Intervention studies with group design targeting expressive phonology for children with developmental speech and language disorder: A systematic review and meta-analysis.

BACKGROUND: Phonological difficulties are prevalent in children with speech and/or language disorders and may hamper their later language outcomes and academic achievements. These children often form a significant proportion of speech and language therapists' caseloads. There is a shortage of information on evidence-based interventions for improving phonological skills in children and adolescents with speech and language disorder. AIMS: The aim of this systematic literature review and meta-analysis was to systematically examine the effects of different intervention approaches on speech production accuracy and phonological representation skills in children with speech and language disorders. METHODS: A preregistered systematic review (International Prospective Register of Systematic Reviews ID: CRD42017076075) adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was completed. Seven electronic databases (PubMed, Web of Science, ERIC, PsychINFO, Cochrane Library, SCOPUS and Linguistics & Language Behavior Abstracts) were searched for studies related to oral language interventions with children with developmental speech and/or language disorder (mean age ranging from 3-18 years) published between January 2006 and August 2022. The included articles reported intervention studies with a group design in which speech production accuracy was the outcome measure. Studies were appraised using the Cochrane risk of bias tool, and individual effect sizes were calculated using standardised means differences when enough data was available. A meta-analysis was conducted obtaining the average standardised mean difference d. Heterogeneity, influence of possible moderator variables and publication bias were explored. RESULTS: The 23 studies that met the inclusion criteria presented low-medium risk of bias. Nine effect sizes were obtained from seven of these studies that presented a pre-post-test with a control group design. Medium-high average effect sizes were found in phonological accuracy. Heterogeneity was found between individual effect sizes. Significant moderator variables and publication bias were not detected. CONCLUSIONS: The results of this meta-analysis indicate positive effects on speech production accuracy. Based on this review, further improvements in the quality of reporting for intervention research are required in developing the evidence base for practice. WHAT THIS PAPER ADDS: What is already known on the subject An increasing number of interventions is available for children and adolescents with developmental speech and/or language disorders. Previous reviews suggest relatively low levels of evidence of interventions having phonology as an outcome measure. What this paper adds to the existing knowledge This review and meta-analysis summarise the intervention evidence from a substantial body of group design studies, indicating positive results from a range of interventions with phonological outcomes. It highlights the need to systematically implement and replicate different intervention procedures to understand factors that will maximise positive outcomes and to grow the evidence base for best practice. What are the potential or actual clinical implications of this study? Tentative evidence is emerging for the effectiveness of various approaches in enhancing speech production accuracy skills of children and adolescents with developmental speech and/or language disorder.

A Novel Fluorescent Gemcitabine Prodrug That Follows a Nucleoside Transporter-Independent Internalization and Bears Enhanced Therapeutic Efficacy With Respect to Gemcitabine.

The multiplexity of cancer has rendered it the second leading cause of mortality worldwide and theragnostic prodrugs have gained popularity in recent years as a means of treatment. Theragnostic prodrugs enable the simultaneous diagnosis and therapy of tumors via high-precision real-time drug release monitoring. Herein, we report the development of the small theragnostic prodrug GF, based on the nucleoside anticancer agent gemcitabine and the fluorescent dye 5(6)-carboxyfluorescein. We have successfully demonstrated its efficient internalization in tumor cells, showing localization throughout both the early and late endocytic pathways. Its mechanism of cell internalization was evaluated, confirming its independence from nucleoside transporters. Its cellular localization via confocal microscopy revealed a clathrin-mediated endocytosis mechanism, distinguishing it from analogous compounds studied previously. Furthermore, GF exhibited stability across various pH values and in human blood plasma. Subsequently, its in vitro cytotoxicity was assessed in three human cancer cell lines (A549, U87 and T98). Additionally, its pharmacokinetic profile in mice was investigated and the consequent drug release was monitored. Finally, its in vivo visualization was accomplished in zebrafish xenotransplantation models and its in vivo efficacy was evaluated in A549 xenografts. The results unveiled an intriguing efficacy profile, positioning GF as a compelling candidate warranting further investigation.

Feasible Peer-Mediated Intervention for Autistic Children Using Minimal Speech: A Qualitative Intervention Development Process.

PURPOSE: Qualitative engagement with stakeholders in the development of interventions can provide insight into strategies to maximize feasibility in real-life settings. We engaged stakeholders (autistic adults, early childhood educators, early childhood sector leaders and policy influencers, parents of autistic children, and speech-language pathologists) to inform the development of an educator-led peer-mediated intervention (PMI) for autistic preschoolers who use minimal speech that is feasible to implement in inclusive early childhood education and care (ECEC) settings. METHOD: A qualitative iterative intervention design process was utilized. Stakeholders (N = 15) attended an online workshop and completed a document review exploring the acceptability and feasibility of the proposed embedded PMI. A two-step analysis procedure using the Theoretical Domains Framework and template analysis was conducted to identify the barriers, enablers, and supports to the implementation of embedded PMI in early childhood settings. RESULTS: While embedded PMI was unanimously acceptable to stakeholders, several participants expressed concerns regarding feasibility. Barriers to the successful integration and implementation of PMI in inclusive preschool contexts included access to skills, knowledge, and resources. Participants identified strategies to overcome modifiable barriers and to enhance the existing enablers. These strategies are reflected in the following themes: build on the familiar, build capacity in augmentative and alternative communication, adopt a whole center approach, adapt to meet the needs of the ECEC setting, and engage in proactive implementation. CONCLUSION: To address barriers to the implementation of embedded PMI, action is needed at various levels: macro (national/policy), meso (organization/setting), and micro (individual). SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25155770.

Hydrogel Membranes from Chitosan-Fish Gelatin-Glycerol for Biomedical Applications: Chondroitin Sulfate Incorporation Effect in Membrane Properties.

Chondroitin sulfate (ChS), chitosan (Chi), and fish gelatin (FG), which are byproducts of a fish-treatment small enterprise, were incorporated with glycerol (Gly) to obtain dense hydrogel membranes with reduced brittleness, candidates for dressing in wound healing applications. The mechanical properties of all samples were studied via Dynamic Mechanical Analysis (DMA) and tensile tests while their internal structure was characterized using Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray Diffraction (XRD) instruments. Their surface morphology was analyzed by ThermoGravimetric Analysis (TGA) method, while their water permeability was estimated via Water Vapor Transmission Rate (WVTR) measurements. Wettability and degradation rate measurements were also carried out. Characterization results indicated that secondary interactions between the natural polymers and the plasticizer create the hydrogel membranes. The samples were amorphous due to the high concentration of plasticizer and the amorphous nature of the natural polymers. The integration of ChS led to decreased decomposition temperature in comparison with the glycerol-free sample, and all the materials had dense structures. Finally, the in vitro endothelial cell attachment studies indicate that the hydrogel membranes successfully support the attachment and survival of primary on the hydrogel membranes and could be appropriate for external application in wound healing applications as dressings.

Implementation Science in School-Based, Universal-Level Intervention Research: A Scoping Review.

PURPOSE: The aim of this study was to map the use of implementation science frameworks, models, and theories in intervention research targeting learning needs in the classroom. METHOD: A scoping review was conducted. Electronic database and manual searches were conducted. Two reviewers independently completed screening, data extraction, and quality appraisal. Qualitative content analysis was undertaken using Nilsen's taxonomy and the domains of the Consolidated Framework for Implementation Research (CFIR). The data were further analyzed using the CFIR valence and strength rating scales. RESULTS: Included papers (n = 22) used a diverse sample of implementation science frameworks and models. Most studies used determinant frameworks to guide data collection and analysis. Few studies used implementation science theory. Most studies were mixed methods (n = 11), published since 2019 (n = 20), and conducted in North America (n = 15). Over half of the interventions targeted social, emotional, and mental health (n = 13). A complex interplay of inner setting factors was identified as having a strong influence on implementation. Teachers' knowledge and beliefs, adaptability, and complexity of interventions were also identified as important considerations when conducting research in this context. CONCLUSIONS: Early engagement with stakeholders in education is recommended when designing universal level speech, language, and communication interventions for use in the ordinary classroom. Adaptive, hybrid designs that test both implementation strategies and effectiveness of interventions may be warranted given the influence of inner setting factors on implementation outcomes.

Exploring the acceptability, feasibility, and appropriateness of a communication-friendly classroom tool for use in Irish schools: A qualitative inquiry.

BACKGROUND: Ten percent of the school-aged population have speech, language, and communication needs (SLCN) that impact access to the curriculum. Successful implementation of classroom-based SLCN interventions can reduce barriers to learning, thereby improving educational outcomes for this vulnerable population. The challenges of implementing innovations in educational settings are well-documented, yet limited studies have addressed such considerations when developing, and piloting universal level SLCN interventions for use in Irish schools. METHODS: A qualitative exploratory study was undertaken to establish the acceptability, feasibility, and appropriateness of a universal level SLCN intervention. An advisory panel of teachers (n = 8) and children with SLCN (n = 2) were engaged as co-researchers in the study. The Communication Supporting Classrooms Observation Tool, developed as part of the Better Communication Project in the UK, was trialled across a diverse sample of school settings (n = 5). Semi-structured interviews were conducted with school practitioners and school leaders, and a deductive content analysis was undertaken using the domains of the Consolidation Framework for Implementation Research. DISCUSSION: The observation tool was viewed as acceptable with suggested additions. Integrating use of the tool within existing data-informed, school self-evaluation processes aimed at supporting school improvement was noted as a potential means of supporting implementation. A knowledge gap in relation to school-based models of support for SLCN was identified which may negatively impact implementation. An implementation strategy targeting coherence, cognitive engagement and contextual integration is indicated if the tool is to be normalised into routine practice in Irish classrooms. Implementation needs appeared to vary at the school level. CONCLUSIONS: The importance of early-stage exploration to guide implementation planning with regards to developing and testing universal level interventions for SLCN in schools is highlighted. Engaging an advisory panel provides important insights to guide implementation decisions. Findings suggest an adaptive design is required when planning implementation studies targeting classroom setting.

Stakeholder Perceptions of the Acceptability of Peer-Mediated Intervention for Minimally Speaking Preschoolers on the Autism Spectrum.

Peer mediated intervention (PMI) is an evidence-based approach to supporting social and communication development for children on the autism spectrum. For PMI to be integrated into everyday practice, it needs to be acceptable to stakeholders. This article engaged with autistic individuals, early childhood educators, parents, and speech and language pathologists on the prospective acceptability of implementing PMI with minimally speaking preschoolers in inclusive preschool settings. Focus groups and semi-structured interviews were conducted. The transcriptions were analyzed qualitatively using reflexive thematic analysis. Stakeholders described PMI as an acceptable intervention approach for this population and provided valuable insights to inform the development and implementation of PMIs. Attention needs to be paid to how to support preschools to adopt a PMI-friendly philosophy.

Editorial Perspective: Maximising the benefits of intervention research for children and young people with developmental language disorder (DLD) - a call for international consensus on standards of reporting in intervention studies for children with and at risk for DLD.

Current methods for reporting interventions do not allow key questions of importance to practitioners, service providers, policy-makers and people with DLD to be answered, and hence limit the implementation of effective interventions in the real world. To extend the existing EQUATOR guidelines to the context of speech language therapy/pathology for children with language disorder and to provide more specific guidance on participants, interventions and outcomes within the CONSORT checklist (used to improve the reporting of randomised controlled trials) and TIDieR (Template for Intervention Description and Replication) to ensure consistency of reporting. We will develop a core team to include representatives from each of the key groups who will either use or be influenced by the final reporting guidance across different countries. To achieve each set of aims, we will conduct reviews of the literature (which present typologies of intervention characteristics in (D)LD and related disorders); carry out focus groups; and use systematic consensus methods such as the Delphi technique, nominal group technique or consensus development conferences. Through the development and adoption of standard intervention reporting criteria, we anticipate that we will overcome the numerous barriers for practitioners, services and policy-makers in applying intervention evidence to practice. We believe that establishing international consensus on reporting guidelines would significantly accelerate progress in DLD research and the ease with which it can be used in clinical practice, by capitalising on the growth in intervention studies to enable international collaboration and new methodologies of data pooling, meta-analyses and cross-study comparisons.

Culturing Human Pluripotent Stem Cells on Micropatterned Silicon Surfaces.

Human pluripotent stem cell culture conditions are constantly being optimized, thus providing insight to the environmental cues that affect cell choices. A wide variety of media, coating materials, and substrates is now available for use, serving different scientific needs. Factors such as material stiffness, roughness, and topography are being recognized to contribute or even direct the acquisition of specific phenotypes. Here, we describe the use of patterned silicon substrates coated with Matrigel for the propagation and differentiation of human pluripotent stem cells.

Translational control in neurovascular brain development.

The human brain carries out complex tasks and higher functions and is crucial for organismal survival, as it senses both intrinsic and extrinsic environments. Proper brain development relies on the orchestrated development of different precursor cells, which will give rise to the plethora of mature brain cell-types. Within this process, neuronal cells develop closely to and in coordination with vascular cells (endothelial cells (ECs), pericytes) in a bilateral communication process that relies on neuronal activity, attractive or repulsive guidance cues for both cell types and on tight-regulation of gene expression. Translational control is a master regulator of the gene-expression pathway and in particular for neuronal and ECs, it can be localized in developmentally relevant (axon growth cone, endothelial tip cell) and mature compartments (synapses, axons). Herein, we will review mechanisms of translational control relevant to brain development in neurons and ECs in health and disease.

The Impact of Intervention Dose Form on Oral Language Outcomes for Children With Developmental Language Disorder.

Purpose The aim of this study was to extract key learning from intervention studies in which qualitative aspects of dosage, dose form, have been examined for children with developmental language disorder (DLD)-in vocabulary, morphosyntax, and phonology domains. This research paper emerged from a pair of systematic reviews, aiming to synthesize available evidence regarding qualitative and quantitative aspects of dosage. While quantitative aspects had been experimentally manipulated, the available evidence for dose form (tasks or activities within which teaching episodes are delivered) was less definitive. Despite this, the review uncovered insights of value to DLD research. Method A preregistered systematic review (PROSPERO ID: CRD42017076663) adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was completed. Included papers were quasi-experimental, randomized controlled trial, or cohort analytic studies, published in any language between January 2006 and May 2019; oral language interventions with vocabulary, morphosyntax, or phonology outcomes; and participants with DLD (M = 3-18 years). The intention was to include papers in which dose form was experimentally manipulated or statistically analyzed, while quantitative dosage aspects were controlled, such that definitive conclusions about optimal dose form could be drawn and gaps in the evidence identified. Results Two hundred and twenty-four papers met the above inclusion criteria; 27 focused on dose form. No study controlled for all quantitative aspects of dosage such that we could effectively address our original research questions. Despite this, key points of learning emerged with implications for future research. Conclusions There is tentative evidence of advantages for explicit over implicit instruction and of the benefits of variability in input, elicited production, and gestural and other visual supports. With careful design of dose form, there is potential to design more efficient interventions. Speech-language pathology research would benefit from an agreed taxonomy of dose form components and standardized reporting of intervention studies, to enable cross-study comparisons and a systematic accrual of knowledge to identify optimal dose form for clinical application.

[Empirically Supported Psychological Treatments for Children and Adolescents: State of the Art].

Empirically Supported Psychological Treatments for Children and Adolescents: State of the Art. BACKGROUND: The empirical evidence accumulated on the efficacy, effectiveness, and efficiency of psychotherapeutic treatments in children and adolescents calls for an update. The main goal of this paper objective was to carry out a selective review of empirically supported psychological treatments for a variety of common psychological disorders and problems in childhood and adolescence. METHOD: A review was carried out of the psychological treatments for different psychological disorders and problems in social-emotional or behavioral adjustment in the child-adolescent population according to the Spanish National Health System (Clinical Practice Guidelines) levels of evidence and degrees of recommendation. RESULTS: The findings suggest that psychological treatments have empirical support for addressing a wide range of psychological problems in these developmental stages. The degree of empirical support ranges from low to high depending on the phenomenon analyzed. The review suggests unequal progress in the different fields of intervention. CONCLUSIONS: From this update, psychologists will be able to make informed decisions when implementing those empirically supported treatments to address the problems that occur in childhood and adolescence.

Embryonic stem cells are devoid of macropinocytosis, a trafficking pathway for activin A in differentiated cells.

Ligand-receptor complexes formed at the plasma membrane are internalised via various endocytic pathways that influence the ultimate signalling output by regulating the selection of interaction partners by the complex along the trafficking route. We report that, in differentiated cells, activin A-receptor complexes are internalised via clathrin-mediated endocytosis (CME) and macropinocytosis (MP), whereas in human embryonic stem cells (hESCs) internalisation occurs via CME. We further show that hESCs are devoid of MP, which becomes functional upon differentiation towards endothelial cells through mesoderm mediators. Our results reveal, for the first time, that MP is an internalisation route for activin A in differentiated cells, and that MP is not active in hESCs and is induced as cells differentiate.

Development of novel GnRH and Tat48-60 based luminescent probes with enhanced cellular uptake and bioimaging profile.

There is a clear need to develop photostable chromophores for bioimaging with respect to the classically utilized green fluorescent dye fluorescein. Along these lines, we utilized a phosphorescent carboxy-substituted ruthenium(ii) polypyridyl [Ru(bipy)2(mcb)]2+ (bipy = 2,2'-bipyridyl and mcb = 4-carboxy-4'-methyl-2,2'-bipyridyl) complex. We developed two luminescent peptide conjugates of the cell-penetrating peptide Tat48-60 consisting of either [Ru(bipy)2(mcb)]2+ or 5(6)-carboxyfluorescein (5(6)-FAM) tethered on the Lys50 of the peptide through amide bond. We confirmed the efficient cellular uptake of both bioconjugates in HeLa cells by confocal microscopy and flow cytometry and proved that the ruthenium-based chromophore possesses enhanced photostability compared to a 5(6)-FAM-based peptide, after continuous laser scanning. Furthermore, we designed and developed a luminescent agent with high photostability, based on the ruthenium core, that could be selectively localized in cancer cells overexpressing the GnRH receptor (GnRH-R). To achieve this, we took advantage of the tumor-homing character of d-Lys6-GnRH which selectively recognizes the GnRH-R. The [Ru(bipy)2(mcb)]2+-d-Lys6-GnRH peptide conjugate was synthesized, and its cellular uptake was evaluated through flow cytometric analysis and live-cell imaging in HeLa and T24 bladder cancer cells as negative and positive controls of GnRH-R, respectively. Besides the selective targeting that the specific conjugate could offer, we also recorded high internalization levels in T24 bladder cancer cells. The ruthenium(ii) polypyridyl peptide-based conjugates we developed is an intriguing approach that offers targeted cell imaging in the Near Infrared region, and simultaneously paves the way for further advancements in the dynamic studies on cellular imaging.

Supporting data on combined transcriptomic and phosphoproteomic analysis of BMP4 signaling in human embryonic stem cells.

Human embryonic stem cells exhibit great potential as a therapeutic tool in regenerative medicine due to their self-renewal and trilineage differentiation capacity. Maintaining this unique cellular state has been shown to rely primarily on the Activin A / TGFß signaling pathway. While most conventional culture media are supplemented with TGFß, in the current study we utilize a modified version of the commercially available mTeSR1, substituting TGFß for Activin A in order to preserve pluripotency. (1) Cells cultured in ActA-mTesR express pluripotency factors NANOG, OCT4 and SOX2 at comparable levels with cells cultured in TGFß-mTeSR. (2) ActA-mTeSR cultured cells retain a physiological karyotype. (3) Cells in ActA-mTeSR maintain their trilineage differentiation capacity as shown in the teratoma formation assay. This system can be used to dissect the role of Activin A, downstream effectors and signaling cascades in human embryonic stem cell responses.

Why Clinicians Choose Their Language Intervention Approach: An International Perspective on Intervention for Children with Developmental Language Disorder.

PURPOSE: Considerable progress has been made in recent years in generating external evidence underpinning interventions for children with developmental language disorder (DLD), but less is known about the practitioner decision-making process underpinning such interventions and whether such decisions are context specific or are internationally generalizable. METHODS: An online survey about clinical practice was developed by members of COST Action IS1406, an EU-funded research network, which included representation from 39 countries. The participants were 2,408 practitioners who answered questions in relation to their decision making for a specific child of their choosing with DLD. Analysis of open-ended questions was undertaken, and data were converted into codes for the purpose of quantitative analysis. RESULTS: Although a wide range of intervention approaches and rationales were reported, the majority of responses referenced a client-centred approach. Level of functioning was used as a rationale only if a child had severe DLD. Practitioners with university level education or above were less likely to report basing intervention on client-centred factors. A number of differently named interventions with variable theoretical and empirical underpinnings were used in different countries. CONCLUSIONS: Specific client and practitioner characteristics have an impact on the intervention approaches and rationales adopted across countries. A limited number of practitioners reported use of external scientific evidence, which suggests that there should be more initiatives in basic training of practitioners and continuing professional development to encourage the uptake of scientific evidence-based practice.

The Influence of Quantitative Intervention Dosage on Oral Language Outcomes for Children With Developmental Language Disorder: A Systematic Review and Narrative Synthesis.

Purpose The aim of this study was to examine the degree to which quantitative aspects of dosage (dose, dose frequency, and total intervention duration) have been examined in intervention studies for children with developmental language disorder (DLD). Additionally, to establish the optimal quantitative dosage characteristics for phonology, vocabulary, and morphosyntax outcomes. Method This registered review (PROSPERO ID CRD42017076663) adhered to PRISMA guidelines. Search terms were included in seven electronic databases. We included peer-reviewed quasi-experimental, randomized controlled trial or cohort analytical studies, published in any language between January 2006 and May 2020. Included articles reported on participants with DLD (M = 3-18 years); oral language interventions with phonology, vocabulary, or morphosyntax outcomes; and experimental manipulation or statistical analysis of any quantitative aspect of dosage. Studies were appraised using the Cochrane risk-of-bias tool. Results Two hundred forty-four articles reported on oral language interventions with children with DLD in the domains of interest; 13 focused on experimentally/statistically manipulating quantitative aspects of dosage. No article reported phonological outcomes, three reported vocabulary, and eight reported morphosyntax. Dose frequency was the most common characteristic manipulated. Conclusions Research is in its infancy, and significant further research is required to inform speech-language pathologists in practice. Dosage characteristics are rarely adequately controlled for their individual effects to be identified. Findings to date suggest that there is a point in vocabulary and morphosyntax interventions after which there are diminishing returns from additional dosage. If dose is high (number of learning opportunities within a session), then the literature suggests that session frequency can be reduced. Frequent, short sessions (2/3 × per week, approximately 2 min) and less frequent, long sessions (1 × per week, approximately 20 min) have yielded the best outcomes when composite language measures have been used; however, replication and further research are required before clinicians can confidently integrate these findings into clinical practice. Supplemental Material https://doi.org/10.23641/asha.13570934.

Addressing implementation considerations when developing universal interventions for speech, language and communication needs in the ordinary classroom: a protocol for a scoping review.

Background: Understanding the factors that influence the implementation of health interventions in the context of education is essential to improving outcomes for children and young people with speech and language needs (SLCN). Yet implementation considerations have not been adequately addressed when developing interventions for this context. The aim of this paper is to present a protocol for a scoping review of existing implementation frameworks that might guide SLCN intervention research in schools.  Methods: In accordance with scoping review guidelines, the study will be conducted in six phases: (1) identification of the research question, (2) identification of potentially relevant studies of Implementation Science frameworks, (3) study screening and selection, (4) charting and extracting data from identified frameworks, (5) collating, summarising and reporting the results and (6) consultation with stakeholders. Two reviewers will conduct the screening and extraction stages independently. Identified frameworks will be collated, and described, and constructs from the IS frameworks will be categorised using domains from the Consolidated Framework for Implementation Research. A draft IS model will be proposed based on the findings of the scoping review. Conclusions: The findings of this review will provide guidance for researchers in addressing implementation considerations when developing universal interventions for SLCN in the ordinary classroom, and ultimately will contribute towards improving outcomes for this vulnerable childhood population.

Reflective practice across speech and language therapy and education: a protocol for an integrative review.

Effective co-practice is considered a linchpin of inclusive education. Speech and language therapists (SLT), in collaboration with teachers, are amongst the professionals who have a role in ensuring inclusion for students. The challenges of collaboration are well documented, with communication considered a potential antidote. Proposals for how collaborative communication can take place often align with models of reflection. Uncertainty around a shared language for reflection within and across the professions of teaching and SLT may pose a barrier to it occurring. Reflection has long been documented as a strategy used by effective clinicians to improve practice. Hence, teachers and SLTs reflecting together could be considered 'a port of entry' for effective collaborative practice. This study aims to synthesise literature and knowledge on the phenomenon of reflective practice across the professions to facilitate collaboration for inclusive education. The method of qualitative evidence synthesis will be an integrative review. A systematic search will be conducted to extract empirical studies, reviews and theoretical papers on the topic of reflection across both professions.  An adapted version of the PRISMA reporting guidelines will be used in the development, design and reporting of this review. Four databases will be searched: CINAHL, SCOPUS, Education Source and ERIC. A web-based search will also be conducted to retrieve relevant policy documents. Included literature will be appraised using the M-MAT and an adapted checklist from the Joanna Briggs Institute. Deductive content analysis will endeavour to determine if a shared language exists about reflection, across the professions of teaching and speech and language therapy. Establishing a shared language represents a first step towards the development of a framework for collaborative reflection between teachers and SLTs. This is turn serves to inform future research, policy and practice regarding how speech and language therapist can work collaboratively with teachers in schools.

Development of programmable gemcitabine-GnRH pro-drugs bearing linker controllable "click" oxime bond tethers and preclinical evaluation against prostate cancer.

Peptide-drug conjugates (PDCs) are gaining considerable attention as anti-neoplastic agents. However, their development is often laborious and time-consuming. Herein, we have developed and preclinically evaluated three PDCs with gemcitabine as the anticancer cytotoxic unit and D-Lys6-GnRH (gonadotropin-releasing hormone; GnRH) as the cancer-targeting unit. These units were tethered via acid-labile programmable linkers to guide a differential drug release rate from the PDC through a combination of ester or amide and "click" type oxime ligations. The pro-drugs were designed to enable the selective targeting of malignant tumor cells with linker guided differential drug release rates. We exploited the oxime bond responsiveness against the acidic pH of the tumor microenvironment and the GnRH endocytosis via the GnRH-R GPCR which is overexpressed on cancer cells. The challenging metabolic properties of gemcitabine were addressed during design of the PDCs. We developed a rapid (1 hour) and cost-effective "click" oxime bond ligation platform to assemble in one-pot the 3 desired PDCs that does not require purification, surpassing traditional time-ineffective and low yield methods. The internalization of the tumor-homing peptide unit in cancer cells, overexpressing the GnRH-R, was first validated through confocal laser microscopy and flow cytometry analysis. Subsequently, the three PDCs were evaluated for their in vitro antiproliferative effect in prostate cancer cells. Their stability and the release of gemcitabine over time were monitored in vitro in cell culture and in human plasma using LC-MS/MS. We then assessed the ability of the developed PDCs to internalize in prostate cancer cells and to release gemcitabine. The most potent analog, designated GOXG1, was used for pharmacokinetic studies in mice. The metabolism of GOXG1 was examined in liver microsomes, as well as in buffers mimicking the pH of intracellular organelles, resulting in the identification of two metabolites. The major metabolite at low pH emanated from the cleavage of the pH-labile oxime bond, validating our design approach. NMR spectroscopy and in vitro radioligand binding assays were exploited for GOXG1 to validate that upon conjugating the drug to the peptide, the peptide microenvironment responsible for its GnRH-R binding is not perturbed and to confirm its high binding potency to the GnRH-R. Finally, the binding of GOXG1 to the GnRH-R and the associated elicitation of testosterone release in mice were also determined. The facile platform established herein for the rapid assembly of PDCs with linker controllable characteristics from aldehyde and aminooxy units through rapid "click" oxime ligation, that does not require purification steps, could pave the way for a new generation of potent cancer therapeutics, diagnostics and theranostics.