose in rat plasma samples. Our findings present a simple enzyme immobilization technique that can be used to construct a glucose assay platform in a convenient multi-well format for high-throughput glucose quantification.

Validation of the Lebanese Medication Adherence Scale among Lebanese diabetic patients.

Background Adherence to oral antidiabetics plays a pivotal role in controlling diabetes. Healthcare workers evaluate this adherence when visited by patients. Objectives The primary objective of this study was to validate the existing LMAS-14 (Lebanese Medication Adherence Scale) in Lebanese diabetic adults. The secondary objective was to evaluate factors affecting adherence among this population. Setting The main five Lebanese governorates. Methods This study was conducted between May and September 2019, and community dwelling adult participants were enrolled using a proportionate random sample. The scale was validated using factor analysis and reliability testing, while bivariate and multivariable analyses assessed correlates of adherence. Main outcomes measures Validity of LMAS-14. Results A total of 308 participants were included, and the response rate was 91.25%. All LMAS-14 items converged over a solution of four factors, explaining a total of 64.39% of the variance (α = 0.859). The cutoff point between controlled and uncontrolled patients was set at 11. The sensitivity and specificity were good at this cutoff (71.1% and 94.74%, respectively). Results showed that 167 (57.2%) patients had good medication adherence. Advanced age (Beta = 0.046; p = 0.001) and having medical coverage (Beta = 1.452; p = 0.005) were significantly associated with higher adherence. Furthermore, adherence to oral antidiabetic drugs (Beta = 1.197; p = 0.018), female gender (Beta = 2.695; p = 0.011), and taking dyslipidemia medication (Beta = 3.527; p = 0.005) predicted higher diabetes control. Conclusion This study validated the LMAS among Lebanese adult diabetic patients taking oral antidiabetic drug. Advanced age and having medical coverage were associated with higher medication adherence. Further national studies are warranted to corroborate our findings.

The effects of luminal and trans-endothelial fluid flows on the extravasation and tissue invasion of tumor cells in a 3D in vitro microvascular platform.

Throughout the process of metastatic dissemination, tumor cells are continuously subjected to mechanical forces resulting from complex fluid flows due to changes in pressures in their local microenvironments. While these forces have been associated with invasive phenotypes in 3D matrices, their role in key steps of the metastatic cascade, namely extravasation and subsequent interstitial migration, remains poorly understood. In this study, an in vitro model of the human microvasculature was employed to subject tumor cells to physiological luminal, trans-endothelial, and interstitial flows to evaluate their effects on those key steps of metastasis. Luminal flow promoted the extravasation potential of tumor cells, possibly as a result of their increased intravascular migration speed. Trans-endothelial flow increased the speed with which tumor cells transmigrated across the endothelium as well as their migration speed in the matrix following extravasation. In addition, tumor cells possessed a greater propensity to migrate in close proximity to the endothelium when subjected to physiological flows, which may promote the successful formation of metastatic foci. These results show important roles of fluid flow during extravasation and invasion, which could determine the local metastatic potential of tumor cells.

Development of a Thymoquinone Polymeric Anticancer Nanomedicine through Optimization of Polymer Molecular Weight and Nanoparticle Architecture.

Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymers by the nanoprecipitation technique. Formulation variables included PCL chain length and NP architecture (matrix-type nanospheres or reservoir-type nanocapsules). The formulations were characterized in terms of their particle size, polydispersity index (PDI), drug loading efficiency, and drug release. An optimized TQ NP formulation in the form of oil-filled nanocapsules (F2-NC) was obtained with a mean hydrodynamic diameter of 117 nm, PDI of 0.16, about 60% loading efficiency, and sustained in vitro drug release. The formulation was then tested in cultured human cancer cell lines to verify its antiproliferative efficacy as a potential anticancer nanomedicine. A pilot pharmacokinetic study was also carried out in healthy mice to evaluate the oral bioavailability of the optimized formulation, which revealed a significant increase in the maximum plasma concentration (Cmax) and a 1.3-fold increase in bioavailability compared to free TQ. Our findings demonstrate that the versatility of polymeric NPs can be effectively applied to design a nanoscale delivery platform for TQ that can overcome its biopharmaceutical limitations.

Tuning the Surface Chemistry of Melanin-Mimetic Polydopamine Nanoparticles Drastically Enhances Their Accumulation into Excised Human Skin.

Melanin-mimetic polydopamine nanoparticles (PDA NPs) are emerging as promising candidates for topical and transdermal drug delivery because they mimic melanin, a naturally occurring skin pigment. However, our knowledge of their interactions with human skin remains limited. Hence, we set out to investigate the role of PDA NP surface chemistry in modulating their skin deposition. PDA NPs were synthesized by base-catalyzed oxidative self-polymerization of dopamine and functionalized with poly(ethylene glycol) (PEG) bearing different termini to obtain neutral, anionic, cationic, and hydrophobic PEGylated NPs. NPs were characterized by dynamic light scattering, transmission electron microscopy, Fourier transform-infrared spectroscopy, and X-ray photoelectron spectroscopy. The NPs were then labeled with rhodamine B, and their skin interactions were investigated both in vitro, using a Strat-M membrane, and ex vivo, using excised whole thickness human skin. In vitro diffusion studies revealed that the NPs did not permeate transdermally, rather the NPs accumulated in the Strat-M membrane after 24 h of incubation. Membrane deposition of the NPs showed a strong dependence on surface chemistry, with anionic (unmodified and carboxyl-terminated PEGylated) NPs achieving the highest accumulation, followed by neutral and cationic NPs, whereas hydrophobic NPs achieved the lowest degree of accumulation. In ex vivo permeation studies, we observed that surface modification of PDA NPs with PEG serving as an antifouling coating is essential to maintaining colloidal stability upon skin contact. Moreover, anionic PEGylated NPs were able to achieve 78% skin accumulation, which was significantly higher than neutral and cationic NPs (51 and 34% accumulation, respectively). Our findings provide important insights into the role of surface chemistry in enhancing the skin accumulation of melanin-mimetic PDA NPs as potential sunscreens and carriers for skin-targeted treatments.

Nature-Inspired Polymerization of Quercetin to Produce Antioxidant Nanoparticles with Controlled Size and Skin Tone-Matching Colors.

Plant polyphenols have received considerable attention in recent years due to their ability to undergo oxidation-triggered self-polymerization, forming biocompatible versatile coatings and templated nanoparticles (NPs) that can be leveraged for a variety of biomedical applications. Here we show for the first time that untemplated NPs can be conveniently synthesized from the abundant plant polyphenol quercetin (QCT) simply by incubation with an oxidizing agent in a universal organic solvent, followed by self-assembly upon gradual addition of water. The process yielded NPs of around 180-200 nm in size with a range of colors that resembled light to medium-brown skin tones. The NPs were characterized by UV-Vis, FT-IR, and 1H-NMR spectroscopy and by dynamic light scattering and transmission electron microscopy to understand their physicochemical properties. Antioxidant and cell viability assays were also conducted to demonstrate the NPs' free-radical scavenging activity and biocompatibility, altogether providing valuable insights into the structure and function of this emerging class of nanomaterials to guide future biomedical applications.

Bioinspired Polymerization of Quercetin to Produce a Curcumin-Loaded Nanomedicine with Potent Cytotoxicity and Cancer-Targeting Potential in Vivo.

Nanomedicine has had a profound impact on the treatment of many diseases, especially cancer. However, synthesis of multifunctional nanoscale drug carriers often requires multistep coupling and purification reactions, which can pose major scale-up challenges. Here, we leveraged bioinspired oxidation-triggered polymerization of catechols to synthesize nanoparticles (NPs) from the plant polyphenol quercetin (QCT) loaded with a hydrophobic anticancer drug, curcumin, and functionalized with poly(ethylene glycol) (PEG) for steric stabilization in one reaction step. NPs were formed by base-catalyzed oxidative self-polymerization of QCT in the presence of curcumin and thiol-terminated PEG upon mixing in a universal solvent (dimethyl sulfoxide), followed by self-assembly with the gradual addition of water. Dynamic light scattering and X-ray photoelectron spectroscopy were used to confirm NP PEGylation. Drug loading was verified by UV-vis spectroscopy. Curcumin-loaded NPs were efficiently internalized by CT26 murine colon cancer cells as determined by flow cytometry and confocal microscopy. NPs also demonstrated sustained release and potent cytotoxicity in vitro. Moreover, in vivo imaging of CT26 tumor-bearing Balb/c mice following tail vein injection of DiR-labeled QCT NPs showed steady tumor accumulation of the NPs up to 24 h. This was further supported by significant tumor uptake of curcumin-loaded QCT NPs as measured by flow cytometry analysis of tumor homogenates. Our findings present a greener synthetic route for the fabrication of drug-loaded surface-functionalized NPs from poorly water-soluble plant polyphenols such as QCT as promising anticancer delivery systems.

Identifying language impairment in bilingual children in France and in Germany.

BACKGROUND: The detection of specific language impairment (SLI) in children growing up bilingually presents particular challenges for clinicians. Non-word repetition (NWR) and sentence repetition (SR) tasks have proven to be the most accurate diagnostic tools for monolingual populations, raising the question of the extent of their usefulness in different bilingual populations. AIMS: To determine the diagnostic accuracy of NWR and SR tasks that incorporate phonological/syntactic complexity as discussed in recent linguistic theory. The tasks were developed as part of the Language Impairment Testing in Multilingual Settings (LITMUS) toolkit, in two different national settings, France and Germany, and investigated children with three different home languages: Arabic, Portuguese and Turkish. METHODS & PROCEDURES: NWR and SR tasks developed in parallel were administered to 151 bilingual children, aged 5;6-8;11, in France and in Germany, to 64 children in speech-language therapy (SLT) and to 87 children not in SLT, whose first language (L1) was Arabic, Portuguese or Turkish. Children were also administered standardized language tests in each of their languages to determine likely clinical status (typical development (TD) or SLI), and parents responded to a questionnaire including questions about early and current language use (bilingualism factors) and early language development (risk factors for SLI). Monolingual controls included 47 TD children and 29 children with SLI. Results were subjected to inter-group comparisons, to diagnostic accuracy calculation, and to correlation and multiple regression analyses. OUTCOMES & RESULTS: In accordance with previous studies, NWR and SR identified SLI in the monolingual children, yielding good to excellent diagnostic accuracy. Diagnostic accuracy in bilingual children was fair to good, generally distinguishing children likely to have SLI from children likely to have TD. Accuracy was necessarily linked to the determination of clinical status, which was based on standardized assessment in each of the child's languages. Positive early development, a composite risk factor for SLI, and not variables related to language exposure and use, generally emerged as the strongest predictor of performance on the two tasks, constituting additional, independent support for the efficacy of NWR and SR in identifying impairment in bilingual children. CONCLUSIONS & IMPLICATIONS: NWR and SR tasks informed by linguistic theory are appropriate for use as part of the diagnostic process for identifying language impairment in bilingual children for whom the language of assessment is different from the home language, in diverse sociolinguistic contexts.

What Machine Learning Can Tell Us About the Role of Language Dominance in the Diagnostic Accuracy of German LITMUS Non-word and Sentence Repetition Tasks.

The present study investigates the performance of 21 monolingual and 56 bilingual children aged 5;6-9;0 on German LITMUS-sentence-repetition (SRT; Hamann et al., 2013) and non-word-repetition-tasks (NWRT; Grimm et al., 2014), which were constructed in accordance with the LITMUS-principles (Language Impairment Testing in Multilingual Settings; Armon-Lotem et al., 2015). Both tasks incorporate phonologically and syntactically complex structures shown to be cross-linguistically challenging for children with Specific Language Impairment (SLI) and aim at minimizing bias against bilingual children while still being indicative of the presence of language impairment across language combinations (see Marinis and Armon-Lotem, 2015; for sentence-repetition; Chiat, 2015 for non-word-repetition). Given the great variability in bilingual language exposure and the potential effect of language experience on language performance in bilingual children, we examined whether background variables related to bilingualism, particularly, the degree language dominance as measured by relative amount of use and exposure, could compromise the diagnostic accuracy of the German LITMUS-SRT and NWRT. We further investigated whether a combination of the two tasks provides better diagnostic accuracy and helps avoid cases of misdiagnosis. To address this, we used an unsupervised machine learning algorithm, the Partitioning-Around-Medoids (PAM, Kaufman and Rousseeuw, 2009), for deriving a clinical category for the children as ± language-impaired based on their performance scores on SRT and NWRT (in isolation and combined) while withholding information about their clinical status based on standardized assessment in their first (home language, L1) and second language (societal language, L2). Subsequently, we calculated diagnostic accuracy and used regression analysis to investigate which background variables (age of onset, length of exposure, degree of language dominance, socio-economic-status, and risk factors for SLI) best explained clinical-group-membership yielded from the PAM-analysis based on the children's NWRT and SRT performance scores. Results show that although language-dominance clearly influences the performance of bilingual typically developing children, especially in the SRT, the diagnostic accuracy of the tools is not compromised by language dominance: while risk factors for SLI were significant predictors for clinical group membership in all models, language dominance did not contribute at all to explaining clinical cluster membership as typically developing or SLI based on any of the combinations of the SRT and NWRT variables. Additionally, results confirm that a combination of SRT scored by correct target structure and the structurally more complex language-dependent part of the NWRT yields better diagnostic accuracy than single measures and is only sensitive to risk factors for SLI and not to dominance levels or SES.