24 results on '"Fordyce K"'
Search Results
2. Technology that upsets the social order — a paradigm shift in assigning lots to tools in a wafer fabricator — the transition from rules to optimization.
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Fordyce, K., Bixby, R., and Burda, R.
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- 2008
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3. The ongoing challenge — an accurate assessment of supply linked to demand to create an enterprise-wide end to end detailed central supply chain plan.
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Fordyce, K., Degbotse, A., Milne, J., Orzell, R., and Wang, C.-T.
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- 2008
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4. Logistics management system: continuous flow manufacturing using knowledge based expert systems.
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Sullivan, G. and Fordyce, K.
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- 1989
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5. P59: Microsatellite unstable (MSI) colorectal cancer (CRC) is characterized by significantly increased epidermal growth factor receptor (EGFR) expression
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Shin, J., Yuan, Z., Mariadason, J., Fordyce, K., Sreeramoju, P., Kent, T., Kim, J., Wang, V., and Weber, T.K.
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- 2007
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6. 37: A del T poly T (8) mutation in the 3’ untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC)
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Shin, J., Yuan, Z., Fordyce, K., Sreeramoju, P., Kent, T., Kim, J., Wang, V., Schneyer, D., and Weber, T.K.
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- 2007
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7. Experiences with COVID-19 economic relief measures among low-wage worker families: a qualitative study.
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Caspi CE, Gombi-Vaca M, Antrum C, Gudaf S, De Marco M, Welle E, Sheppard B, Fordyce K, and Pratt R
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- Humans, Female, Male, Adult, United States, Poverty, Middle Aged, Interviews as Topic, Child, COVID-19 psychology, COVID-19 epidemiology, Qualitative Research
- Abstract
Background: Economic stability is a core social determinant of health and a necessary condition for maintaining food security, housing stability, and both physical and mental health. Using a qualitative approach, we identified barriers, facilitators, and participant perceptions about utilizing these relief measures. This study aimed to understand experiences with COVID-19 economic relief measures among low-wage worker households with children during the COVID-19 pandemic., Methods: The study conducted semi-structured qualitative interviews from low-wage workers in households with children in two U.S. cities in 2022 (n = 40). The sample was recruited from a larger study which included survey measures of demographics and receipt or utilization of a range of relief measures with both broad and narrow eligibility criteria (e.g., Economic Impact Payments, expanded Supplemental Nutrition Assistance Program (SNAP), Pandemic Electronic Benefit Transfer (P-EBT), expanded Child Tax Credit, expanded unemployment insurance, and the eviction moratorium). A thematic analysis of 40 interviews was conducted using a constructivist approach to grounded theory, from which barriers, facilitators, and participant perceptions were identified., Results: Interviews identified burdensome administrative processes, administrative errors, and a lack of information as barriers to access among those who were eligible; automatic processes for distributing benefits was identified as a facilitator. Participants expressed positive perceptions about benefits, mixed with some ambivalence about the need to receive them and concern over their discontinuation., Conclusions: A segment of the population at risk of economic instability identified both barriers and facilitators to receiving an array of economic relief measures during the COVID-19 pandemic. Findings suggest that providing automatic processes for enrollment and reliable information streams for learning about benefits can bolster benefit receipt among those at risk of economic instability. These findings can contribute to the base of knowledge for policymakers involved in responding to the next public health emergency., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval in accordance with the Declaration of Helsinki was obtained from the Institutional Review Boards at the University of Minnesota (STUDY00002094), University of North Carolina (18–0168), and University of Connecticut (H20-0087); informed consent was obtained for study participation. Consent for publication: Participants provided consent for publication of transcribed language excerpts without identifiers; no other individual data are contained within the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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8. Design of a pragmatic trial integrating human papillomavirus (HPV) self-sampling into primary care to reduce cervical cancer screening disparities in Somali American individuals: The Isbaar project.
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Lin J, Winer RL, Barsness CB, Desai J, Fordyce K, Ghebre R, Ibrahim AM, Mohamed S, Ramer T, Szpiro AA, Weiner BJ, Yohe S, and Pratt R
- Abstract
Background: Somali American individuals have lower cervical cancer screening rates than the U.S. general population. Offering HPV self-sampling in primary care clinics could increase screening rates in Somali American individuals by addressing screening barriers., Methods: The Isbaar Project is a Hybrid Type 2 effectiveness-implementation study of a patient-centered, culturally tailored HPV self-sampling intervention for Somali American individuals. Guided by the Consolidated Framework for Implementation Research and Social Cognitive Theory, we conducted focus groups with Somali American individuals, and interviews with clinicians and clinic staff to inform refinement and development of implementation strategies. HPV self-sampling was then implemented as a usual care screening option at 3 community-based primary care clinics in Minneapolis, Minnesota in February 2023. The primary objective is to assess the effect of implementing in-clinic HPV self-sampling on screening completion in Somali American individuals. The secondary objective is to assess the effect of implementing HPV self-sampling on screening completion in all patients. Using difference-in-difference methods, we will evaluate changes in screening rates one-year pre and post implementation and compare changes with control clinics followed over the same time period. Using RE-AIM, we will conduct a post-implementation mixed methods analysis of processes and strategies needed to successfully implement HPV self-sampling in primary care., Conclusions: The study was designed to evaluate a real-world in-clinic HPV self-sampling intervention for Somali American individuals, generating data on both effectiveness and implementation applicable to other community-based clinics in the U.S. The objective of this report is to describe the rationale and design of the study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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9. Autistic and autism community perspectives on infant and family support in the first two years of life: Findings from a community consultation survey.
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Bent CA, Aulich A, Constantine C, Fidock E, Dwyer P, Green C, Smith J, Gurba AN, Harrington LT, Gore KE, Rabba AS, Ayton LN, Fordyce K, Green J, Jellett R, Kennedy LJ, MacDuffie KE, Meera SS, Watson LR, Whitehouse AJ, and Hudry K
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Lay Abstract: Most support programmes for Autistic children are available only after they are diagnosed. Research suggests that parenting supports may be helpful for parents and their infants, when provided in the first 2 years of life - before a formal diagnosis is given, but when information suggests an infant is more likely to be Autistic. However, we do not know how acceptable these types of supports might be to the Autistic and autism communities. We asked 238 Autistic and non-autistic people - some of whom were parents, and some of whom were professionals working in research, health and education - about their perspectives on very-early supports. People generally agreed that it could be acceptable to work with parents to help them understand and support their child's specific needs and unique ways of communicating. People suggested a variety of support strategies could be acceptable, including parent education, changing the environment to meet an infant's needs, and creating opportunities for infants' to make choices and exercise control. People preferred respectful and accurate language - including the term 'support' (rather than 'intervention') and 'early-in-life' (rather than 'at-risk' of autism, or 'pre-emptive' when describing developmental stage). Continuing to work with community members will help to make sure autism support programmes are relevant and helpful., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Several authors have been involved in the development (JG, LRW, SSM) and/or evaluation (AA, AJOW, CAB, CG, JG, JS, KH, LRW, SSM) of support programmes for young Autistic children. JG and LH receive royalties and/or other benefits from training related to a specific support model. AJOW, JG, JS, KF, LH, RJ and SSM are/have been employed by and/or have/have had roles with service providers that support young Autistic children. These potential conflicts of interest were managed within the research team by engaging Autistic and non-Autistic researchers and community members with no known conflicts of interest (ANG, ASR, CC, EF, KEG, KEM, LNA, LJK, PD).
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- 2024
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10. Integrating HPV self-collect into primary care to address cervical cancer screening disparities.
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Pratt R, Barsness CB, Lin J, Desai J, Fordyce K, Ghebre R, Hassan F, Ibrahim A, Ramer T, Szpiro A, Weiner BJ, Xiong S, Yohe S, and Winer RL
- Abstract
Human papillomavirus (HPV) self-collect shows promise to increase cervical cancer screening rates in underscreened populations, such as Somali patients, but little is known about how to integrate such an approach in primary care. In this study, primary care providers and staff who provide primary care services to Somali women were asked for their views on integrating HPV self-collect into routine care to address cervical cancer screening disparities. Thirty primary care providers and staff participated in semi-structured interviews exploring their views on HPV self-collect and their anticipated needs or barriers to implementing this approach into the clinic generally and with specific patient populations, such as Somali women. A thematic analysis using the constructivist version of grounded theory was undertaken. Providers and staff anticipate positive patient reaction to the option of HPV self-collect, and were interested in using this approach both for Somali patients and for all patients in general. HPV self-collect was viewed as straightforward to integrate into existing clinic workflows. Providers largely lacked awareness of the evidence supporting primary HPV testing and HPV self-collect specifically, sharing concerns about effectiveness of self-collect and the lack of a physical exam. Providers felt clinic-wide staff education and patient education, along with strategies to address disparities, such as cultural and linguistic tailoring would be needed for successful implementation. Integrating HPV self-collect as an option in the cervical cancer screening process in a primary care clinical encounter offers considerable opportunity to address health disparities and may benefit all patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)
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- 2024
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11. Correction to: Spoken Language Change in Children on the Autism Spectrum Receiving Community-Based Interventions.
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Trembath D, Stainer M, Caithness T, Dissanayake C, Eapen V, Fordyce K, Frewer V, Frost G, Hudry K, Iacono T, Mahler N, Masi A, Paynter J, Pye K, Quan S, Shellshear L, Sutherland R, Sievers S, Thirumanickam A, Westerveld MF, and Tucker M
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- 2023
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12. Spoken Language Change in Children on the Autism Spectrum Receiving Community-Based Interventions.
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Trembath D, Stainer M, Caithness T, Dissanayake C, Eapen V, Fordyce K, Frewer V, Frost G, Hudry K, Iacono T, Mahler N, Masi A, Paynter J, Pye K, Quan S, Shellshear L, Sutherland R, Sievers S, Thirumanickam A, Westerveld MF, and Tucker M
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- Child, Preschool, Child, Humans, Communication, Autism Spectrum Disorder therapy, Autistic Disorder, Child Development Disorders, Pervasive, Language Development Disorders
- Abstract
We assessed the spoken language of 73 preschool aged children on the autism spectrum receiving community-based early intervention at two time points, approximately 7 months apart. Using the Spoken Language Benchmarks, there was a small non-significant change in the proportion of children transitioning from below, to at or above, Phase 3 (word combinations). Using binomial regression, a model comprising seven of nine clinician-proposed child-related predictors explained 64% of the variance. None of the predictors were individually significant, although a large effect size (OR = 16.71) was observed for children's baseline rate of communicative acts. The findings point to substantial unmet clinical need in children with minimal verbal language, but also the relevance of clinician-proposed predictors of their spoken language outcomes., (© 2022. The Author(s).)
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- 2023
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13. Clinical outcomes and associated predictors of early intervention in autism spectrum disorder: a study protocol.
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Masi A, Dissanayake C, Alach T, Cameron K, Fordyce K, Frost G, Grove R, Heussler H, Silove N, Sulek R, Tucker M, Williams K, and Eapen V
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- Child, Cohort Studies, Early Intervention, Educational, Humans, Prospective Studies, Quality of Life, Autism Spectrum Disorder therapy
- Abstract
Introduction: Research highlights the importance of early intervention for children with autism spectrum disorder with better outcomes associated with earlier access to early intensive intervention (EII) programmes. However, there is significant variability in response to EII despite children receiving the same programmes., Methods and Analysis: A prospective, multisite cohort study using a pre-post design assesses the predictors of early intervention outcomes for children who receive EII through six early intervention services (Autism Specific Early Learning and Care Centres, ASELCCs) across Australia. Child and family characteristics at entry to and exit from ASELCCs are ascertained using measures of autism symptoms (Autism Diagnostic Observation Schedule-2; Social Communication Questionnaire); cognitive, language and developmental skills (Mullen Scale of Early Learning); adaptive function (Vineland Adaptive Behaviour Scale-second Edition); behaviours (Child Behaviour Checklist-1.5 to 5 years; Restricted Repetitive Behaviour Scale); parental stress (Parent Stress Index-4 Short Form); quality of life (Quality of Life in Autism Scale) and a semistructured family history questionnaire for sociodemographic, family and psychosocial characteristics. Characteristics at entry are used as predictors of outcome at exit following EII approximately 12 months later. The change in score from baseline to exit will be the primary outcome of interest. The mediating role of family and psychosocial factors will also be considered., Ethics Approval: University of New South Wales Human Research Ethics Committee (HC14267)., Dissemination of Results: Findings will be published in peer-reviewed journals and presented at conferences. A report summarising data and the interpretation of data will be published., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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14. Clinician Proposed Predictors of Spoken Language Outcomes for Minimally Verbal Children with Autism Spectrum Disorder.
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Trembath D, Sutherland R, Caithness T, Dissanayake C, Eapen V, Fordyce K, Frost G, Iacono T, Mahler N, Masi A, Paynter J, Pye K, Reilly S, Rose V, Sievers S, Thirumanickam A, Westerveld M, and Tucker M
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- Autism Spectrum Disorder epidemiology, Autism Spectrum Disorder therapy, Child, Child, Preschool, Comprehension physiology, Female, Focus Groups methods, Humans, Language Development Disorders epidemiology, Language Development Disorders therapy, Male, Predictive Value of Tests, Prognosis, Autism Spectrum Disorder diagnosis, Health Personnel, Language, Language Development Disorders diagnosis, Speech-Language Pathology methods
- Abstract
Our aim was to explore insights from clinical practice that may inform efforts to understand and account for factors that predict spoken language outcomes for children with Autism Spectrum Disorder who use minimal verbal language. We used a qualitative design involving three focus groups with 14 speech pathologists to explore their views and experiences. Using the Framework Method of analysis, we identified 9 themes accounting for 183 different participant references to potential factors. Participants highlighted the relevance of clusters of fine-grained social, communication, and learning behaviours, including novel insights into prelinguistic vocal behaviours. The participants suggested the potential value of dynamic assessment in predicting spoken language outcomes. The findings can inform efforts to developing clinically relevant methods for predicting children's communication outcomes.
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- 2021
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15. "The big wide world of school": Supporting children on the autism spectrum to successfully transition to primary school: Perspectives from parents and early intervention professionals.
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Chen N, Miller S, Milbourn B, Black MH, Fordyce K, Van Der Watt G, Alach T, Masi A, Frost G, Tucker M, Eapen V, and Girdler S
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Background: The transition to primary school is often a complex and uncertain time for autistic children and their families. Understanding how best to develop school readiness and support transition to primary school for autistic children is essential. School readiness and transition planning are influenced by a range of personal and contextual factors, and it is important to understand the perspectives of the various stakeholders involved in the transition process., Methods: A qualitative exploration employing focus groups and interviews was undertaken with early intervention (EI) staff (n = 45) and parents (n = 18) across Australia to understand their perspectives on school readiness and the transition to primary school., Results: Thematic analysis identified four emerging themes facilitating transition including: 1) building the child; 2) building the parents; 3) building the receiving school; and, 4) connecting the system., Conclusion: Findings highlight the need to consider school readiness and transition planning from a holistic perspective, ensuring clear, collaborative and ongoing communication between parents, teachers and EI staff, using a strength-based approach, and individualizing transition planning., Competing Interests: Conflicts of interest The authors received grants from Australian Government, Department of Social Services and Cooperative Research Centre for Living with Autism., (© 2020 Authors.)
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- 2020
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16. Brief Report: Perceived Evidence and Use of Autism Intervention Strategies in Early Intervention Providers.
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Paynter J, Luskin-Saxby S, Keen D, Fordyce K, Frost G, Imms C, Miller S, Sutherland R, Trembath D, Tucker M, and Ecker U
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- Adult, Autism Spectrum Disorder psychology, Female, Humans, Male, Autism Spectrum Disorder therapy, Early Intervention, Educational methods, Evidence-Based Practice methods, Health Knowledge, Attitudes, Practice
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Use of empirically unsupported practices is a challenge in the field of autism spectrum disorder (ASD). We explored whether attitudes and perceived evidence were linked to intended practice use in early intervention staff. Seventy-one participants completed ratings of the evidence base, current and future use of six ASD intervention practices, and reported attitudes to research and evidence-based practice. Participants reported greater use and rated the evidence base higher for the empirically supported practices. However, variability in accuracy of evidence base ratings was observed across individuals. Higher perceived evidence was linked to greater future use intentions for empirically supported and unsupported practices. The need for accurate information across practice types is highlighted. Self-report methodology limitations and future research directions are discussed.
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- 2020
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17. Evaluation of a template for countering misinformation-Real-world Autism treatment myth debunking.
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Paynter J, Luskin-Saxby S, Keen D, Fordyce K, Frost G, Imms C, Miller S, Trembath D, Tucker M, and Ecker U
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- Humans, Public Health methods, Autistic Disorder, Communication
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Misinformation poses significant challenges to evidence-based practice. In the public health domain specifically, treatment misinformation can lead to opportunity costs or direct harm. Alas, attempts to debunk misinformation have proven sub-optimal, and have even been shown to "backfire", including increasing misperceptions. Thus, optimized debunking strategies have been developed to more effectively combat misinformation. The aim of this study was to test these strategies in a real-world setting, targeting misinformation about autism interventions. In the context of professional development training, we randomly assigned participants to an "optimized-debunking" or a "treatment-as-usual" training condition and compared support for non-empirically-supported treatments before, after, and six weeks following completion of online training. Results demonstrated greater benefits of optimized debunking immediately after training; thus, the implemented strategies can serve as a general and flexible debunking template. However, the effect was not sustained at follow-up, highlighting the need for further research into strategies for sustained change., Competing Interests: The authors have declared that no competing interests exist.
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- 2019
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18. Transition from early intervention program to primary school in children with autism spectrum disorder.
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Eapen V, Grove R, Aylward E, Joosten AV, Miller SI, Van Der Watt G, Fordyce K, Dissanayake C, Maya J, Tucker M, and DeBlasio A
- Abstract
Aim: To evaluate the characteristics that are associated with successful transition to school outcomes in preschool aged children with autism., Methods: Twenty-one participants transitioning from an early intervention program were assessed at two time points; at the end of their preschool placement and approximately 5 mo later following their transition to school. Child characteristics were assessed using the Mullen Scales of Early Learning, Vineland Adaptive Behaviour Scales, Social Communication Questionnaire and the Repetitive Behaviour Scale. Transition outcomes were assessed using Teacher Rating Scale of School Adjustment and the Social Skills Improvement System Rating Scales to provide an understanding of each child's school adjustment. The relationship between child characteristics and school outcomes was evaluated., Results: Cognitive ability and adaptive behaviour were shown to be associated with successful transition to school outcomes including participation in the classroom and being comfortable with the classroom teacher. These factors were also associated with social skills in the classroom including assertiveness and engagement., Conclusion: Supporting children on the spectrum in the domains of adaptive behaviour and cognitive ability, including language skills, is important for a successful transition to school. Providing the appropriate support within structured transition programs will assist children on the spectrum with this important transition, allowing them to maximise their learning and behavioural potential., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.
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- 2017
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19. Utilisation of evidence-based practices by ASD early intervention service providers.
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Paynter JM, Ferguson S, Fordyce K, Joosten A, Paku S, Stephens M, Trembath D, and Keen D
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- Adult, Australia, Child, Child, Preschool, Early Intervention, Educational standards, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Young Adult, Autism Spectrum Disorder therapy, Early Intervention, Educational methods, Evidence-Based Practice methods
- Abstract
A number of autism intervention practices have been demonstrated to be effective. However, the use of unsupported practices persists in community early intervention settings. Recent research has suggested that personal, professional and workplace factors may influence intervention choices. The aim of this research was to investigate knowledge and use of strategies, organisational culture, individual attitudes, sources of information and considerations informing intervention choices by early intervention providers. An online survey was completed by 72 early intervention providers from four organisations across Australia. Providers reported high levels of trust and access of information from internal professional development, therapists and external professional development. A range of considerations including child factors, family values and research were rated as important in informing intervention choices. Participants reported greater knowledge and use of evidence-based and emerging practices than unsupported. Levels of use were linked to levels of knowledge, as well as some organisational and attitudinal factors. Areas for future research and implications are discussed.
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- 2017
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20. EP4 and EP2 receptor activation of protein kinase A by prostaglandin E2 impairs macrophage phagocytosis of Clostridium sordellii.
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Rogers LM, Thelen T, Fordyce K, Bourdonnay E, Lewis C, Yu H, Zhang J, Xie J, Serezani CH, Peters-Golden M, and Aronoff DM
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- Cell Line, Cyclic AMP metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Dinoprostone immunology, Humans, Immune Tolerance, Immunity, Innate, Phagocytosis, Protein Isoforms metabolism, Clostridium Infections immunology, Clostridium sordellii immunology, Macrophages immunology, Receptors, Prostaglandin E, EP2 Subtype metabolism, Receptors, Prostaglandin E, EP4 Subtype metabolism
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Problem: Clostridium sordellii causes endometrial infections, but little is known regarding host defenses against this pathogen., Method of Study: We tested the hypothesis that the immunoregulatory lipid prostaglandin (PG) E2 suppresses human macrophage clearance of C. sordellii through receptor-induced increases in intracellular cyclic adenosine monophosphate (cAMP). The THP-1 macrophage cell line was used to quantify C. sordellii phagocytosis., Results: PGE2 increased cAMP levels, activated protein kinase A (PKA), and inhibited the class A scavenger receptor-dependent phagocytosis of C. sordellii. Activation of the EP2 and EP4 receptors increased intracellular cAMP and inhibited phagocytosis, with evidence favoring a more important role for EP4 over EP2. This was supported by EP receptor expression data and the use of pharmacological receptor antagonists. In addition, the PKA isoform RI appeared to be more important than RII in mediating the suppression of ingestion of C. sordellii., Conclusion: The endogenous lipid mediator PGE2 impairs human innate immune responses against C. sordellii., (© 2013 John Wiley & Sons Ltd.)
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- 2014
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21. An A13 repeat within the 3'-untranslated region of epidermal growth factor receptor (EGFR) is frequently mutated in microsatellite instability colon cancers and is associated with increased EGFR expression.
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Yuan Z, Shin J, Wilson A, Goel S, Ling YH, Ahmed N, Dopeso H, Jhawer M, Nasser S, Montagna C, Fordyce K, Augenlicht LH, Aaltonen LA, Arango D, Weber TK, and Mariadason JM
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- 3' Untranslated Regions, Animals, Cell Line, Tumor, Colonic Neoplasms enzymology, ErbB Receptors genetics, Gene Amplification, Humans, Mice, Mice, SCID, Microsatellite Instability, RNA, Messenger biosynthesis, RNA, Messenger genetics, Ribonuclease III antagonists & inhibitors, Ribonuclease III genetics, Sequence Deletion, Colonic Neoplasms genetics, ErbB Receptors biosynthesis, Genes, erbB-1, Mutation, Poly A genetics, Repetitive Sequences, Nucleic Acid
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Colorectal cancers (CRC) with microsatellite instability (MSI) have clinical, pathologic, genetic, and epigenetic features distinct from microsatellite-stable CRC. Examination of epidermal growth factor receptor (EGFR) mRNA and protein expression levels in a panel of colon cancer cell lines identified strong expression of EGFR in multiple cell lines with MSI. Although no relationship between EGFR overexpression and the length of a CA dinucleotide repeat in intron 1 was observed, a variant A13/A14 repeat sequence within the 3'-untranslated region (3'-UTR) of the EGFR gene was identified, which was mutated by either mononucleotide or dinucleotide adenosine deletions in 64% of MSI cell lines and 69% of MSI colon tumors. Using a Tet-Off system, we show that this mutation increases EGFR mRNA stability in colon cancer cells, providing a mechanistic basis for EGFR overexpression in MSI colon cancer cell lines. To determine whether this mutation is a driver or a bystander event in MSI colon cancer, we examined the effect of pharmacologic and molecular inhibition of EGFR in EGFR 3'-UTR mutant MSI cell lines. Cell lines with an EGFR 3'-UTR mutation and that were wild-type (WT) for downstream signaling mediators in the Ras/BRAF and PIK3CA/PTEN pathways were sensitive to EGFR inhibition, whereas those harboring mutations in these signaling mediators were not. Furthermore, in cell lines WT for downstream signaling mediators, those with EGFR 3'-UTR mutations were more sensitive to EGFR inhibition than EGFR 3'-UTR WT cells, suggesting that this mutation provides a growth advantage to this subset of MSI colon tumors.
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- 2009
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22. Solid-contact electrochemical polyion sensors for monitoring peptidase activities.
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Fordyce K and Shvarev A
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- Arginine analysis, Arginine metabolism, Electrochemistry, Ions chemistry, Reproducibility of Results, Sensitivity and Specificity, Time Factors, Trypsin metabolism, Biosensing Techniques methods, Peptide Hydrolases analysis, Peptide Hydrolases metabolism, Protamines analysis, Protamines metabolism
- Abstract
We report here on improved solid-contact electrochemical polyion sensors for the detection of polyion protamine. The polymeric membrane sensors were fabricated with a conducting polymer as an ion-electron transduction layer. We observed that decreasing the magnitude of the applied current pulse caused a significant improvement of the sensor sensitivity to low protamine levels. The protamine sensors exhibited a stable and reversible response to protamine concentrations ranging from 0.05 to 30 mg L-1. The sensors were used for monitoring peptidase activities utilizing galvanostatically controlled solid-contact membrane sensors. The polyion protamine was used as a substrate to detect the activity of the protease trypsin. The enzyme activity was continuously monitored by measuring the protamine concentration as it is cleaved by enzyme into smaller fragments to which the sensor is less sensitive. In the presence of a given level of protamine the initial rate of reaction can be linearly related to the trypsin activity within a 0-5 U mL-1 concentration range. The interference with the enzymatic reaction product arginine was specifically examined.
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- 2008
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23. A del T poly T (8) mutation in the 3' untranslated region (UTR) of the CDK2-AP1 gene is functionally significant causing decreased mRNA stability resulting in decreased CDK2-AP1 expression in human microsatellite unstable (MSI) colorectal cancer (CRC).
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Shin J, Yuan Z, Fordyce K, Sreeramoju P, Kent TS, Kim J, Wang V, Schneyer D, and Weber TK
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- 3' Untranslated Regions genetics, Cell Line, Tumor, Colorectal Neoplasms physiopathology, Gene Expression Regulation, Neoplastic, Green Fluorescent Proteins genetics, Humans, Microsatellite Instability, Nucleic Acid Conformation, RNA, Messenger chemistry, RNA, Messenger genetics, RNA, Neoplasm chemistry, RNA, Neoplasm genetics, Colorectal Neoplasms genetics, Gene Deletion, RNA Stability genetics, Tumor Suppressor Proteins genetics
- Abstract
Background: We have previously published results indicating that decreased expression of CDK2-AP1 in MSI human colorectal cancer is associated with deletion mutations in the poly (T) 8 repeat sequence within the 3'-UTR of the CDK2-AP1 gene. In this study, we test the hypothesis that the del T mutation results in decreased CDK2-AP1 expression by causing reduced mRNA stability., Methods: We introduced wild-type and mutant 3'-UTR sequences fused to a green fluorescent protein (GFP) gene separately into human CRC cell lines and quantified the expression of the GFP gene. Native CDK2-AP1 mRNA stability was measured in human CRC cell lines, using an actinomycin D assay and the mRNA structure folding software mfold 3.2., Results: Mutant GFP-3'-UTR samples demonstrated significantly reduced GFP expression compared with wild-type GFP-3'-UTR as measured by both FACS and real-time PCR. Both the actinomycin D assay and mfold software demonstrated significantly reduced mRNA stability for the del T poly (T) 8 transcript compared with the wild type., Conclusions: In summary, these novel results support our hypotheses that the del T poly (T) 8 observed in the 3'-UTR of the CDK2-AP1 gene in human MSI CRC is functionally significant and results in decreased CDK2-AP1 expression. The results also indicate the mechanism of this decreased expression is caused at least in part by decreased mRNA stability.
- Published
- 2007
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24. Pulsed galvanostatic control of solid-state polymeric ion-selective electrodes.
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Perera H, Fordyce K, and Shvarev A
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We report on galvanostatically controlled solid-state reversible ion-selective sensors for cationic analytes utilizing a conducting polymer as a transduction layer between the polymeric membrane and electron-conductive substrate. The instrumental control of polymeric membrane ion-selective electrodes based on electrochemically induced periodic ion extraction in alternating galvanostatic/potentiostatic mode was introduced recently creating exciting possibilities to detect clinically relevant polyions such as heparin and protamine and drastically improve the sensitivity of ion-selective sensors limited by the Nernst equation. The present study forms the basis for development of reliable, robust, and possibly maintenance-free sensors that can be fabricated using screen-printing technology. Various aspects of the development of solid-contact galvanostatically controlled ion-selective electrodes with a conducting polymer as a transduction layer are considered in the present work on the example of a model system based on a sodium-selective membrane. The protamine-selective solid-contact sensor was fabricated and characterized, which represents the next step toward commercially viable polyion sensing technology. A substantial improvement of a low detection limit (0.03 mg L-1) was achieved. A simplified diffusion-based theoretical model is discussed predicting the polarization at the interface of the conducting polymer and the membrane, which can cause the disruption of the sensor response function at relatively small current densities.
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- 2007
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