bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between speech, oromotor, language and cognitive abilities in children with Down's syndrome
Authors: Cleland Joanne , Wood Sara , Hardcastle William , Wishart Jennifer , Timmins Claire 
Published: December 2009

Background:Children and young people with Down's syndrome present with deficits in expressive speech and language, accompanied by strengths in vocabulary comprehension compared with non‐verbal mental age. Intelligibility is particularly low, but whether speech is delayed or disordered is a controversial topic. Most studies suggest a delay, but no studies explore the relationship between cognitive or language skills and intelligibility.Aims:This study sought to determine whether severity of speech disorder correlates with language and cognitive level and to classify the types of errors, developmental or non‐developmental, that occur in the speech of children and adolescents with Down's syndrome.Methods & Procedures:Fifteen children and adolescents with Down's syndrome (aged 9–18 years) were recruited. Participants completed a battery of standardized speech, language and cognitive assessments. The phonology assessment was subject to phonological and phonetic analyses. Results from each test were correlated to determine relationships.Outcome & Results:Individuals with Down's syndrome present with deficits in receptive and expressive language that are not wholly accounted for by their cognitive delay. Receptive vocabulary is a strength in comparison with expressive and receptive language skills, but it was unclear from the findings whether it is more advanced compared with non‐verbal cognitive skills. The majority of speech errors were developmental in nature, but all of the children with Down's syndrome showed at least one atypical or non‐developmental speech error.Conclusions & Implications:Children with Down's syndrome present with speech disorders characterized by atypical, and often unusual, errors alongside many developmental errors. A lack of correlation between speech and cognition or language measures suggests that the speech disorder in Down's syndrome is not simply due to cognitive delay. Better differential diagnosis of speech disorders in Down's syndrome is required, allowing interventions to target the specific disorder in each individual.
Issues in developing valid assessments of speech pathology students' performance in the workplace
Authors: McAllister Sue , Lincoln Michelle , Ferguson Alison , McAllister Lindy 
Published: December 2009

Background: Workplace‐based learning is a critical component of professional preparation in speech pathology. A validated assessment of this learning is seen to be ‘the gold standard’, but it is difficult to develop because of design and validation issues. These issues include the role and nature of judgement in assessment, challenges in measuring quality, and the relationship between assessment and learning. Valid assessment of workplace‐based performance needs to capture the development of competence over time and account for both occupation specific and generic competencies.Aims: This paper reviews important conceptual issues in the design of valid and reliable workplace‐based assessments of competence including assessment content, process, impact on learning, measurement issues, and validation strategies. It then goes on to share what has been learned about quality assessment and validation of a workplace‐based performance assessment using competency‐based ratings. The outcomes of a four‐year national development and validation of an assessment tool are described.Methods & Procedures: A literature review of issues in conceptualizing, designing, and validating workplace‐based assessments was conducted. Key factors to consider in the design of a new tool were identified and built into the cycle of design, trialling, and data analysis in the validation stages of the development process.Outcomes & Results: This paper provides an accessible overview of factors to consider in the design and validation of workplace‐based assessment tools. It presents strategies used in the development and national validation of a tool COMPASS®, used in an every speech pathology programme in Australia, New Zealand, and Singapore. The paper also describes Rasch analysis, a model‐based statistical approach which is useful for establishing validity and reliability of assessment tools.Conclusions & Implications: Through careful attention to conceptual and design issues in the development and trialling of workplace‐based assessments, it has been possible to develop the world's first valid and reliable national assessment tool for the assessment of performance in speech pathology.
Developmental complexity of the stimuli included in mispronunciation detection tasks
Authors: McNeill Brigid C. , Hesketh Anne 
Published: December 2009

Background: Phonological representations are important for speech and literacy development. Mispronunciation detection tasks have been proposed as an appropriate measure of phonological representations for children with speech disorder. There has been limited analysis, however, of the developmental complexity of task stimuli. Further, the tasks have not been used widely with typical populations.Aims: The study aimed to examine the developmental progression of children's performance on a mispronunciation detection task, to evaluate the complexity of the task's stimuli, and to analyse the association between task performance and other skills important for literacy success.Methods & Procedures: A cross‐sectional design was used to compare the mispronunciation detection performance of monolingual children within mainstream classrooms aged 4;0–4;5 (n = 26), 4;6–5;0 (n = 49), and 5;1–5;6 (n = 64). Comparison of the complexity of vowel mismatches, single consonant mismatches, consonant deletion mismatches, and consonant transposition mismatches was conducted.Outcomes & Results: Children in the youngest age group were outperformed by the older age groups in the phonological representation task. Fine‐grained mismatches were more difficult to detect than coarse‐grained mismatches. There was a trend for vowel substitutions to be the most difficult mismatch to detect. Performance in the mispronunciation detection task was moderately correlated with the children's receptive vocabulary, speech, phonological awareness, and letter knowledge skills.Conclusions & Implications: Mismatch type must be taken into account when designing mispronunciation detection tasks. Access to segmental phonological representations is related to speech, language, and letter knowledge in children from mainstream classrooms.
A Wearable System to Assist Walking of Parkinson´s Disease Patients
Authors: Plotnik M. , Roggen D. , Giladi N. , Hausdorff J. M. , Tröster G. , Bächlin M. 
Published: December 2009

Summary
Background: About 50% of the patients with advanced Parkinson’s disease (PD) suffer from freezing of gait (FOG), which is a sudden and transient inability to walk. It often causes falls, interferes with daily activities and significantly impairs quality of life. Because gait deficits in PD patients are often resistant to pharmacologic treatment, effective non-pharmacologic treatments are of special interest.
Objectives: The goal of our study is to evaluate the concept of a wearable device that can obtain real-time gait data, processes them and provides asistance based on pre-determined specifications.
Methods: We developed a real-time wearable FOG detection system that automatically provides a cueing sound when FOG is detected and which stays until the subject resumes walking. We evaluated our wearable assistive technology in a study with 10 PD patients. Over eight hours of data was recorded and a questionnaire was filled out by each patient.
Results: Two hundred and thirty-seven FOG events have been identified by professional physiotherapists in a post-hoc video analysis. The device detected the FOG events online with a sensitivity of 73.1% and a specificity of 81.6% on a 0.5 sec frame-based evaluation.
Conclusions: With this study we show that online assistive feedback for PD patients is possible. We present and discuss the patients’ and physiotherapists’ perspectives on wear-abilty and performance of the wearable assistant as well as their gait performance when using the assistant and point out the next research steps. Our results demonstrate the benefit of such a context-aware system and motivate further studies.
Expression of Soluble Vascular Endothelial Growth Factor Receptor-1 in Human Monocyte-Derived Mature Dendritic Cells Contributes to Their Antiangiogenic Property
Authors: Kishuku Masatoshi , Nishioka Yasuhiko , Abe Shinji , Kishi Jun , Ogino Hirokazu , Aono Yoshinori , Azuma Momoyo , Kinoshita Katsuhiro , Rentsenhand Batmungh , Makino Hideki , Ranjan Priya , Minakuchi Kazuo , Sone Saburo 
Published: December 2009

AbstractThe soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1) is produced from endothelial cells by alternative splicing of VEGFR-1 mRNA, and can inhibit angiogenesis by blocking the biological effects of VEGF. In this study, we show the expression of a large amount of sVEGFR-1 in human monocyte-derived mature dendritic cells (mDCs). As compared with monocytes and immature DCs, mDCs generated by TNF-α or soluble CD40L with IFN-γ, but not LPS or other stimuli, preferentially produce sVEGFR-1. We also detected the mRNA of sVEGFR-1 generated by alternative splicing of VEGFR-1 mRNA in mDCs induced by TNF-α. The production of sVEGFR-1 showed a distinct contrast to those of VEGF in each DC matured with various stimuli. The supernatant of DCs matured with TNF-α or soluble CD40L with IFN-γ showed inhibition of the tube formation of HUVECs, which was neutralized by anti-VEGFR-1 Ab, indicating that sVEGFR-1 secreted from mDCs was biologically active. Interestingly, the supernatant of mDCs generated with LPS increased HUVEC capillary-like formation in vitro. The ratio of sVEGFR-1 to VEGF clearly reflected the net angiogenic property of mDCs. Administration of mDCs induced by TNF-α into the s.c. tumor of PC-14 cells implanted in SCID mice demonstrated the inhibition of tumor growth via reduction of the number of CD31-positive vessels, indicating their in vivo antiangiogenic potential. These results suggest that sVEGFR-1 produced by mDCs contribute to their antiangiogenic property, and the ratio of sVEGFR-1 to VEGF might be a useful tool for evaluating their ability to regulate angiogenesis mediated by VEGF.
Neuronal IκB Kinase β Protects Mice from Autoimmune Encephalomyelitis by Mediating Neuroprotective and Immunosuppressive Effects in the Central Nervous System
Authors: Emmanouil Mary , Taoufik Era , Tseveleki Vivian , Vamvakas Sotiris-Spyros , Tselios Theodore , Karin Michael , Lassmann Hans , Probert Lesley 
Published: December 2009

AbstractSome aspects of CNS-directed autoimmunity in multiple sclerosis are modeled in mice by immunization with myelin Ags where tissue damage is driven by myelin-reactive Th1 and Th17 effector lymphocytes. Whether the CNS plays an active role in controlling such autoimmune diseases is unknown. We used mice in which IκB kinase β was deleted from Ca2+/calmodulin-dependent kinase IIα-expressing neurons (nIKKβKO) to investigate the contribution of neuronal NF-κB to the development of myelin oligodendrocyte glycoprotein 35–55-induced experimental autoimmune encephalomyelitis. We show that nIKKβKO mice developed a severe, nonresolving disease with increased axon loss compared with controls and this was associated with significantly reduced CNS production of neuroprotective factors (vascular endothelial growth factor, CSF1-R, and FLIP) and increased production of proinflammatory cytokines (IL-6, TNF, IL-12, IL-17, and CD30L) and chemokines. The isolation of CNS-infiltrating monocytes revealed greater numbers of CD4+ T cells, reduced numbers of NK1.1+ cells, and a selective accumulation of Th1 cells in nIKKβKO CNS from early in the disease. Our results show that neurons play an important role in determining the quality and outcome of CNS immune responses, specifically that neuronal IκB kinase β is required for neuroprotection, suppression of inflammation, limitation of Th1 lymphocyte accumulation, and enhancement of NK cell recruitment in experimental autoimmune encephalomyelitis-affected CNS and stress the importance of neuroprotective strategies for the treatment of multiple sclerosis.
Mammalian Target of Rapamycin Inhibition and Alloantigen-Specific Regulatory T Cells Synergize To Promote Long-Term Graft Survival in Immunocompetent Recipients
Authors: Raimondi Giorgio , Sumpter Tina L. , Matta Benjamin M. , Pillai Mahesh , Corbitt Natasha , Vodovotz Yoram , Wang Zhiliang , Thomson Angus W. 
Published: December 2009

Abstract
Minimization of immunosuppression and donor-specific tolerance to MHC-mismatched organ grafts are important clinical goals. The therapeutic potential of regulatory T cells (Tregs) has been demonstrated, but conditions for optimizing their in vivo function posttransplant in nonlymphocyte-depleted hosts remain undefined. In this study, we address mechanisms through which inhibition of the mammalian target of rapamycin (Rapa) synergizes with alloantigen-specific Treg (AAsTreg) to permit long-term, donor-specific heart graft survival in immunocompetent hosts. Crucially, immature allogeneic dendritic cells allowed AAsTreg selection in vitro, with minimal expansion of unwanted (Th17) cells. The rendered Treg potently inhibited T cell proliferation in an Ag-specific manner. However, these AAsTreg remained unable to control T cells stimulated by allogeneic mature dendritic cells, a phenomenon dependent on the release of proinflammatory cytokines. In vivo, Rapa administration reduced danger-associated IL-6 production, T cell proliferation, and graft infiltration. Based on these observations, AAsTreg were administered posttransplant (day 7) in combination with a short course of Rapa and rendered &gt;80% long-term (&gt;150 d) graft survival, a result superior to that achieved with polyclonal Treg. Moreover, graft protection was alloantigen-specific. Significantly, long-term graft survival was associated with alloreactive T cell anergy. These findings delineate combination of transient mammalian target of Rapa inhibition with appropriate AAsTreg selection as an effective approach to promote long-term organ graft survival.
Dual Control of Antitumor CD8 T Cells through the Programmed Death-1/Programmed Death-Ligand 1 Pathway and Immunosuppressive CD4 T Cells: Regulation and Counterregulation
Authors: Currie Andrew J. , Prosser Amy , McDonnell Alison , Cleaver Amanda L. , Robinson Bruce W. S. , Freeman Gordon J. , van der Most Robbert G. 
Published: December 2009

AbstractTumors have evolved multiple mechanisms to evade immune destruction. One of these is expression of T cell inhibitory ligands such as programmed death-ligand 1 (PD-L1; B7-H1). In this study, we show that PD-L1 is highly expressed on mesothelioma tumor cells and within the tumor stroma. However, PD-L1 blockade only marginally affected tumor growth and was associated with the emergence of activated programmed death-1+ ICOS+ CD4 T cells in tumor-draining lymph nodes, whereas few activated CD8 T cells were present. Full activation of antitumor CD8 T cells, characterized as programmed death-1+ ICOS+ Ki-67+ and displaying CTL activity, was only observed when CD4 T cells were depleted, suggesting that a population of suppressive CD4 T cells exists. ICOS+ foxp3+ regulatory T cells were found to be regulated through PD-L1, identifying one potentially suppressive CD4 T cell population. Thus, PD-L1 blockade activates antitumor CD8 T cell most potently in the absence of CD4 T cells. These findings have implications for the development of PD-L1-based therapies.
Inhibition of IL-17A Attenuates Atherosclerotic Lesion Development in ApoE-Deficient Mice
Authors: Erbel Christian , Chen Lili , Bea Florian , Wangler Susanne , Celik Sultan , Lasitschka Felix , Wang Ying , Böckler Dittmar , Katus Hugo A. , Dengler Thomas J. 
Published: December 2009

Abstract
The importance of an (auto)immune response in atherogenesis is becoming increasingly well understood. IL-17A-expressing T cells modulate immune cell trafficking, initiating inflammation and cytokine production in (auto)immune diseases. In human carotid artery plaques, we previously showed the presence of IL-17A-producing T cells and IL-23; however, IL-17A effects on atherogenesis have not been studied. Aortic root sections from 8-wk-old apolipoprotein E-deficient mice fed a standard chow diet were examined after 12 wk for lesion area, plaque composition, cellular infiltration, cytokine expression, and apoptosis. The treatment group (n = 15) received anti-IL-17A Ab and the controls (n = 10) received irrelevant Abs. Inhibition of IL-17A markedly reduced atherosclerotic lesion area (p &lt; 0.001), maximal stenosis (p &lt; 0.001), and vulnerability of the lesion. IL-17A mAb-treated mice showed reduced cellular infiltration, down-regulation of activation markers on endothelium and immune cells (e.g., VCAM-1), and reduced cytokine/chemokine secretion (e.g., IL6, TNFα, CCL5). To investigate possible mechanisms, different atherogenic cell types (e.g., macrophages, dendritic cells, HUVECs, vascular smooth muscle cells) were stimulated with IL-17A in addition to TNF-α, IFN-γ, or LPS to induce cellular activation or apoptosis in vitro. Stimulation with IL-17A induced proinflammatory changes in several atherogenic cell types and apoptotic cell death in murine cells. Functional blockade of IL-17A reduces atherosclerotic lesion development and decreases plaque vulnerability, cellular infiltration, and tissue activation in apolipoprotein E-deficient mice. The present data support a pathogenic role of IL-17A in the development of atherosclerosis by way of its widespread proinflammatory and proapoptotic effects on atherogenic cells.
Crucial Role of Phospholipase Cε in Induction of Local Skin Inflammatory Reactions in the Elicitation Stage of Allergic Contact Hypersensitivity
Authors: Hu Lizhi , Edamatsu Hironori , Takenaka Nobuyuki , Ikuta Shuzo , Kataoka Tohru 
Published: December 2009

Abstract
Phospholipase Cε (PLCε) is an effector of Ras/Rap small GTPases. We previously demonstrated that PLCε plays a crucial role in development of phorbor ester-induced skin inflammation, which is intimately involved in the promotion of skin carcinogenesis. In this study, we have examined its role in local skin inflammatory reactions during development of contact hypersensitivity toward a hapten 2,4-dinitrofluorobenzene (DNFB). PLCε+/+ and PLCε−/− mice were sensitized with DNFB, followed by a DNFB challenge on the ears. PLCε−/− mice exhibited substantially attenuated inflammatory reactions compared with PLCε+/+ mice as shown by suppression of ear swelling, neutrophil infiltration, and proinflammatory cytokine production. In contrast, the extent and kinetics of CD4+ T cell infiltration showed no difference depending on the PLCε background. Adoptive transfer of CD4+ T cells from the sensitized mice to naive mice between PLCε+/+ and PLCε−/− backgrounds indicated that PLCε exerts its function in cells other than CD4+ T cells, presumably fibroblasts or keratinocytes of the skin, to augment inflammatory reactions during the elicitation stage of contact hypersensitivity. Moreover, dermal fibroblasts and epidermal keratinocytes cultured from the skin expressed proinflammatory cytokines in a PLCε-dependent manner on stimulation with T cell-derived cytokines such as IL-17, IFN-γ, TNF-α, and IL-4. These results indicate that PLCε plays a crucial role in induction of proinflammatory cytokine expression in fibroblasts and keratinocytes at the challenged sites, where infiltrated CD4+ T cells produce their intrinsic cytokines, thereby augmenting the local inflammatory reactions.
Cell Surface Externalization of Annexin A1 as a Failsafe Mechanism Preventing Inflammatory Responses during Secondary Necrosis
Authors: Blume Karin E. , Soeroes Szabolcs , Waibel Michaela , Keppeler Hildegard , Wesselborg Sebastian , Herrmann Martin , Schulze-Osthoff Klaus , Lauber Kirsten 
Published: December 2009

AbstractThe engulfment of apoptotic cells is of crucial importance for tissue homeostasis in multicellular organisms. A failure of this process results in secondary necrosis triggering proinflammatory cytokine production and autoimmune disease. In the present study, we investigated the role of annexin A1, an intracellular protein that has been implicated in the efficient removal of apoptotic cells. Consistent with its function as bridging protein in the phagocyte synapse, opsonization of apoptotic cells with purified annexin A1 strongly enhanced their phagocytic uptake. A detailed analysis, however, surprisingly revealed that annexin A1 was hardly exposed to the cell surface of primary apoptotic cells, but was strongly externalized only on secondary necrotic cells. Interestingly, while the exposure of annexin A1 failed to promote the uptake of these late secondary necrotic cells, it efficiently prevented induction of cytokine production in macrophages during engulfment of secondary necrotic cells. Our results therefore suggest that annexin A1 exposure during secondary necrosis provides an important failsafe mechanism counteracting inflammatory responses, even when the timely clearance of apoptotic cells has failed.
Asynchronous RAG-1 Expression during B Lymphopoiesis
Authors: Welner Robert S. , Esplin Brandt L. , Garrett Karla P. , Pelayo Rosana , Luche Hervé , Fehling Hans Jörg , Kincade Paul W. 
Published: December 2009

AbstractChanges in cell surface markers and patterns of gene expression are commonly used to construct sequences of events in hematopoiesis. However, the order may not be as rigid as once thought and it is unclear which changes represent the best milestones of differentiation. We developed a fate-mapping model where cells with a history of RAG-1 expression are permanently marked by red fluorescence. This approach is valuable for appreciating lymphoid-lineage relationships without need for irradiation and transplantation. Hematopoietic stem cells (HSC) as well as myeloid and dendritic cell progenitors were unlabeled. Also as expected, most previously identified RAG-1+ early lymphoid progenitors in bone marrow and all lymphoid-affiliated cells were marked. Of particular interest, there was heterogeneity among canonical common lymphoid progenitors (CLP) in bone marrow. Labeled CLP expressed slightly higher levels of IL-7Rα, displayed somewhat less c-Kit, and generated CD19+ lymphocytes faster than the unlabeled CLP. Furthermore, CLP with a history of RAG-1 expression were much less likely to generate dendritic and NK cells. The RAG-1-marked CLP were lineage stable even when exposed to LPS, while unlabeled CLP were redirected to become dendritic cells in response to this TLR4 ligand. These findings indicate that essential events in B lymphopoiesis are not tightly synchronized. Some progenitors with increased probability of becoming lymphocytes express RAG-1 while still part of the lineage marker-negative Sca-1+c-Kithigh (LSK) fraction. Other progenitors first activate this locus after c-Kit levels have diminished and cell surface IL-7 receptors are detectable.