Multilevel factors predict treatment response following semantic feature-based intervention in bilingual aphasia.

Semantic feature-based treatments (SFTs) are effective rehabilitation strategies for word retrieval deficits in bilinguals with aphasia (BWA). However, few studies have prospectively evaluated the effects of key parameters of these interventions on treatment outcomes. This study examined the influence of intervention-level (i.e., treatment language and treatment sessions), individual-level (baseline naming severity and age), and stimulus-level (i.e., lexical frequency, phonological length, and phonological neighborhood density) factors on naming improvement in a treated and untreated language for 34 Spanish-English BWA who completed 40 hours of SFT. Results revealed significant improvement over time in both languages. In the treated language, individuals who received therapy in their L1 improved more. Additionally, higher pre-treatment naming scores predicted greater response to treatment. Finally, a frequency effect on baseline naming accuracy and phonological effects on accuracy over time were associated with differential treatment gains. These findings indicate that multilevel factors are influential predictors of bilingual treatment outcomes.

Dedoping of Intraband Silver Selenide Colloidal Quantum Dots through Strong Electronic Coupling at Organic/Inorganic Hybrid Interfaces.

Colloidal quantum dot (CQD) infrared (IR) photodetectors can be fabricated and operated with larger spectral tunability, fewer limitations in terms of cooling requirements and substrate lattice matching, and at a potentially lower cost than detectors based on traditional bulk materials. Silver selenide (Ag2Se) has emerged as a promising sustainable alternative to current state-of-the-art toxic semiconductors based on lead, cadmium, and mercury operating in the IR. However, an impeding gap in available absorption bandwidth for Ag2Se CQDs exists in the short-wave infrared (SWIR) region due to degenerate doping by the environment, switching the CQDs from intrinsic interband semiconductors in the near-infrared (NIR) to intraband absorbing CQDs in the mid-wave infrared (MWIR). Herein, we show that the small molecular p-type dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) can be used to extract electrons from the 1Se state of MWIR active Ag2Se CQDs to activate their intrinsic energy gap in the SWIR window. We demonstrate quenching of the MWIR Ag2Se absorbance peak, shifting of nitrile vibrational peaks characteristic of charge-neutral F4-TCNQ, as well as enhanced CQD absorption around ∼2500 nm after doping both in ambient and under air-free conditions. We elucidate the doping mechanism to be one that involves an integer charge transfer akin to doping in semiconducting polymers. These indications of charge transfer are promising milestones on the path to achieving sustainable SWIR Ag2Se CQD photodetectors.

Vanishing Confinement Regime in Terahertz HgTe Nanocrystals Studied under Extreme Conditions of Temperature and Pressure.

While HgTe nanocrystals (NCs) in the mid-infrared region have reached a high level of maturity, their far-infrared counterparts remain far less studied, raising the need for an in-depth investigation of the material before efficient device integration can be considered. Here, we explore the effect of temperature and pressure on the structural, spectroscopic, and transport properties of HgTe NCs displaying an intraband absorption at 10 THz. The temperature leads to a very weak modulation of the spectrum as opposed to what was observed for strongly confined HgTe NCs. HgTe NC films present ambipolar conduction with a clear prevalence of electron conduction as confirmed by transistor and thermoelectric measurements. Under the application of pressure, the material undergoes phase transitions from the zinc blende to cinnabar phase and later to the rock salt phase which we reveal using joint X-ray diffraction and infrared spectroscopy measurements. We discuss how the pressure existence domain of each phase is affected by the particle size.

Clinical perspectives and strategies for confronting disparities in social determinants of health for Hispanic bilinguals with aphasia.

Disparities in social determinants of health (SDOH) such as socioeconomic status and access to quality healthcare present serious barriers to enrollment in clinical rehabilitation programs for individuals who have experienced a stroke, especially for those who identify with a racial-ethnic minority group. Hispanic bilinguals with aphasia (HBWA) are one marginalized group who face even greater enrollment challenges since post-stroke language impairment and limited English proficiency make it difficult to advocate for one's needs and identify appropriate rehabilitation programs. Given the increasing representation of Hispanic individuals in the U.S. (projected to be 30% of the population in 2050), it is imperative that clinicians counter disparities in stroke care by facilitating access to clinical services for HBWA. However, the Hispanic population remains largely understudied in the stroke and aphasia literature, due in part to reduced opportunities to enroll in large-scale clinical research studies. In this paper we highlight how our team at Boston University has designed and implemented a variety of recruitment practices, assessment modifications, and treatment accommodations to circumvent the known barriers to participation in clinical research experienced by HBWA. Furthermore, we discuss the importance of cultural responsiveness and demonstrate how including principles of sensitivity and humility in clinical trial protocols improves participant enrollment and retention. Although clinical adjustments in this study were developed for use with HBWA, the effectiveness of the procedures suggests they may be useful blueprints for expanding access to research opportunities for various marginalized groups.

Telerehabilitation for Word Retrieval Deficits in Bilinguals With Aphasia: Effectiveness and Reliability as Compared to In-person Language Therapy.

Background: Bilinguals with post-stroke aphasia (BWA) require treatment options that are sensitive to their particular bilingual background and deficits across languages. However, they may experience limited access to bilingual clinical resources due to reduced availability of bilingual practitioners, geographical constraints, and other difficulties. Telerehabilitation can improve access to bilingual clinical services for BWA and facilitate the delivery of specific language treatments at distance, but more evidence on its effectiveness and reliability is needed. This study aimed to determine the equivalence of effectiveness and reliability of a semantic treatment for word retrieval deficits in BWA delivered via telerehabilitation relative to in-person therapy. Methods: We examined the retrospective data of 16 BWA who received 20 sessions of therapy based on semantic feature analysis for word retrieval deficits in person (n = 8) or via telerehabilitation (n = 8). The two groups were comparable on age, years of education, time of post-stroke onset, aphasia severity, and naming ability in both languages. Treatment effectiveness (i.e., effect sizes in the treated and the untreated language, and change on secondary outcome measures) and reliability (i.e., clinician adherence to treatment protocol) were computed for each delivery modality and compared across groups. Results: Significant improvements were observed in most patients, with no significant differences in treatment effect sizes or secondary outcomes in the treated and the untreated language between the teletherapy group and the in-person therapy group. Also, the average percentage of correctly delivered treatment steps by clinicians was high for both therapy delivery methods with no significant differences between the telerehabilitation vs. the in-person modality. Discussion: This study provides evidence of the equivalence of treatment gains between teletherapy and in-person therapy in BWA and the high reliability with which treatment for word retrieval deficits can be delivered via telerehabilitation, suggesting that the essential treatment components of the intervention can be conducted in a comparable manner in both delivery modalities. We further discuss the benefits and potential challenges of the implementation of telerehabilitation for BWA. In the future, telerehabilitation may increase access to therapy for BWA with varying linguistic and cultural backgrounds, thus, offering a more inclusive treatment approach to this population.

Predicting treatment outcomes for bilinguals with aphasia using computational modeling: Study protocol for the PROCoM randomised controlled trial.

INTRODUCTION: Bilinguals with aphasia (BWA) present varying degrees of lexical access impairment and recovery across their two languages. Because both languages may benefit from therapy, identifying the optimal target language for treatment is a current challenge for research and clinical practice. Prior research has demonstrated that the BiLex computational model can accurately simulate lexical access in healthy bilinguals, and language impairment and treatment response in bilingual aphasia. Here, we aim to determine whether BiLex can predict treatment outcomes in BWA in the treated and the untreated language and compare these outcome predictions to determine the optimal language for rehabilitation. METHODS AND ANALYSIS: The study involves a prospective parallel-group, double-blind, randomised controlled trial. Forty-eight Spanish-English BWA will receive 20 sessions of semantic treatment for lexical retrieval deficits in one of their languages and will complete assessments in both languages prior and after treatment. Participants will be randomly assigned to an experimental group receiving treatment in the optimal language determined by the model or a control group receiving treatment in the language opposite to the model's recommendation. Primary treatment outcomes include naming probes while secondary treatment outcomes include tests tapping additional language domains. Treatment outcomes will be compared across the two groups using 2×2 mixed effect models for repeated measures Analysis of variance (ANOVA) on metrics of treatment effects commonly employed in rehabilitation studies (ie, effect size and percentage change). ETHICS AND DISSEMINATION: All procedures included in this protocol (protocol number 29, issue date: 19 March 2019) were approved by the Boston University Charles River Campus Institutional Review Board at Boston, Massachusetts (reference number: 4492E). The results of this study will be published in peer-reviewed scientific journals and will be presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT02916524.

Synthesis of luminescent core/shell α-Zn3P2/ZnS quantum dots.

Metal chalcogenide nanoparticles offer vast control over their optoelectronic properties via size, shape, composition, and morphology which has led to their use across fields including optoelectronics, energy storage, and catalysis. While cadmium and lead-based nanocrystals are prevalent in applications, concerns over their toxicity have motivated researchers to explore alternate classes of nanomaterials based on environmentally benign metals such as zinc and tin. The goal of this research is to identify material systems that offer comparable performance to existing metal chalcogenide systems from abundant, recyclable, and environmentally benign materials. With band gaps that span the visible through the infrared, II-V direct band gap semiconductors such as tetragonal zinc phosphide (α-Zn3P2) are promising candidates for optoelectronics. To date, syntheses of α-Zn3P2 nanoparticles have been hindered because of the toxicity of zinc and phosphorus precursors, surface oxidation, and defect states leading to carrier trapping and low photoluminescence quantum yield. This work reports a colloidal synthesis of quantum confined α-Zn3P2 nanoparticles from common phosphorus precursor tris(trimethylsilyl)phosphine and environmentally benign zinc carboxylates. Shelling of the nanoparticles with zinc sulfide is shown as a method of preventing oxidation and improving the optical properties of the nanoparticles. These results show a route to stabilizing α-Zn3P2 nanoparticles for optoelectronic device applications.

High-performance thermoelectric silver selenide thin films cation exchanged from a copper selenide template.

Over the past decade, Ag2Se has attracted increasing attention due to its potentially excellent thermoelectric (TE) performance as an n-type semiconductor. It has been considered a promising alternative to Bi-Te alloys and other commonly used yet toxic and/or expensive TE materials. To optimize the TE performance of Ag2Se, recent research has focused on fabricating nanosized Ag2Se. However, synthesizing Ag2Se nanoparticles involves energy-intensive and time-consuming techniques with poor yield of final product. In this work, we report a low-cost, solution-processed approach that enables the formation of Ag2Se thin films from Cu2-x Se template films via cation exchange at room temperature. Our simple two-step method involves fabricating Cu2-x Se thin films by the thiol-amine dissolution of bulk Cu2Se, followed by soaking Cu2-x Se films in AgNO3 solution and annealing to form Ag2Se. We report an average power factor (PF) of 617 ± 82 µW m-1 K-2 and a corresponding ZT value of 0.35 at room temperature. We obtained a maximum PF of 825 µW m-1 K-2 and a ZT value of 0.46 at room temperature for our best-performing Ag2Se thin-film after soaking for 5 minutes. These high PFs have been achieved via full solution processing without hot-pressing.

Colloidal quantum dots for thermal infrared sensing and imaging.

Colloidal quantum dots provide a powerful materials platform to engineer optoelectronics devices, opening up new opportunities in the thermal infrared spectral regions where no other solution-processed material options exist. This mini-review collates recent research reports that push the technological envelope of colloidal quantum dot-based photodetectors toward mid- and long-wavelength infrared. We survey the synthesis and characterization of various thermal infrared colloidal quantum dots reported to date, discuss the basic theory of device operation, review the fabrication and measurement of photodetectors, and conclude with the future prospect of this emerging technology.

Matrix-Induced Autologous Chondrocyte Implantation (MACI) Using a Cell-Seeded Collagen Membrane Improves Cartilage Healing in the Equine Model.

BACKGROUND: Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has inherent advantages including surgical implantation via arthroscopy or miniarthrotomy, the elimination of periosteal harvest, and the use of tissue adhesive in lieu of sutures. This study evaluated the efficacy of the MACI implant in an equine full-thickness cartilage defect model at 1 year. METHODS: Autologous chondrocytes were seeded onto a collagen type-I/III membrane and implanted into one of two 15-mm defects in the femoral trochlear ridge of 24 horses. Control defects either were implanted with cell-free collagen type-I/III membrane (12 horses) or were left ungrafted as empty defects (12 horses). An additional 3 horses had both 15-mm defects remain empty as nonimplanted joints. The repair was scored by second-look arthroscopy (12 weeks), and necropsy examination (53 weeks). Healing was assessed by arthroscopic scoring, gross assessment, histology and immunohistology, cartilage matrix component assay, and gene expression determination. Toxicity was examined by prostaglandin E2 formation in joint fluid, and lymph node morphology combined with histologic screening of organs. RESULTS: MACI-implanted defects had improved gross healing and composite histologic scores, as well as increases in chondrocyte predominance, toluidine blue-stained matrix, and collagen type-II content compared with scaffold-only implanted or empty defects. There was minimal evidence of reaction to the implant in the synovial membrane (minor perivascular cuffing), subchondral bone, or cartilage. There were no adverse clinical effects, signs of organ toxicity, or evidence of chondrocytes or collagen type-I/III membrane in draining lymph nodes. CONCLUSIONS: The MACI implant appeared to improve cartilage healing in a critical-sized defect in the equine model compared with collagen matrix alone. CLINICAL RELEVANCE: These results indicate that the MACI implant is quick to insert, provides chondrocyte security in the defect, and improves cartilage healing compared with ACI.

RNA Interference Mediated Interleukin-1ß Silencing in Inflamed Chondrocytes Decreases Target and Downstream Catabolic Responses.

Posttraumatic activation of the catabolic cascade plays a major role in degradation of cartilage. Interleukin-1ß (IL-1ß), a primary instigator in the catabolic axis, is upregulated in chondrocytes following injury. IL-1ß activates key degradative enzymes, including MMPs and aggrecanases, and other proinflammatory mediators such as PGE2 which contribute to ECM breakdown. Posttranscriptional silencing of IL-1ß by RNA interference (RNAi) may drive a reduction in IL-1ß. We hypothesized that transduction of chondrocytes using rAAV2 expressing a short hairpin RNAi motif targeting IL-1ß (shIL-1ß) would significantly decrease IL-1ß expression and, in turn, decrease expression of other catabolic enzymes. Chondrocyte cultures were transduced with rAAV2-tdT-shIL-1ß in serum-free media. The fluorescent protein, tdTomato, was used to determine transduction efficiency via flow cytometry and fluorescent microscopy. Cells were stimulated with lipopolysaccharide (LPS) 48 hours following transduction. After 24-hour stimulation, supernatants were collected for cytokine analysis, and cells lysed for gene expression analysis. IL-1ß knockdown led to significantly decreased expression of IL-1ß, TNF-α, and ADAMTS5. PGE2 synthesis was also significantly downregulated. Overall, effective silencing of IL-1ß using rAAV2 vector expressing a short hairpin IL-1ß knockdown sequence was shown. Additionally, significant downstream effects were evident, including decreased expression of TNF-α and ADAMTS5. Targeted silencing of catabolic cytokines may provide a promising treatment avenue for osteoarthritic (OA) joints.

A double-blind, placebo-controlled study of sertraline with naltrexone for alcohol dependence.

INTRODUCTION: Significant preclinical evidence exists for a synergistic interaction between the opioid and the serotonin systems in determining alcohol consumption. Naltrexone, an opiate receptor antagonist, is approved for the treatment of alcohol dependence. This double-blind placebo-controlled study examined whether the efficacy of naltrexone would be augmented by concurrent treatment with sertraline, a selective serotonin receptor uptake inhibitor (SSRI). METHODS: One hundred and thirteen participants meeting DSM IV alcohol dependence criteria, who were abstinent from alcohol between 5 and 30 days, were randomly assigned to receive one of two treatments at two sites. One group received naltrexone 12.5 mg once daily for 3 days, 25 mg once daily for 4 days, and 50 mg once daily for the next 11 weeks, together with placebo sertraline. The other group received naltrexone as outlined and simultaneously received sertraline 50 mg once daily for 2 weeks, followed by 100 mg once daily for 10 weeks. Both groups received group relapse prevention psychotherapy on a weekly basis. RESULTS: Compliance and attendance rates were comparable and high. The groups did not differ on the two primary outcomes, time to first drink and time to relapse to heavy drinking, or on secondary treatment outcomes. With the exception of sexual side effects which were more common in the combination group, most adverse events were similar for the two conditions. CONCLUSIONS: As the doses are tested in combination with specialized behavioral therapy, this study does not provide sufficient evidence for the combined use of sertraline and naltrexone above naltrexone alone.

Gene therapy in musculoskeletal repair.

Local and regional gene therapy has improved healing in preclinical trials of articular and other muculoskeletal conditions. Combinations of cell supplementation and cells overexpressing growth factor genes have shown promising results for improving cartilage repair, enhancing delayed union of fractures, and driving organized tendon repair. Proof of concept has been developed using viral vectors, predominantly adenovirus, to deliver growth factor genes, such as BMP-2, TGF-beta1, and IGF-I. Integrating vectors, such as retrovirus and lentivirus, have improved the duration of gene-induced repair, however, increased risk factors have limited broad application. Cartilage repair can be improved using chondrocyte or stem cell transplantation with cells expressing IGF-I, BMP-2, or FGF-2. In cartilage injury and secondary osteoarthritis models, a combination of IL-1 knockdown and growth factor supplementation has restored cartilage matrix and stabilized the osteoarthritic process. Ultimately, nonviral vectors may provide similar control of catabolic activity in cartilage and synovial structures, which may further improve outcome after chondrocyte or mesenchymal stem cell (MSC) implantation. MSCs derived from bone marrow, fat, or other connective tissues provide a multipotent cell source that may be privileged vectors for skeletal gene therapy. MSCs expressing BMP-2, TGF-beta1, LMP-1, IGF-I, or GDF-5 have enhanced cartilage, bone, and tendon repair. Overall, the field of orthopedic gene therapy for enhanced tissue repair has made significant preclinical advances. Combining existing cell transplant technology to deliver differentiated cells in a minimally invasive way, with genes that improve matrix formation, provides a manageable protocol for a persisting anabolic impact.

Effects of gpx4 haploid insufficiency on GPx4 activity, selenium concentration, and paraquat-induced protein oxidation in murine tissues.

Selenium-dependent glutathione peroxidase-4 (GPx4) catalyzes the reduction of phospholipid hydroperoxides. Because a full gpx4 knockout is embryonic lethal, we examined the effect of deletion of one copy of gpx4 on the activities of three selenoperoxidases (GPx1, GPx3, and GPx4), selenium concentrations, and pro-oxidant-induced protein oxidation in various tissues of mice. A total of 32 gpx4 hemizygous (GPx4+/-) and wild-type (WT) mice (8- to 10-weeks old; 16 males and 16 females) were fed a selenium-adequate diet and given an intraperitoneal injection of paraquat (PQ; 24 mg/kg body wt) or phosphate-buffered saline (PBS). All mice were euthanized 4 hrs after injection to collect tissues for analyses. In PBS-treated mice, GPx4 activities in lung, liver, kidney, and testes of GPx4+/- mice were 24-39% lower (P < 0.05) than in WT mice. Among PQ-treated mice, only testis GPx4 activity in GPx4+/- mice was significantly lower (54% P < 0.05) than WT mice. Selenium concentration in testes, but not in other tissues, was reduced (34% P < 0.05) in GPx4+/- mice compared with WT mice, irrespective of treatment. Tissue GPx1 activities and plasma GPx3 and alanine aminotransferase (ALT) activities were unaffected by PQ treatment or gpx4 hemizygosity. Total protein carbonyl was elevated (73% P < 0.05) by PQ only in lung, and this effect of PQ was independent of genotypes. In conclusion, gpx4 haploid insufficiency reduced GPx4 activities and/or selenium concentrations, but had no effect on pro-oxidant-induced protein oxidation in various tissues of mice.

Discordant 16S and 23S rRNA gene phylogenies for the genus Helicobacter: implications for phylogenetic inference and systematics.

Analysis of 16S rRNA gene sequences has become the primary method for determining prokaryotic phylogeny. Phylogeny is currently the basis for prokaryotic systematics. Therefore, the validity of 16S rRNA gene-based phylogenetic analyses is of fundamental importance for prokaryotic systematics. Discrepancies between 16S rRNA gene analyses and DNA-DNA hybridization and phenotypic analyses have been noted in the genus Helicobacter. To clarify these discrepancies, we sequenced the 23S rRNA genes for 55 helicobacter strains representing 41 taxa (>2,700 bases per sequence). Phylogenetic-tree construction using neighbor-joining, parsimony, and maximum likelihood methods for 23S rRNA gene sequence data yielded stable trees which were consistent with other phenotypic and genotypic methods. The 16S rRNA gene sequence-derived trees were discordant with the 23S rRNA gene trees and other data. Discrepant 16S rRNA gene sequence data for the helicobacters are consistent with the horizontal transfer of 16S rRNA gene fragments and the creation of mosaic molecules with loss of phylogenetic information. These results suggest that taxonomic decisions must be supported by other phylogenetically informative macromolecules, such as the 23S rRNA gene, when 16S rRNA gene-derived phylogeny is discordant with other credible phenotypic and genotypic methods. This study found Wolinella succinogenes to branch with the unsheathed-flagellum cluster of helicobacters by 23S rRNA gene analyses and whole-genome comparisons. This study also found intervening sequences (IVSs) in the 23S rRNA genes of strains of 12 Helicobacter species. IVSs were found in helices 10, 25, and 45, as well as between helices 31' and 27'. Simultaneous insertion of IVSs at three sites was found in H. mesocricetorum.

Detoxification as a gateway to long-term treatment: assessing two interventions.

Two interventions designed to increase the likelihood of entry into long-term treatment upon discharge from hospital detoxification are compared in a randomized controlled trial. The 279 study participants were treated for heroin and/or cocaine dependence on detoxification wards in two hospitals in a poor, predominantly Hispanic, neighborhood in New York City. One-third of the participants entered and remained in long-term treatment for the first 30 days after discharge from detoxification, 23% were in treatment for 1-29 days, and 43% received no treatment in the 30 days. Neither of the interventions--one, a brief motivational psychotherapy, the other, a series of treatment-related videos--is found to be significantly superior to treatment as usual in increasing the likelihood of utilization of long-term treatment. While weaknesses in the interventions themselves need to be examined, it is also concluded that conditions on the detoxification wards may hamper effective intervention.

Absence of photoreceptor rescue with D-cis-diltiazem in the rd mouse.

PURPOSE: Because of a previous report suggesting that D-cis-diltiazem slows retinal degeneration in rd mice, this study was undertaken to examine the effect of D-cis-diltiazem on photoreceptor structure and function in this line of mice. METHODS: Mice were randomly assigned to daily intraperitoneal injections of D-cis-diltiazem or saline between postnatal days 9 and 24. On postnatal day 26 or 27, retinal function was assessed by recording dark-adapted bright-flash ERGs in all animals. Retinal morphology was examined in fixed sections and in immunolabeled frozen sections. Examiners were masked to the treatment group assignment. RESULTS: On postnatal days 26 and 27, diltiazem- and saline-treated mice had only one row of remaining photoreceptor cells throughout most of the central retina. Cone cells in the periphery had remnants of inner segments. Total cell counts and separate counts of rod and cone photoreceptor cells by immunostaining were similar in the diltiazem- versus saline-treated mice. Both groups of mice had, on average, comparable subnormal ERG amplitudes. CONCLUSIONS: D-cis-Diltiazem had no detectable effect on preservation of photoreceptor structure and function in rd mice.